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Cited by 541Nutrition and Health StudiesFolate and B Vitamins ResearchTrace Elements in Health

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Open access
Tardy, Anne-Laure, Pouteau, Etienne, Marquez, Daniel, Yilmaz, Cansu, Scholey, Andrew·2020·Nutrients
DOI 10.3390/nu12010228PMC PMC7019700
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Abstract

Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.

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Written from the paper’s full text.

TL;DR

This narrative review synthesizes biochemical and clinical evidence that selected B vitamins, vitamin C, iron, magnesium, and zinc are required for cellular energy production, oxygen transport, antioxidant defense, and neuronal function, and that inadequate status can contribute to physical/mental fatigue and cognitive or psychological symptoms. Supplementation appears most beneficial in people with low or deficient intake/status, though the evidence base is heterogeneous and often lacks baseline nutrient assessment.

Key findings

  • The review identifies roles for vitamins B1, B2, B3, B5, B6, B8, B9, B12, vitamin C, iron, magnesium, and zinc in energy-yielding metabolism, oxygen transport, oxidative stress control, neurotransmitter synthesis, and neuronal structure; all B vitamins except folate participate in at least one energy-production step, and a shortfall in any can be rate-limiting.
  • Inadequate intakes/status are common and linked to fatigue or cognitive outcomes: 68% of Mexican women had folate intakes below the EAR, 55% of Turkish adults had thiamine intakes below the EAR, and in 1253 Chinese adults followed for 5 years, more than 97% had inadequate riboflavin intake at baseline, associated with increased anemia risk. In more than 15,000 UK adults aged 40–79, the lowest vitamin C quartile (<41 µmol/L) versus the highest (>66 µmol/L) had significantly increased odds of poor physical functional health and poor vitality.
  • Supplementation trials report benefits especially in deficient or low-status groups: a meta-analysis of six RCTs in nonanemic iron-deficient premenopausal women found an overall decrease in fatigue complaints of more than 60%; a 12-week trial of 80 mg elemental iron daily in 198 women reduced fatigue by 48% versus 29% with placebo; 2 or 4 mg riboflavin for 8 weeks raised hemoglobin in 119 mildly deficient young British women; and 10 g intravenous vitamin C in 141 office workers lowered fatigue scores at 2 h and 1 day.
  • Cognitive/psychological findings include improved global cognitive function, information-processing speed, and memory storage after 800 µg/day folic acid for 3 years in 818 healthy adults; a 13-year B6+B9+B12 trial in 5,442 women showed no overall cognitive improvement but preserved cognition in those with low baseline B-vitamin intake; multiple-micronutrient meta-analyses generally favored benefits, especially in poor baseline mood or nutrient status.

Methods

  • Narrative review selecting nine vitamins (B1, B2, B3, B5, B6, B8, B9, B12, C) and three minerals (iron, magnesium, zinc) based on authorized European health claims for fatigue, cognition, and psychological outcomes.
  • Summarizes biochemical pathways and clinical evidence, prioritizing human data from healthy general populations and subjects with inadequate nutrient intake/status; includes observational studies and supplementation trials, with some animal or preclinical evidence where human data are lacking.
  • No systematic search, quality appraisal, or meta-analysis is described; evidence is synthesized narratively.

Limitations

  • Stated: few studies address supplementation effects on physical fatigue, with data lacking especially for niacin, pyridoxine, and cobalamin; many supplementation studies use large doses above daily nutritional requirements, demonstrating proof of concept but not appropriate amounts or target nutrient status.
  • Stated: many supplementation trials enroll subjects without clear baseline nutritional status, so populations may include both sufficient and deficient subjects, potentially diluting effects; multiple-micronutrient studies are difficult to interpret.
  • Evident: as a narrative review, it lacks a systematic search/selection strategy and formal risk-of-bias assessment; micronutrient selection was based on authorized health claims, which may constrain scope and introduce selection bias.

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Integrity signals

Registry

Crossref · 10.3390/nu12010228

Cites

200 of 200 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

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  • Interpretationreasoning

    In cases of inadequate intake, vitamin and mineral supplementation may become a means to meet adequate intake.

    “In such cases, vitamin and mineral supplementation may become a means to meet adequate intake.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Food choice or availability often precludes a varied and balanced diet rich in nutrient-dense foods.
    • Rests on an assumption: A significant proportion of the population in emerging and developed countries does not meet their optimum dietary needs.
  • Premisecitation

    In an investigation of 24 healthy men and women aged 24 to 72 years, lack of sleep or poor sleep was the major reported cause of fatigue.

    “In an investigation of the experience of fatigue in 24 healthy men and women aged 24 to 72 years [13], lack of sleep or poor sleep was the major reported cause”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Gledhill J. A qualitative study of the characteristics and representation of fatigue in a French speaking population of cancer patients and healthy subjects Eur. J. Oncol. Nurs. 2005 9 294 312 294–312, discussion 294–312 10.1016/j.ejon.2004.11.002 16298549 source

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  • Premisecitation

    In many Americans, intake falls below the EAR or Adequate Intake levels.

    “Although the majority of Americans consume sufficient amounts of most nutrients to offset clinical symptoms, in many individuals intake falls below the EAR or Adequate Intake levels [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Dietary Guidelines Advisory Committee Scientific Report of the 2015 Dietary Guidelines Advisory Committee: Advisory Report to the Secretary of Health and Human Services and the Secretary of Agriculture U.S. Department of Agriculture, Agricultural Research Service Washington, DC, USA 2015

      Not checked in the free run.

  • Interpretationcitation

    After considering average adult weight, brain and muscle emerge as the most metabolically active structures, even at rest.

    “However, after considering the average adult weight of these organs, brain (1.33 kg) and muscle (26.3 kg) emerge as the most metabolically active structures, even at rest [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Wang Z. Ying Z. Bosy-Westphal A. Zhang J. Schautz B. Later W. Heymsfield S.B. Muller M.J. Specific metabolic rates of major organs and tissues across adulthood: Evaluation by mechanistic model of resting energy expenditure Am. J. Clin. Nutr. 2010 92 1369 1377 10.3945/ajcn.2010.29885 20962155 PMC2980962 source

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  • Premisenone given

    Under normal physiological and nutritional conditions, the major energy fuel for the brain is glucose.

    “Under normal physiological and nutritional conditions, the major energy fuel for the brain is glucose.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 92
  • Classified as probably not a substantial claim. 12
  • The quote only partly states this claim. 5

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    Premisecitation

    In that investigation, affective consequences of fatigue were reported as changes in mood and lack of motivation in 75% of subjects, and low spirit and lack of vitality in 50%.

    “Affective consequences of fatigue were reported as changes in mood and lack of motivation in 75% of subjects, low spirit and lack of vitality in 50%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Gledhill J. A qualitative study of the characteristics and representation of fatigue in a French speaking population of cancer patients and healthy subjects Eur. J. Oncol. Nurs. 2005 9 294 312 294–312, discussion 294–312 10.1016/j.ejon.2004.11.002 16298549 source

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    Premisecitation

    In that investigation, more than half of subjects reported diminished concentration and memory difficulties.

    “In addition, more than half of subjects reported a diminished concentration and memory difficulties [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Gledhill J. A qualitative study of the characteristics and representation of fatigue in a French speaking population of cancer patients and healthy subjects Eur. J. Oncol. Nurs. 2005 9 294 312 294–312, discussion 294–312 10.1016/j.ejon.2004.11.002 16298549 source

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  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    Fatigue is often described as a perceived lack of energy or a feeling of low vitality.

    “Conversely, fatigue is often described as a perceived lack of energy or a feeling of low vitality [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Ryan R.M. Frederick C. On energy, personality, and health: Subjective vitality as a dynamic reflection of well-being J. Pers. 1997 65 529 565 10.1111/j.1467-6494.1997.tb00326.x 9327588 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    An enhanced feeling of well-being, a reduction in mental and physical fatigue, and improvements in psychological and cognitive functions are among the commonly reported motivations for taking supplements.

    “An enhanced feeling of well-being, a reduction in mental and physical fatigue and improvements in psychological and cognitive functions are also among the commonly reported motivations for taking supplements [8,9].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] Bailey R.L. Gahche J.J. Miller P.E. Thomas P.R. Dwyer J.T. Why US adults use dietary supplements JAMA Int. Med. 2013 173 355 361 10.1001/jamainternmed.2013.2299 23381623 source

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    • cites [9] Sekhri K. Kaur K. Public knowledge, use and attitude toward multivitamin supplementation: A cross-sectional study among general public Int. J. Appl. Basic Med. Res. 2014 4 77 80 10.4103/2229-516X.136780 25143880 PMC4137646 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In that investigation, physical aspects of fatigue included a lack of energy in two-thirds of subjects, with reduced stamina and a lack of strength reported in half of the cohort.

    “Physical aspects of fatigue included a lack of energy in two-thirds of subjects, with reduced stamina and a lack of strength reported in half of the cohort.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Gledhill J. A qualitative study of the characteristics and representation of fatigue in a French speaking population of cancer patients and healthy subjects Eur. J. Oncol. Nurs. 2005 9 294 312 294–312, discussion 294–312 10.1016/j.ejon.2004.11.002 16298549 source

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    Premisecitation

    Subclinical or inadequate intakes (insufficiencies) are frequent worldwide, with variations according to age groups and country.

    “Conversely, subclinical or inadequate intakes (sometimes referred to as ‘insufficiencies’) are frequent worldwide, albeit with variations according to age groups and country [3,4].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Griffiths J.K. Vitamin deficiencies Hunter’s Tropical Medicine and Emerging Infectious Disease 9th ed. Magil A.J. Hill D.R. Solomon T. Ryan E.T. Elsevier London, UK 2013 997 1002

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    • cites [4] Rippin H.L. Hutchinson J. Jewell J. Breda J.J. Cade J.E. Adult Nutrient Intakes from Current National Dietary Surveys of European Populations Nutrients 2017 9 1288 10.3390/nu9121288 29186935 PMC5748739

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Energy, vitality and fatigue are interrelated concepts, with energy and vitality and fatigue sometimes seen as opposite ends of the same continuum.

    “Energy, vitality and fatigue are interrelated concepts, with the first two and the last sometimes seen as opposite ends of the same continuum (although they may be distinct psychological constructs [11]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Aouizerat B.E. Gay C.L. Lerdal A. Portillo C.J. Lee K.A. Lack of energy: An important and distinct component of HIV-related fatigue and daytime function J. Pain Symptom Manag. 2013 45 191 201 10.1016/j.jpainsymman.2012.01.011 PMC3547130 22917712 source

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    Premisecitation

    Thiamine (vitamin B1) dietary intakes are below EAR in 55% of Turkish adults of both genders.

