Vitamin D and Autism Spectrum Disorder: A Literature Review
Open accessAbstract
Low vitamin D status in early development has been hypothesised as an environmental risk factor for Autism Spectrum Disorder (ASD), given the concurrent increase in the prevalence of these two conditions, and the association of vitamin D with many ASD-associated medical conditions. Identification of vitamin D-ASD factors may provide indications for primary and secondary prevention interventions. We systematically reviewed the literature for studies on vitamin D-ASD relationship, including potential mechanistic pathways. We identified seven specific areas, including: latitude, season of conception/birth, maternal migration/ethnicity, vitamin D status of mothers and ASD patients, and vitamin D intervention to prevent and treat ASD. Due to differences in the methodological procedures and inconsistent results, drawing conclusions from the first three areas is difficult. Using a more direct measure of vitamin D status—that is, serum 25(OH)D level during pregnancy or childhood—we found growing evidence for a relationship between vitamin D and ASD. These findings are supported by convincing evidence from experimental studies investigating the mechanistic pathways. However, with few primary and secondary prevention intervention trials, this relationship cannot be determined, unless randomised placebo-controlled trials of vitamin D as a preventive or disease-modifying measure in ASD patients are available.
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Written from the paper’s full text.
TL;DR
This systematic literature review examines vitamin D and Autism Spectrum Disorder across seven areas, finding growing evidence from serum 25(OH)D studies and mechanistic pathways but inconsistent results for latitude, season, and migration. It concludes that randomized placebo-controlled trials are needed before vitamin D can be confirmed as a preventive or disease-modifying measure for ASD.
Key findings
- Latitude, season, and migration studies were inconsistent: AD prevalence ranged from 10.9 per 10,000 in China to 60.0 in Sweden, and PDD from 6.3 in Iran to 181.0 in Japan; winter conception was associated with AD in one study (OR 1.06, 95% CI 1.02–1.10) but summer conception in another (OR 1.86, 95% CI 1.01–3.37), while a Danish cohort found no association.
- In the case-control literature on vitamin D status in ASD patients, nine studies reported significantly lower 25(OH)D in ASD versus controls, one reported a borderline difference, and four found no significant difference; examples include Bener et al. (46.0 ± 20.5 vs. 54.0 ± 21.0 nmol/L, p = 0.004), Tostes et al. (approximately 35 nmol/L lower, p < 0.001), and Gong et al. (58% vs. 33% with 25(OH)D <50 nmol/L, p = 0.01).
- Maternal vitamin D findings were mixed: Whitehouse et al. (2013) found no difference in maternal 25(OH)D at 18 weeks among mothers of children with and without clinical ASD (n = 929), but the lower tertile (<45 nmol/L) was associated with higher attention-switching subscale scores (OR 5.46, 95% CI 1.29–23.05); Whitehouse et al. (2012) found maternal 25(OH)D <46 nmol/L associated with language difficulties at ages 5 and 10.
- Intervention evidence was limited: one prevention study reported an autism recurrence rate of approximately 5% versus 20% in other studies after maternal vitamin D 5000 IU/day during pregnancy, 7000 IU during breastfeeding, and 1000 IU to infants, but it was small and uncontrolled; treatment studies showed improvements in some open-label trials, but no randomized placebo-controlled trials were identified.
Methods
- Systematic literature search up to 31 January 2016 in PubMed, Web of Knowledge, EBSCO OVID, MEDLINE, PsycARTICLES, PsycINFO, SocINDEX, and Google Scholar, using distinct search strategies for seven areas: latitude; season of conception/birth; maternal migration/ethnicity; maternal vitamin D status; vitamin D status of ASD patients; maternal vitamin D intervention to prevent ASD; and vitamin D intervention to treat ASD.
- Inclusion criteria varied by area; for example, latitude studies required prevalence estimates, DSM-IV/ICD-10 case ascertainment, and children <8 years, while vitamin D status studies were case-control comparisons of individuals with ASD versus healthy controls. The review is a narrative synthesis, with mechanistic pathways presented separately.
Limitations
- Stated in the paper: conclusions are difficult because of methodological differences and inconsistent results; there are few primary and secondary prevention intervention trials and no randomized placebo-controlled trials; many included studies had small samples, lacked control or placebo arms, did not control for confounders or season, used crude proxies such as latitude or season, or had high attrition.
- Evident from the text: the review is narrative rather than meta-analytic; causality cannot be determined from the case-control studies, and reverse causality is possible because children with ASD may have less sun exposure, lower physical activity, and lower dietary vitamin D intake; intervention evidence includes open-label trials, a case report, and one small randomized trial without a placebo arm.
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Integrity signals
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Cites
Statistics
Claims the paper makes
0 of 374 cited sources checked · 0 supported · 0 flagged
- Findingcitation
The AD prevalence estimate per 10,000 ranged from 10.9 in China to 60.0 in Sweden.
“The AD prevalence estimate per 10,000 ranged from 10.9 in China [36] to 60.0 in Sweden [40].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [36] Zhang, 2005, Autism and mental retardation of young children in china, Biomed. Environ. Sci.
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- cites [40] Gillberg, 1999, Brief report: Autism and asperger syndrome in seven-year-old children: A total population study, J. Autism Dev. Disord. source
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- Findingown data
The review observed a latitudinal variation in the prevalence estimate for AD and PDD, with lower latitudes reporting lower prevalence estimates and vice versa.
“Consistent with these findings, we also observed a latitudinal variation in the prevalence estimate for AD and PDD, with those in the lower latitudes reporting lower prevalence estimates and vice versa.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Latitude is a reasonable proxy measure for vitamin D status.
- Findingreasoning
Using serum 25(OH)D level during pregnancy or childhood as a direct measure of vitamin D status, the review found growing evidence for a relationship between vitamin D and ASD.
“Using a more direct measure of vitamin D status—that is, serum 25(OH)D level during pregnancy or childhood—we found growing evidence for a relationship between vitamin D and ASD.”
Quote in the paperSubstantial claim - Findingcitation
Not all studies showed an association between season of birth and risk of autism.
“Not all studies showed an association between season of birth and risk of autism [64,77,79,81,83,84,85,86].”
Quote in the paperNot a substantial claim0 of 8 sources checked- cites [64] Hultman, 2002, Perinatal risk factors for infantile autism, Epidemiology (Camb. Mass.) source
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- cites [77] Atladottir, 2007, Variation in incidence of neurodevelopmental disorders with season of birth, Epidemiology (Camb. Mass.) source
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- cites [79] 2014, Serum vitamin D and folate levels in children with Autism Spectrum Disorders, Res. Autism Spectr. Disord. source
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- cites [81] Meguid, 2010, Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in egyptian children with autism, J. Altern. Complement. Med. (New York NY) source
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- cites [83] Kolevzon, 2006, Effects of season of birth on Autism Spectrum Disorders: Fact or fiction?, Am. J. Psychiatry source
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- cites [84] Nijman, 2000, Birth patterns in mentally retarded autistic patients, J. Autism Dev. Disord. source
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- cites [85] Stevens, 2000, Season of birth effects in autism, J. Clin. Exp. Neuropsychol. source
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- cites [86] Landau, 1999, Season of birth in autism: A fiction revisited, J. Autism Dev. Disord. source
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- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
- Findingcitation
March birth as a risk factor for autism has been reported by several studies from Canada, Denmark, the US and Israel.
“March birth as a risk factor for autism has also been reported by several studies from Canada [92], Denmark [80,88], the US [85] and Israel [87].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [92] Konstantareas, 1986, Season of birth in infantile autism, Child Psychiatry Hum. Dev. source
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- cites [80] Maimburg, 2010, Neonatal jaundice, autism, and other disorders of psychological development, Pediatrics source
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- cites [88] Mouridsen, 1994, Season of birth in infantile autism and other types of childhood psychoses, Child Psychiatry Hum. Dev. source
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- cites [85] Stevens, 2000, Season of birth effects in autism, J. Clin. Exp. Neuropsychol. source
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- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
- Findingcitation
Spring birth has been associated with increased risk of autism in studies conducted in Canada, Japan, the US, Sweden, and the UK.
“Spring birth has been associated with increased risk of autism in studies conducted in Canada [92], Japan [91], the US [82], Sweden [78,90], and the UK [76].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [92] Konstantareas, 1986, Season of birth in infantile autism, Child Psychiatry Hum. Dev. source
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- cites [91] Tanoue, 1988, Epidemiology of infantile autism in southern Ibaraki, Japan: Differences in prevalence in birth cohorts, J. Autism Dev. Disord. source
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- cites [82] Lee, 2008, Variation in season of birth in singleton and multiple births concordant for Autism Spectrum Disorders, Paediatr. Perinat. Epidemiol. source
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- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
- Premisecitation
Translation of a screening or diagnostic instrument may adversely affect its psychometric properties and therefore its sensitivity in picking up cues for autism.
“Translation of a screening or diagnostic instrument may adversely affect its psychometric properties and therefore its sensitivity in picking up the cues for autism [43].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [43] Samadi, 2012, A national study of the prevalence of autism among five-year-old children in Iran, Autism source
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- Premisenone given
Several methodological factors affect ASD prevalence estimates, including classification systems, case ascertainment and participants' age.
“There are several methodological factors that affect the prevalence estimates of ASD and these include classification systems, case ascertainment and participants’ age.”
Quote in the paperNot a substantial claim - Premisecitation
In studies using DSM-III, ASD prevalence is much lower than in those using DSM-IV or the Chinese classification system of Medical Disorders (CCMD).
“In studies using DSM—III, the prevalence is much lower than in those using DSM-IV or the Chinese classification system of Medical Disorders (CCMD) [34].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Wan, 2013, Prevalence of Autism Spectrum Disorders among children in China: A systematic review, Shanghai Arch. Psychiatry
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- Interpretationreasoning
The low prevalence estimates for AD in China and PDD in Iran and UAE despite high prevalence of low vitamin D status may be due to methodological issues (screening and diagnostic characteristics) and underreporting.
“However, the low prevalence estimate for AD in China and PDD in Iran and UAE despite having high prevalence of low vitamin D status [56,57,58] may be due to methodological issues (screening and diagnostic characteristics) and underreporting.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [56] Xiao, J.P., Zang, J., Pei, J.J., Xu, F., Zhu, Y., and Liao, X.P. (2015). Low maternal vitamin D status during the second trimester of pregnancy: A cross-sectional study in Wuxi, China. PLoS ONE, 10. source
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- cites [57] Kelishadi, 2013, Determinants of hypovitaminosis D in pregnant women and their newborns in a sunny region, Int. J. Endocrinol. source
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- cites [58] Thomas, 2011, Vitamin D deficiency and sun avoidance among university students at Abu Dhabi, United Arab Emirates, Dermatoendocrinology source
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- Interpretationreasoning
The findings of a relationship between vitamin D and ASD are supported by convincing evidence from experimental studies investigating the mechanistic pathways.
“These findings are supported by convincing evidence from experimental studies investigating the mechanistic pathways.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The higher PDD prevalence estimate in Japan compared with European countries may be partly explained by the higher prevalence of low vitamin D status among Japanese women than European women.
“The higher prevalence estimate for PDD in Japan compared with European countries may also, in part, be explained by the higher prevalence of low vitamin D status among Japanese women than European women.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Due to differences in methodological procedures and inconsistent results, drawing conclusions from the first three areas (latitude, season of conception/birth, maternal migration/ethnicity) is difficult.
“Due to differences in the methodological procedures and inconsistent results, drawing conclusions from the first three areas is difficult.”
Quote in the paperSubstantial claim - Premisecitation
Grant et al. (2013) reported an inverse relationship between solar UVB radiation doses and the prevalence of ASD.
“Grant et al. (2013) reported an inverse relationship between the solar UVB radiation doses and the prevalence of ASD [60].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [60] Grant, 2013, Autism prevalence in the united states with respect to solar UV-B doses: An ecological study, Dermatoendocrinology source
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- Premisecitation
In a US study, the proportion of children with ASD with intellectual disability was significantly different between black, Hispanic and white children: 48%, 38% and 25%, respectively.
“In a study from the US, the proportion of children with ASD with intellectual disability was significantly different between black, Hispanic and white children: 48%, 38% and 25%, respectively [71].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [71] (2014). Prevalence of Autism Spectrum Disorder among children aged 8 years—Autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill. Summ., 63, 1–21.
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- Premisecitation
van der Ven et al. (2013) reported a decreased risk for ASD in children whose mothers were born in developing countries compared with those born in developed countries.
“van der Ven et al. (2013), however, reported a decreased risk for ASD in children whose mothers were born in developing countries compared with those born in developed countries [70].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [70] Termorshuizen, 2013, An incidence study of diagnosed autism-spectrum disorders among immigrants to The Netherlands, Acta Psychiatr. Scand. source
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- Premisecitation
Aggregation of different months into seasons or half years can result in different results or even loss of information.
“Aggregation of different months into seasons or half years can result in different results or even loss of information.”
Quote in the paperSubstantial claim - Premisecitation
Atladottir et al. (2007) found no association between season of conception or birth and incidence rate of ASD and ASD subcategories in a cohort born in Denmark between 1990 and 1999.
“Lastly, Atladottir et al. (2007) found no association between season of conception or birth on incidence rate of ASD and ASD subcategories in a cohort born in Denmark between 1990 and 1999 [77].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [77] Atladottir, 2007, Variation in incidence of neurodevelopmental disorders with season of birth, Epidemiology (Camb. Mass.) source
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- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
- Premisecitation
Williams et al. (2008) reported that the odds of having a child with ASD among mothers born outside Australia significantly increased compared with those born in Australia, OR 1.4 (95% CI 1.0-1.9; p = 0.009).
“Williams et al. (2008) reported that the odds of having a child with ASD among mothers born outside Australia significantly increased compared with those born in Australia, 1.4 (95% CI, 1.0–1.9; p = 0.009) [66].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [66] Williams, 2008, Perinatal and maternal risk factors for Autism Spectrum Disorders in new South Wales, Australia, Child. Care. Health Dev. source
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- Premisecitation
The risk of having a child diagnosed with both autism and mental retardation increased two-fold in foreign-born black, Vietnamese and Filipino mothers.
“The risk of having a child diagnosed with both autism and mental retardation increased two-fold in foreign-born black, Vietnamese and Filipino mothers [69].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [69] Becerra, 2014, Autism Spectrum Dsiorders and race, ethnicity, and nativity: A population-based study, Pediatrics source
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- Premisecitation
Zerbo et al. (2011) reported a 6% increase in the risk of AD in children conceived during winter compared with summer months in California between 1990 and 2002 (OR 1.06, 95% CI 1.02-1.10).
“While controlling for several variables including year of conception and maternal residence at birth, Zerbo et al. (2011) reported a 6% (OR 1.06, 95% CI 1.02–1.10) increase in the risk of AD in children conceived during winter compared with summer months in California between 1990 and 2002 [75].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [75] Zerbo, 2011, Month of conception and risk of autism, Epidemiology (Camb. Mass.) source
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- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
- Premisecitation
Keen et al. (2010) reported an adjusted OR ranging from 1.2 (95% CI 0.8-1.9) in children of European mothers born outside the UK to 10.0 (95% CI 5.5-18.1) in children of Caribbean mothers compared with mothers born in the UK.
“Keen et al. (2010) reported an adjusted OR ranging from 1.2 (95% CI, 0.8–1.9) in children of European mothers born outside the UK to 10.0 (95% CI, 5.5–18.1) in children of Caribbean mothers compared with mothers born in the UK [63].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [63] Keen, 2010, Autism, ethnicity and maternal immigration, Br. J. Psychiatry source
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- Premisecitation
Maimburg et al. (2010) reported increased risk for infantile autism in those born in winter (October to March).
“In contrast, Maimburg et al. (2010) reported increased risk for infantile autism in those born in winter (October to March) [80].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [80] Maimburg, 2010, Neonatal jaundice, autism, and other disorders of psychological development, Pediatrics source
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- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
- Premisecitation
It is well documented that diagnostic variability contributes significantly to ASD prevalence estimates.
“It is well documented that diagnostic variability contributes significantly to the prevalence estimates [34].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Wan, 2013, Prevalence of Autism Spectrum Disorders among children in China: A systematic review, Shanghai Arch. Psychiatry
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- Premisecitation
Children conceived during winter months, when sun exposure is limited and vitamin D status is lower, were reported to have a higher risk of developing autism later in life than those conceived during summer months.
“Children conceived during the winter months, when sun exposure is limited and vitamin D status is lower, were reported to have a higher risk of developing autism later in life than those conceived during the summer months [74].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [74] Mazumdar, S., Liu, K.Y., Susser, E., and Bearman, P. (2012). The disappearing seasonality of autism conceptions in California. PLoS ONE, 7. source
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- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
- Interpretationreasoning
The lack of season of birth variation does not exclude the possibility of an association if autism with comorbidities was considered.
“As such, the lack of season of birth variation does not exclude the possibility of an association if autism with comorbidities was considered.”
Quote in the paperSubstantial claim - Premisecitation
Whitehouse et al. (2013) did not find any difference in 25(OH)D concentrations among mothers of children with and without clinical ASD (n = 929) while controlling for several variables.
“The authors did not find any difference in 25(OH)D concentrations among mothers of children with and without clinical ASD (n = 929) while controlling for several variables (maternal education, socioeconomic status, maternal race, age at conception, maternal smoking, alcohol intake during pregnancy, parity, infant health and sex).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [100] Whitehouse, 2013, Maternal vitamin D levels and the autism phenotype among offspring, J. Autism Dev. Disord. source
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- Premisecitation
Gale et al. (2008) could not find any relationship between maternal 25(OH)D concentration during pregnancy and child's intelligence and psychological health at ages 9 months and 9 years.
