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Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human

Open access
Jee, Hye Jin, Lee, Sang Goo, Bormate, Katrina Joy, Jung, Yi-Sook·2020·Nutrients
DOI 10.3390/nu12103080PMC PMC7601837
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Abstract

Caffeine occurs naturally in various foods, such as coffee, tea, and cocoa, and it has been used safely as a mild stimulant for a long time. However, excessive caffeine consumption (1~1.5 g/day) can cause caffeine poisoning (caffeinism), which includes symptoms such as anxiety, agitation, insomnia, and gastrointestinal disorders. Recently, there has been increasing interest in the effect of caffeine consumption as a protective factor or risk factor for neurological and psychiatric disorders. Currently, the importance of personalized medicine is being emphasized, and research on sex/gender differences needs to be conducted. Our review focuses on the effect of caffeine consumption on several neurological and psychiatric disorders with respect to sex differences to provide a better understanding of caffeine use as a risk or protective factor for those disorders. The findings may help establish new strategies for developing sex-specific caffeine therapies.

Verified 2026-10-10 · 1 reference not checked yet

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review summarizes sex differences in the prevalence/incidence of several neurological and psychiatric disorders and in caffeine’s risk or protective effects. It concludes that caffeine’s benefits and risks vary by sex and sometimes by age, but that few studies directly analyze sex/gender differences.

Key findings

  • Sex differences in disease burden are reported: stroke incidence/prevalence is generally higher in men, but stroke mortality is higher in women (24.7% vs. 19.7%); chronic insomnia is higher in women (12.9% vs. 6.2%); two-thirds of Alzheimer’s disease patients are women; Parkinson’s disease is more common in men (approximate ratio 2:1); depression and anxiety are generally more common in women.
  • Caffeine’s effects differ by sex: stroke protection appears greater in women; dementia risk reduction appears greater in women; Parkinson’s disease protection appears greater in men; sleep disturbance risk increases similarly in both sexes.
  • For depression, >2 cups/day was associated with a 24% lower incidence versus no coffee, and women with the highest caffeine intake (≥550 mg/d) had lower depression risk than those with <100 mg/d. For anxiety, effects were more pronounced in men, especially adolescent boys.
  • Caffeine poisoning is noted at excessive intake of 1~1.5 g/day; average US adult intake is 179 mg/day, and caffeine half-life is 2–10 h (average 3.7 h).

Methods

  • Narrative review of human studies on sex differences in the prevalence/incidence of neurological and psychiatric disorders and on caffeine consumption as a risk or protective factor.
  • Synthesizes epidemiological, cohort, case-control, and some trial evidence across stroke, sleep disorder, dementia, Parkinson’s disease, depression, anxiety, and neuromuscular disease, with findings summarized in Table 1 and Table 2.
  • Main analysis is qualitative, disorder-by-disorder comparison of effects in men versus women; no new primary data are collected.

Limitations

  • The paper states that few studies have analyzed individual sex/gender differences in caffeine’s effects on neurological disorders, that some results are controversial (e.g., stroke), and that further studies are needed for sex-specific caffeine strategies.
  • The paper states that little research exists on caffeine and anxiety, and on sex differences and mechanisms in neuromuscular disease.
  • Evident from the text: as a narrative review, it does not report a systematic search, formal quality appraisal, or meta-analysis, and it relies heavily on observational studies that may be confounded by age, hormones, lifestyle, and other factors.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/nu12103080

Cites

128 of 129 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 89 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    There are sex-specific differences in the activity and expression of many CYP isoforms.

    “Accumulating evidence has shown sex-specific differences in the activity and expression of many CYP isoforms [15,16,17].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [15] Scandlyn, 2008, Sex-specific differences in CYP450 isoforms in humans, Expert Opin. Drug Metab. Toxicol. source

      Not checked in the free run.

    • cites [16] Yang, 2012, Sex Differences in the Expression of Drug-Metabolizing and Transporter Genes in Human Liver, J. Drug Metab. Toxicol. source

      Not checked in the free run.

    • cites [17] Tanaka, 1999, Gender-related differences in pharmacokinetics and their clinical significance, J. Clin. Pharm. Ther. source

      Not checked in the free run.

  • Premisecitation

    Caffeine changes estrogen levels in women.

    “There are also reports that caffeine changes estrogen levels in women [6].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Sisti, 2015, Caffeine, coffee, and tea intake and urinary estrogens and estrogen metabolites in premenopausal women, Cancer Epidemiol. Biomark. Prev. source

      Not checked in the free run.

  • Premisecitation

    In 2018 Canada, using THINC-it, women had a higher rate of severe depression than men.

    “In 2018, in Canada, the THINC-integrated tool (THINC-it), a newly developed cognitive tool, was used to evaluate cognitive impairment in patients suffering from major depressive disorder (MDD). It was reported that women had a higher rate of severe depression than men [47].”
    • Also stated in: § 2.1. Stroke · plain
      “The incidence of more severe depression is higher in women.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Rempel, 2019, The Impact of Gender on Interferon-Associated Depression and Anxiety, J. Interferon Cytokine Res. source

      Not checked in the free run.

  • Premisecitation

    Stressed women are more prone to depression than stressed men.

    “These data revealed that stressed women were more prone to depression than stressed men [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Ohl, 2010, Trait anxiety affects decision-making differently in healthy men and women: Towards gender-specific endophenotypes of anxiety, Neuropsychologia source

      Not checked in the free run.