    “and thiamine (vitamin B1) dietary intakes are below EAR in 55% of Turkish adults of both genders [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Ministry of Health of Turkey Dietary Guidelines. Publication n°1046 Ministry of Health of Turkey Ankara, Turkey Available online: https://dosyasb.saglik.gov.tr/Eklenti/10922,17ocaktuberingilizcepdf.pdf?0 (accessed on 2 January 2020)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    68% of Mexican women have folate (vitamin B9) intakes below the estimated average requirement (EAR).

    “For example, 68% of Mexican women have folate (vitamin B9) intakes below the estimated average requirement (EAR) [5]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Pedroza-Tobias A. Hernandez-Barrera L. Lopez-Olmedo N. Garcia-Guerra A. Rodriguez-Ramirez S. Ramirez-Silva I. Villalpando S. Carriquiry A. Rivera J.A. Usual Vitamin Intakes by Mexican Populations J. Nutr. 2016 146 1866S 1873S 10.3945/jn.115.219162 27511936 source

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    Premisecitation

    The proportional energy need of the adult human brain is more than twice that of adult non-primate vertebrates, which allocate only 2% to 8% of their basal metabolism to their brain; this may be related to the higher development and larger neuronal number of the human brain.

    “The proportional energy need of the adult human brain is more than twice that of adult non-primate vertebrates, which allocate only 2% to 8% of their basal metabolism to their brain; this may be related to the higher development and larger neuronal number of the human brain [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Herculano-Houzel S. Scaling of brain metabolism with a fixed energy budget per neuron: Implications for neuronal activity, plasticity and evolution PLoS ONE 2011 6 e17514 10.1371/journal.pone.0017514 21390261 PMC3046985 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Limitation in energy supply is a classical hypothesis of muscle fatigue; limitations in the energy-generating processes likely limit the rates of energy expenditure and hence performance.

    “Limitation in energy supply is a classical hypothesis of muscle fatigue; it seems likely that limitations in the energy-generating processes indeed limit the rates of energy expenditure and hence performance [26].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Sahlin K. Tonkonogi M. Soderlund K. Energy supply and muscle fatigue in humans Acta Physiol. Scand. 1998 162 261 266 10.1046/j.1365-201X.1998.0298f.x 9578371 source

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    Premisecitation

    Compromised oxygen delivery can harm the brain, with chronic hypoxia resulting in impaired intellectual function.

    “Compromised oxygen delivery can harm the brain, with chronic hypoxia resulting in impaired intellectual function [33].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Hogan A.M. Pit-ten Cate I.M. Vargha-Khadem F. Prengler M. Kirkham F.J. Physiological correlates of intellectual function in children with sickle cell disease: Hypoxaemia, hyperaemia and brain infarction Dev. Sci. 2006 9 379 387 10.1111/j.1467-7687.2006.00503.x 16764611 source

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    Premisenone given

    The brain consumes approximately 3.5 mL O2 per minute and per 100 g of tissue, which corresponds to 20% of the oxygen needs of the whole body.

    “The brain consumes approximately 3.5 mL O2 per minute and per 100 g of tissue, which corresponds to 20% of the oxygen needs of the whole body.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Mental and physical fatigue are experienced when energy does not meet ongoing demands of the brain and muscles respectively.

    “Mental and physical fatigue are experienced when these do not meet ongoing demands of the brain and muscles respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Resting muscle consumes about 1 ml O2 per minute and per 100 g of tissue, but oxygen consumption can increase up to 50-fold in contracting muscle when exercising, enabling enhanced performance.

    “Resting muscle consumes ‘only’ 1 ml O2 per minute and per 100 g of tissue, but oxygen consumption can increase up to 50-fold in contracting muscle, when exercising [34], and this enables enhanced performance [35].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] Rink C. Khanna S. Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke Antioxid. Redox Signal. 2011 14 1889 1903 10.1089/ars.2010.3474 20673202 PMC3078506 source

      Not checked in the free run.

    • cites [35] Mairbaurl H. Red blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells Front. Physiol. 2013 4 332 10.3389/fphys.2013.00332 24273518 PMC3824146 source

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    Premisecitation

    Intrinsic electrochemical activity occurs continually, including during sleep, and mental work adds only a small increment (less than 5%) to basal neural activity.

    “Intrinsic electrochemical activity occurs continually, including during sleep, and mental work thus only adds a small increment (less than 5%) to the basal neural activity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Raichle M.E. The restless brain: How intrinsic activity organizes brain function Philos. Trans. R. Soc. B Biol. Sci. 2015 370 10.1098/rstb.2014.0172 PMC4387513 25823869 source

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    Premisecitation

    During anemia, when hemoglobin levels are decreased, oxygen delivery is impaired, with consequences for cognitive and physical performance, and perceived fatigue and tiredness.

    “During anemia, i.e., when the levels of hemoglobin (the oxygen carrier) are decreased, oxygen delivery is impaired, with consequences for not only cognitive [36] and physical [35] performance, but also perceived fatigue and tiredness [37].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [36] Schneider A.L. Jonassaint C. Sharrett A.R. Mosley T.H. Astor B.C. Selvin E. Coresh J. Gottesman R.F. Hemoglobin, Anemia, and Cognitive Function: The Atherosclerosis Risk in Communities Study J. Gerontol. A Biol. Sci. Med. Sci. 2016 71 772 779 10.1093/gerona/glv158 26363510 PMC4888383 source

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    • cites [35] Mairbaurl H. Red blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells Front. Physiol. 2013 4 332 10.3389/fphys.2013.00332 24273518 PMC3824146 source

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    • cites [37] Acaster S. Dickerhoof R. DeBusk K. Bernard K. Strauss W. Allen L.F. Qualitative and quantitative validation of the FACIT-fatigue scale in iron deficiency anemia Health Qual. Life Outcomes 2015 13 60 10.1186/s12955-015-0257-x 25980742 PMC4434873 source

      Not checked in the free run.

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    Premisecitation

    Large amounts of ATP are dedicated to maintaining the resting energy potential and to managing neurotransmitter synthesis and processing within synapses.

    “Large amounts of ATP are dedicated to maintaining the resting energy potential and to manage neurotransmitter synthesis and processing within synapses [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Harris J.J. Jolivet R. Attwell D. Synaptic energy use and supply Neuron 2012 75 762 777 10.1016/j.neuron.2012.08.019 22958818 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The adult human brain makes up only 2% of body weight but consumes approximately 20% of the energy deriving from glucose, which provides the bioenergetic basis for neurotransmission.

    “The adult human brain makes up only 2% of the body weight, but it consumes approximately 20% of the energy deriving from glucose, which provides the bioenergetic basis for neurotransmission.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Herculano-Houzel S. Scaling of brain metabolism with a fixed energy budget per neuron: Implications for neuronal activity, plasticity and evolution PLoS ONE 2011 6 e17514 10.1371/journal.pone.0017514 21390261 PMC3046985 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The link between fatigue and risk of road traffic accidents is well established, including in car drivers and rail freight-regulating employees.

    “The link between fatigue and risk of road traffic accidents is well established, including in car drivers [20] and rail freight-regulating employees [21].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Mollicone D. Kan K. Mott C. Bartels R. Bruneau S. van Wollen M. Sparrow A.R. Van Dongen H.P.A. Predicting performance and safety based on driver fatigue Accid. Anal. Prev. 2019 126 142 145 10.1016/j.aap.2018.03.004 29622267 source

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    • cites [21] Rudin-Brown C.M. Harris S. Rosberg A. How shift scheduling practices contribute to fatigue amongst freight rail operating employees: Findings from Canadian accident investigations Accid. Anal. Prev. 2019 126 64 69 10.1016/j.aap.2018.01.027 29397875 source

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    Premisecitation

    Under resting conditions, fractional daily energy expenditure is highest for heart and kidney (each approximately 440 kcal/kg), then brain (approximately 240 kcal/kg), then liver (200 kcal/kg), while resting skeletal muscle needs only approximately 13 kcal/kg.

    “Under resting conditions, the fractional daily energy expenditure is the highest for heart and kidney (each approximately 440 kcal/kg), then for the brain (approximately 240 kcal/kg), then the liver (200 kcal/kg), while the resting skeletal muscle would need only approximately 13 kcal/kg.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Wang Z. Ying Z. Bosy-Westphal A. Zhang J. Schautz B. Later W. Heymsfield S.B. Muller M.J. Specific metabolic rates of major organs and tissues across adulthood: Evaluation by mechanistic model of resting energy expenditure Am. J. Clin. Nutr. 2010 92 1369 1377 10.3945/ajcn.2010.29885 20962155 PMC2980962 source

      Not checked in the free run.

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    Premisecitation

    Fatigue from overnight hospital shifts resulted in worse diagnostic performance among radiologists, and the mean time to first fixate on a fracture increased by 34% among the fatigued physicians.

    “Fatigue from overnight hospital shifts resulted in worse diagnostic performance among radiologists, and the mean time to first fixate on a fracture increased by 34% among the fatigued physicians [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Hanna T.N. Zygmont M.E. Peterson R. Theriot D. Shekhani H. Johnson J.O. Krupinski E.A. The Effects of Fatigue From Overnight Shifts on Radiology Search Patterns and Diagnostic Performance J. Am. Coll. Radiol. 2018 15 1709 1716 10.1016/j.jacr.2017.12.019 29366599 PMC6054573 source

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    Premisecitation

    Pantothenic acid-dependent palmitoylation of certain neuronal proteins is needed for release of neurotransmitters in the synapse, and is thus mandatory for transduction of information in the brain.

    “Pantothenic acid-dependent palmitoylation of certain neuronal proteins is needed for release of neurotransmitters in the synapse, and is thus mandatory for transduction of information in the brain [83].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Trumbo P.R. Pantothenic acid Modern Nutrition in Health and Disease 11th ed. Ross A.C. Caballero B. Cousins R.J. Lippincott Williams & Wilkins Baltimore, MD, USA 2014 351 357

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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    Premisecitation

    Each molecule of ATP binds to a magnesium ion to compose its biologically functional form; in the cell, most of the ATP is present as Mg-ATP complexes.