“By contrast, Gale et al. (2008) could not find any relationship between maternal 25(OH)D concentration during pregnancy and child’s intelligence and psychological health at ages 9 months and 9 years [104].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [104] Gale, 2008, Maternal vitamin D status during pregnancy and child outcomes, Eur. J. Clin. Nutr. source
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- Premisecitation
Fernell et al. (2010) found that more than 60% and 85% of mothers of Somali origin had 25(OH)D <25 nmol/L in spring and autumn, respectively, compared to only one mother of Swedish origin in both seasons.
“More than 60% and 85% of mothers of Somali origin had 25(OH)D <25 nmol/L in spring and autumn, respectively, compared to only one mother of Swedish origin in both seasons.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Fernell, 2010, Serum levels of 25-hydroxyvitamin D in mothers of swedish and of somali origin who have children with and without autism, Acta Paediatr. source
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- Premisecitation
The findings reflect a trend similar to Konstantreas et al. (1986) and Stevens et al. (2000) of a more pronounced seasonal effect on low functioning and/or nonverbal autism.
“This reflects a trend similar to the Konstantreas et al. (1986) [92] and Stevens et al. (2000) [85] findings of a more pronounced seasonal effect on low functioning and or nonverbal autism.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Whitehouse et al. (2012) reported a significant positive relationship between the severity of maternal vitamin D deficiency and the severity of language impairment (mild and moderate to severe) in children at five and 10 years of age.
“Whitehouse et al. (2012) reported a significant positive relationship between the severity of maternal vitamin D deficiency and the severity of the language impairment (mild and moderate to severe) in children at five and 10 years of age [94].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [94] Whitehouse, 2012, Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development, Pediatrics source
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- Premisecitation
Stubbs, Henley and Green (2016) found that the recurrence rate of autism was approximately four-fold less than that of other studies (5% vs. 20%).
“The recurrence rate of autism was approximately four-fold less than that of other studies (5% vs. 20%).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [106] Stubbs, 2016, Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings?, Med. Hypotheses source
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- Interpretationcitation
The lack of seasonal deviation in Middle Eastern/African origin populations could be due to the narrow range and low year-round mean 25(OH)D concentrations in these populations (28.5-33.3 nmol/L in winter and summer, respectively).
“This could be due to the narrow range and low year-round mean 25(OH)D concentrations in these populations (28.5–33.3 nmol/L in winter and summer, respectively) [93].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [93] Kanan, 2013, Year-round vitamin D deficiency among saudi female out-patients, Public Health Nutr. source
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- Interpretationreasoning
The inconsistent findings could be, in part, attributed to important methodological issues and the timing of blood collection during pregnancy.
“The inconsistent findings could be, in part, attributed to important methodological issues and the timing of blood collection during pregnancy.”
Quote in the paperSubstantial claim - Interpretationreasoning
The absent association between season of birth and autism in some studies may be attributed, at least in part, to the definition of season.
“The absent association in these studies may be attributed, at least in part, to the definition of season (discussed previously).”
Quote in the paperNot a substantial claim - Premisecitation
Fernell et al. (2010) found that the difference in 25(OH)D concentrations was not significantly different between mothers with and without a child with autism for either ethnicity.
“The difference in 25(OH)D concentrations was not significantly different between mothers with and without a child with autism for either ethnicity.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Fernell, 2010, Serum levels of 25-hydroxyvitamin D in mothers of swedish and of somali origin who have children with and without autism, Acta Paediatr. source
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- Premisecitation
Maternal 25(OH)D concentrations were not associated with the total score and four out of five subscales of Autism Like Quotient among 406 offspring.
“Maternal 25(OH)D concentrations were not associated with the total score and four out of five subscales of Autism Like Quotient (autistic-like traits) among 406 offspring.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [100] Whitehouse, 2013, Maternal vitamin D levels and the autism phenotype among offspring, J. Autism Dev. Disord. source
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- Premisecitation
Compared to children of mothers in the higher tertiles, children of mothers in the lower tertile (25(OH)D <45 nmol/L) had higher scores on the attention switching subscale (OR 5.46, 95% CI 1.29-23.05, p < 0.05) while controlling for several potential confounders, including season of blood collection.
“However, compared to children of mothers in the higher tertiles, children of mothers in the lower tertile (25(OH)D <45 nmol/L) had higher scores on attention switching subscale (OR 5.46, 95% CI, 1.29–23.05, p < 0.05) while controlling for several potential confounders, including season of blood collection.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [100] Whitehouse, 2013, Maternal vitamin D levels and the autism phenotype among offspring, J. Autism Dev. Disord. source
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- Premisecitation
Maternal 25(OH)D concentration <46 nmol/L was associated with significant language difficulties in the offspring at ages 5 and 10 years compared with those offspring of mothers with 25(OH)D concentrations >70 nmol/L, while controlling for several variables.
“While controlling for several variables, maternal 25(OH)D concentration <46 nmol/L was associated with significant language difficulties in the offspring at ages 5 and 10 years compared with those offspring of mothers with 25(OH)D concentrations >70 nmol/L [94].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [94] Whitehouse, 2012, Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development, Pediatrics source
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- Premisecitation
Maternal 25(OH)D concentration >75 nmol/L in pregnancy was associated with increased mental and psychomotor scores in infants at 14 months compared to those with 25(OH)D concentrations <50 nmol/L.
“Maternal 25(OH)D concentration >75 nmol/L in pregnancy was associated with increased mental and psychomotor scores in infants at 14 months compared to those with 25(OH)D concentrations <50 nmol/L [103].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [103] Morales, 2012, Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development, Pediatrics source
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- Interpretationreasoning
The lack of difference in Fernell et al. could be attributed to the very low and narrow maternal 25(OH)D concentration among mothers of Somali origin, which does not allow the relationship between vitamin D status of mothers and risk of ASD to be addressed.
“Furthermore, a lack of difference could be also attributed to the very low and narrow maternal 25(OH)D concentration among mothers of Somali origin which does not allow the relationship between vitamin D status of mothers and risk of ASD to be addressed.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Maternal 25(OH)D concentrations during pregnancy and infants' neuropsychological health might have differed between the many lost to follow-up and this could have biased the results.
“Maternal 25(OH)D concentrations during pregnancy and infants’ neuropsychological health might have differed between the many lost to follow-up and this could have biased the results.”
Quote in the paperSubstantial claim - Premisecitation
Tostes et al. (2012) reported that mean 25(OH)D concentration of children with ASD of different ethnic groups was lower by approximately 35 nmol/L than healthy age and sex matched controls (p < 0.001).
“Tostes et al. (2012) reported that mean 25(OH)D concentration of children with ASD of different ethnic groups was lower by approximately 35 nmol/L than healthy age and sex matched controls (p < 0.001) [110].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [110] Tostes, 2012, Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism, Trends Psychiatry Psychother. source
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- Premisecitation
Children on the severe end of the spectrum had lower mean 25(OH)D concentration than those with mild/moderate ASD (30 ± 15 vs. 53 ± 21 nmol/L).
“Children on the severe end of the spectrum had lower mean 25(OH)D concentration than those with mild/moderate ASD (30 ± 15 vs. 53 ± 21 nmol/L, respectively).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
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- Premisecitation
Kocovska et al. found that a larger proportion had 25(OH)D <50 nmol/L in cases than controls (88% in ASD group vs. 58% in sibling and parents each and 65% in healthy controls).
“Furthermore, a larger proportion had 25(OH)D <50 nmol/L in cases than controls (88% in ASD group vs. 58% in sibling and parents each and 65% in healthy controls).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [108] Kocovska, 2014, Vitamin D in the general population of young adults with autism in the faroe islands, J. Autism Dev. Disord. source
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- Premisecitation
Bener et al. found that circulating levels of 25(OH)D were inversely correlated with autism severity measured by ADOS.
“Circulating levels of 25(OH)D were inversely correlated with autism severity measured by Autism Diagnostic Observation Schedule (ADOS).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [118] Bener, 2014, Is high prevalence of vitamin D deficiency evidence for autism disorder? In a highly endogamous population, J. Pediatr. Neurosci. source
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- Premisecitation
Gong et al. found that autism severity measured by CARS negatively correlated with 25(OH)D concentrations (r = −0.4, p < 0.001) while controlling for several covariates including age, sex, season, magnesium, BMI, calcium and phosphate.
“Autism severity—measured by Childhood Autism Rating Scale (CARS)—negatively correlated with 25(OH)D concentrations (r = −0.4, p < 0.001) while controlling for several covariates including age, sex, season, magnesium, BMI, calcium and phosphate.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [112] Gong, 2014, Serum 25-hydroxyvitamin D levels in Chinese children with Autism Spectrum Disorders, Neuroreport source
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- Premisecitation
Mostafa and Al-Ayadi found that cases had significantly higher anti-MAG anti-autoantibodies than controls.
“Cases also had significantly higher anti-myelin-associated glycoprotein (anti-MAG) anti-autoantibodies than controls.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
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- Premisecitation
Bener et al. found that factors associated with autism were serum calcium, 25(OH)D, blood relative, BMI, physical activity, child order, and ferritin.
“Factors associated with autism were serum calcium, 25(OH)D, blood relative, BMI, physical activity, child order, and ferritin.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [118] Bener, 2014, Is high prevalence of vitamin D deficiency evidence for autism disorder? In a highly endogamous population, J. Pediatr. Neurosci. source
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- Premisecitation
Fernell et al. (2015) did not find any differences between cases and controls of Middle Eastern/African origin.
“On the other hand, the authors did not find any differences between cases and controls of Middle Eastern/African origin.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
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- Premisecitation
Serum 25(OH)D concentrations negatively correlated with CARS scores (r = −0.50, p < 0.0001).
“and serum 25(OH)D concentrations negatively correlated with CARS scores (r = −0.50, p < 0.0001) [111].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
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- Interpretationcitation
The lack of association in the Middle Eastern and African group may be attributed to the small sample size and very low mean 25(OH)D concentrations (11.5 ± 7.1 and 7.0 ± 5.0 nmol/L).
“The lack of association in Middle Eastern and African group may in part, be attributed to the small sample size and very low mean 25(OH)D concentrations in these two ethnic groups, 11.5 ± 7.1 and 7.0 ± 5.0 nmol/L, respectively.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
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- Premisecitation
Mostafa and Al-Ayadi found that children on the severe end of the spectrum had significantly higher anti-MAG anti-autoantibodies levels than those with mild/moderate ASD.
“Children on the severe end of the spectrum had significantly higher anti-MAG anti-autoantibodies levels than those with mild/moderate ASD.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
Not checked in the free run.
- Study design and conductnone given
A limitation of studies including family members is that cases and controls cannot be matched on age and sex.
“A limitation to those studies including family members is that cases and controls cannot be matched on age and sex.”
Quote in the paperNot a substantial claim - Premisecitation
Fernell et al. (2015) reported significantly lower mean 25(OH)D concentration at birth in autistic children of Scandinavian and other European origins than their non-ASD sibling controls.
“Using siblings or family members as controls to minimize confounding by socio-demographic factors, Fernell et al. (2015) reported significantly lower mean 25(OH)D concentration at birth in autistic children of Scandinavian and other European origins than their non-ASD sibling controls [78].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
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- Premisecitation
Gong et al. (2013) reported a larger proportion of children with ASD having 25(OH)D concentrations <50 nmol/L as compared to healthy controls (58% vs. 33%, p = 0.01).
“Examining both cases and controls for autistic-like features, Gong et al. (2013) reported a larger proportion of children with ASD having 25(OH)D concentrations <50 nmol/L as compared to healthy controls (58% vs. 33%, respectively p = 0.01) [112].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [112] Gong, 2014, Serum 25-hydroxyvitamin D levels in Chinese children with Autism Spectrum Disorders, Neuroreport source
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- Premisecitation
Mostafa and Al-Ayadi found that children with ASD displayed significantly lower 25(OH)D concentration than healthy controls.
“Children with ASD displayed significantly lower 25(OH)D concentration than healthy controls.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
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- Premisecitation
Bener et al. (2014) found that children with ASD had significantly lower 25(OH)D concentrations than healthy age, sex and ethnicity matched controls (46.0 ± 20.5 vs. 54.0 ± 21.0 nmol/L, p = 0.004).
“Children with ASD had significantly lower 25(OH)D concentrations than healthy age, sex and ethnicity matched controls (46.0 ± 20.5 vs. 54.0 ± 21.0 nmol/L, respectively, p = 0.004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [118] Bener, 2014, Is high prevalence of vitamin D deficiency evidence for autism disorder? In a highly endogamous population, J. Pediatr. Neurosci. source
Not checked in the free run.
- Premisecitation
Gong et al. found that when vitamin D status of study groups was compared according to the four seasons, children with ASD had lower summer 25(OH)D concentrations than controls (p = 0.02).
“When vitamin D status of study groups was compared according to the four seasons, children with ASD had lower summer 25(OH)D concentrations than controls (p = 0.02).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [112] Gong, 2014, Serum 25-hydroxyvitamin D levels in Chinese children with Autism Spectrum Disorders, Neuroreport source
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- Premisecitation
Kocovska et al. (2014) showed that ASD individuals had significantly lower 25(OH)D concentrations than their siblings, parents and healthy controls while adjusting for season of blood sampling.
“Kocovska et al. (2014) showed that ASD individuals had significantly lower 25(OH)D concentrations than their siblings, parents and healthy controls while adjusting for season of blood sampling (no one in ASD group had his/her blood sample drawn in winter) [108].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [108] Kocovska, 2014, Vitamin D in the general population of young adults with autism in the faroe islands, J. Autism Dev. Disord. source
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- Premisecitation
Neumeyer et al. found that despite comparable total energy intake and caloric intake from specific macronutrients, calcium and vitamin D intake was lower in cases than controls.
“Despite comparable total energy intake and caloric intake from specific macronutrients among study groups, calcium and vitamin D intake was lower in cases than controls.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
Not checked in the free run.
- Interpretationcitation
Due to repetitive and restricted dietary behaviours, ASD children are at increased risk of low dietary vitamin D intake.
“Moreover, due to repetitive and restricted dietary behaviours, ASD children are at increased risk of low dietary vitamin D intake [128,129].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [128] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with Autism Spectrum Disorders, Pediatrics source
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- cites [129] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
Not checked in the free run.
- Interpretationreasoning
Patients with ASD are likely to have medical conditions and use medications-affecting vitamin D metabolism or absorption-that have not been considered in these studies.
“Patients with ASD are likely to have medical conditions and use medications—affecting vitamin D metabolism or absorption—that have not been considered in these studies.”
Quote in the paperSubstantial claim - Premisecitation
Neumeyer et al. found that cases had marginally lower serum 25(OH)D concentration than controls (67 ± 5 vs. 79 ± 4 nmol/L, p = 0.05).
“Furthermore, cases had marginally lower serum 25(OH)D concentration than controls (67 ± 5 vs. 79 ± 4 nmol/L, p = 0.05).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
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- Premisecitation
Evidence suggests that a large proportion of children with ASD do not meet vitamin D requirements.
“Evidence suggests that a large proportion of children with ASD do not meet vitamin D requirements [126,132,133,134,135,136].”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [126] Stewart, 2015, Dietary supplementation in children with Autism Spectrum Disorders: Common, insufficient, and excessive, J. Acad. Nutr. Diet. source
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- cites [132] Hyman, 2012, Nutrient intake from food in children with autism, Pediatrics source
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- cites [133] Moore, E., Crook, T., James, J., Gonzales, D., and Hakkak, R. (2012). Nutrient intake among children with autism. J. Nutr. Disord. Ther. source
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- cites [134] Cornish, 1998, A balanced approach towards healthy eating in autism, J. Hum. Nutr. Diet. source
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- cites [135] Lindsay, 2006, Dietary status and impact of risperidone on nutritional balance in children with autism: A pilot study, J. Intellect. Dev. Disabil. source
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- cites [136] George, 2013, Calcium and vitamin D intake of boys who have autism, Infant Child Adolesc. Nutr. source
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- Premisecitation
Hashemzadeh et al. (2015) failed to show any difference in 25(OH)D concentrations between children with ASD aged 3-12 years (n = 13) and age and sex matched typically developing children (n = 14).
“Hashemzadeh et al. (2015) failed to show any difference in 25(OH)D concentrations between children with ASD aged 3–12 years (n = 13), and age and sex matched typically developing children (n = 14) [115].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [115] Hashemzadeh, 2015, Comparative study of vitamin D levels in children with Autism Spectrum Disorder and normal children: A case-control study, J. Fundam. Ment. Health
Not checked in the free run.
- Interpretationreasoning
The cause and effect relationship from these case-control studies cannot be determined.
“The cause and effect relationship from these case-control studies cannot be determined.”
Quote in the paperSubstantial claim - Interpretationreasoning
The comparable levels of 25(OH)D among ASD cases and controls in Ugur et al. could be attributed to the nationwide vitamin D supplementation after initiation of ASD.
“The comparable levels of 25(OH)D among ASD cases and controls in this study could therefore be attributed to the nationwide vitamin D supplementation after initiation of ASD.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [79] 2014, Serum vitamin D and folate levels in children with Autism Spectrum Disorders, Res. Autism Spectr. Disord. source
Not checked in the free run.
- Premisecitation
Neumeyer et al. (2013) reported a higher proportion of boys with ASD having 25(OH)D concentrations <80 nmol/L than healthy boys (77% vs. 37%, p = 0.02).