    “Indeed, each molecule of ATP binds to a magnesium ion (Mg2 +) to compose its biologically functional form: in the cell, most of the ATP is present as Mg-ATP complexes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Pilchova I. Klacanova K. Tatarkova Z. Kaplan P. Racay P. The Involvement of Mg2+ in Regulation of Cellular andMitochondrial Functions Oxid. Med. Cell. Longev. 2017 2017 6797460 10.1155/2017/6797460 28757913 PMC5516748 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Adequate supply of each B vitamin is required for appropriate functioning of the energy-production system and a shortfall in any one of them will be rate limiting for energy production, with potentially severe metabolic and health consequences.

    “Adequate supply of each B vitamin is required for appropriate functioning of the energy-production system and a shortfall in any one of them will be rate limiting for energy production, with potentially severe metabolic and health consequences.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    One hemoglobin molecule can transport four oxygen molecules, and as a result blood carries 50-70 times more oxygen than would plasma alone.

    “One hemoglobin molecule can thus transport four oxygen molecules, and as a result blood carries 50–70 times more oxygen than would plasma alone.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Aggett P.J. Iron Present Knowledge in Nutrition 10th ed. Erdman J.W. Macdonald I.A. Zeisel S.H. Wiley-Blackwell Washington, DC, USA 2012 506 520

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  • May combine two claims.

    Premisereasoning

    In the nervous system, magnesium is important for neuromuscular coordination and optimal nerve transmission.

    “In the nervous system, magnesium is thus important for neuromuscular coordination and optimal nerve transmission.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Kirkland A.E. Sarlo G.L. Holton K.F. The Role of Magnesium in Neurological Disorders Nutrients 2018 10 730 10.3390/nu10060730 PMC6024559 29882776 source

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  • May combine two claims.

    Premisecitation

    Higher magnesium intakes are associated with lower oxygen needs and better cardiorespiratory indices in aerobic exercise.

    “On the contrary, higher magnesium intakes have been reported to be associated with lower oxygen needs and better cardiorespiratory indices in aerobic exercise [115,117].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [115] Zhang Y. Xun P. Wang R. Mao L. He K. Can Magnesium Enhance Exercise Performance? Nutrients 2017 9 946 10.3390/nu9090946 PMC5622706 28846654 source

      Not checked in the free run.

    • cites [117] Lukaski H.C. Magnesium, zinc, and chromium nutriture and physical activity Am. J. Clin. Nutr. 2000 72 585S 593S 10.1093/ajcn/72.2.585S 10919964 source

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  • May combine two claims.

    Premisecitation

    Magnesium deficiency impairs physical performance, and magnesium intake or serum magnesium concentrations are positively associated with muscle strength, muscle performance or muscle power.

    “Magnesium deficiency has been shown to impair physical performance, while several cross-sectional surveys have reported a positive association between magnesium intake or serum magnesium concentrations and outcomes related to muscle strength, muscle performance or muscle power [115].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [115] Zhang Y. Xun P. Wang R. Mao L. He K. Can Magnesium Enhance Exercise Performance? Nutrients 2017 9 946 10.3390/nu9090946 PMC5622706 28846654 source

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    Premisecitation

    Magnesium protects against excessive excitation leading to cell death by interacting with the aspartate receptor, blocking the calcium channel, and must be removed for glutamatergic excitatory signalling to occur.

    “It is also useful to protect against excessive excitation leading to cell death: it interacts with the aspartate receptor, by blocking the calcium channel in this receptor, and must be removed for glutamatergic excitatory signalling to occur.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Kirkland A.E. Sarlo G.L. Holton K.F. The Role of Magnesium in Neurological Disorders Nutrients 2018 10 730 10.3390/nu10060730 PMC6024559 29882776 source

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  • May combine two claims.

    Premisecitation

    Low magnesium levels may theoretically increase glutamatergic neurotransmission, which can lead to oxidative stress and neuronal cell death.

    “Low magnesium levels may theoretically increase glutamatergic neurotransmission, which can lead to oxidative stress and neuronal cell death [97].”
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    • cites [97] Kirkland A.E. Sarlo G.L. Holton K.F. The Role of Magnesium in Neurological Disorders Nutrients 2018 10 730 10.3390/nu10060730 PMC6024559 29882776 source

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    Premisecitation

    Deficiencies in cobalamin can result in diminished energy and exercise tolerance, together with fatigue and shortness of breath, and these hematologic symptoms regress and disappear with supplementation with vitamin B12.

    “Deficiencies in cobalamin (vitamin B12) can result in diminished energy and exercise tolerance, together with fatigue and shortness of breath. These hematologic symptoms regress and disappear with supplementation with vitamin B12, for which doses and routes will depend on the cause and severity of deficiency [109].”
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    • cites [109] Stabler S.P. Clinical practice. Vitamin B12 deficiency N. Engl. J. Med. 2013 368 149 160 10.1056/NEJMcp1113996 23301732

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    Premisenone given

    Frank deficiencies in most vitamins and minerals have been associated with lethargy or physical fatigue, which can also be observed in marginal deficiencies, but these symptoms are often missed because they are nonspecific.

    “Frank deficiencies in most vitamins and minerals have been associated with lethargy or physical fatigue, which can also be observed in marginal deficiencies, but these symptoms are often missed because they are nonspecific.”
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    Premisecitation

    Iron deficiency decreases physical performance, work efficiency and working capacity.

    “Besides increasing perceived fatigue, iron deficiency is also known to decrease physical performance, work efficiency and working capacity [113].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [113] Haas J.D. Brownlie T.T. Iron deficiency and reduced work capacity: A critical review of the research to determine a causal relationship J. Nutr. 2001 131 676S 688S 676S–688S, discussion 688S–690S 10.1093/jn/131.2.676S 11160598 source

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    Premisecitation

    High concentrations of zinc are present in synaptic vesicles of specific neurons, called 'zinc-containing' neurons, where it has a major role in controlling synaptic excitability by modulating neurotransmission mediated by both glutamate and gamma-aminobutyric acid.

    “High concentrations of zinc are present in the synaptic vesicles of specific neurons, called ‘zinc-containing’ neurons, where it has a major role in controlling synaptic excitability by modulating neurotransmission mediated by both glutamate and gamma-aminobutyric acid.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Sensi S.L. Paoletti P. Bush A.I. Sekler I. Zinc in the physiology and pathology of the CNS Nat. Rev. Neurosci. 2009 10 780 791 10.1038/nrn2734 19826435 source

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    Premisecitation

    Vitamin B5 deficiency experimentally induced in humans causes headache, fatigue, insomnia, and excessive fatigue after daily walk, which decrease and disappear after 4 weeks of supplementation with 4 g pantothenic acid daily.

    “After approximately 6 weeks, subjects complained of headache, fatigue, insomnia, and they reported excessive fatigue after their daily walk; symptoms decreased then disappeared after 4 weeks of supplementation with 4 g pantothenic acid daily [103].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [103] Hodges R.E. Ohlson M.A. Bean W.B. Pantothenic acid deficiency in man J. Clin. Investig. 1958 37 1642 1657 10.1172/JCI103756 13587673 PMC1062846 source

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    Premisecitation

    Beriberi, the disease resulting from severe thiamine deficiency, affects several organs, including the muscular and peripheral nervous systems, and causes fatigue, ataxia, muscle pain, and dyspnoea on exertion.

    “Beriberi, the disease resulting from severe thiamine (vitamin B1) deficiency affects several organs, including the muscular and peripheral nervous systems [99]. General symptoms include fatigue, ataxia due to muscle weakness in the legs and arms, muscle pain and tenderness, and dyspnoea on exertion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [99] Whitfield K.C. Bourassa M.W. Adamolekun B. Bergeron G. Bettendorff L. Brown K.H. Cox L. Fattal-Valevski A. Fischer P.R. Frank E.L. Thiamine deficiency disorders: Diagnosis, prevalence, and a roadmap for global control programs Ann. N. Y. Acad. Sci. 2018 1430 3 43 10.1111/nyas.13919 30151974 PMC6392124 source

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    Premisereasoning

    Common symptoms of iron deficiency in adults include fatigue and low resistance to exertion, which can be related to low delivery of oxygen to body tissues and decreased activity of iron-containing enzymes.

    “Common symptoms of iron deficiency in adults include fatigue and low resistance to exertion. These symptoms can be related to low delivery of oxygen to body tissues and decreased activity of iron-containing enzymes.”
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    Premisecitation

    One of the most typical features of pyridoxine deficiency is microcytic anemia, due to defective hemoglobin biosynthesis and characterised by symptoms of weakness, tiredness or fatigue.

    “One of the most typical features of pyridoxine (vitamin B6) deficiency is microcytic anemia, due to defective hemoglobin biosynthesis and characterised by symptoms of weakness, tiredness or fatigue [105].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [105] Rosenthal T.C. Majeroni B.A. Pretorius R. Malik K. Fatigue: An overview Am. Fam. Physician 2008 78 1173 1179 19035066

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    Premisecitation

    Zinc is potently neurotoxic and could increase neuronal death during transient global ischemia and brain trauma, but neurons have numerous homeostatic systems to maintain zinc concentrations at levels that are nontoxic.

    “Zinc is also potently neurotoxic and could increase neuronal death during transient global ischemia and brain trauma, but neurons have numerous homeostatic systems to maintain zinc concentrations at levels that are nontoxic [89].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Sensi S.L. Paoletti P. Bush A.I. Sekler I. Zinc in the physiology and pathology of the CNS Nat. Rev. Neurosci. 2009 10 780 791 10.1038/nrn2734 19826435 source

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    Premisecitation

    Intravenous vitamin C improves cancer- and chemotherapy-related symptoms, including fatigue, and overall functioning.

    “Several recent studies have indicated that intravenous vitamin C led to significant improvements of these symptoms and found that not only overall health, but also physical, role, cognitive, emotional, and social functioning were improved [126].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [126] Carr A.C. Vissers M.C. Cook J.S. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life Front. Oncol. 2014 4 283 10.3389/fonc.2014.00283 25360419 PMC4199254 source

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    Premisecitation

    Magnesium supplementation reduces the perception of fatigue in breast cancer women and may improve endurance performance in physically active students.