“Neumeyer et al. (2013) [114] reported higher proportion of boys with ASD having 25(OH)D concentrations <80 nmol/L than healthy boys (77% vs. 37%, p = 0.02).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
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- Premisecitation
Average vitamin D intake was 62% and 49% of dietary recommended intake (DRI) in boys with ASD aged 7-8 and 9-12 years, respectively.
“Average vitamin D intake was 62% and 49% of dietary recommended intake (DRI) in boys with ASD aged 7–8 and 9–12 years, respectively [136].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [136] George, 2013, Calcium and vitamin D intake of boys who have autism, Infant Child Adolesc. Nutr. source
Not checked in the free run.
- Premisecitation
Molloy et al. (2010) included boys with catheters placed for tonsillectomies as controls.
“Molloy et al. (2010) [113] included boys with catheters placed for tonsillectomies as controls.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [113] Molloy, 2010, Plasma 25(OH)D concentration in children with Autism Spectrum Disorder, Dev. Med. Child Neurol. source
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- Premisecitation
Daily vitamin D intake was 199 ± 176 IU and 320 ± 119 IU in ASD and typically developing children, respectively (p < 0.05).
“Daily vitamin D intake was 199 ± 176 IU and 320 ± 119 IU in ASD and typically developing children, respectively (p < 0.05) [129].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [129] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
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- Premisecitation
Ucuz et al. (2015) failed to show any significant differences across groups on ABC and Denver II.
“In another study from Turkey, however, despite improvement in scores on ABC and Denver II in both treatment and control groups, Ucuz et al. (2015) failed to show any significant differences across groups [141].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
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- Premisecitation
Jia et al. (2015) reported that shifting serum 25(OH)D concentration in a 32 month old child with ASD from 31 nmol/L to 203 nmol/L after two months of high dose vitamin D3 supplementation improved autistic core symptoms.
“In a recent case report, Jia et al. (2015) reported that shifting serum 25(OH)D concentration in a 32 month old child with ASD from 31 nmol/L to 203 nmol/L after two months of high dose vitamin D3 supplementation (150,000 IU per month administered intramuscularly plus 400 IU per day orally) improved autistic core symptoms [139].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [139] Jia, 2015, Core symptoms of autism improved after vitamin D supplementation, Pediatrics source
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- Premisecitation
VDR increases during development.
“VDR has been shown to be present early in development, to increase during development, and to be present in the adult brain—all indicative of a role for vitamin D in the developing and adult brain [145].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [145] Cui, 2013, The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain, Neuroscience source
Not checked in the free run.
- Study design and conductcitation
Ucuz et al. (2015) had a small sample size of <11 participants per group.
“This study had a small sample size of <11 participants per group.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
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- Premisecitation
Azzam et al. (2015) reported comparable improvements in CARS, social IQ, and Autism Treatment Evaluation Checklist scores in both vitamin D supplemented (six months) and control groups in children with ASD.
“In a randomised controlled trial including only children with ASD, Azzam et al. (2015), similarly, reported comparable improvements in scores on CARS, social IQ, and Autism Treatment Evaluation Checklist in both vitamin D supplemented (six months) and control groups [140].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [140] Azzam, 2015, Autism and vitamin D: An intervention study, Middle East Curr. Psychiatry source
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- Premisecitation
The brain chemistry of children with ASD may differ from that of children with developmental delay.
“The brain chemistry of children with ASD may differ from that of children with developmental delay [142], and as such the response to vitamin D supplement—that may affect brain chemistry [143]—could vary.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [142] Corrigan, 2013, Atypical developmental patterns of brain chemistry in children with Autism Spectrum Disorder, JAMA Psychiatry source
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- Study design and conductcitation
In Ucuz et al. (2015), children were not randomly assigned to study groups.
“Furthermore, children were not randomly assigned to study groups and neither baseline nor follow up 25(OH)D concentrations were reported.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
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- Premisecitation
VDR and enzymes involved in vitamin D metabolism have been identified in several regions of the brain, including neurons and glial cells.
“Vitamin D receptors (VDR) and enzymes involved in vitamin D metabolism have been identified in several regions of the brain including neurons and glial cells [144].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [144] Eyles, 2005, Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain, J. Chem. Neuroanat. source
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- Premisecitation
The improvement in Ucuz et al. (2015) was more pronounced in those receiving vitamin D supplement.
“To note, the improvement was more pronounced in those receiving vitamin D supplement.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
Not checked in the free run.
- Study design and conductcitation
Azzam et al. (2015) lacked a placebo arm.
“Although no quality appraisal can be performed for this study, what is clear is that this study had a small sample size and lacked a placebo arm.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [140] Azzam, 2015, Autism and vitamin D: An intervention study, Middle East Curr. Psychiatry source
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- Premisecitation
Jia et al. reported scores on Autism Behaviour Checklist, CARS and Severity of Illness of Clinical Global Impression increased from 80, 35 and 6 at baseline to 39, 28 and 4 at follow up, respectively.
“Scores on Autism Behaviour Checklist, Childhood Autism Rating Scale (CARS) and Severity of Illness of Clinical Global Impression increased from 80, 35 and 6 at the baseline to 39, 28 and 4 at the follow up, respectively.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [139] Jia, 2015, Core symptoms of autism improved after vitamin D supplementation, Pediatrics source
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- Premisecitation
VDR is present in the adult brain.
“VDR has been shown to be present early in development, to increase during development, and to be present in the adult brain—all indicative of a role for vitamin D in the developing and adult brain [145].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [145] Cui, 2013, The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain, Neuroscience source
Not checked in the free run.
- Study design and conductown data
Azzam et al. (2015) had a small sample size.
“Although no quality appraisal can be performed for this study, what is clear is that this study had a small sample size and lacked a placebo arm.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [140] Azzam, 2015, Autism and vitamin D: An intervention study, Middle East Curr. Psychiatry source
Not checked in the free run.
- Premisecitation
VDR is present early in development.
“VDR has been shown to be present early in development, to increase during development, and to be present in the adult brain—all indicative of a role for vitamin D in the developing and adult brain [145].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [145] Cui, 2013, The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain, Neuroscience source
Not checked in the free run.
- Interpretationreasoning
Findings from Ucuz et al. (2015) cannot be extrapolated to children with ASD only.
“It should be noted that the findings from this study cannot be extrapolated to children with ASD only.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
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- Premisecitation
Several case-control studies have shown that children with ASD have lower vitamin D intakes than typically developing controls.
“However, several case-control studies have shown that children with ASD have lower vitamin D intakes than typically developing controls [114,128,129,130].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
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- cites [128] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with Autism Spectrum Disorders, Pediatrics source
Not checked in the free run.
- cites [129] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
Not checked in the free run.
- cites [130] Bandini, 2010, Food selectivity in children with Autism Spectrum Disorders and typically developing children, J. Pediatr. source
Not checked in the free run.
- Interpretationreasoning
No firm conclusions can be drawn from early interventional studies of vitamin D in ASD until randomised placebo-controlled trials with sufficient sample size are undertaken.
“In summary, although these early interventional studies provided encouraging results, no firm conclusions can be drawn until randomised placebo-controlled trials with sufficient sample size are undertaken.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [140] Azzam, 2015, Autism and vitamin D: An intervention study, Middle East Curr. Psychiatry source
Not checked in the free run.
- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
Not checked in the free run.
- Premisecitation
Autistic and schizophrenic patients had the lowest median 25(OH)D concentrations compared to other psychiatric disorders, 32 (25th-75th percentile, 23-39) nmol/L and 35 (24-53) nmol/L, respectively, vs. >40 in other patients.
“Autistic and schizophrenic patients had the lowest median 25(OH)D concentrations compared to other psychiatric disorders, 32 (25th–75th percentile, 23–39) nmol/L and 35 (24–53) nmol/L, respectively, vs. >40 in other patients.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [119] Humble, 2010, Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: Relations with season, age, ethnic origin and psychiatric diagnosis, J. Steroid Biochem. Mol. Biol. source
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- Premisecitation
The only study linking vitamin D metabolic gene variants to ASD risk is by Schmidt et al.
“The only study linking vitamin D metabolic gene variants to ASD risk is by Schmidt et al. [148].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [148] Schmidt, 2015, Selected vitamin D metabolic gene variants and risk for Autism Spectrum Disorder in the charge study, Early Hum. Dev. source
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- Premisecitation
Treatment with vitamin D has a protective effect on persistent biochemical features comparable to those reported clinically in autistic patients.
“It has been documented that treatment with vitamin D has a protective effect on persistent biochemical features comparable to those reported clinically in autistic patients and ameliorates neurotoxicity, inflammation and DNA damage in propionic acid-intoxicated rats [156].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [156] Alfawaz, 2014, Protective and restorative potency of vitamin D on persistent biochemical autistic features induced in propionic acid-intoxicated rat pups, BMC Complement. Altern. Med. source
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- Premisecitation
Schmidt et al. illustrated that risk for ASD was increased in children inheriting the GG genotype of the CYP2R1 gene.
“The authors illustrated that the risk for ASD was increased in children inheriting the AA genotype of the GC gene (D binding protein), the GG genotype of the CYP2R1 gene (a catalyst enzyme involved in the transformation of vitamin D to 25(OH)D), and paternal Taql and Bsml genotypes of the VDR gene, highlighting the possible aetiological role of low vitamin D in ASD.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [148] Schmidt, 2015, Selected vitamin D metabolic gene variants and risk for Autism Spectrum Disorder in the charge study, Early Hum. Dev. source
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- Premisecitation
Only a small percentage of autism cases are clearly linked to genetic causes.
“Autism is considered to be driven genetically [146,147], though only small percentage of cases are clearly linked to genetic causes [22].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Schaaf, 2011, Solving the autism puzzle a few pieces at a time, Neuron source
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- Premisecitation
Treatment with vitamin D decreases 8-hydroxy-2-deoxyguanosin, a marker of endogenous oxidative damage to DNA.
“Treatment with vitamin D has been shown to decrease 8—hydroxy–2—deoxyguanosin, a marker of endogenous oxidative damage to DNA [150], increase Bax, a protein coding gene involved in apoptosis [150], regulates poly-ADP-ribose polymerase activity in the DNA damage response pathway [151], stabilize chromosomal structure and prevent double strand breaks [152].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [150] Fedirko, 2010, Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: A randomized clinical trial, Cancer Epidemiol. Biomark. Prev. source
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- Premisecitation
Alabdali et al. (2014) reported autistic children having lower levels of glutathione-transferase and vitamin E in plasma than healthy controls.
“Alabdali et al. (2014) reported autistic children having higher levels of mercury and lead than healthy controls, and lower levels of glutathione-transferase and vitamin E in plasma [157].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [157] Alabdali, 2014, A key role for an impaired detoxification mechanism in the etiology and severity of Autism Spectrum Disorders, Behav. Brain Func. source
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- Premisecitation
Pretreatment of cells exposed to toxicants with 1,25(OH)2D enhanced intracellular gamma-glutamyl transpeptidase and glutathione in the intracellular pool.
“Using cell culture models, Shinpo et al. (2000) and Garcion et al. (1999) indicated that pretreatment of cells exposed to toxicants with 1,25(OH)2D attenuated reactive oxygen species and nitric oxide, and enhanced intracellular gamma-glytamyl transpeptidase (an enzyme involved in glutathione synthesis) and glutathione in the intracellular pool [158,159].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [158] Shinpo, 2000, Effect of 1,25-dihydroxyvitamin D3 on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by l-buthionine sulfoximine and 1-methyl-4-phenylpyridine, J. Neurosci. Res. source
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- cites [159] Garcion, 1999, 1,25-dihydroxyvitamin D3 regulates the synthesis of γ-glutamyl transpeptidase and glutathione levels in rat primary astrocytes, J. Neurochem. source
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- Premisecitation
Exposure to heavy metals and impaired detoxification system have been involved in the aetiology of ASD in a subset of individuals.
“Exposure to heavy metals and impaired detoxification system, another abnormality in a subset of individuals with ASD, have also been involved in the aeitiology of ASD [157].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [157] Alabdali, 2014, A key role for an impaired detoxification mechanism in the etiology and severity of Autism Spectrum Disorders, Behav. Brain Func. source
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- Premisecitation
Alabdali et al. (2014) reported autistic children having higher levels of mercury and lead than healthy controls.
“Alabdali et al. (2014) reported autistic children having higher levels of mercury and lead than healthy controls, and lower levels of glutathione-transferase and vitamin E in plasma [157].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [157] Alabdali, 2014, A key role for an impaired detoxification mechanism in the etiology and severity of Autism Spectrum Disorders, Behav. Brain Func. source
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- Premisecitation
Children with ASD have higher levels of oxidised glutathione and F2-isoprostane than typically developing children.
“Recent evidence shows that children with ASD have lower levels of total glutathion and glutathione peroxidase (an enzyme involved in antioxidant defense and detoxification), higher levels of oxidised glutathione and F2—isoprostane (a marker of oxidative stress and lipid peroxidation) and reduced capacity for methylation than typically developing children [16,153].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [16] Mostafa, 2010, Oxidative stress in egyptian children with autism: Relation to autoimmunity, J. Neuroimmunol. source
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- cites [153] James, 2004, Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism, Am. J. Clin. Nutr. source
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- Premisecitation
Oxidative stress and reduced redox/antioxidant capacity in peripheral tissue are associated with anti-neuronal positivity.
“Oxidative stress and reduced redox/antioxidant capacity in cerebellum and temporal cortex have been shown to have functional consequences for chronic inflammatory response, mitochondrial dysfunction and protein and DNA damage [3], and in peripheral tissue have been associated with anti-neuronal positivity [16] and clinical features of autism [15].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Mostafa, 2010, Oxidative stress in egyptian children with autism: Relation to autoimmunity, J. Neuroimmunol. source
Not checked in the free run.
- Premisecitation
Oxidative stress and reduced redox/antioxidant capacity in peripheral tissue are associated with clinical features of autism.
“Oxidative stress and reduced redox/antioxidant capacity in cerebellum and temporal cortex have been shown to have functional consequences for chronic inflammatory response, mitochondrial dysfunction and protein and DNA damage [3], and in peripheral tissue have been associated with anti-neuronal positivity [16] and clinical features of autism [15].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] Ghezzo, A., Visconti, P., Abruzzo, P.M., Bolotta, A., Ferreri, C., Gobbi, G., Malisardi, G., Manfredini, S., Marini, M., and Nanetti, L. (2013). Oxidative stress and erythrocyte membrane alterations in children with autism: Correlation with clinical features. PLoS ONE, 8. source
Not checked in the free run.
- Interpretationcitation
Low vitamin D status has been implicated in the pathophysiology of ASD in several ways.
“Low vitamin D status has been implicated in pathophysiology of ASD in several ways.”
Quote in the paperSubstantial claim - Premisecitation
Treatment with vitamin D increases Bax, a protein coding gene involved in apoptosis.
“Treatment with vitamin D has been shown to decrease 8—hydroxy–2—deoxyguanosin, a marker of endogenous oxidative damage to DNA [150], increase Bax, a protein coding gene involved in apoptosis [150], regulates poly-ADP-ribose polymerase activity in the DNA damage response pathway [151], stabilize chromosomal structure and prevent double strand breaks [152].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [150] Fedirko, 2010, Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: A randomized clinical trial, Cancer Epidemiol. Biomark. Prev. source
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- Premisecitation
Children with ASD have lower levels of total glutathione and glutathione peroxidase than typically developing children.
“Recent evidence shows that children with ASD have lower levels of total glutathion and glutathione peroxidase (an enzyme involved in antioxidant defense and detoxification), higher levels of oxidised glutathione and F2—isoprostane (a marker of oxidative stress and lipid peroxidation) and reduced capacity for methylation than typically developing children [16,153].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [16] Mostafa, 2010, Oxidative stress in egyptian children with autism: Relation to autoimmunity, J. Neuroimmunol. source
Not checked in the free run.
- cites [153] James, 2004, Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism, Am. J. Clin. Nutr. source
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- Premisecitation
Mounting evidence suggests that low vitamin D status is involved in the aetiology of the abnormalities associated with ASD.
“Mounting evidence suggests that low vitamin D status is involved in the aetiology of the mentioned abnormalities [105].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [105] Groves, 2014, Vitamin D as a neurosteroid affecting the developing and adult brain, Annu. Rev. Nutr. source
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- Premisecitation
Vitamin D can protect the genome from daily life insults such as oxidative stress and toxins.
“Vitamin D regulates cell profilation and differentiation and can protect the genome from daily life insults such as oxidative stress and toxins (for a comprehensive review refer to [149]).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [149] Armstrong, 2012, Does vitamin D protect against DNA damage?, Mutat. Res-Fund. Mol. Mech. Mut. source
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- Premisecitation
Treatment with vitamin D regulates poly-ADP-ribose polymerase activity in the DNA damage response pathway.
“Treatment with vitamin D has been shown to decrease 8—hydroxy–2—deoxyguanosin, a marker of endogenous oxidative damage to DNA [150], increase Bax, a protein coding gene involved in apoptosis [150], regulates poly-ADP-ribose polymerase activity in the DNA damage response pathway [151], stabilize chromosomal structure and prevent double strand breaks [152].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [151] Mabley, 2007, Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D, Int. J. Mol. Med.
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- Premisecitation
Pretreatment of cells exposed to toxicants with 1,25(OH)2D attenuated reactive oxygen species and nitric oxide.
“Using cell culture models, Shinpo et al. (2000) and Garcion et al. (1999) indicated that pretreatment of cells exposed to toxicants with 1,25(OH)2D attenuated reactive oxygen species and nitric oxide, and enhanced intracellular gamma-glytamyl transpeptidase (an enzyme involved in glutathione synthesis) and glutathione in the intracellular pool [158,159].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [158] Shinpo, 2000, Effect of 1,25-dihydroxyvitamin D3 on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by l-buthionine sulfoximine and 1-methyl-4-phenylpyridine, J. Neurosci. Res. source
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- cites [159] Garcion, 1999, 1,25-dihydroxyvitamin D3 regulates the synthesis of γ-glutamyl transpeptidase and glutathione levels in rat primary astrocytes, J. Neurochem. source
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- Premisecitation
Schmidt et al. illustrated that risk for ASD was increased in children inheriting the AA genotype of the GC gene.
“The authors illustrated that the risk for ASD was increased in children inheriting the AA genotype of the GC gene (D binding protein), the GG genotype of the CYP2R1 gene (a catalyst enzyme involved in the transformation of vitamin D to 25(OH)D), and paternal Taql and Bsml genotypes of the VDR gene, highlighting the possible aetiological role of low vitamin D in ASD.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [148] Schmidt, 2015, Selected vitamin D metabolic gene variants and risk for Autism Spectrum Disorder in the charge study, Early Hum. Dev. source
Not checked in the free run.
- Premisecitation
Children with ASD have reduced capacity for methylation than typically developing children.
“Recent evidence shows that children with ASD have lower levels of total glutathion and glutathione peroxidase (an enzyme involved in antioxidant defense and detoxification), higher levels of oxidised glutathione and F2—isoprostane (a marker of oxidative stress and lipid peroxidation) and reduced capacity for methylation than typically developing children [16,153].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [16] Mostafa, 2010, Oxidative stress in egyptian children with autism: Relation to autoimmunity, J. Neuroimmunol. source
Not checked in the free run.
- cites [153] James, 2004, Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism, Am. J. Clin. Nutr. source
Not checked in the free run.
- Premisecitation
Children with ASD have elevated levels of pro-inflammatory cytokines including IL-6, TNF-α, and IFN-γ in different tissues.
“Furthermore, evidence suggests that children with ASD have elevated levels of pro-inflammatory cytokines including, interleukin 6 (IL–6), tumour necrosis factor alpha (TNF–α), and interferon gamma (IFN-γ) in different tissues [3,4,5,6,7].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [3] Rose, 2012, Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain, Transl. Psychiatry source
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- cites [4] Ashwood, 2011, Elevated plasma cytokines in Autism Spectrum Disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome, Brain Behav. Immun. source
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- cites [5] Chez, 2007, Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children, Pediatr. Neurol. source
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- cites [6] Napolioni, 2013, Plasma cytokine profiling in sibling pairs discordant for Autism Spectrum Disorder, J. Neuroinflamm. source
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- cites [7] Molloy, 2006, Elevated cytokine levels in children with Autism Spectrum Disorder, J. Neuroimmunol. source
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- Premisecitation
Several lines of evidence indicate oxidative stress and mitochondrial dysfunction are prevalent in individuals with ASD.
“There are presently several lines of evidence indicating oxidative stress and mitochondrial dysfunction are prevalent in individuals with ASD [3,10,11,12,13,14,15,16].”
Quote in the paperSubstantial claim0 of 8 sources checked- cites [3] Rose, 2012, Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain, Transl. Psychiatry source
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- cites [10] Ming, 2005, Increased excretion of a lipid peroxidation biomarker in autism, Prostaglandins Leukot. Essent. Fatty Acids source
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- cites [11] Giulivi, 2010, Mitochondrial dysfunction in autism, JAMA source
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- cites [12] Napoli, 2014, Deficits in bioenergetics and impaired immune response in granulocytes from children with autism, Pediatrics source
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- cites [13] Rose, S., Frye, R.E., Slattery, J., Wynne, R., Tippett, M., Pavliv, O., Melnyk, S., and James, S.J. (2014). Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS ONE, 9. source
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- cites [14] Melnyk, 2012, Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism, J. Autism Dev. Disord. source
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- cites [15] Ghezzo, A., Visconti, P., Abruzzo, P.M., Bolotta, A., Ferreri, C., Gobbi, G., Malisardi, G., Manfredini, S., Marini, M., and Nanetti, L. (2013). Oxidative stress and erythrocyte membrane alterations in children with autism: Correlation with clinical features. PLoS ONE, 8. source
Not checked in the free run.
- cites [16] Mostafa, 2010, Oxidative stress in egyptian children with autism: Relation to autoimmunity, J. Neuroimmunol. source
Not checked in the free run.
- Premisecitation
Low vitamin D status is associated with increased inflammatory, oxidative, and endothelial activation biomarkers in obese individuals.
“Evidence shows that 25(OH)D concentrations correlate significantly positively with glutathione levels in healthy adult populations [154], and low vitamin D status is associated with increased inflammatory, oxidative and endothelial activation biomarkers in obese individuals [155].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [155] 2012, Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children, J. Pediatr. source
Not checked in the free run.
- Premisecitation
Schmidt et al. illustrated that risk for ASD was increased in children inheriting paternal Taql and Bsml genotypes of the VDR gene.
“The authors illustrated that the risk for ASD was increased in children inheriting the AA genotype of the GC gene (D binding protein), the GG genotype of the CYP2R1 gene (a catalyst enzyme involved in the transformation of vitamin D to 25(OH)D), and paternal Taql and Bsml genotypes of the VDR gene, highlighting the possible aetiological role of low vitamin D in ASD.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [148] Schmidt, 2015, Selected vitamin D metabolic gene variants and risk for Autism Spectrum Disorder in the charge study, Early Hum. Dev. source
Not checked in the free run.
- Premisecitation
25(OH)D concentrations correlate significantly positively with glutathione levels in healthy adult populations.
“Evidence shows that 25(OH)D concentrations correlate significantly positively with glutathione levels in healthy adult populations [154], and low vitamin D status is associated with increased inflammatory, oxidative and endothelial activation biomarkers in obese individuals [155].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [154] Alvarez, 2014, Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults, Clin. Endocrinol. source
Not checked in the free run.
- Interpretationcitation
These results support an association between vitamin D status and ASD.
“All of these results support an association between vitamin D status and ASD.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [148] Schmidt, 2015, Selected vitamin D metabolic gene variants and risk for Autism Spectrum Disorder in the charge study, Early Hum. Dev. source
Not checked in the free run.
- Premisecitation
Both ASD and MS have been characterised by immunological abnormalities and dysfunctional myelination, at least in a subset of individuals.
“Both conditions have been characterised by immunological abnormalities and dysfunctional myelination, at least in a subset of individuals [170,171].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Vitamin D metabolites direct dendritic cells toward a more tolerogenic state.
“For example, vitamin D metabolites have been shown to decrease the secretion of IL-6 and TNF-α [162], enhance the expression of anti-inflammatory cytokines such as interleukin 10 (IL–10) from activated B cells [163], and to direct dendritic cells (DCs) toward a more tolerogenic state [164].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [164] Keresztes, 2009, 1,25-dihydroxyvitamin D3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype, J. Immunol. source
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- Premisecitation
Binding of brain serotonin transporter was significantly lower in adults with high functioning autism than healthy controls.
“While the binding of brain serotonin transporter was significantly lower in adults with high functioning autism than healthy controls, the binding of brain dopamine transporter was significantly higher in autistic patients [184].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [184] Nakamura, 2010, Brain serotonin and dopamine transporter bindings in adults with high-functioning autism, Arch. Gen. Psychiatry source
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- Premisecitation
Mostafa and Al-Ayadi reported significantly higher proportion of children with ASD having anti-MAG antiautoantibodies, anti-ganglioside M1, anti-neuronal and anti-nuclear antibodies than typically developing controls.
“Mostafa and Al-Ayadi reported significantly higher proportion of children with ASD having anti-MAG antiautoantibodies, anti-ganglioside M1, anti-neuronal and anti-nuclear antibodies than typically developing controls, that positively correlated with the severity of autism symptoms (CARS scores) [109,165,166,167].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
Not checked in the free run.
- cites [165] Mostafa, 2011, Increased serum levels of anti-ganglioside m1 auto-antibodies in autistic children: Relation to the disease severity, J. Neuroinflamm. source
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- cites [166] Mostafa, 2009, Serum anti-nuclear antibodies as a marker of autoimmunity in egyptian autistic children, Pediatr. Neurol. source
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- cites [167] Mostafa, 2012, The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children, Eur. J. Paediatr. Neurol. source
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- Premisecitation
Family history of autoimmune diseases was reported to be higher in children with ASD than controls.
“Family history of autoimmune diseases was reported to be higher in children with ASD than controls [166,168].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [166] Mostafa, 2009, Serum anti-nuclear antibodies as a marker of autoimmunity in egyptian autistic children, Pediatr. Neurol. source
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- cites [168] Mostafa, 2008, Serum anti-myelin-associated glycoprotein antibodies in egyptian autistic children, J. Child Neurol. source
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- Premisecitation
Activation of microglia is a prominent feature of autism.
“The activation of microglia, the unique resident cells of the central nervous system, is the prominent feature of autism [160] and is associated with increased several pro-inflammatory cytokines [161].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [160] Morgan, 2010, Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism, Biol. Psychiatry source
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- Premisecitation
Two ASD-associated independent gene variants, including a gene variant regulating STX1 phosphorylation and dopamine transporter, that alter dopamine transporter function have been identified.
“Recently, two ASD associated independent gene variants, including a gene variants regulating STX1 phosphorylation (regulates neurotransmitter transporter) and dopamine transporter, that alter dopamine transporter function have been identified [188].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [188] Cartier, 2015, Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation and the dopamine transporter (HDAT R51W) in dopamine neurotransmission and behaviors, EBioMedicine source
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- Premisecitation
Autism is considered as an autoimmune disease in a subset of individuals.
“Autism is also considered as an autoimmune disease in a subset of individuals.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Singh, 2009, Phenotypic expression of autoimmune autistic disorder (AAD): A major subset of autism, Ann. Clin. Psychiatry
Not checked in the free run.
- Premisecitation
Binding of brain dopamine transporter was significantly higher in autistic patients than healthy controls.
“While the binding of brain serotonin transporter was significantly lower in adults with high functioning autism than healthy controls, the binding of brain dopamine transporter was significantly higher in autistic patients [184].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [184] Nakamura, 2010, Brain serotonin and dopamine transporter bindings in adults with high-functioning autism, Arch. Gen. Psychiatry source
Not checked in the free run.
- Premisecitation
Multiple Sclerosis (MS) was identified to be significantly associated with ASD using a genome-wide data set of ASD and autoimmune disorders.
“Using a genome-wide data set of ASD and autoimmune disorders, Multiple Sclerosis (MS) was identified to be significantly associated with ASD [169].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [169] Jung, 2011, Identification of autoimmune gene signatures in autism, Transl. Psychiatry source
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- Premisecitation
Abnormal serotonin concentrations in the brain and tissues outside the blood-brain barrier have been reported in populations with ASD.
“Lower levels of plasma oxytocin [185] and abnormal serotonin concentrations in the brain and tissues outside the blood-brain barrier have been reported in populations with ASD [186,187].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [186] Chugani, 1999, Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children, Ann. Neurol. source
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- cites [187] Mulder, 2004, Platelet serotonin levels in Pervasive Developmental Disorders and mental retardation: Diagnostic group differences, within-group distribution, and behavioral correlates, J. Am. Acad. Child Adolesc. Psychiatry source
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- Premisecitation
Anti-MAG antiautoantibodies correlated negatively with serum 25(OH)D concentrations (r = −0.86, p < 0.001).
“Furthermore, anti-MAG antiautoantibodies correlated negatively with serum 25(OH)D concentrations (r = −0.86, p < 0.001) [109], and anti-nuclear antibody positive healthy controls were significantly more likely to be deficient in vitamin D than antibody negative healthy controls (71% vs. 22%, respectively, p = 0.003) [172].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
Not checked in the free run.
- Premisecitation
Vitamin D metabolites decrease the secretion of IL-6 and TNF-α.
“For example, vitamin D metabolites have been shown to decrease the secretion of IL-6 and TNF-α [162], enhance the expression of anti-inflammatory cytokines such as interleukin 10 (IL–10) from activated B cells [163], and to direct dendritic cells (DCs) toward a more tolerogenic state [164].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [162] Almerighi, 2009, 1α,25-dihydroxyvitamin D3 inhibits CD40l-induced pro-inflammatory and immunomodulatory activity in human monocytes, Cytokine source
Not checked in the free run.
- Premisecitation
Vitamin D analogues upregulate NGF in cultured glial cells and embryonic hippocampal cells.
“Vitamin D analogues have been shown to upregulate NGF in cultured glial cell and embryonic hippocampal cells [177,178], to decrease the percentage of cultured hippocampal cells undergoing mitosis [178], and to decrease BDNF and concommitantly to improve memory in postmenopausal women [179].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [177] Neveu, 1994, 1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells, Mol. Brain Res. source
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- cites [178] Brown, 2003, 1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons, Neurosci. Lett. source
Not checked in the free run.
- Premisecitation
Elevated autoantibodies in the brain, specifically anti-myelin basic protein antibodies, have been reported in autism.
“Elevated autoantibodies in the brain, specifically anti-myelin basic protein antibodies have been reported in autism [9].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Singh, 2009, Phenotypic expression of autoimmune autistic disorder (AAD): A major subset of autism, Ann. Clin. Psychiatry
Not checked in the free run.
- Premisecitation
Vitamin D metabolites enhance the expression of anti-inflammatory cytokines such as IL-10 from activated B cells.
“For example, vitamin D metabolites have been shown to decrease the secretion of IL-6 and TNF-α [162], enhance the expression of anti-inflammatory cytokines such as interleukin 10 (IL–10) from activated B cells [163], and to direct dendritic cells (DCs) toward a more tolerogenic state [164].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [163] Heine, 2008, 1,25-dihydroxyvitamin D3 promotes IL-10 production in human b cells, Eur. J. Immunol. source
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- Premisecitation
Abnormal levels of several neurotrophic factors such as NGF and BDNF have been reported in a subset of individuals with ASD.
“Abnormal levels of several neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factors (BDNF) have been reported in subset of individuals with ASD [175,176].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [175] Wang, 2015, Increased serum levels of brain-derived neurotrophic factor in Autism Spectrum Disorder, Neuroreport source
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- cites [176] Dincel, 2013, Serum nerve growth factor levels in autistic children in turkish population: A preliminary study, Indian J. Med. Res.
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- Premisecitation
Vitamin D analogues decrease the percentage of cultured hippocampal cells undergoing mitosis.
“Vitamin D analogues have been shown to upregulate NGF in cultured glial cell and embryonic hippocampal cells [177,178], to decrease the percentage of cultured hippocampal cells undergoing mitosis [178], and to decrease BDNF and concommitantly to improve memory in postmenopausal women [179].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [178] Brown, 2003, 1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons, Neurosci. Lett. source
Not checked in the free run.
- Premisecitation
Vitamin D has been shown to modify the expression of several genes involved in axogenesis and myelination.
“Vitamin D has also been shown to modify the expression of several genes involved in axogenesis and myelination [173].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [173] Chabas, J.-F., Stephan, D., Marqueste, T., Garcia, S., Lavaut, M.-N., Nguyen, C., Legre, R., Khrestchatisky, M., Decherchi, P., and Feron, F. (2013). Cholecalciferol (vitamin D3) improves myelination and recovery after nerve injury. PLoS ONE, 8. source
Not checked in the free run.
- Premisecitation
Activation of microglia is associated with increased several pro-inflammatory cytokines.
“The activation of microglia, the unique resident cells of the central nervous system, is the prominent feature of autism [160] and is associated with increased several pro-inflammatory cytokines [161].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [161] Vargas, 2005, Neuroglial activation and neuroinflammation in the brain of patients with autism, Ann. Neurol. source
Not checked in the free run.
- Premisecitation
Lower levels of plasma oxytocin have been reported in populations with ASD.
“Lower levels of plasma oxytocin [185] and abnormal serotonin concentrations in the brain and tissues outside the blood-brain barrier have been reported in populations with ASD [186,187].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [185] Modahl, 1998, Plasma oxytocin levels in autistic children, Biol. Psychiatry source
Not checked in the free run.
- Premisecitation
Anti-nuclear antibody positive healthy controls were significantly more likely to be deficient in vitamin D than antibody negative healthy controls (71% vs. 22%, p = 0.003).
“Furthermore, anti-MAG antiautoantibodies correlated negatively with serum 25(OH)D concentrations (r = −0.86, p < 0.001) [109], and anti-nuclear antibody positive healthy controls were significantly more likely to be deficient in vitamin D than antibody negative healthy controls (71% vs. 22%, respectively, p = 0.003) [172].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [172] Ritterhouse, 2011, Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus, Ann. Rheum. Dis. source
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- Premisecitation
Multiple lines of evidence suggest an involvement of dysregulated neurotransmitter systems (serotonergic, oxytocinergic, and dopaminergic) in autism.
“Multiple lines of evidence suggest an involvement of dysregulated neurotransmitter systems (serotonergic, oxytocinergic and dopaminergic systems) in autism.”