    “Supplementation with 400 or 800 mg magnesium daily for 4 weeks has been shown to reduce the perception of fatigue in 25 breast cancer women experiencing hot flushes in an uncontrolled pilot trial [134].”
    • Also stated in: § 6.2. Effects of Supplementation with Vitamins and Minerals on Physical Fatigue · hedged
      “One intervention study in physically active college students found that endurance performance during submaximal exercise increased after magnesium supplementation (8 mg/kg/day, which is 500 mg/day approximately for a body weight of 60 kg), thus suggesting a possible beneficial impact on the perception of exercise-related fatigue [135].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [134] Park H. Parker G.L. Boardman C.H. Morris M.M. Smith T.J. A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients Support. Care Cancer 2011 19 859 863 10.1007/s00520-011-1099-7 21271347 PMC3085555 source

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    • cites [135] Brilla L.R. Gunther K.B. Effect of magnesium supplementation on exercise time to exhaustion Med. Exerc. Nutr. Health 1995 4 230

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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    Premisecitation

    Pantothenic acid deficiency results in neurological dysfunction, including acute encephalopathy in dogs and personality changes in humans.

    “Deficiency in pantothenic acid (vitamin B5) results in neurological dysfunction. Dogs treated with an antagonist of vitamin B5 that induces a deficiency of pantothenic acid developed an acute encephalopathy [144].”
    • Also stated in: § 7.1. Impact of Vitamins and Minerals Frank Deficiencies on Mental Fatigue and Cognitive or Psychological Functions · plain
      “Experimentally induced deficiency in pantothenic acid results in personality changes [103].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [144] Noda S. Haratake J. Sasaki A. Ishii N. Umezaki H. Horie A. Acute encephalopathy with hepatic steatosis induced by pantothenic acid antagonist, calcium hopantenate, in dogs Liver 1991 11 134 142 10.1111/j.1600-0676.1991.tb00506.x 1886458 source

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    • cites [103] Hodges R.E. Ohlson M.A. Bean W.B. Pantothenic acid deficiency in man J. Clin. Investig. 1958 37 1642 1657 10.1172/JCI103756 13587673 PMC1062846 source

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    Premisecitation

    Iron deficiency is associated with lower work capacity in agricultural workers, and iron supplementation increases work capacity and productivity.

    “Iron deficiency has been shown to be associated with lower work capacity for agricultural workers in several developing countries, including China, Colombia, Guatemala, Indonesia, Kenya, and Sri Lanka, in men and in women. Iron supplementation increased work capacity and output, with productivity gains, and take-home pay ranged from 10% to 30% above previous levels [127].”
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    • cites [127] World Health Organization Nutritional Anaemias: Tools for Effective Prevention and Control Licence: CC BY-NC-SA 3.0 IGO World Health Organization Geneva, Switzerland 2017

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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    Premisecitation

    Riboflavin supplementation (2 or 4 mg daily for 8 weeks) increases blood hemoglobin and improves riboflavin status in mildly deficient young women.

    “In 119 young British women, aged 19–25 years, who were mildly deficient in riboflavin, daily supplementation with 2 or 4 mg riboflavin for 8 weeks resulted in an increase in blood hemoglobin, which was correlated to the improvement in riboflavin status.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119] Powers H.J. Hill M.H. Mushtaq S. Dainty J.R. Majsak-Newman G. Williams E.A. Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) Am. J. Clin. Nutr. 2011 93 1274 1284 10.3945/ajcn.110.008409 21525198 source

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    Premisecitation

    Early correction of thiamine deficiency can fully reverse symptoms and prevent brain damage; persistent deficiency causes permanent brain damage and irreversible cognitive dysfunction.

    “When thiamine deficiency is corrected early enough, symptoms can be fully reversed and significant brain damage can be prevented. However permanent brain damage and irreversible cognitive dysfunction will occur if thiamine deficiency persists and this can be critical as encephalopathies linked to thiamine deficiency remain largely undiagnosed [141].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [141] Isenberg-Grzeda E. Kutner H.E. Nicolson S.E. Wernicke-Korsakoff-syndrome: Under-recognized and under-treated Psychosomatics 2012 53 507 516 10.1016/j.psym.2012.04.008 23157990 source

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    Premisecitation

    Riboflavin supplementation (100 mg) before and during an ultramarathon reduces muscle pain and soreness and improves run times 3 and 5 days after the race.

    “Muscle pain and soreness ratings during and immediately after the race were found to be significantly lower for the riboflavin-treated group. When performance on 400 min runs was measured, 3 and 5 days after the ultramarathon, times were significantly faster for the riboflavin-treated group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [120] Hoffman M.D. Valentino T.R. Stuempfle K.J. Hassid B.V. A Placebo-Controlled Trial of Riboflavin for Enhancement of Ultramarathon Recovery Sports Med. Open 2017 3 14 10.1186/s40798-017-0081-4 28349501 PMC5368102 source

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    Premisecitation

    Long-term niacin deficiency can lead to neurological symptoms, including depression and loss of memory, which attenuate or disappear following niacin intake.

    “Long-term niacin (vitamin B3) deficiency can lead to neurological symptoms, including depression and loss of memory [102]. These symptoms attenuate or disappear following niacin intake, confirming its role in the brain and nervous system [143].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [102] Hegyi J. Schwartz R.A. Hegyi V. Pellagra: Dermatitis, dementia, and diarrhea Int. J. Dermatol. 2004 43 1 5 10.1111/j.1365-4632.2004.01959.x 14693013 source

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    • cites [143] Oldham M.A. Ivkovic A. Pellagrous encephalopathy presenting as alcohol withdrawal delirium: A case series and literature review Addict. Sci. Clin. Pract. 2012 7 12 10.1186/1940-0640-7-12 23186222 PMC3542555 source

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    Premisecitation

    Iron supplementation improves maximal and submaximal exercise performance and VO2max in nonanemic iron-deficient individuals and athletes.

    “However, a meta-analysis gathering data from 15 studies carried out in endurance athletes found a moderate but significant favorable effect on VO2max of iron intervention (oral iron in most studies, with dosages varying from 10 to 300 mg/day and for durations ranging from 14 to 84 days).”
    • Also stated in: § 6.2. Effects of Supplementation with Vitamins and Minerals on Physical Fatigue · boosted
      “A meta-analysis on 22 studies found that iron supplementation improved both maximal exercise performance and submaximal exercise performance, demonstrated by a lower heart rate required to achieve defined workloads [132].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [131] Burden R.J. Morton K. Richards T. Whyte G.P. Pedlar C.R. Is iron treatment beneficial in, iron-deficient but non-anemic (IDNA) endurance athletes? A systematic review and meta-analysis Br. J. Sports Med. 2015 49 1389 1397 10.1136/bjsports-2014-093624 25361786 source

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    • cites [132] Pasricha S.R. Low M. Thompson J. Farrell A. De-Regil L.M. Iron supplementation benefits physical performance in women of reproductive age: A systematic review and meta-analysis J. Nutr. 2014 144 906 914 10.3945/jn.113.189589 24717371 source

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    • cites [133] Pompano L.M. Haas J.D. Increasing Iron Status through Dietary Supplementation in Iron-Depleted, Sedentary Women Increases Endurance Performance at Both Near-Maximal and Submaximal Exercise Intensities J. Nutr. 2019 149 231 239 10.1093/jn/nxy271 30649365 source

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    Premisecitation

    Early-life iron deficiency may produce irreversible neural changes and is associated with poor motor and cognitive development outcomes in children.

    “Early-life iron deficiency may produce irreversible neural changes when neurogenesis and differentiation of brain regions are occurring; numerous observational studies have shown associations between iron deficiency and/or associated anemia and poor motor and cognitive development outcomes in children.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [150] Grantham-McGregor S. Ani C. A review of studies on the effect of iron deficiency on cognitive development in children J. Nutr. 2001 131 649S 666S 10.1093/jn/131.2.649S 11160596 source

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    Premisecitation

    Low dietary intake of pantothenic acid is correlated with low scores in Global Assessment of Functioning in adults with mood disorders, and children with depressive symptoms have lower vitamin B5 intakes.

    “Positive correlations exist between low dietary intakes of pantothenic acid (vitamin B5) (together with other macronutrients and micronutrients) and low scores obtained by 97 adults with mood disorders in the Global Assessment of Functioning, a questionnaire designed to evaluate social, occupational, and psychological functioning [155].”
    • Also stated in: § 7.2. Relationships between Vitamin and Mineral Dietary Intake or Status and Mental Fatigue and Cognitive or Psychological Functions · hedged
      “Similar findings come from a study in 710 Spanish school children that suggest that children with depressive symptoms had lower intakes of vitamin B5, as well as of other B vitamins [156].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [155] Davison K.M. Kaplan B.J. Nutrient intakes are correlated with overall psychiatric functioning in adults with mood disorders Can. J. Psychiatry 2012 57 85 92 10.1177/070674371205700205 22340148 source

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    • cites [156] Rubio-López N. Morales-Suárez-Varela M. Pico Y. Livianos-Aldana L. Llopis-González A. Nutrient Intake and Depression Symptoms in Spanish Children: The ANIVA Study Int. J. Environ. Res. Public Health 2016 13 352 10.3390/ijerph13030352 PMC4809015 27011198 source

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    Premisecitation

    Low folate status and/or low dietary folate intake are associated with depression and anxiety in adults and elderly.

    “Low folate (vitamin B9) blood status and/or low dietary intakes of folates are associated with psychological symptoms such as depression and anxiety in adults and elderly subjects.”
    • Also stated in: § 7.2. Relationships between Vitamin and Mineral Dietary Intake or Status and Mental Fatigue and Cognitive or Psychological Functions · plain
      “In 2266 Japanese adults (mean age 43.5 years), those with depressive symptoms were found to have lower dietary energy-adjusted folate intakes than those without depressive mood [158].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [158] Miyaki K. Song Y. Htun N.C. Tsutsumi A. Hashimoto H. Kawakami N. Takahashi M. Shimazu A. Inoue A. Kurioka S. Folate intake and depressive symptoms in Japanese workers considering SES and job stress factors: J-HOPE study BMC Psychiatry 2012 12 33 10.1186/1471-244X-12-33 22521003 PMC3439709 source

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    • cites [159] Yary T. The association between dietary intake of folate and physical activity with psychological dimensions of depressive symptoms among students from Iran Biomed. Res. Int. 2013 2013 582693 10.1155/2013/582693 24324965 PMC3845418 source

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    • cites [161] Bender A. Hagan K.E. Kingston N. The association of folate and depression: A meta-analysis J. Psychiatr. Res. 2017 95 9 18 10.1016/j.jpsychires.2017.07.019 28759846 source

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    Premisecitation

    A negative relationship exists between depressive symptoms and intake of B vitamins, including pyridoxine, in elderly Japanese females, but not males; higher pyridoxine intake is associated with better psychomotor speed in young adults.