Quote in the paperNot a substantial claim0 of 5 sources checked- cites [180] Crockett, 2008, Serotonin modulates behavioral reactions to unfairness, Science source
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- cites [181] Anagnostou, 2012, Intranasal oxytocin versus placebo in the treatment of adults with Autism Spectrum Disorders: A randomized controlled trial, Mol. Autism source
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- cites [182] Naranjo, 2001, The role of the brain reward system in depression, Prog. Neuropsychopharmacol. Biol. Psychiatry source
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- cites [183] Staal, 2012, Brief report: The dopamine-3-receptor gene (DRD3) is associated with specific repetitive behavior in Autism Spectrum Disorder (ASD), J. Autism Dev. Disord. source
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- cites [184] Nakamura, 2010, Brain serotonin and dopamine transporter bindings in adults with high-functioning autism, Arch. Gen. Psychiatry source
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- Interpretationreasoning
Evidence suggests that vitamin D has a neuroprotective effect through its neurotrophic and immunomodulatory properties.
“Evidence suggests that vitamin D has a neuroprotectory effect through its neurotrophic and immunomodulatory properties.”
Quote in the paperSubstantial claim - Premisecitation
These antibodies positively correlated with the severity of autism symptoms (CARS scores).
“Mostafa and Al-Ayadi reported significantly higher proportion of children with ASD having anti-MAG antiautoantibodies, anti-ganglioside M1, anti-neuronal and anti-nuclear antibodies than typically developing controls, that positively correlated with the severity of autism symptoms (CARS scores) [109,165,166,167].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
Not checked in the free run.
- cites [165] Mostafa, 2011, Increased serum levels of anti-ganglioside m1 auto-antibodies in autistic children: Relation to the disease severity, J. Neuroinflamm. source
Not checked in the free run.
- cites [166] Mostafa, 2009, Serum anti-nuclear antibodies as a marker of autoimmunity in egyptian autistic children, Pediatr. Neurol. source
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- cites [167] Mostafa, 2012, The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children, Eur. J. Paediatr. Neurol. source
Not checked in the free run.
- Interpretationreasoning
There are some indications that early exposure to inadequate vitamin D may interact with other factors and contribute to the aetiology of autism.
“However, there are some indications that early exposure to inadequate vitamin D may interact with other factors and contribute to the aetiology of autism, low vitamin D status might be highly prevalent in populations with ASD, and intervention with vitamin D might be beneficial in reducing autism symptoms among those who have ASD.”
Quote in the paperSubstantial claim - Interpretationreasoning
There are some indications that low vitamin D status might be highly prevalent in populations with ASD.
“However, there are some indications that early exposure to inadequate vitamin D may interact with other factors and contribute to the aetiology of autism, low vitamin D status might be highly prevalent in populations with ASD, and intervention with vitamin D might be beneficial in reducing autism symptoms among those who have ASD.”
Quote in the paperSubstantial claim - Premisecitation
Pre-treatment with calcitriol protects rats' striatum and accumbens from methamphetamine-induced reduction in dopamine and serotonin.
“Pre-treatment with calcitriol has been shown to protect rats’ striatum and accumbens from methamphetamine-induced reduction in dopamine and serotonin [143].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [143] Cass, 2006, Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine, Ann. N. Y. Acad. Sci. source
Not checked in the free run.
- Premisecitation
Vitamin D and its analogues potentiate anticonvulsant activity of antiepileptic drugs in animal studies.
“Vitamin D and its analogues have been shown to increase seizure threshold, potentiate anticonvulsant activity of antiepileptic drugs, and to decrease the severity of seizures in animal studies [194,195,196].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [194] Kalueff, 2005, Anticonvulsant effects of 1,25-dihydroxyvitamin D in chemically induced seizures in mice, Brain Res. Bull. source
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- cites [195] Borowicz, 2007, Cholecalciferol enhances the anticonvulsant effect of conventional antiepileptic drugs in the mouse model of maximal electroshock, Eur. J. Pharmacol. source
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- cites [196] Siegel, 1984, Administration of 1,25-dihydroxyvitamin D3 results in the elevation of hippocampal seizure threshold levels in rats, Brain Res. source
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- Premisecitation
Vitamin D and its analogues increase seizure threshold in animal studies.
“Vitamin D and its analogues have been shown to increase seizure threshold, potentiate anticonvulsant activity of antiepileptic drugs, and to decrease the severity of seizures in animal studies [194,195,196].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [194] Kalueff, 2005, Anticonvulsant effects of 1,25-dihydroxyvitamin D in chemically induced seizures in mice, Brain Res. Bull. source
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- cites [195] Borowicz, 2007, Cholecalciferol enhances the anticonvulsant effect of conventional antiepileptic drugs in the mouse model of maximal electroshock, Eur. J. Pharmacol. source
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- cites [196] Siegel, 1984, Administration of 1,25-dihydroxyvitamin D3 results in the elevation of hippocampal seizure threshold levels in rats, Brain Res. source
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- Interpretationreasoning
Conclusions are not yet possible due to inconsistent results, different methodological approaches, and very few trials in the current literature.
“Conclusions are not yet possible due to the inconsistent results, different methodological approaches employed, and very few trials in the current literature.”
Quote in the paperSubstantial claim - Premisecitation
Vitamin D receptors have been identified in dopamine neurones in human substantia nigra.
“Vitamin D receptors have been identified in dopamine neurones in humans substantia nigra [145], and vitamin D response elements on genes involved in serotonin and oxytocin synthesis [189].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [145] Cui, 2013, The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain, Neuroscience source
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- Premisecitation
Vitamin D response elements are present on genes involved in serotonin and oxytocin synthesis.
“Vitamin D receptors have been identified in dopamine neurones in humans substantia nigra [145], and vitamin D response elements on genes involved in serotonin and oxytocin synthesis [189].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [189] Patrick, 2014, Vitamin D hormone regulates serotonin synthesis. Part 1: Relevance for autism, FASEB J. source
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- Premisecitation
Correction of vitamin D deficiency in patients with seizures decreased the frequency of seizures by 30%-40%.
“Correction of vitamin D deficiency in patients with seizures, decreased the frequency of seizures by 30%–40% [197,198].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [197] Clemens, 2012, Correction of vitamin D deficiency improves seizure control in epilepsy: A pilot study, Epilepsy Behav. source
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- cites [198] Christiansen, 1974, “Anticonvulsant action” of vitamin D in epileptic patients? A controlled pilot study, Br. Med. J. source
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- Interpretationcitation
These deficiencies can exacerbate the condition.
“It should be noted that at the same time, antiepileptic drugs impair vitamin D and calcium metabolism, leading to reduced levels of vitamin D and calcium [125], and these deficiencies can, on the other hand, exacerbate the condition.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [125] Menon, 2010, The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism—A longitudinal study, Seizure source
Not checked in the free run.
- Premisecitation
Vitamin D and its analogues decrease the severity of seizures in animal studies.
“Vitamin D and its analogues have been shown to increase seizure threshold, potentiate anticonvulsant activity of antiepileptic drugs, and to decrease the severity of seizures in animal studies [194,195,196].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [194] Kalueff, 2005, Anticonvulsant effects of 1,25-dihydroxyvitamin D in chemically induced seizures in mice, Brain Res. Bull. source
Not checked in the free run.
- cites [195] Borowicz, 2007, Cholecalciferol enhances the anticonvulsant effect of conventional antiepileptic drugs in the mouse model of maximal electroshock, Eur. J. Pharmacol. source
Not checked in the free run.
- cites [196] Siegel, 1984, Administration of 1,25-dihydroxyvitamin D3 results in the elevation of hippocampal seizure threshold levels in rats, Brain Res. source
Not checked in the free run.
- Interpretationreasoning
There are some indications that intervention with vitamin D might be beneficial in reducing autism symptoms among those who have ASD.
“However, there are some indications that early exposure to inadequate vitamin D may interact with other factors and contribute to the aetiology of autism, low vitamin D status might be highly prevalent in populations with ASD, and intervention with vitamin D might be beneficial in reducing autism symptoms among those who have ASD.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 22
- May combine two claims. 90
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThe review identified seven specific areas of vitamin D-ASD relationship research: latitude, season of conception/birth, maternal migration/ethnicity, vitamin D status of mothers and ASD patients, and vitamin D intervention to prevent and treat ASD.
“We identified seven specific areas, including: latitude, season of conception/birth, maternal migration/ethnicity, vitamin D status of mothers and ASD patients, and vitamin D intervention to prevent and treat ASD.”
Quote in the paperNot a substantial claimMay combine two claims.
FindingcitationThe PDD prevalence estimate ranged from 6.3 in Iran to 181.0 in Japan, and on average was >30 in Europe.
“The PDD prevalence estimate ranged from 6.3 in Iran [43] to 181.0 in Japan [45], and, on average, was >30 in Europe.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [43] Samadi, 2012, A national study of the prevalence of autism among five-year-old children in Iran, Autism source
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- cites [45] Kawamura, 2008, Reevaluating the incidence of Pervasive Developmental Disorders: Impact of elevated rates of detection through implementation of an integrated system of screening in Toyota, Japan, Psychiatry Clin. Neurosci. source
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Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThe review identified ASD prevalence data for eight countries.
“Our literature search identified prevalence data for eight countries [17,36,37,38,39,40,41,42,43,44,45].”
Quote in the paperNot a substantial claim0 of 10 sources checked- cites [17] Chakrabarti, 2001, Pervasive Developmental Disorders in preschool children, JAMA source
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- cites [36] Zhang, 2005, Autism and mental retardation of young children in china, Biomed. Environ. Sci.
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- cites [37] Baird, 2000, A screening instrument for autism at 18 months of age: A 6-year follow- up study, J. Am. Acad. Child Adolesc. Psychiatry source
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- cites [38] Chakrabarti, 2005, Pervasive Developmental Disorders in preschool children: Confirmation of high prevalence, Am. J. Psychiatry source
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- cites [39] Arvidsson, 1997, Autism in 3–6-year-old children in a suburb of goteborg, sweden, Autism source
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- cites [40] Gillberg, 1999, Brief report: Autism and asperger syndrome in seven-year-old children: A total population study, J. Autism Dev. Disord. source
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- cites [41] Mattila, 2011, Autism Spectrum Disorders according to DSM-IV-TR and comparison with DSM-5 draft criteria: An epidemiological study, J. Am. Acad. Child Adolesc. Psychiatry source
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- cites [42] Eapen, 2007, Prevalence of Pervasive Developmental Disorders in preschool children in the uae, J. Trop. Pediatr. source
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- cites [43] Samadi, 2012, A national study of the prevalence of autism among five-year-old children in Iran, Autism source
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- cites [44] Lejarraga, 2008, Screening for developmental problems at primary care level: A field programme in San Isidro, Argentina, Paediatr. Perinat. Epidemiol. source
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May combine two claims.
FindingcitationMost studies showed increased risk of ASD among children of migrant parents, while some reported no association or even decreased risk.
“Most studies showed increased risk of ASD among children of migrant parents [61,62,63,64,65,66,67,69,70], while some reported no association [61,65,68,69] or even decreased risk [61,68,69,70].”
Quote in the paperNot a substantial claim0 of 10 sources checked- cites [61] Magnusson, 2012, Migration and Autism Spectrum Disorder: Population-based study, Br. J. Psychiatry source
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- cites [62] Maimburg, 2006, Perinatal risk factors and infantile autism, Acta Psychiatr. Scand. source
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- cites [63] Keen, 2010, Autism, ethnicity and maternal immigration, Br. J. Psychiatry source
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- cites [64] Hultman, 2002, Perinatal risk factors for infantile autism, Epidemiology (Camb. Mass.) source
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- cites [65] Lauritsen, 2005, Effects of familial risk factors and place of birth on the risk of autism: A nationwide register-based study, J. Child Psychol. Psychiatry source
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- cites [66] Williams, 2008, Perinatal and maternal risk factors for Autism Spectrum Disorders in new South Wales, Australia, Child. Care. Health Dev. source
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- cites [67] Haglund, N.G.S., and Källén, K.B.M. (2010). Risk factors for autism and asperger syndrome: Perinatal factors and migration. Autism. source
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- cites [69] Becerra, 2014, Autism Spectrum Dsiorders and race, ethnicity, and nativity: A population-based study, Pediatrics source
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- cites [70] Termorshuizen, 2013, An incidence study of diagnosed autism-spectrum disorders among immigrants to The Netherlands, Acta Psychiatr. Scand. source
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- cites [68] Croen, 2002, Descriptive epidemiology of autism in a California population: Who is at risk?, J. Autism Dev. Disord. source
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May combine two claims.
FindingcitationOf 14 studies, nine reported significant differences in 25(OH)D concentrations between cases and controls, one borderline difference, and four found no significant differences among study groups.
“Of 14 studies, nine reported significant differences in 25(OH)D concentrations between cases and controls [78,81,108,109,110,111,112,117,118], one borderline difference [114], and four found no significant differences among study groups [79,113,115,116].”
Quote in the paperSubstantial claim0 of 10 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
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- cites [81] Meguid, 2010, Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in egyptian children with autism, J. Altern. Complement. Med. (New York NY) source
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- cites [108] Kocovska, 2014, Vitamin D in the general population of young adults with autism in the faroe islands, J. Autism Dev. Disord. source
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- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
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- cites [110] Tostes, 2012, Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism, Trends Psychiatry Psychother. source
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- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
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- cites [112] Gong, 2014, Serum 25-hydroxyvitamin D levels in Chinese children with Autism Spectrum Disorders, Neuroreport source
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- cites [117] Feng, J., Shan, L., Du, L., Wang, B., Li, H., Wang, W., Wang, T., Dong, H., Yue, X., and Xu, Z. (2016). Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr. Neurosci. source
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- cites [118] Bener, 2014, Is high prevalence of vitamin D deficiency evidence for autism disorder? In a highly endogamous population, J. Pediatr. Neurosci. source
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- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
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May combine two claims.
Findingown dataOur literature review identified a large number of observational studies but very few intervention trials investigating the relationship between vitamin D and ASD.
“Our literature review identified a large number of observational studies but very few intervention trials investigating the relationship between vitamin D and ASD.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationASD is genetically driven and can be triggered by environmental risk factors.
“It is now believed that ASD is genetically driven and can be triggered by environmental risk factors [22].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Schaaf, 2011, Solving the autism puzzle a few pieces at a time, Neuron source
Not checked in the free run.
May combine two claims.
PremisecitationApproximately 95% of Japanese pregnant women have been reported to have 25(OH)D levels <50 nmol/L; corresponding figures in the UK and Latin America are 55% and 37%, respectively.
“Approximately 95% of Japanese pregnant women have been reported to have 25(OH)D levels <50 nmol/L; the corresponding figures in the UK and Latin America have been reported to be 55% and 37%, respectively [51,52], a finding confirmed by a systematic review of global maternal and new born vitamin D status [53].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [51] McAree, 2013, Vitamin D deficiency in pregnancy—Still a public health issue, Mater. Child. Nutr. source
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- cites [52] Pena, H.R., de Lima, M.C., Brandt, K.G., de Antunes, M.M., and da Silva, G.A. (2015). Influence of preeclampsia and gestational obesity in maternal and newborn levels of vitamin D. BMC Pregnancy Childbirth, 15. source
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- cites [53] Saraf, R., Morton, S.M., Camargo, C.A., and Grant, C.C. (2015). Global summary of maternal and newborn vitamin D status—A systematic review. Mater. Child. Nutr. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationASD prevalence estimates have increased dramatically, with recent estimates of 90 to 250 per 10,000 individuals compared with previous estimates of less than 10 per 10,000.
“While previous prevalence studies identified less than 10 in 10,000 individuals [17], recent estimates suggest rates of 90 to 250 in 10,000 individuals [1,18,19,20].”
Quote in the paperNot a substantial claim0 of 5 sources checked- cites [17] Chakrabarti, 2001, Pervasive Developmental Disorders in preschool children, JAMA source
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- cites [1] New Zealand Guidelines Group (2010). A resource to Help Identify Autism Spectrum Disorder, New Zealand Guidelines Group.
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- cites [18] Baio, J. (2012). Prevalence of Autism Spectrum Disorders—Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2008, Centers for Disease Control and Prevention. Morbidity and mortality weekly report; Surveillance summaries.
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- cites [19] Ghanizadeh, 2008, A preliminary study on screening prevalence of pervasive developmental disorder in schoolchildren in iran, J. Autism Dev. Disord. source
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- cites [20] Kogan, 2009, Prevalence of parent-reported diagnosis of Autism Spectrum Disorder among children in the us, 2007, Pediatrics source
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May combine two claims.
InterpretationreasoningWith few primary and secondary prevention intervention trials, the vitamin D-ASD relationship cannot be determined unless randomised placebo-controlled trials of vitamin D as a preventive or disease-modifying measure in ASD patients are available.
“However, with few primary and secondary prevention intervention trials, this relationship cannot be determined, unless randomised placebo-controlled trials of vitamin D as a preventive or disease-modifying measure in ASD patients are available.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationMandatory vitamin D food fortification and dietary supplementation policies may have improved vitamin D status in Finnish populations and may explain the lower AD prevalence estimate in Finland compared with Sweden.
“Mandatory vitamin D food fortification of certain foods and dietary supplementation policies may have improved vitamin D status in Finish populations [48,49,50], and may explain the lower prevalence estimate for AD in this country.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [48] Piirainen, 2006, Impact of national fortification of fluid milks and margarines with vitamin D on dietary intake and serum 25-hydroxyvitamin D concentration in 4-year-old children, Eur. J. Clin. Nutr. source
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- cites [49] Tylavsky, 2006, Strategies to improve vitamin D status in northern european children: Exploring the merits of vitamin D fortification and supplementation, J. Nutr. source
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- cites [50] Laaksi, 2006, Vitamin D fortification as public health policy: Significant improvement in vitamin D status in young finnish men, Eur. J. Clin. Nutr. source
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May combine two claims.