    “A negative relationship has been found between depressive symptoms and the levels of intake of B vitamins, including pyridoxine (vitamin B6) in 914 elderly Japanese females, but not in 720 males [157].”
    • Also stated in: § 7.2. Relationships between Vitamin and Mineral Dietary Intake or Status and Mental Fatigue and Cognitive or Psychological Functions · plain
      “In addition, a cohort of 3136 young adults has been followed for at least 20 years from age 18 to 30 years and those in the highest quintile of dietary pyridoxine intake at baseline (i.e., a median intake of 3.0 mg/day) had better results in psychomotor speed tests 20 to 25 years later than those with the lowest dietary intake of pyridoxine (median 0.7 mg/day) [153].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [157] Nguyen T.T.T. Tsujiguchi H. Kambayashi Y. Hara A. Miyagi S. Yamada Y. Nakamura H. Shimizu Y. Hori D. Suzuki F. Relationship between Vitamin Intake and Depressive Symptoms in Elderly Japanese Individuals: Differences with Gender and Body Mass Index Nutrients 2017 9 1319 10.3390/nu9121319 PMC5748769 29207502 source

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    • cites [153] Qin B. Xun P. Jacobs D.R. Jr. Zhu N. Daviglus M.L. Reis J.P. Steffen L.M. Van Horn L. Sidney S. He K. Intake of niacin, folate, vitamin B-6, and vitamin B-12 through young adulthood and cognitive function in midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) study Am. J. Clin. Nutr. 2017 106 1032 1040 10.3945/ajcn.117.157834 28768650 PMC5611785 source

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    Premisecitation

    Positive associations exist between niacin status and risk of Alzheimer disease and cognitive decline, and higher niacin intake is associated with better cognitive test results.

    “Positive associations have been found between niacin (vitamin B3) status and the risk of Alzheimer disease and cognitive decline [152].”
    • Also stated in: § 7.2. Relationships between Vitamin and Mineral Dietary Intake or Status and Mental Fatigue and Cognitive or Psychological Functions · plain
      “In addition, in a cohort of 3136 American adults followed for 20 years from age 18 to 30 years, those in the highest quintile of dietary niacin intake at baseline (i.e., a median intake of 24.7 mg/day) had better results in cognitive tests 20–25 years later than did those with the lowest dietary intake of niacin (median 8.6 mg/day, so below the US recommendation, set at 15 mg daily) [153].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [152] Morris M.C. Evans D.A. Bienias J.L. Scherr P.A. Tangney C.C. Hebert L.E. Bennett D.A. Wilson R.S. Aggarwal N. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline J. Neurol. Neurosurg. Psychiatry 2004 75 1093 1099 10.1136/jnnp.2003.025858 15258207 PMC1739176 source

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    • cites [153] Qin B. Xun P. Jacobs D.R. Jr. Zhu N. Daviglus M.L. Reis J.P. Steffen L.M. Van Horn L. Sidney S. He K. Intake of niacin, folate, vitamin B-6, and vitamin B-12 through young adulthood and cognitive function in midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) study Am. J. Clin. Nutr. 2017 106 1032 1040 10.3945/ajcn.117.157834 28768650 PMC5611785 source

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    • cites [154] Kim J.Y. Kang S.W. Relationships between Dietary Intake and Cognitive Function in Healthy Korean Children and Adolescents J. Lifestyle Med. 2017 7 10 17 10.15280/jlm.2017.7.1.10 28261556 PMC5332116 source

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    Premisecitation

    Cobalamin deficiency induces neurological dysfunction, including myelopathy, neuropathy and neuropsychiatric abnormalities, and is associated with mental and cognitive impairment up to dementia.

    “Cobalamin (vitamin B12) deficiency induces neurological dysfunction, including myelopathy, neuropathy and neuropsychiatric abnormalities. Such neurological damage has been reported in 20–30% of cases of vitamin B12 deficiency [147], and can even occur before serum vitamin B12 concentrations reach a level that would be considered deficient by standard criteria.”
    • Also stated in: § 7.1. Impact of Vitamins and Minerals Frank Deficiencies on Mental Fatigue and Cognitive or Psychological Functions · plain
      “In addition, deficiencies in vitamin B12 are associated with mental and cognitive impairment, such as irritability, memory loss, depression, and cognitive disturbances up to dementia [148].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [147] O’Leary F. Samman S. Vitamin B(12) in Health and Disease Nutrients 2010 2 299 316 10.3390/nu2030299 22254022 PMC3257642 source

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    • cites [148] Hunt A. Harrington D. Robinson S. Vitamin B12 deficiency BMJ 2014 349 g5226 10.1136/bmj.g5226 25189324 source

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    Premisecitation

    Lower biochemical vitamin B12 status in children and adolescents is associated with impaired school performance, mental and social development, and short-term memory and attention.

    “Cross-sectional studies in older children or adolescents most often found that lower biochemical vitamin B12 status was associated with impaired school performance and mental and social development, as well as short-term memory and attention [164].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [164] Venkatramanan S. Armata I.E. Strupp B.J. Finkelstein J.L. Vitamin B-12 and Cognition in Children Adv. Nutr. 2016 7 879 888 10.3945/an.115.012021 27633104 PMC5015033 source

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    • cites [168] Louwman M.W. van Dusseldorp M. van de Vijver F.J. Thomas C.M. Schneede J. Ueland P.M. Refsum H. van Staveren W.A. Signs of impaired cognitive function in adolescents with marginal cobalamin status Am. J. Clin. Nutr. 2000 72 762 769 10.1093/ajcn/72.3.762 10966896 source

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    Premisecitation

    In a case-control study in people aged over 60 years, vitamin C intake from foods was significantly lower in depressive subjects (109 mg/day) than in non-depressive subjects (143 mg/day), although above the recommended amount in all subjects.

    “In a case-control study in people aged over 60 years, vitamin C intake from foods was above the recommended amount in all subjects, but was significantly lower (109 mg/day) in depressive subjects versus non depressive ones (143 mg/day) [175].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [175] Payne M.E. Steck S.E. George R.R. Steffens D.C. Fruit, vegetable, and antioxidant intakes are lower in older adults with depression J. Acad. Nutr. Diet. 2012 112 2022 2027 10.1016/j.jand.2012.08.026 23174689 PMC3520090 source

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    Premisecitation

    Accumulated homocysteine is a suspected risk factor for cognitive dysfunction and dementia, although this point remains controversial.

    “which is a suspected risk factor for cognitive dysfunction and dementia, although this point remains controversial [94,171,172].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [94] Kennedy D.O. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review Nutrients 2016 8 68 10.3390/nu8020068 26828517 PMC4772032 source

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    • cites [171] Ji X. Cui N. Liu J. Neurocognitive Function Is Associated With Serum Iron Status in Early Adolescents Biol. Res. Nurs. 2017 19 269 277 10.1177/1099800417690828 28196427 PMC5675069 source

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    • cites [172] Moretti R. Caruso P. The Controversial Role of Homocysteine in Neurology: From Labs to Clinical Practice Int. J. Mol. Sci. 2019 20 231 10.3390/ijms20010231 PMC6337226 30626145 source

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    Premisecitation

    In that study, attention, memory and learning were affected, and cognitive performance decreased as the severity of iron deficiency increased.

    “Attention, memory and learning were affected and data show that cognitive performance decreased when the severity of iron deficiency increased [178].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [178] Murray-Kolb L.E. Beard J.L. Iron treatment normalizes cognitive functioning in young women Am. J. Clin. Nutr. 2007 85 778 787 10.1093/ajcn/85.3.778 17344500 source

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    Premisecitation

    Higher maternal vitamin B12 status and/or intake during pregnancy is associated with improved cognitive measures in children.

    “Higher maternal vitamin B12 status and/or higher vitamin B12 intakes during pregnancy have been prospectively associated with improved measures of cognition in 330 children later in life.”
    • Also stated in: § 7.2. Relationships between Vitamin and Mineral Dietary Intake or Status and Mental Fatigue and Cognitive or Psychological Functions · plain
      “In Nepalese children aged 2–12 months, the vitamin B12 status was biochemically assessed and was found significantly associated, 5 years later, with improved development and performance on assessments of social perception and visuospatial abilities [167].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [164] Venkatramanan S. Armata I.E. Strupp B.J. Finkelstein J.L. Vitamin B-12 and Cognition in Children Adv. Nutr. 2016 7 879 888 10.3945/an.115.012021 27633104 PMC5015033 source

      Not checked in the free run.

    • cites [167] Kvestad I. Hysing M. Shrestha M. Ulak M. Thorne-Lyman A.L. Henjum S. Ueland P.M. Midttun O. Fawzi W. Chandyo R.K. Vitamin B-12 status in infancy is positively associated with development and cognitive functioning 5 y later in Nepalese children Am. J. Clin. Nutr. 2017 105 1122 1131 10.3945/ajcn.116.144931 28330909 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Systematic reviews show no association between blood vitamin B12 concentrations and cognitive decline or dementia, but some studies using newer biomarkers find associations between low vitamin B12 status and enhanced risk of dementia or cognitive decline.

    “However, more recent systematic reviews have less clear conclusions: no association was found between blood vitamin B12 concentrations and cognitive decline or dementia, but four studies that assessed vitamin B12 status with newer biomarkers found associations between low vitamin B12 status and an enhanced risk of diagnosis with dementia or cognitive decline [165].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] Doets E.L. van Wijngaarden J.P. Szczecinska A. Dullemeijer C. Souverein O.W. Dhonukshe-Rutten R.A. Cavelaars A.E. van ‘t Veer P. Brzozowska A. de Groot L.C. Vitamin B12 intake and status and cognitive function in elderly people Epidemiol. Rev. 2013 35 2 21 10.1093/epirev/mxs003 23221971 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Excessive iron deposits become prevalent in the cerebral region upon ageing and even more so in the brains of subjects with Parkinson disease or Alzheimer disease, where they are associated with neurodegeneration.

    “excessive iron deposits become prevalent in the cerebral region upon ageing and even more so in the brains of subjects suffering from Parkinson disease [179] or Alzheimer disease [180] diseases, where they are associated with the neurodegeneration observed in these pathologies.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [179] Abeyawardhane D.L. Lucas H.R. Iron Redox Chemistry and Implications in the Parkinson’s Disease Brain Oxid. Med. Cell. Longev. 2019 2019 4609702 10.1155/2019/4609702 31687080 PMC6803728 source

      Not checked in the free run.