InterpretationreasoningLiving at higher latitudes might be associated with lower doses of UVB radiation, if not compensated by more sun exposure or ingestion of vitamin D rich foods or supplements, and consequently increased risk of ASD.
“Accordingly, living at higher latitudes might be associated with lower doses of UVB radiation, if not compensated by more sun exposure or ingestion of vitamin D rich foods or supplements, and consequently increased risk of ASD.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Latitude is a reasonable proxy measure for vitamin D status.
May combine two claims.
PremisecitationChildren of black ethnicity had increased risk for AD, 2.6 (1.3-5.0), while the risk for Asperger Syndrome and PDD-NOS decreased in these children, 0.5 (0.2-1.0).
“While children of black ethnicity had increased risk for AD, 2.6 (1.3–5.0), the risk for Asperger Syndrome and PDD-NOS decreased in these children 0.5 (0.2–1.0) [72].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [72] Croen, 2007, Maternal and paternal age and risk of Autism Spectrum Disorders, Arch. Pediatr. Adolesc. Med. source
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May combine two claims.
PremisecitationMagnusson et al. (2012) reported an increased risk of low functioning autism and decreased risk of high functioning autism in children of migrant parents in Sweden, with risk ratios 1.2 (1.0-1.4) and 0.5 (0.4-0.6), respectively.
“Magnusson et al. (2012) reported an increased risk of low functioning autism and decreased risk of high functioning autism in children of migrant parents in Sweden, 1.2 (1.0–1.4) and 0.5 (0.4–0.6), respectively [61], a finding confirmed by Williams et al. 2008 [66] and Becerra et al. (2014) [69].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [61] Magnusson, 2012, Migration and Autism Spectrum Disorder: Population-based study, Br. J. Psychiatry source
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- cites [66] Williams, 2008, Perinatal and maternal risk factors for Autism Spectrum Disorders in new South Wales, Australia, Child. Care. Health Dev. source
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- cites [69] Becerra, 2014, Autism Spectrum Dsiorders and race, ethnicity, and nativity: A population-based study, Pediatrics source
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May combine two claims.
PremisecitationHebert et al. (2010) reported an increased rate of children later diagnosed with ASD in those conceived during summer in the UK, with a conception rate of 9.5/1000 vs. 5.7/1000 in summer and winter, respectively, and an OR of 1.86 (1.01-3.37).
“By contrast, Hebert et al. (2010) reported an increased rate of children later diagnosed with ASD in those conceived during summer in the UK; with a conception rate of 9.5/1000 vs. 5.7/1000 in summer (June—August) and winter (December-February) months, respectively, with a corresponding peak in spring births, an OR of 1.86 (1.01–3.37) [76].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [76] Hebert, 2010, Association of autistic spectrum disorder with season of birth and conception in a UK cohort, Autism Res. source
Not checked in the free run.
- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
May combine two claims.
PremisecitationThe risk of AD was reported to be higher in children of mothers born in Mexico and in East Asian countries living in the US than in children of mothers born in the US.
“The risk of AD was reported to be higher in children of mothers born in Mexico and in East Asian countries living in the US than those of mothers born in the US [68,69].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [68] Croen, 2002, Descriptive epidemiology of autism in a California population: Who is at risk?, J. Autism Dev. Disord. source
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- cites [69] Becerra, 2014, Autism Spectrum Dsiorders and race, ethnicity, and nativity: A population-based study, Pediatrics source
Not checked in the free run.
May combine two claims.
PremisecitationLee et al. (2008) reported three peaks during spring, summer and autumn months in singleton and multiple births concordant with ASD, and an 87% decreased risk for multiple births concordant for ASD in males in winter compared to other seasons (relative risk 0.18, 95% CI 0.04, 0.82; p < 0.05).
“Lee et al. (2008) reported three peaks during spring, summer and autumn months in singleton and multiple births concordant with ASD (n = 1051), and an 87% decreased risk for multiple births concordant for ASD in males in winter (December) compared to other seasons [relative risk 0.18, 95% CI 0.04, 0.82; p < 0.05) [82].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [82] Lee, 2008, Variation in season of birth in singleton and multiple births concordant for Autism Spectrum Disorders, Paediatr. Perinat. Epidemiol. source
Not checked in the free run.
- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningA possible explanation for the increased risk of severe disability among children of darker-skinned migrant mothers is that these mothers are at increased risk of low vitamin D status and moving to northern latitudes with lower solar UVB radiation may exacerbate the condition.
“A possible explanation is that mothers with darker skin are at increased risk of low vitamin D status and moving to northern latitudes with lower solar UVB radiation may exacerbate the condition and thereby lead to more severe disability among their children.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductreasoningNot all studies controlled for sun exposure variables; therefore it is difficult to relate these results directly to the vitamin D-ASD relationship.
“Finally, not all studies controlled for sun exposure variables; therefore it is difficult to relate these results directly to vitamin D-ASD relationship.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningThe aetiology of AD might be different from those of Asperger Syndrome and PDD-NOS in different race/ethnic groups, and low vitamin D status, highly prevalent in some race/ethnic groups, could exacerbate the condition and cause AD.
“An explanation is that the aetiology of AD might be different from those of Asperger Syndrome and PDD-NOS in different race/ethnic group and that low vitamin D status which is highly prevalent in some race/ethnic groups, could exacerbate the condition, and cause AD.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningLandau et al. (1999) included cases with autism from different regions with different environmental influences and controls were individuals with mental retardation; inclusion of these disorders in the control group may mask the seasonal variability among groups.
“Landau et al. (1999) included cases with autism from different regions with different environmental influences and controls were individuals with mental retardation [86]. Disorders of neurodevelopment may share the same environmental influences and inclusion of these disorders in the control group may mask the seasonal variability among groups.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [86] Landau, 1999, Season of birth in autism: A fiction revisited, J. Autism Dev. Disord. source
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Study design and conductcitationOnly three males were clinically diagnosed with ASD at follow up in Whitehouse et al. (2013), and extrapolating these results to the broader ASD population should be done with caution.
“It should be noted that only three males were clinically diagnosed with ASD at follow up and extrapolating these results to the broader ASD population should be done with caution.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [100] Whitehouse, 2013, Maternal vitamin D levels and the autism phenotype among offspring, J. Autism Dev. Disord. source
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PremisecitationFennell et al. (2015) did not find any seasonal deviations for ASD populations from typically developing controls of Middle Eastern/African origin, though the season of birth difference was significant in cases and controls of Swedish origin (38% in spring vs. 18% in summer; p < 0.05).
“For instance, Fennell et al. (2015) did not find any seasonal deviations for ASD populations from the typically developing controls of Middle Eastern/African origin, though the season of birth difference was significant in cases and controls of Swedish origin (38% in spring vs. 18% in summer; p < 0.05) [78].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
Not checked in the free run.
- Rests on an assumption: Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
May combine two claims.
InterpretationcitationDepending on the timing of exposure to low vitamin D status, different brain areas might be affected and the consequence might be different neurodevelopment and cognitive outcomes in infants.
“These findings suggest that depending on the timing of the exposure to low vitamin D status, different brain areas might be affected and the consequence might be different neurodevelopment and cognitive outcomes in infants [105].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [105] Groves, 2014, Vitamin D as a neurosteroid affecting the developing and adult brain, Annu. Rev. Nutr. source
Not checked in the free run.
May combine two claims.
InterpretationcitationKolevzon et al. (2006) identified cases through a screening programme for military services in Israel, and Orthodox women were exempted from military service; therefore some autistic cases might have been missed.
“Kolevzon et al. (2006), identified cases through a screening programme for military services in Israel and Orthodox women were exempted from the military service. Therefore, some autistic cases might have been missed [83].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [83] Kolevzon, 2006, Effects of season of birth on Autism Spectrum Disorders: Fact or fiction?, Am. J. Psychiatry source
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PremisecitationEnvironmental factors including pesticides, infection, nutritional factors and maternal biochemistry vary by season, have been hypothesised to be implicated in the aetiology of ASD, and need to be taken into consideration when interpreting the literature on season of conception/birth and risk of ASD.
“These environmental factors include application of pesticides [95], infection [96], nutritional factors [97] and maternal biochemistry [98], all of which have been hypothesised to be implicated in the aetiology of ASD, and need to be taken into consideration when interpreting the literature on season of conception/birth and risk of ASD.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [95] Shelton, 2014, Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The charge study, Environ. Health Perspect. source
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- cites [96] Lee, 2015, Maternal hospitalization with infection during pregnancy and risk of Autism Spectrum Disorders, Brain Behav. Immun. source
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- cites [97] Lyall, 2014, Maternal lifestyle and environmental risk factors for Autism Spectrum Disorders, Int. J. Epidemiol. source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningDifferences in the seasonal effect of birth and risk of low and high functioning autism might be attributed to different etiological factors or to the same etiological factors but of different intensity.
“The differences in the seasonal effect of birth and risk of low and high functioning autism might be attributed to different etiological factors or to the same etiological factors but of different intensity.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationSome studies did not find a season/month of birth effect on aggregated samples but reported seasonal deviations from the general population in autism with comorbidities such as language and developmental delay.
“Interestingly, some studies did not find a season/month of birth effect on aggregated samples but reported seasonal deviations from the general population in autism with comorbidities such as language and developmental delay [84,85].”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationWhitehouse et al. (2012) and Morale et al. (2012) showed that lower maternal 25(OH)D concentration in pregnancy (weeks 18 and 13.5, respectively) was associated with more language difficulties and mental and psychomotor outcomes in offspring, respectively.
“Consistent with these findings, Whitehouse et al. (2012) and Morale et al. (2012) also showed that lower maternal 25(OH)D concentration in pregnancy (weeks 18 and 13.5, respectively) was associated with more language difficulties and mental and psychomotor outcomes in offspring, respectively [94,103].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [94] Whitehouse, 2012, Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development, Pediatrics source
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- cites [103] Morales, 2012, Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development, Pediatrics source
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May combine two claims.
PremisecitationYeates Frederiks et al. (2000) did not find an effect of season of birth on autism rate in the aggregated sample, but found a significant seasonal trend for low functioning autism (autism with IQ < 35) with increased rates for autistic births in the second quarter of the year.
“For example, Yeates Frederiks et al. (2000) did not find an effect of season of birth on autism rate in the aggregated sample, but they found a significant seasonal trend for low functioning autism (autism with IQ < 35) (increased rates for autistic births in the second quarter of the year) [84].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [84] Nijman, 2000, Birth patterns in mentally retarded autistic patients, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
Study design and conductcitationWhitehouse et al. (2013) had only 14% of offspring from the original cohort complete the study, and the high attrition rate was biased toward the loss of mothers with lower socioeconomic status.
“A limitation of this study is that only 14% of offspring from the original cohort completed the study. The high attrition rate was biased toward the loss of mothers with lower socioeconomic status.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [100] Whitehouse, 2013, Maternal vitamin D levels and the autism phenotype among offspring, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
Study design and conductcitationAt follow-up, the sample size was smaller (n = 178) and the attrition rate was higher (70%) in the Gale et al. study than in the Whitehouse et al. and Morales et al. studies (n = 412 and 50% and n = 1826 and 25%, respectively).
“At the follow-up, the sample size was smaller (n = 178) and the attrition rate was higher (70%) in the Gale et al. study [104] than the Whitehouse et al. and Morales et al. studies (n = 412 and 50% and n = 1826 and 25%, respectively) [94,103].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [104] Gale, 2008, Maternal vitamin D status during pregnancy and child outcomes, Eur. J. Clin. Nutr. source
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- cites [94] Whitehouse, 2012, Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development, Pediatrics source
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- cites [103] Morales, 2012, Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development, Pediatrics source
Not checked in the free run.
May combine two claims.
Study design and conductown dataFernell et al. (2010) is limited by its small sample size and the long time period since pregnancy (average age of more than 4 years).
“This study is limited, however, by its small sample size and the long time period since pregnancy (average age of more than 4 years).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Fernell, 2010, Serum levels of 25-hydroxyvitamin D in mothers of swedish and of somali origin who have children with and without autism, Acta Paediatr. source
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May combine two claims.
PremisecitationEvidence shows that both lower socioeconomic status and lower maternal education are associated with lower vitamin D status.
“On the other hand, evidence shows that both lower socioeconomic status and lower maternal education are associated with lower vitamin D status [101,102].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [101] Wakayo, T., Belachew, T., Vatanparast, H., and Whiting, S.J. (2015). Vitamin D deficiency and its predictors in a country with thirteen months of sunshine: The case of school children in central Ethiopia. PLoS ONE, 10. source
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- cites [102] Rabenberg, 2015, Vitamin D status among adults in germany—Results from the German health interview and examination survey for adults (DEGS1), BMC Public Health source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe small sample size in the Meguid et al. (2010), Ugar et al. (2014) and Fernell et al. (2015) studies (all n < 70) may have contributed to their non-significant findings.
“Furthermore, the small sample size in the Meguid et al. (2010), Ugar et al. (2014) and Fernell et al. (2015) studies (all n < 70) may have contributed to their non-significant findings.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone givenSeason of birth is a crude proxy measure for sun exposure and, more specifically, vitamin D status; many other potentially relevant factors vary by season.
“Finally, seasonal of birth is a crude proxy measure for sun exposure and, more specifically, vitamin D status; many other potentially relevant factors vary by season.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationMostafa and Al-Ayadi found that 40% of children with ASD had 25(OH)D concentrations <25 nmol/L, while no one from the control group had 25(OH)D concentrations in that range.
“While 40% of children with ASD had 25(OH)D concentrations <25 nmol/L, no one from control group had 25(OH)D concentrations in that range.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
Not checked in the free run.
May combine two claims.
Study design and conductcitationIn Fernell et al., season of birth corresponded to the season of blood sampling and was not controlled for in statistical analysis.
“Season of birth which corresponded to the season of blood sampling in this study was not controlled for in statistical analysis.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
Not checked in the free run.
May combine two claims.
InterpretationcitationThese findings point to a link between low vitamin D status, autoimmunity and autism.
“These findings point to a link between low vitamin D status, autoimmunity and autism.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationMostafa and Al-Ayadi found that 25(OH)D concentrations correlated negatively with CARS scores (r = −0.84, p < 0.001) and anti-MAG anti-autoantibodies (r = −0.86, p < 0.001).
“Furthermore, 25(OH)D concentrations correlated negatively with CARS scores, (r = −0.84, p < 0.001) and anti-MAG anti-autoantibodies (r = −0.86, p < 0.001).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
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Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning25(OH)D concentrations of those entering the Feng et al. study in April could be different from those entering September due to potentially limited sun exposure during winter months.
“To note, 25(OH)D concentrations of those entering the study in April could be different of those entering September due to a potentially limited sun exposure during winter months.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [117] Feng, J., Shan, L., Du, L., Wang, B., Li, H., Wang, W., Wang, T., Dong, H., Yue, X., and Xu, Z. (2016). Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr. Neurosci. source
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May combine two claims.
PremisecitationMeguid et al. (2010) and Saad et al. (2015) thoroughly examined all children, including cases and controls, for medical conditions and mental disorders, and reported that two groups of Egyptian children with ASD had significantly lower levels of 25(OH)D compared to age, sex and socio-economic status matched healthy controls.
“Meguid et al. (2010) [81] and Saad et al. (2015) [111] also thoroughly examined all children, including both cases and controls, for medical conditions and mental disorders, and reported that two groups of Egyptian children with ASD had significantly lower levels of 25(OH)D compared to age, sex and socio-economic status matched healthy controls.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [81] Meguid, 2010, Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in egyptian children with autism, J. Altern. Complement. Med. (New York NY) source
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- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
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May combine two claims.
PremisecitationFeng et al. (2016) reported a higher proportion of ASD children having 25(OH)D concentrations <25 nmol/L (13% vs. 0%, p = 0.03) and <75 nmol/L (71% vs. 62%, p = 0.03) than healthy typically developing controls.
“In a recent large study from China, Feng et al. (2016) reported higher proportion of ASD children having 25(OH)D concentrations <25 nmol/L (13% vs. 0%, p = 0.03) and <75 nmol/L (71% vs. 62%, p = 0.03) than healthy typically developing controls [117].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [117] Feng, J., Shan, L., Du, L., Wang, B., Li, H., Wang, W., Wang, T., Dong, H., Yue, X., and Xu, Z. (2016). Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr. Neurosci. source
Not checked in the free run.
May combine two claims.
PremisecitationSeason of birth was not significantly different between cases and controls in the Middle Eastern/African groups, but it was significantly different across groups of Scandinavian and other European origins (10% vs. 35% of cases and controls in summer).
“It should be also noted that season of birth was not significantly different between cases and controls in the latter ethnic groups, but it was significantly different across groups of Scandinavian and other European origins (10% vs. 35% of cases and controls in summer, respectively).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationMostafa and Al-Ayadi (2012) collected all blood samples from Saudi Arabian children with ASD and healthy controls during summer months.
“Similarly, Mostafa and Al-Ayadi (2012) collected all blood samples from Saudi Arabian children with ASD and healthy controls during summer months [109].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [109] Mostafa, 2012, Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity, J. Neuroinflamm. source
Not checked in the free run.
May combine two claims.
PremisecitationMean 1,25(OH)2D and calcium concentrations were also lower in children with ASD than healthy controls.