    • cites [180] Wang T. Xu S.F. Fan Y.G. Li L.B. Guo C. Iron Pathophysiology in Alzheimer’s Diseases Adv. Exp. Med. Biol. 2019 1173 67 104 10.1007/978-981-13-9589-5_5 31456206 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Magnesium is known to reduce the intensity of addiction to alcohol and other substances, and alcohol abusers have lower plasma and intracellular magnesium concentrations than healthy subjects.

    “magnesium is known to reduce the intensity of addiction to alcohol and other substances and alcohol abusers have lower plasma and intracellular magnesium concentrations, compared with healthy subjects [188].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [188] Nechifor M. Magnesium in drug abuse and addiction Magnesium in the Central Nervous System Vink R. Nechifor M. University of Adelaide Press Adelaide, Australia 2011 331 342 29920014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In the same study, adolescents with excessive blood iron (above 175 μg/dL) displayed lower accuracy in spatial processing and longer reaction time in abstraction and mental flexibility, suggesting a safe window for iron benefits.

    “adolescents with excessive blood iron (above 175 µg/dL) displayed a lower accuracy in the spatial processing ability task and a longer reaction time when abstraction and mental flexibility were assessed, suggesting the existence of a safe window for iron benefits [171].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [171] Ji X. Cui N. Liu J. Neurocognitive Function Is Associated With Serum Iron Status in Early Adolescents Biol. Res. Nurs. 2017 19 269 277 10.1177/1099800417690828 28196427 PMC5675069 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Zinc deficiency is suspected to be a mediator of toxic effects of alcohol abuse, including at the brain level, and zinc status is generally low in alcoholic patients.

    “Zinc deficiency is suspected to be a mediator of toxic effects of alcohol abuse, including at the brain level, and zinc status is generally low in alcoholic patients [193].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [193] Skalny A.V. Skalnaya M.G. Grabeklis A.R. Skalnaya A.A. Tinkov A.A. Zinc deficiency as a mediator of toxic effects of alcohol abuse Eur. J. Nutr. 2018 57 2313 2322 10.1007/s00394-017-1584-y 29177978 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the same study, the highest magnesium serum concentration (above 0.90 mmol/L) was also associated with a similar risk increase, suggesting an optimal status in between.

    “a similar risk increase was also associated with the highest magnesium serum concentration (above 0.90 mmol/L), suggesting the existence of an optimal status in between [181].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [181] Kieboom B.C.T. Licher S. Wolters F.J. Ikram M.K. Hoorn E.J. Zietse R. Stricker B.H. Ikram M.A. Serum magnesium is associated with the risk of dementia Neurology 2017 89 1716 1722 10.1212/WNL.0000000000004517 28931641 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    According to meta-analyses, both insufficient dietary magnesium intakes and low magnesium biological status are associated with a higher risk of depression.

    “According to meta-analyses, both insufficient dietary magnesium intakes [182,183] and low magnesium biological status [184] are associated with a higher risk of depression.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [182] Derom M.L. Sayon-Orea C. Martinez-Ortega J.M. Martinez-Gonzalez M.A. Magnesium and depression: A systematic review Nutr. Neurosci. 2013 16 191 206 10.1179/1476830512Y.0000000044 23321048 source

      Not checked in the free run.

    • cites [183] Li B. Lv J. Wang W. Zhang D. Dietary magnesium and calcium intake and risk of depression in the general population: A meta-analysis Aust. N. Z J. Psychiatry 2017 51 219 229 10.1177/0004867416676895 27807012 source

      Not checked in the free run.

    • cites [184] Cheungpasitporn W. Thongprayoon C. Mao M.A. Srivali N. Ungprasert P. Varothai N. Sanguankeo A. Kittanamongkolchai W. Erickson S.B. Hypomagnesaemia linked to depression: A systematic review and meta-analysis Intern. Med. J. 2015 45 436 440 10.1111/imj.12682 25827510 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a meta-analysis of nine studies, high dietary zinc intake appears linked to better protection against depression, with a relative risk of 0.67 (95% confidence interval 0.58-0.76); associations were significant in both cross-sectional and prospective studies.

    “In a meta-analysis of nine studies, a high dietary zinc intake appears to be linked to better protection against depression, with a meaningful relative risk of 0.67 (95% confidence interval: 0.58–0.76); associations were significant both in cross-sectional and in prospective studies [192].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [192] Li Z. Li B. Song X. Zhang D. Dietary zinc and iron intake and risk of depression: A meta-analysis Psychiatry Res. 2017 251 41 47 10.1016/j.psychres.2017.02.006 28189077 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 428 Chinese adolescents aged 12 years with low iron status (below 75 μg/dL), performance was slower in tasks measuring abstraction and mental flexibility and spatial processing abilities were lower than in those with normal iron status.

    “428 Chinese adolescents 12 years of age and with a low iron status (below 75 µg/dL) had slower performance in tasks that measured abstraction and mental flexibility and lower spatial processing abilities compared with those with normal iron status.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [171] Ji X. Cui N. Liu J. Neurocognitive Function Is Associated With Serum Iron Status in Early Adolescents Biol. Res. Nurs. 2017 19 269 277 10.1177/1099800417690828 28196427 PMC5675069 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Alzheimer disease, zinc at physiological levels suppresses β-amyloid-induced neurotoxicity by selectively precipitating aggregation intermediates; at high levels, zinc binding to β-amyloid may enhance fibrillar β-amyloid aggregation, leading to neurodegeneration.

    “in patients suffering from Alzheimer disease, zinc at physiological levels suppresses β-amyloid-induced neurotoxicity by selectively precipitating aggregation intermediates; however, at high levels, the binding of zinc to β-amyloid may rather enhance fibrillar β-amyloid aggregation, leading to neurodegeneration [194].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [194] Mezzaroba L. Alfieri D.F. Colado Simao A.N. Vissoci Reiche E.M. The role of zinc, copper, manganese and iron in neurodegenerative diseases Neurotoxicology 2019 74 230 241 10.1016/j.neuro.2019.07.007 31377220 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a meta-analysis of 32 studies including 7089 children aged 5-12 years, iron supplementation in anemic children significantly improved measures of attention and concentration, global cognitive scores and intelligence quotient.

    “a meta-analysis of 32 studies that included 7089 children aged 5–12 years. Iron supplementation in anemic children significantly improved measures of attention and concentration, global cognitive scores and intelligence quotient [205].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [205] Low M. Farrell A. Biggs B.A. Pasricha S.R. Effects of daily iron supplementation in primary-school-aged children: Systematic review and meta-analysis of randomized controlled trials CMAJ 2013 185 E791 802 10.1503/cmaj.130628 24130243 PMC3832580 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 140 Indian adolescents aged 12-16 years who consumed for 6 months a biofortified iron-rich millet compared with conventional millet, attention and memory performance increased significantly, and ferritin level increased vs placebo (30 vs 22 μg/L).

    “attention and memory performance increased significantly in 140 Indian adolescents aged 12–16 years who consumed for 6 months a biofortified iron-rich millet compared with conventional millet, which increased their ferritin level vs. placebo (30 vs. 22 µg/L) [206].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [206] Scott S.P. Murray-Kolb L.E. Wenger M.J. Udipi S.A. Ghugre P.S. Boy E. Haas J.D. Cognitive Performance in Indian School-Going Adolescents Is Positively Affected by Consumption of Iron-Biofortified Pearl Millet: A 6-Month Randomized Controlled Efficacy Trial J. Nutr. 2018 148 1462 1471 10.1093/jn/nxy113 30016516 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A systematic review identified ten supplementation trials in premenopausal women; seven found that iron supplementation improved several dimensions of mood and cognition, including memory and intellectual ability.

    “A systematic review has identified ten supplementation trials in premenopausal women, a population at higher risk of iron deficiency because of enhanced requirements. Seven of these studies found that iron supplementation improved several dimensions of mood and cognition, including memory and intellectual ability [208].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [208] Lomagno K.A. Hu F. Riddell L.J. Booth A.O. Szymlek-Gay E.A. Nowson C.A. Byrne L.K. Increasing iron and zinc in pre-menopausal women and its effects on mood and cognition: A systematic review Nutrients 2014 6 5117 5141 10.3390/nu6115117 25405366 PMC4245583 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several lines of evidence suggest that excessive iron accumulation can be detrimental to brain structures and could be associated with brain ageing and neurodegenerative disorders.

    “several lines of evidence suggest that excessive iron accumulation can be detrimental to brain structures and could be associated with brain ageing and neurodegenerative disorders [207].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [207] Ward R.J. Zucca F.A. Duyn J.H. Crichton R.R. Zecca L. The role of iron in brain ageing and neurodegenerative disorders Lancet Neurol. 2014 13 1045 1060 10.1016/S1474-4422(14)70117-6 25231526 PMC5672917 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Following iron supplementation (60 mg daily for 4 months), 149 young American women with iron deficiency anemia at baseline experienced significant improvement in serum ferritin (22.8 μg/L vs 9.2 μg/L in placebo) associated with a 5-fold improvement in cognitive performance.

    “Following iron supplementation (60 mg daily for 4 months), 149 young American women with iron deficiency anemia at baseline experienced a significant improvement in serum ferritin (22.8 µg/L vs. 9.2 µg/L in the placebo group) that was associated with a 5-fold improvement in cognitive performance [178].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [178] Murray-Kolb L.E. Beard J.L. Iron treatment normalizes cognitive functioning in young women Am. J. Clin. Nutr. 2007 85 778 787 10.1093/ajcn/85.3.778 17344500 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a report of three cases, alcoholic men with latent scurvy associated with extreme lassitude who received high doses of vitamin C (500 to 1000 mg/day for 3 months) had regression of symptoms, greatly improved quality of life, and possibility of return to work.

    “a recent report of three cases indicated that, in alcoholic men with latent scurvy associated with extreme lassitude, supplementation with high doses of vitamin C (500 to 1000 mg/day for 3 months) allowed the regression of the symptoms, greatly improved the quality of life, and gave the possibility of a return to work [204].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [204] Lux-Battistelli C. Battistelli D. Latent scurvy with tiredness and leg pain in alcoholics: An underestimated disease three case reports Medicine (Baltim.) 2017 96 e8861 10.1097/MD.0000000000008861 PMC5709001 29382002 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In an earlier study, high-dose thiamine (50 mg daily for 2 months) or placebo in 120 young adult women with adequate thiamine status improved thiamine status in treated subjects, associated with improved attention and a trend toward improved mood.