“Mean 1,25(OH)2D and calcium concentrations was also lower in children with ASD than healthy controls [81]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [81] Meguid, 2010, Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in egyptian children with autism, J. Altern. Complement. Med. (New York NY) source
Not checked in the free run.
May combine two claims.
InterpretationcitationInclusion of older siblings may confound the findings by younger parental age, and inclusion of apparently healthy younger siblings may risk including siblings with ASD who may develop ASD later in life in the control group.
“Furthermore, inclusion of older siblings may confound the findings by younger parental age, and inclusion of apparently healthy younger siblings, on the other hand, may run the risk of including siblings with ASD who may develop ASD later in life in the control group [78,108].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [78] Fernell, 2015, Autism Spectrum Disorder and low vitamin D at birth: A sibling control study, Mol. Autism source
Not checked in the free run.
- cites [108] Kocovska, 2014, Vitamin D in the general population of young adults with autism in the faroe islands, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
PremisecitationIn the Meguid and Saad studies, season of birth was taken into account but no significant differences were found in either group.
“The season of birth was taken into account in both studies but no significant differences were found in either group.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [81] Meguid, 2010, Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in egyptian children with autism, J. Altern. Complement. Med. (New York NY) source
Not checked in the free run.
- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductcitationTo control for seasonal variation, the Feng et al. study lasted for six months; April-September corresponding to spring and summer months.
“To control for seasonal variation, the study lasted for six months; April—September corresponding to spring and summer months.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [117] Feng, J., Shan, L., Du, L., Wang, B., Li, H., Wang, W., Wang, T., Dong, H., Yue, X., and Xu, Z. (2016). Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr. Neurosci. source
Not checked in the free run.
May combine two claims.
Study design and conductown dataThe Stubbs et al. study had a small sample size and lacked a control arm.
“To note, this study had a small sample size and lacked a control arm.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [106] Stubbs, 2016, Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings?, Med. Hypotheses source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationIn Tostes et al., neither ethnicity nor season of blood sampling was considered in the statistical analysis.
“Neither ethnicity nor season of blood sampling was considered in the statistical analysis.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [110] Tostes, 2012, Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism, Trends Psychiatry Psychother. source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductcitationTo avoid seasonal variations in 25(OH)D concentrations, all blood samples in this study were drawn during the same two months (May and June).
“To avoid seasonal variations in 25(OH)D concentrations, all blood samples in this study were drawn during same two months (May and June).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductreasoningDoing sub-analysis in studies with small sample size results in even smaller sample sizes for each group, which could compromise the validity of the findings.
“It should be noted that doing sub-analysis in studies with small sample size results in even smaller sample sizes for each group, which could compromise the validity of the latter findings.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationChildren in Molloy et al. were suffering from some form of acute inflammation, which potentially had an effect on 25(OH)D levels.
“Children were suffering from some form of acute inflammation, which potentially had an effect on 25(OH)D levels [120,121].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [120] Waldron, 2013, Vitamin D: A negative acute phase reactant, J. Clin. Pathol. source
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- cites [121] Hummel, 2014, Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells, J. Steroid Biochem. Mol. Biol. source
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May combine two claims.
Study design and conductcitationNeumeyer et al. had a small sample size (n = 18) with the sample size calculated based on differences in bone mineral density rather than 25(OH)D concentrations.
“Small sample size was a limitation of this study (n = 18) with the sample size calculated based on differences in bone mineral density rather than 25(OH)D concentrations.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
PremisecitationApproximately 11% and 73% of ASD children and typically developing children had high physical activity levels, respectively, and fewer ASD children were exposed to sun than healthy controls (p = 0.002).
“Approximately 11% and 73% of ASD children and typically developing children had high physical activity levels, respectively [114], and fewer ASD children were exposed to sun than healthy controls (p = 0.002) [118].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
Not checked in the free run.
- cites [118] Bener, 2014, Is high prevalence of vitamin D deficiency evidence for autism disorder? In a highly endogamous population, J. Pediatr. Neurosci. source
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May combine two claims.
InterpretationreasoningThe lack of difference in Adams et al. could in part be attributed to methodological issues; neither cases nor controls were assessed for autism manifestations by researchers and confounders such as ethnicity, season of blood sampling, medical conditions and medication use were not controlled for in statistical analysis.
“The lack of difference could in part be attributed to some methodological issues; neither cases nor controls were assessed for autism manifestations by researchers and confounders such as ethnicity, season of blood sampling, medical conditions and medication use were not controlled for in statistical analysis.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [116] Adams, 2011, Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity, Nutr. Metab. (Lond.) source
Not checked in the free run.
May combine two claims.
PremisecitationAccording to parental report, ASD children had significantly more sedentary behaviours than typically developing controls, a finding confirmed by Neumeyer et al. (2013) and Bener et al. (2014).
“Along those lines, according to parental report, ASD children had significantly more sedentary behaviours than typically developing controls, a finding confirmed by Neumeyer et al. (2013) and Bener et al. (2014) [118].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [118] Bener, 2014, Is high prevalence of vitamin D deficiency evidence for autism disorder? In a highly endogamous population, J. Pediatr. Neurosci. source
Not checked in the free run.
May combine two claims.
PremisecitationAdams et al. (2011) reported statistically significant differences in several biomarkers indicative of increased oxidative stress, reduced capacity for detoxification and energy transport, and vitamin deficiency in children with ASD than controls, but plasma 25(OH)D did not differ across study groups.
“Although Adams et al. (2011) reported statistically significant differences in several biomarkers indicative of increased oxidative stress, reduced capacity for detoxification and energy transport, and vitamin deficiency in children with ASD than controls, plasma 25(OH)D did not differ across study groups [116].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [116] Adams, 2011, Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity, Nutr. Metab. (Lond.) source
Not checked in the free run.
May combine two claims.
PremisecitationInflammation, gastrointestinal issues, antiepileptic drugs and genetics are among factors affecting vitamin D metabolism or absorption.
“Inflammation [120,121], gastrointestinal issues [123,124], antiepileptic drugs [125] and genetics are among these factors.”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [120] Waldron, 2013, Vitamin D: A negative acute phase reactant, J. Clin. Pathol. source
Not checked in the free run.
- cites [121] Hummel, 2014, Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells, J. Steroid Biochem. Mol. Biol. source
Not checked in the free run.
- cites [123] Khayyat, 2015, Vitamin D deficiency in patients with irritable bowel syndrome: Does it exist?, Oman Med. J. source
Not checked in the free run.
- cites [124] Joseph, 2009, 25 (OH) vitamin D level in crohn’s disease: Association with sun exposure & disease activity, Indian J. Med. Res.
Not checked in the free run.
- cites [125] Menon, 2010, The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism—A longitudinal study, Seizure source
Not checked in the free run.
May combine two claims.
PremisecitationStewart et al. (2015) reported a probable risk of inadequate intake of six micronutrients in >40% of children with ASD, one of which was vitamin D.
“Using three-day food records, Stewart et al. (2015) reported a probable risk of inadequate intake of six micronutrients in >40% of children with ASD, one of which was vitamin D [126].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [126] Stewart, 2015, Dietary supplementation in children with Autism Spectrum Disorders: Common, insufficient, and excessive, J. Acad. Nutr. Diet. source
Not checked in the free run.
May combine two claims.
PremisecitationAlthough these studies illustrated a large proportion of children with ASD not meeting the recommendations for vitamin D intake, they did not find any evidence that dietary intake of vitamin D in children with ASD differed from that of typically developing controls.
“Although these studies illustrated a large proportion of children with ASD not meeting the recommendations for vitamin D intake, they did not find any evidence that dietary intake of vitamin D in children with ASD differed from that of typically developing controls.”
Quote in the paperNot a substantial claim0 of 6 sources checked- cites [126] Stewart, 2015, Dietary supplementation in children with Autism Spectrum Disorders: Common, insufficient, and excessive, J. Acad. Nutr. Diet. source
Not checked in the free run.
- cites [132] Hyman, 2012, Nutrient intake from food in children with autism, Pediatrics source
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- cites [133] Moore, E., Crook, T., James, J., Gonzales, D., and Hakkak, R. (2012). Nutrient intake among children with autism. J. Nutr. Disord. Ther. source
Not checked in the free run.
- cites [134] Cornish, 1998, A balanced approach towards healthy eating in autism, J. Hum. Nutr. Diet. source
Not checked in the free run.
- cites [135] Lindsay, 2006, Dietary status and impact of risperidone on nutritional balance in children with autism: A pilot study, J. Intellect. Dev. Disabil. source
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- cites [136] George, 2013, Calcium and vitamin D intake of boys who have autism, Infant Child Adolesc. Nutr. source
Not checked in the free run.
May combine two claims.
InterpretationcitationChildren with ASD may receive less sunlight due to lower outdoor activity and have inadequate intake of vitamin D, i.e., reverse causality.
“Furthermore, children with ASD may receive less sunlight due to lower outdoor activity and have inadequate intake of vitamin D [114,118,126,127,128,129,130,131,132,133,134,135,136], i.e., reverse causality.”
Quote in the paperSubstantial claim0 of 10 sources checked- cites [114] Neumeyer, 2013, Bone density in peripubertal boys with Autism Spectrum Disorders, J. Autism Dev. Disord. source
Not checked in the free run.
- cites [118] Bener, 2014, Is high prevalence of vitamin D deficiency evidence for autism disorder? In a highly endogamous population, J. Pediatr. Neurosci. source
Not checked in the free run.
- cites [126] Stewart, 2015, Dietary supplementation in children with Autism Spectrum Disorders: Common, insufficient, and excessive, J. Acad. Nutr. Diet. source
Not checked in the free run.
- cites [127] Must, A., Phillips, S.M., Curtin, C., Anderson, S.E., Maslin, M., Lividini, K., and Bandini, L.G. (2013). Comparison of sedentary behaviors between children with Autism Spectrum Disorders and typically developing children. Autism. source
Not checked in the free run.
- cites [128] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with Autism Spectrum Disorders, Pediatrics source
Not checked in the free run.
- cites [129] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
Not checked in the free run.
- cites [130] Bandini, 2010, Food selectivity in children with Autism Spectrum Disorders and typically developing children, J. Pediatr. source
Not checked in the free run.
- cites [131] 2015, Nutritional status of children with Autism Spectrum Disorders (ASDs): A case—Control study, J. Autism Dev. Disord. source
Not checked in the free run.
- cites [132] Hyman, 2012, Nutrient intake from food in children with autism, Pediatrics source
Not checked in the free run.
- cites [133] Moore, E., Crook, T., James, J., Gonzales, D., and Hakkak, R. (2012). Nutrient intake among children with autism. J. Nutr. Disord. Ther. source
Not checked in the free run.
May combine two claims.
Study design and conductown dataHashemzadeh et al. had the smallest sample size and limited statistical power to detect differences among groups.
“This study had the smallest sample size, a limited statistical power to detect differences among groups.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [115] Hashemzadeh, 2015, Comparative study of vitamin D levels in children with Autism Spectrum Disorder and normal children: A case-control study, J. Fundam. Ment. Health
Not checked in the free run.
May combine two claims.
PremisecitationThree other studies that failed to show any relationship had somewhat larger sample sizes (ranging from 54 to 71 per group) and controlled for several covariates and matched controls to cases on several attributes.
“Three other studies that also failed to show any relationship had somewhat larger sample sizes (ranging from 54 to 71 per group) and controlled for several covariates [113] and matched controls to cases on several attributes [79,116].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [113] Molloy, 2010, Plasma 25(OH)D concentration in children with Autism Spectrum Disorder, Dev. Med. Child Neurol. source
Not checked in the free run.
- cites [79] 2014, Serum vitamin D and folate levels in children with Autism Spectrum Disorders, Res. Autism Spectr. Disord. source
Not checked in the free run.
- cites [116] Adams, 2011, Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity, Nutr. Metab. (Lond.) source
Not checked in the free run.
May combine two claims.
PremisecitationThe Ugur et al. (2014) study was conducted in Turkey, where a national free vitamin D supplementation campaign has been implemented by government to eliminate vitamin D deficiency rickets.
“The study by Ugur et al. (2014) [79] was conducted in Turkey, where a national free vitamin D supplementation campaign has been implemented by government to eliminate vitamin D deficiency rickets [122].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [79] 2014, Serum vitamin D and folate levels in children with Autism Spectrum Disorders, Res. Autism Spectr. Disord. source
Not checked in the free run.
- cites [122] Ozkan, 2009, Prevalence of vitamin D deficiency rickets in the eastern part of Turkey, Eur. J. Pediatr. source
Not checked in the free run.
May combine two claims.
PremisecitationEven though vitamin D intake was improved in response to vitamin D supplementation, it did not reach the adequate intake in 30%-40% of children.
“Even though vitamin D intake was improved in response to vitamin D supplementation, it did not reach the adequate intake in 30%–40% of children.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [126] Stewart, 2015, Dietary supplementation in children with Autism Spectrum Disorders: Common, insufficient, and excessive, J. Acad. Nutr. Diet. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe scenario would be worse if more children of African American, mixed-race/ethnicity and less educated parents were enrolled because the socio-demographic characteristics of the study population was biased toward highly educated parents and those of white ethnicity.
“The scenario would be worse if more children of African American, mixed-race/ethnicity and less educated parents were enrolled because the socio-demographic characteristics of the study population was biased toward highly educated parents and those of white ethnicity who might have been more concerned about nutrition.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [126] Stewart, 2015, Dietary supplementation in children with Autism Spectrum Disorders: Common, insufficient, and excessive, J. Acad. Nutr. Diet. source
Not checked in the free run.
May combine two claims.
InterpretationreasoningLow vitamin D status could be a risk factor for ASD if it occurs during a critical period of development, or alternatively, could be a condition that appears as the disease progresses.
“Thus, low vitamin D status could be a risk factor for ASD if it occurs during critical period of development, or alternatively, could be a condition that appears as the disease progresses.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationEmond et al. (2010) and Zimmer et al. (2012) reported that children with ASD had late introduction of solids after six months, were difficult to feed and very choosy from 15-54 months, had less varied diet from 24 months, and ate fewer food on average at older ages, all of which affected their nutritional status.
“Emond et al. (2010) and Zimmer et al. (2012) reported that children with ASD had late introduction of solids after six months, were difficult to feed and very choosy from 15–54 months, had less varied diet from 24 months, and ate fewer food on average at older ages, all of which affected their nutritional status [128,129].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [128] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with Autism Spectrum Disorders, Pediatrics source
Not checked in the free run.
- cites [129] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
PremisecitationBoth Emond and Zimmer studies showed that children with ASD had significantly lower dietary intakes of vitamin D than controls.
“Both studies showed that children with ASD had significantly lower dietary intakes of vitamin D than controls.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [128] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with Autism Spectrum Disorders, Pediatrics source
Not checked in the free run.
- cites [129] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
PremisecitationMari-Bausent et al. (2015) reported children with ASD having lower dietary vitamin D intake than healthy controls, though the difference was not statistically significant (79 ± 60 vs. 104 ± 97 IU/day, p = 0.06).
“In a recent case-control study, Mari-Bausent et al. (2015) reported children with ASD having lower dietary vitamin D intake than healthy controls, though the difference was not statistically significant (79 ± 60 vs. 104 ± 97 IU/day, respectively, p = 0.06) [131].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [131] 2015, Nutritional status of children with Autism Spectrum Disorders (ASDs): A case—Control study, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
PremisecitationFeng et al. (2016) reported a significant improvement in scores on CARS (total) and Autism Behaviour Checklist (total and all subscales apart from sensory scores), which was more pronounced in 3 year old or younger children than older children.
“The authors reported a significant improvement in scores on CARS (total) and Autism Behaviour Checklist (total and all subscales apart from sensory scores), which was more pronounced in 3 year old or younger children than older children.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [117] Feng, J., Shan, L., Du, L., Wang, B., Li, H., Wang, W., Wang, T., Dong, H., Yue, X., and Xu, Z. (2016). Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr. Neurosci. source
Not checked in the free run.
May combine two claims.
PremisecitationMore children with ASD did not meet the estimated average requirement (EAR) for vitamin D intake than healthy controls (79% vs. 55%, p = 0.01), and more selective eaters with ASD were at increased risk for inadequate intake (58% vs. 5%, p = 0.01).
“More children with ASD did not also meet the estimated average requirement (EAR) for vitamin D intake than healthy controls (79% vs. 55%, p = 0.01) [130], and more selective eaters with ASD were at increased risk for inadequate intake (58% vs. 5%, p = 0.01) [129].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [130] Bandini, 2010, Food selectivity in children with Autism Spectrum Disorders and typically developing children, J. Pediatr. source
Not checked in the free run.
- cites [129] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningThe findings from this single patient cannot be generalised to all autistic patients but it does encourage further research in this area.
“The findings from this single patient cannot be generalised to all autistic patients but it does encourage further research in this area.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [139] Jia, 2015, Core symptoms of autism improved after vitamin D supplementation, Pediatrics source
Not checked in the free run.
May combine two claims.
InterpretationcitationResponse to vitamin D supplement could vary between children with ASD and children with developmental delay because vitamin D may affect brain chemistry.
“The brain chemistry of children with ASD may differ from that of children with developmental delay [142], and as such the response to vitamin D supplement—that may affect brain chemistry [143]—could vary.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [143] Cass, 2006, Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine, Ann. N. Y. Acad. Sci. source
Not checked in the free run.
May combine two claims.
PremisecitationA large proportion of both groups did not meet the dietary recommended intake for vitamin D (88% of children with ASD and 75% of typically developing children, p = 0.16), a finding confirmed by others.