    “An earlier study had assessed the effects of a high dose (50 mg daily for 2 months) of thiamine or placebo on 120 young adult women with adequate thiamine status at the study outset. Thiamine status, assessed via transketolase activation, was improved in treated subjects and this was associated with improved attention and a trend toward improved mood [197].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [197] Benton D. Griffiths R. Haller J. Thiamine supplementation mood and cognitive functioning Psychopharmacology (Berl.) 1997 129 66 71 10.1007/s002130050163 9122365 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    No effect of 5 mg/day folic acid was found in another trial in 24 healthy elderly subjects; these subjects had normal cognitive function and normal blood folate levels at baseline, suggesting they may not have been in a position to benefit from supplementation.

    “Conversely, no effect of 5 mg/day of folic acid was found in another trial in 24 healthy elderly subjects. However, these subjects had a normal cognitive function and normal blood folate levels at baseline, suggesting that they may not have been in a position to benefit from supplementation [200].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [200] Pathansali R. Mangoni A.A. Creagh-Brown B. Lan Z.C. Ngow G.L. Yuan X.F. Ouldred E.L. Sherwood R.A. Swift C.G. Jackson S.H. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects Arch. Gerontol. Geriatr. 2006 43 127 137 10.1016/j.archger.2005.10.002 16359741 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Findings regarding the effect of folate supplementation on cognitive outcomes are mixed but globally indicative of a favorable effect.

    “Findings regarding the effect of folate (vitamin B9) supplementation on cognitive outcomes are mixed but globally indicative of a favorable effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In 428 Chinese adolescents aged 12 years, either iron deficiency or excessive iron levels contribute to reduced neurocognitive performance in a domain-specific manner, indicating that a balance should be found.

    “Another study, in 428 Chinese adolescents aged 12 years, found that either iron deficiency or excessive iron levels contribute to reduced neurocognitive performance in a domain-specific manner [171], indicating that a balance should be found.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [171] Ji X. Cui N. Liu J. Neurocognitive Function Is Associated With Serum Iron Status in Early Adolescents Biol. Res. Nurs. 2017 19 269 277 10.1177/1099800417690828 28196427 PMC5675069 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    As a whole, studies suggest that supplementation with folic acid can be effective for improving cognitive function, especially in populations with low baseline folic acid status, some degree of cognitive impairment, and supplemented for a duration sufficient to restore folate status.

    “As a whole, studies suggest that supplementation with folic acid can be effective for improving cognitive function and this can be seen especially in population with low baseline folic acid status, with some degree of cognitive impairment and who are supplemented for a duration sufficient to restore their folate status.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the most severely stressed subjects, the combination of magnesium with vitamin B6 was more effective than magnesium alone, possibly through vitamin B6 facilitating cellular uptake of magnesium.

    “In the most severely stressed subjects, the combination of magnesium with vitamin B6 was more effective than magnesium alone, possibly through vitamin B6 facilitating cellular uptake of magnesium [211].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [211] Pouteau E. Kabir-Ahmadi M. Noah L. Mazur A. Dye L. Hellhammer J. Pickering G. Dubray C. Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial PLoS ONE 2018 13 e0208454 10.1371/journal.pone.0208454 30562392 PMC6298677

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Depressive symptoms can be mitigated by appropriate magnesium supplementation, as suggested by a recent meta-analysis in which more than half of studies indicated a decreased risk of depression with higher magnesium intakes, the largest risk reduction being observed with 320 mg/day.

    “depressive symptoms can also be mitigated by appropriate magnesium supplementation, as suggested by a recent meta-analysis in which more than half of the studies indicated a decreased risk of depression with higher magnesium intakes, the largest risk reduction being observed with 320 mg/day [183].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [183] Li B. Lv J. Wang W. Zhang D. Dietary magnesium and calcium intake and risk of depression in the general population: A meta-analysis Aust. N. Z J. Psychiatry 2017 51 219 229 10.1177/0004867416676895 27807012 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that meta-analysis, benefits on depressive symptoms failed to reach statistical significance, but conclusions were stronger for stress.

    “Benefits on depressive symptoms failed to reach statistical significance, but conclusions were stronger for stress.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [219] Young L.M. Pipingas A. White D.J. Gauci S. Scholey A. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and ‘At-Risk’ Individuals Nutrients 2019 11 2232 10.3390/nu11092232 31527485 PMC6770181 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Clinical studies assessing the effect of zinc on humans' cognitive outcomes are less numerous and do not provide a clear-cut picture.

    “Clinical studies assessing the effect of zinc on humans’ cognitive outcomes are less numerous and do not provide a clear-cut picture.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    There is ample clinical evidence for a role of selected individual vitamins and minerals in enhancing mood, well-being and cognitive functions and in reducing symptoms of mental fatigue.

    “There is thus ample clinical evidence for a role of selected individual vitamins and minerals in contributing to enhance mood, well-being and cognitive functions as well as to reduce symptoms of mental fatigue.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Interpretationcitation

    Published systematic reviews or meta-analyses in the area most often confirmed favorable effects for micronutrient interventions.

    “Published in the last few years, they most often confirmed favorable effects for micronutrient interventions.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [215] Lam L.F. Lawlis T.R. Feeding the brain—The effects of micronutrient interventions on cognitive performance among school-aged children: A systematic review of randomized controlled trials Clin. Nutr. 2017 36 1007 1014 10.1016/j.clnu.2016.06.013 27395329 source

      Not checked in the free run.

    • cites [216] Eilander A. Gera T. Sachdev H.S. Transler C. van der Knaap H.C. Kok F.J. Osendarp S.J. Multiple micronutrient supplementation for improving cognitive performance in children: Systematic review of randomized controlled trials Am. J. Clin. Nutr. 2010 91 115 130 10.3945/ajcn.2009.28376 19889823 source

      Not checked in the free run.

    • cites [218] Long S.J. Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: A meta-analysis Psychosom. Med. 2013 75 144 153 10.1097/PSY.0b013e31827d5fbd 23362497 source

      Not checked in the free run.

    • cites [219] Young L.M. Pipingas A. White D.J. Gauci S. Scholey A. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and ‘At-Risk’ Individuals Nutrients 2019 11 2232 10.3390/nu11092232 31527485 PMC6770181 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 387 healthy adults aged 55-87 years, zinc supplementation (0, 15, or 30 mg/day) had a beneficial effect of either zinc dose on spatial working memory, but not on several other measures.

    “one had tested zinc supplementation (0, 15, or 30 mg/day) in 387 healthy adults aged 55–87 years, and found a beneficial effect of either zinc dose on spatial working memory, but not on several other measures [214].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [214] Maylor E.A. Simpson E.E. Secker D.L. Meunier N. Andriollo-Sanchez M. Polito A. Stewart-Knox B. McConville C. O’Connor J.M. Coudray C. Effects of zinc supplementation on cognitive function in healthy middle-aged and older adults: The ZENITH study Br. J. Nutr. 2006 96 752 760 17010236 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Supplementation studies confirm this, although many enroll subjects without a clear assessment of their baseline nutritional status, so the populations may include subjects both with and without a deficient or sub-deficient status.

    “This is confirmed by supplementation studies, although many are enrolling subjects without a clear assessment of their baseline nutritional status, so the populations may include subjects both with and without a deficient or sub-deficient status.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Many supplementation studies enroll subjects without a clear assessment of their baseline nutritional status, so the populations may include subjects both with and without a deficient or sub-deficient status.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Many vitamins and minerals have a role in the synthesis of neurotransmitters, development and maintenance of neuronal membranes, and brain receptor modification, with consequences for brain activation and thus cognitive function.

    “many vitamins and minerals have a role in the synthesis of neurotransmitters, development and maintenance of neuronal membranes, and brain receptor modification, with obvious consequences for brain activation and thus cognitive function.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Public Health Authorities have reviewed the existing evidence about health hazards associated with excessive intakes of all vitamins and minerals and have provided guidelines about tolerable upper limits of daily intake that should be followed.

    “Public Health Authorities have reviewed the existing evidence about health hazards associated with excessive intakes of all vitamins and minerals and have provided guidelines about tolerable upper limits of daily intake of vitamins and minerals that should be followed [223].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [223] EFSA Tolerable Upper Intake Levels for Vitamins and Minerals 2006 Available online: http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf (accessed on 9 January 2020)

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Consuming adequate intakes of vitamins and minerals contributes to maintenance of normal cognitive function and to enhanced well-being by decreasing perceived mental and physical fatigue and favoring positive mood.

    “consuming adequate intakes of vitamins and minerals contributes to maintenance of normal cognitive function and to enhanced well-being by decreasing perceived mental and physical fatigue and favoring positive mood.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Oxygen generates oxidative reactive species, which are potentially harmful and need to be controlled by the anti-oxidative defences of the organism, in which vitamin C plays a key role.

    “Oxygen is mandatory, but also generates oxidative reactive species, which are potentially harmful so need to be controlled by the anti-oxidative defences of the organism, in which vitamin C plays a key role.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Besides energy, muscles and brain need oxygen delivered by hemoglobin in red blood cells; this process requires efficient erythropoiesis, for which iron and several B vitamins are critical.

    “Besides energy, muscles and brain also need oxygen, which should be delivered by the hemoglobin present in red blood cells; this process requires an efficient erythropoiesis, for which iron and also several B vitamins are critical.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Efficient and safe supplementation should consider the chemical form of vitamins and minerals, which can affect their bioavailability, and the duration of treatment, which should be sufficient to restore adequate status in people whose intakes are not sufficient.

    “efficient and safe supplementation should carefully consider practical dimensions, such as the chemical form of vitamins and minerals, which can affect their bioavailability, or the duration of treatment, which should be sufficient to ensure the restoration of adequate status in people where intakes are not sufficient”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Severe deficiencies are no longer common, but there is some evidence that sub-clinical or marginal deficiencies can have negative consequences on physical and mental fatigue, as well as on cognitive and psychological functions.

    “Severe deficiencies are no longer common, but there is some evidence that sub-clinical or marginal deficiencies can have negative consequences on physical and mental fatigue, as well as on cognitive and psychological functions.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Severe deficiencies of vitamins and minerals are no longer common.

  • May combine two claims.

    Interpretationreasoning

    Because there is a close interplay between micronutrients across the successive steps of energy production, all of them should be available simultaneously as the whole system may be slowed down by a lack in a single one of them.

    “because there is a close interplay between these micronutrients across the successive steps of energy production, all of them should be available simultaneously as the whole system may be slowed down by a lack in a single one of them.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Isolating the effect of a single component is often clinically difficult because nutrient deficiencies, especially mild ones, often result in nonspecific symptoms and tend to result from unbalanced food intakes, which are likely to lead to inadequate intakes in multiple nutrients.

    “Isolating the effect of a single component is often clinically difficult: nutrient deficiencies, especially mild ones, often result in nonspecific symptoms and they tend to result from unbalanced food intakes, which are likely to lead to inadequate intakes in multiple nutrients.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Nutrient deficiencies, especially mild ones, often result in nonspecific symptoms and tend to result from unbalanced food intakes, which are likely to lead to inadequate intakes in multiple nutrients.

  • May combine two claims.

    Premisecitation

    Neurotoxicity can be observed following excessive doses of vitamin B6, approximately 1 g daily, whereas recommended intakes are in the mg range.

    “neurotoxicity can be observed following excessive doses of vitamin B6, approximately 1 g daily, whereas recommended intakes are in the mg range [223].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [223] EFSA Tolerable Upper Intake Levels for Vitamins and Minerals 2006 Available online: http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf (accessed on 9 January 2020)

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    In most cases, remaining within the order of magnitude of the recommended daily allowance will provide the needed safety level.

    “In most cases, remaining within the order of magnitude of the recommended daily allowance will provide the needed safety level.”
    Quote in the paperSubstantial claim
100 of 100

  • The paper relies on this without support.

    For many micronutrients, the nature of their involvement in molecular and cellular reactions that translate into physiological and functional effects is poorly understood.

    “In many other instances, however, the nature of the involvement of micronutrients in molecular and cellular reactions that translate into physiological and functional effects is poorly understood.”

  • The paper relies on this without support.

    The available scientific rationale for authorized claims about effects of vitamins and minerals on fatigue, cognition or psychological functions is often based on theoretical biochemical grounds and clinical features seen during frank clinical deficiencies, rather than on robust, empirical, physiological data.

    “However, the available scientific rationale for these is often based on theoretical biochemical grounds and clinical features seen during frank clinical deficiencies, rather than on robust, empirical, physiological data.”

  • The paper relies on this without support.

    Frank clinical deficiencies of vitamins and minerals are relatively uncommon, particularly in developed countries.

    “Such clinical deficiencies are relatively uncommon, particularly in developed countries.”

  • The paper relies on this without support.

    Food choice or availability often precludes a varied and balanced diet rich in nutrient-dense foods.

    “There is ample evidence, however, that food choice or availability often preclude such a diet.”

  • The paper relies on this without support.

    A significant proportion of the population in emerging and developed countries does not meet their optimum dietary needs.

    “This can lead to a significant proportion of the population not meeting their optimum dietary needs, in emerging and developed countries.”

  • The paper relies on this without support.

    Calcium signalling is strongly integrated with nucleotide metabolism and the energy status of the cell, which are both dependent on NAD.

    “Calcium signalling is strongly integrated with nucleotide metabolism and the energy status of the cell, which are both dependent on NAD.”

  • The authors state this as an assumption.

    The key role of biotin in the energetic metabolism of all cells, including in brain and nerves, participates in the normal functioning of the nervous system.

    “The mechanisms leading to these neurological disorders are not well known, but it could reasonably be assumed that the key role of biotin in the energetic metabolism of all cells, including in brain and nerves, participates in the normal functioning of the nervous system [29].”

  • The paper relies on this without support.

    When vitamins and minerals are supplied in adequate amounts to humans, their biochemical properties translate into normal physiological functions.

    “When vitamins and minerals are supplied in adequate amounts to humans, their biochemical properties translate into normal physiological functions.”

  • The paper relies on this without support.

    When supply is below requirements, frank deficiencies may occur, manifesting with clinical symptoms.

    “When the supply is below requirements, frank deficiencies may occur, that manifest themselves with clinical symptoms.”

  • The paper relies on this without support.

    Anxiety and depression are mediated by dysfunctional glutaminergic neurotransmission.

    “Anxiety and depression are mediated by dysfunctional glutaminergic neurotransmission and there is thus a rationale for an effect of magnesium on these outcomes.”

  • The paper relies on this without support.

    Skeletal muscle and brain are the most energy-demanding organs in the human body.

    “the organs supportive of these functions, skeletal muscle and brain, are the most energy-demanding ones in the human body.”

  • The paper relies on this without support.

    Severe deficiencies of vitamins and minerals are no longer common.

    “Severe deficiencies are no longer common, but there is some evidence that sub-clinical or marginal deficiencies can have negative consequences”

  • The paper relies on this without support.

    Many supplementation studies enroll subjects without a clear assessment of their baseline nutritional status, so the populations may include subjects both with and without a deficient or sub-deficient status.

    “many are enrolling subjects without a clear assessment of their baseline nutritional status, so the populations may include subjects both with and without a deficient or sub-deficient status.”

  • The paper relies on this without support.

    Nutrient deficiencies, especially mild ones, often result in nonspecific symptoms and tend to result from unbalanced food intakes, which are likely to lead to inadequate intakes in multiple nutrients.

    “nutrient deficiencies, especially mild ones, often result in nonspecific symptoms and they tend to result from unbalanced food intakes, which are likely to lead to inadequate intakes in multiple nutrients.”
14 of 14

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?

  • Many of these nutrients serve as cofactors for enzymes, supporting synthesis of neurotransmitters, myelination, cell signaling, and metabolic pathways.

    “Many of these nutrients serve as cofactors for enzymes, supporting for example the synthesis of neurotransmitters, myelination, cell signaling, and metabolic pathways [56].”

    From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [56]

Cites

Flagged first, then by citations

Research works printed but not linked: 19

  1. Magil, A.J., Hill, D.R., Solomon, T., and Ryan, E.T. (2013). Vitamin deficiencies. Hunter’s Tropical Medicine and Emerging Infectious Disease, Elsevier. [9th ed.].
  2. Ross, A.C., Caballero, B., and Cousins, R.J. (2014). Riboflavin. Modern Nutrition in Health and Disease, Lippincott Williams & Wilkins. [11th ed.].
  3. Shils, M., Shike, M., Ross, A., Caballero, B., and Cousins, R. (2006). Vitamin B6. Modern Nutrition in Health and Disease, Lippincott Williams and Wilkins.
  4. Erdman, J.W., Macdonald, I.A., and Zeisel, S.H. (2012). Present Knowledge in Nutrition, Wiley-Blackwell. · DOI · Paper page
  5. Shils, M.E., Shike, M., Ross, A.C., Caballero, B., and Cousins, R.J. (2006). Modern Nutrition in Health and Disease, Lippincott Williams and Wilkins.
  6. Erdman, J.W., Macdonald, I.A., and Zeisel, S.H. (2012). Iron. Present Knowledge in Nutrition, Wiley-Blackwell. [10th ed.]. · DOI · Paper page
  7. Erdman, J.W., Macdonald, I.A., and Zeisel, S.H. (2012). Magnesium. Present Knowledge in Nutrition, International Life Sciences Institute, John Wiley & Sons, Inc.. [10th ed.]. · DOI · Paper page
  8. Ross, C.A., Caballero, B., Cousins, R.J., Tucker, K.L., and Ziegler, T.R. (2014). Magnesium. Modern Nutrition in Health and Disease, Lippincott Williams & Wilkins. [11th ed.].
  9. Erdman, J.W., Macdonald, I.A., and Zeisel, S.H. (2012). Folate. Present Knowledge in Nutrition, Wiley-Blackwell. · DOI · Paper page
  10. Zempleni, J., Rucker, R.B., McCormick, D.B., and Suttie, J.W. (2007). Riboflavin (Vitamin B2). Handbook of Vitamins, CRC Press. [4th ed.].
  11. Erdman, J.W., Macdonald, I.A., and Zeisel, S.H. (2012). Present Knowledge in Nutrition, Wiley-Blackwell. [10th ed.]. · DOI · Paper page
  12. Shils, M.E., Shike, M., Ross, A.C., Caballero, B., and Cousins, R.J. (2006). Zinc. Modern Nutrition in Health and Disease, Lippincott Williams and Wilkins. [11th ed.].
  13. Erdman, J.W., Macdonald, I.A., and Zeisel, S.H. (2012). Zinc. Present Knowledge in Nutrition, Wiley-Blackwell. · DOI · Paper page
  14. Ross, A.C., Caballero, B., and Cousins, R.J. (2014). Pantothenic acid. Modern Nutrition in Health and Disease, Lippincott Williams & Wilkins. [11th ed.].
  15. Lavoisier, 2009, Mécanismes d’action moléculaire et rôles des vitamines, Encyclopedie des Vitamines, Volume 1, 353
  16. Ross, A.C., Caballero, B., and Cousins, R.J. (2014). Niacin. Modern Nutrition in Health and Disease, Lippincott Williams & Wilkins. [11th ed.].
  17. Erdman, J., Macdonald, I., and Zeisel, S. (2012). Pantothenic acid. Present Knowledge in Nutrition, Wiley-Blackwell. · DOI · Paper page
  18. Brilla, 1995, Effect of magnesium supplementation on exercise time to exhaustion, Med. Exerc. Nutr. Health, 4, 230
  19. Bourgeois, 1987, Rôle du Magne-B6 dans les Manifestations Anxieuses en Pratique Medicale Courante, Psychiatr. Pract. Med., 39, 18

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Authors
Tardy, A.-L., Pouteau, E., Marquez, D., Yilmaz, C., & Scholey, A.
Affiliations
  • Sanofi (France) (FR)
  • Sanofi Consumer Healthcare, 04000 México City, Mexico
  • Sanofi (Turkey) (TR)
  • Swinburne University of Technology (AU)
Corresponding author
Tardy, Anne-Laure
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2020-01-16
Volume
12
Issue
1
Pages
228
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu12010228
PMC
PMC7019700
OpenAlex
W3000061404
Semantic Scholar
55c8642efdd92c9120bec1ef4d2a775e7a79fa48
Cited by
541
References
200
Citations by year
2026: 101 · 2025: 117 · 2024: 99 · 2023: 99 · 2022: 74 · 2021: 34 · 2020: 17
FWCI
9.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Swinburne figshare (Swinburne University of Technology) (submittedVersion)
Funders
Sanofi
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
vitamins, minerals, micronutrients, B vitamins, vitamin C, iron, magnesium, zinc, energy metabolism, fatigue, cognitive function, brain function, muscle function, micronutrient deficiency
MeSH terms
Affect, Animals, Ascorbic Acid, Ascorbic Acid Deficiency, Cognition, Cognition Disorders, Energy Metabolism, Fatigue, Humans, Iron, Magnesium, Minerals, Nutritional Status, Vitamin B Complex, Vitamin B Deficiency, Vitamins, Zinc

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

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