“A large proportion of both groups did not meet the dietary recommended intake for vitamin D (88% of children with ASD and 75% of typically developing children, p = 0.16), a finding confirmed by others [137,138].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [131] 2015, Nutritional status of children with Autism Spectrum Disorders (ASDs): A case—Control study, J. Autism Dev. Disord. source
Not checked in the free run.
- cites [137] Farmer, 2013, Dietary adequacy of children with autism compared with controls and the impact of restricted diet, J. Dev. Behav. Pediatr. source
Not checked in the free run.
- cites [138] Herndon, 2009, Does nutritional intake differ between children with Autism Spectrum Disorders and children with typical development?, J. Autism Dev. Disord. source
Not checked in the free run.
May combine two claims.
Study design and conductcitationOther limitations of Saad et al. were its drop-out rate of approximately 22% and the lack of a placebo or comparison arm.
“Other limitations of this study were its drop-out rate of approximately 22% and the lack of a placebo or comparison arm.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
Not checked in the free run.
May combine two claims.
PremisecitationIn Ucuz et al. (2015), both treatment and control groups showed improvement in ABC and Denver II scores.
“In another study from Turkey, however, despite improvement in scores on ABC and Denver II in both treatment and control groups, Ucuz et al. (2015) failed to show any significant differences across groups [141].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
Not checked in the free run.
May combine two claims.
PremisecitationSaad et al. (2015) found that CARS scores decreased by 3.5-6.5 points in all 16 patients with final 25(OH)D >100 nmol/L, by 1.5-4.5 points in 31 out of 49 patients with 25(OH)D levels 75-97.5 nmol/L and no improvements in all 18 patients with 25(OH)D levels <75 nmol/L.
“CARS scores decreased by 3.5–6.5 points in all 16 patients with final 25(OH)D >100 nmol/L, by 1.5–4.5 points in 31 out of 49 patients with 25(OH)D levels 75–97.5 nmol/L and no improvements in all 18 patients with 25(OH)D levels <75 nmol/L had improvements.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
Not checked in the free run.
May combine two claims.
PremisecitationWith the exception of the inappropriate speech subscale of ABC, all other measures (irritability, stereotypic behaviour, social withdrawal and hyperactivity) improved significantly after treatment.
“With the exception of inappropriate speech subscale of ABC, all other measures (irritability, stereotypic behaviour, social withdrawal and hyperactivity) improved significantly after treatment.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
Not checked in the free run.
May combine two claims.
Study design and conductcitationIn Ucuz et al. (2015), neither baseline nor follow-up 25(OH)D concentrations were reported.
“Furthermore, children were not randomly assigned to study groups and neither baseline nor follow up 25(OH)D concentrations were reported.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [141] Ucuz, 2015, The relationship between vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship?, Int. J. Dev. Disabil. source
Not checked in the free run.
May combine two claims.
Study design and conductcitationNo conclusion can be drawn from Humble et al. because it was not designed to assess the efficacy of vitamin D on autism, no placebo or control arm was included, different doses and types of vitamin D were used, and levels of 25(OH)D after treatment were not reported.
“No conclusion can be drawn from this study because it was not designed to assess the efficacy of vitamin D on autism and it was part of clinical practice, no placebo or control arm was included, different doses and types of vitamin D was used, and levels of 25(OH)D after treatment was not reported.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [119] Humble, 2010, Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: Relations with season, age, ethnic origin and psychiatric diagnosis, J. Steroid Biochem. Mol. Biol. source
Not checked in the free run.
May combine two claims.
Study design and conductcitationSaad et al. had a relatively large sample size and limited seasonal effects by drawing all blood samples during the summer months, though the baseline and follow-up levels of 25(OH)D were not reported.
“This study had a relatively large sample size and also limited seasonal effects by drawing all blood samples during the summer months, though the baseline and follow-up levels of 25(OH)D were not reported.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [111] Saad, K., Abdel-Rahman, A.A., Elserogy, Y.M., Al-Atram, A.A., Cannell, J.J., Bjorklund, G., Abdel-Reheim, M.K., Othman, H.A., El-Houfey, A.A., and Abd El-Aziz, N.H. (2015). Vitamin D status in Autism Spectrum Disorders and the efficacy of vitamin D supplementation in autistic children. Nutr. Neurosci. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHumble et al. (2010) reported a considerable improvement in psychosis or depression with the effective treatment of vitamin D deficiency in several patients.
“Humble et al. (2010), in a clinical quality assurance project, reported a considerable improvement in psychosis or depression with the effective treatment of vitamin D deficiency in several patients.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [119] Humble, 2010, Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: Relations with season, age, ethnic origin and psychiatric diagnosis, J. Steroid Biochem. Mol. Biol. source
Not checked in the free run.
May combine two claims.
PremisecitationVitamin D regulates cell proliferation and differentiation.
“Vitamin D regulates cell profilation and differentiation and can protect the genome from daily life insults such as oxidative stress and toxins (for a comprehensive review refer to [149]).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [149] Armstrong, 2012, Does vitamin D protect against DNA damage?, Mutat. Res-Fund. Mol. Mech. Mut. source
Not checked in the free run.
May combine two claims.
InterpretationcitationThe presence of VDR early in development, increasing during development, and in the adult brain indicates a role for vitamin D in the developing and adult brain.
“VDR has been shown to be present early in development, to increase during development, and to be present in the adult brain—all indicative of a role for vitamin D in the developing and adult brain [145].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [145] Cui, 2013, The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain, Neuroscience source
Not checked in the free run.
May combine two claims.
PremisecitationOxidative stress and reduced redox/antioxidant capacity in cerebellum and temporal cortex have functional consequences for chronic inflammatory response, mitochondrial dysfunction, and protein and DNA damage.
“Oxidative stress and reduced redox/antioxidant capacity in cerebellum and temporal cortex have been shown to have functional consequences for chronic inflammatory response, mitochondrial dysfunction and protein and DNA damage [3], and in peripheral tissue have been associated with anti-neuronal positivity [16] and clinical features of autism [15].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] Rose, 2012, Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain, Transl. Psychiatry source
Not checked in the free run.
May combine two claims.
PremisecitationTreatment with vitamin D ameliorates neurotoxicity, inflammation, and DNA damage in propionic acid-intoxicated rats.
“It has been documented that treatment with vitamin D has a protective effect on persistent biochemical features comparable to those reported clinically in autistic patients and ameliorates neurotoxicity, inflammation and DNA damage in propionic acid-intoxicated rats [156].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [156] Alfawaz, 2014, Protective and restorative potency of vitamin D on persistent biochemical autistic features induced in propionic acid-intoxicated rat pups, BMC Complement. Altern. Med. source
Not checked in the free run.
May combine two claims.
PremisecitationTreatment with vitamin D stabilizes chromosomal structure and prevents double strand breaks.
“Treatment with vitamin D has been shown to decrease 8—hydroxy–2—deoxyguanosin, a marker of endogenous oxidative damage to DNA [150], increase Bax, a protein coding gene involved in apoptosis [150], regulates poly-ADP-ribose polymerase activity in the DNA damage response pathway [151], stabilize chromosomal structure and prevent double strand breaks [152].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [152] Chatterjee, 2001, Vitamin D and genomic stability, Mutat. Res-Fund. Mol. Mech. Mut. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAutism is considered to be driven genetically.
“Autism is considered to be driven genetically [146,147], though only small percentage of cases are clearly linked to genetic causes [22].”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationNeurotrophins are involved in the development, maintenance, survival, and synapsis of neurons.
“Neurotrophins are involved in the development, maintenance, survival and synapsis of neurons [105].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [105] Groves, 2014, Vitamin D as a neurosteroid affecting the developing and adult brain, Annu. Rev. Nutr. source
Not checked in the free run.
May combine two claims.
PremisecitationVitamin D analogues decrease BDNF and concomitantly improve memory in postmenopausal women.
“Vitamin D analogues have been shown to upregulate NGF in cultured glial cell and embryonic hippocampal cells [177,178], to decrease the percentage of cultured hippocampal cells undergoing mitosis [178], and to decrease BDNF and concommitantly to improve memory in postmenopausal women [179].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [179] Pozzi, F., Aloe, L., Frajese, G.V., and Frajese, G. (2013). Vitamin D (Calcifediol) supplementation modulates NGF and BDNF and improves memory function in postmenopausal women: A pilot study. Res. Endocrinol., 2013. source
Not checked in the free run.
May combine two claims.
PremisecitationThese neurotransmitter systems play key roles in neurotransmission, brain maturation, cortical organisation, and behaviours including social and repetitive behaviour.
“These systems play key roles in neurotransmission, brain maturation, cortical organisation and behaviours (including social behaviour and repetitive behaviour) [180,181,182,183,184].”
Quote in the paperNot a substantial claim0 of 5 sources checked- cites [180] Crockett, 2008, Serotonin modulates behavioral reactions to unfairness, Science source
Not checked in the free run.
- cites [181] Anagnostou, 2012, Intranasal oxytocin versus placebo in the treatment of adults with Autism Spectrum Disorders: A randomized controlled trial, Mol. Autism source
Not checked in the free run.
- cites [182] Naranjo, 2001, The role of the brain reward system in depression, Prog. Neuropsychopharmacol. Biol. Psychiatry source
Not checked in the free run.
- cites [183] Staal, 2012, Brief report: The dopamine-3-receptor gene (DRD3) is associated with specific repetitive behavior in Autism Spectrum Disorder (ASD), J. Autism Dev. Disord. source
Not checked in the free run.
- cites [184] Nakamura, 2010, Brain serotonin and dopamine transporter bindings in adults with high-functioning autism, Arch. Gen. Psychiatry source
Not checked in the free run.
May combine two claims.
InterpretationcitationThese findings suggest an important role of vitamin D in autoantibody production and ASD pathogenesis, perhaps similar to other autoimmune diseases such as MS and systemic lupus erythematosus.
“These findings suggest an important role of vitamin D in autoantibody production and ASD pathogenesis, perhaps similar to other autoimmune diseases, such as MS and systemic lupus erythematosus [172,174].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [172] Ritterhouse, 2011, Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus, Ann. Rheum. Dis. source
Not checked in the free run.
- cites [174] Mokry, L.E., Ross, S., Ahmad, O.S., Forgetta, V., Smith, G.D., Leong, A., Greenwood, C.M., Thanassoulis, G., and Richards, J.B. (2015). Vitamin D and risk of multiple sclerosis: A mendelian randomization study. PLoS Med., 12. source
Not checked in the free run.
May combine two claims.
PremisecitationVitamin D has an effect on the immune system and can directly affect immune cells.
“It is well known that vitamin D has an effect on immune system and can directly affect immune cells.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [162] Almerighi, 2009, 1α,25-dihydroxyvitamin D3 inhibits CD40l-induced pro-inflammatory and immunomodulatory activity in human monocytes, Cytokine source
Not checked in the free run.
- cites [163] Heine, 2008, 1,25-dihydroxyvitamin D3 promotes IL-10 production in human b cells, Eur. J. Immunol. source
Not checked in the free run.
- cites [164] Keresztes, 2009, 1,25-dihydroxyvitamin D3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype, J. Immunol. source
Not checked in the free run.
May combine two claims.
PremisecitationCalcitriol upregulates the expression of calcium binding proteins (calbindin and parvalbumin) and inhibits the expression of L-type Ca2+ channels.
“Calcitriol upregulates the expression of calcium binding proteins (calbindin and parvalbumin) and inhibits the expression of L-type Ca2+ channels [199].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [199] Kalueff, 2004, Mechanisms of neuroprotective action of vitamin D3, Biochemistry
Not checked in the free run.
May combine two claims.
PremisecitationVitamin D exerts its roles, in part, through its antioxidant and anti-inflammatory effects and through its inhibitory effect on Ca2+ influx in the brain.
“Vitamin D exerts its roles, in part, through its antioxidant and anti-inflammatory effects and also through its inhibitory effect on Ca2+ influx in the brain.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [199] Kalueff, 2004, Mechanisms of neuroprotective action of vitamin D3, Biochemistry
Not checked in the free run.
May combine two claims.
PremisecitationThe above mentioned disorders may contribute to the aetiology of epilepsy, which is highly prevalent in populations with ASD.
“Finally, the above mentioned disorders may contribute to the aetiology of epilepsy, which is highly prevalent in populations with ASD [190].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [190] Frye, 2015, Metabolic and mitochondrial disorders associated with epilepsy in children with Autism Spectrum Disorder, Epilepsy Behav. source
Not checked in the free run.
May combine two claims.
PremisecitationAntiepileptic drugs impair vitamin D and calcium metabolism, leading to reduced levels of vitamin D and calcium.
“It should be noted that at the same time, antiepileptic drugs impair vitamin D and calcium metabolism, leading to reduced levels of vitamin D and calcium [125], and these deficiencies can, on the other hand, exacerbate the condition.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [125] Menon, 2010, The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism—A longitudinal study, Seizure source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAccording to retrospective follow-up studies, 25% of individuals with autism exhibited epileptic seizures.
“According to retrospective follow up studies, 37% and 25% of the individuals with autism exhibited epilepsy and epileptic seizures, respectively [191,192].”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenAnimal and human cellular, biological, and physiologic studies have provided compelling evidence for numerous roles of vitamin D in various body processes, some of which are involved in the pathobiology of ASD.
“Animal and human cellular, biological, and physiologic studies have provided compelling evidence for numerous roles of vitamin D in various body processes, some of which are involved in the pathobiology of ASD.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationInfants of mothers taking antiepileptic drugs during pregnancy have been shown to be at increased risk of being diagnosed with ASD and having low 25(OH)D concentrations.
“Infants of mothers taking antiepileptic drugs during pregnancy have been shown to be at increased risk of being diagnosed with ASD and having low 25(OH)D concentrations [193].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [193] Bromley, 2008, Autism Spectrum Disorders following in utero exposure to antiepileptic drugs, Neurology source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAccording to retrospective follow-up studies, 37% of individuals with autism exhibited epilepsy.
“According to retrospective follow up studies, 37% and 25% of the individuals with autism exhibited epilepsy and epileptic seizures, respectively [191,192].”
Quote in the paperNot a substantial claim0 of 2 sources checked
The authors state this as an assumption.
Latitude is a reasonable proxy measure for vitamin D status.
“The latitude differences in prevalence estimates for autism should be interpreted with caution since they assume that latitude is a reasonable proxy measure for vitamin D status.”
The paper relies on this without support.
Season of conception or birth is a proxy for vitamin D status, such that winter conception/birth reflects lower sun exposure and lower vitamin D status.
“Children conceived during the winter months, when sun exposure is limited and vitamin D status is lower, were reported to have a higher risk of developing autism later in life than those conceived during the summer months [74].”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is some evidence that vitamin D may have therapeutic benefits in reducing autism symptomatology among diagnosed cases.
“There was also some evidence that vitamin D may have therapeutic benefits in reducing autism symptomatology among diagnosed cases.”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [161]
A recent systematic review concluded there are indications that deficiencies in vitamin D during early development interact with other risks, possibly contributing to the etiology of autism.
“This review concluded that there are indications that deficiencies in vitamin D during early development interacts with other risks, possibly contributing to the etiology of autism.”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [161]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Reported risk reduction conflicts with relative risk
MinorA relative risk of 0.18 corresponds to an 82% reduction, not an 87% reduction.
“an 87% decreased risk for multiple births concordant for ASD in males in winter (December) compared to other seasons”
“relative risk 0.18, 95% CI 0.04, 0.82; p < 0.05”
Included-study count is one too low
MinorExcluding two studies from 16 leaves 14, not 13. The section also subsequently discusses 14 studies.
Reported 13 · recomputed 14
“Two of the 16 studies were excluded because either the full article was in Chinese [107], or cases were not compared with typically developing controls [119]. All 13 studies included in this review have been published over the past five years.”
Follow-up scores are described as increasing although all fell
MinorEach listed follow-up score is lower than its corresponding baseline score.
“Scores on Autism Behaviour Checklist, Childhood Autism Rating Scale (CARS) and Severity of Illness of Clinical Global Impression increased”
“from 80, 35 and 6 at the baseline to 39, 28 and 4 at the follow up, respectively.”
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“Autism is considered to be driven genetically [146,147], though only small percentage of cases are clearly linked to genetic causes [22].”
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“0 [41] Finland, Northern Ostrobothnia 63.”
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Background1,25‐dihydroxyvitamin D <sub>3</sub> promotes IL‐10 production in human B cells
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- Authors
- Mazahery, H., Camargo, C., Conlon, C., Beck, K., Kruger, M., & Von Hurst, P.
- Affiliations
- Massey University (NZ)
- Harvard University (US)
- Institute of Food Science and Technology—School of Food and Nutrition, Massey University, Palmerston North 4474, New Zealand
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2016-04-21
- Volume
- 8
- Issue
- 4
- Pages
- 236
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC4848704
- OpenAlex
- W2337574406
- Cited by
- 110
- References
- 205
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 13 · 2022: 10 · 2021: 11 · 2020: 17 · 2019: 11 · 2018: 10 · 2017: 16 · 2016: 7
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Massey Research Online (Massey University) (submittedVersion)
- Funders
- Massey University
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- vitamin D, autism spectrum disorder, vitamin D status, serum 25-hydroxyvitamin D, environmental risk factors, maternal vitamin D status, season of birth, latitude, maternal migration, ethnicity, vitamin D supplementation, prevention, mechanistic pathways
- MeSH terms
- Autism Spectrum Disorder, Female, Humans, Pregnancy, Vitamin D Deficiency
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