  • Premisecitation

    PD incidence rates are consistently higher in men than in women at all ages.

    “According to several studies, the onset of PD in men occurs, on average, two years earlier than in women, and the incidence rate in men is twice as high as that in women [73].”
    • Also stated in: § 2.1. Stroke · plain
      “Incidence rates were consistently higher in men than in women at all ages for PD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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      Not checked in the free run.

  • Classified as probably not a substantial claim. 10
  • May combine two claims. 43
  • The quote only partly states this claim. 1

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

    Premisecitation

    The half-life of caffeine is 2 to 10 h (average 3.7 h), and caffeine is mainly excreted by urine after being metabolized in the liver.

    “Additionally, depending on endogenous and exogenous factors, the half-life of caffeine is 2 to 10 h (average 3.7 h), and is mainly excreted by urine after being metabolized in the liver [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Shulman, 2002, Is there a connection between estrogen and Parkinson’s disease?, Park. Relat. Disord. source

      Not checked in the free run.

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    Premisecitation

    Estrogen has a neuroprotective or neurotrophic effect and regulates the dopamine system of the black striatum.

    “Since estrogen has a neuroprotective or neurotrophic effect and regulates the dopamine system of the black striatum [7], estrogen regulates the effect of caffeine on the dopamine system and suggests that a complex interaction between caffeine, estrogen, and dopamine exists in the basal ganglia system [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Shulman, 2002, Is there a connection between estrogen and Parkinson’s disease?, Park. Relat. Disord. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Excessive caffeine consumption (1-1.5 g/day) can cause caffeine poisoning (caffeinism), with symptoms including anxiety, agitation, insomnia, gastrointestinal disorders, tremors, and mental disorders.

    “However, excessive caffeine consumption (1~1.5 g/day) can cause caffeine poisoning (caffeinism), which includes symptoms such as anxiety, agitation, insomnia, and gastrointestinal disorders.”
    • Also stated in: § 1. Introduction · plain
      “However, excessive caffeine consumption (1~1.5 g/day) can cause caffeine poisoning (caffeinism), which includes symptoms such as anxiety, agitation, insomnia, gastrointestinal disorders, tremors, and mental disorders [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Willson, 2018, The clinical toxicology of caffeine: A review and case study, Toxicol. Rep. source

      Not checked in the free run.

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

    Premisecitation

    Caffeine action is mediated via antagonism of adenosine receptors, inhibition of phosphodiesterase, release of calcium from intracellular stores, and antagonism of benzodiazepine receptors.

    “Caffeine action is thought to be mediated via several mechanisms: the antagonism of adenosine receptors, the inhibition of phosphodiesterase, the release of calcium from intracellular stores, and the antagonism of benzodiazepine receptors [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Institute of Medicine (2001). Caffeine for the Sustainment of Mental Task Performance, The National Academies Press.

      Not checked in the free run.

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

    Premisecitation

    Caffeine resistance and rate of caffeine metabolism vary greatly between people, especially depending on activity of the CYP1A2 gene.

    “Caffeine resistance and the rate of caffeine metabolism vary greatly from person to person, especially depending on the activity of the cytochrome P450 1A2 (CYP1A2) gene, encoding an enzyme that breaks down caffeine [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Sisti, 2015, Caffeine, coffee, and tea intake and urinary estrogens and estrogen metabolites in premenopausal women, Cancer Epidemiol. Biomark. Prev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Estrogen regulates the effect of caffeine on the dopamine system, suggesting a complex interaction between caffeine, estrogen, and dopamine in the basal ganglia system.

    “Since estrogen has a neuroprotective or neurotrophic effect and regulates the dopamine system of the black striatum [7], estrogen regulates the effect of caffeine on the dopamine system and suggests that a complex interaction between caffeine, estrogen, and dopamine exists in the basal ganglia system [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Cappelletti, 2015, Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?, Curr. Neuropharmacol. source

      Not checked in the free run.

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

    Premisecitation

    CYP1A2 is a major enzyme responsible for metabolism of caffeine and plays an important role in metabolism of estrogen and coffee.

    “CYP1A2 is a major enzyme responsible for the metabolism of purine alkaloid (1,3,7-trimethylxanthine), a caffeine that occurs naturally in coffee beans, and plays an important role in the metabolism of estrogen and coffee [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Guessous, 2012, Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension, Hum. Mol. Genet. source

      Not checked in the free run.

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    Premisecitation

    Caffeine has psychostimulant effects via modulation of dopaminergic neurons, contributing to an attenuated risk for depression in coffee drinkers.

    “Caffeine also has psychostimulant effects via modulation of the dopaminergic neuron [10], contributing to an attenuated risk for depression in coffee drinkers [7].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Shulman, 2002, Is there a connection between estrogen and Parkinson’s disease?, Park. Relat. Disord. source

      Not checked in the free run.

    • cites [10] Ciruela, 2008, Adenosine A1-A2A receptor heteromers: New targets for caffeine in the brain, Front. Biosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a prospective US study of 505 patients with first ischemic stroke, no sex differences were found in stroke severity, stroke subtype, or infarct size and location, but mortality was higher in women.

    “A prospective study from the USA conducted on 505 patients with first ischemic stroke (ischemic stroke genetics study) found that 270 patients (55%) were men and 229 (45%) were women [33]. In their study, no sex differences were found in stroke severity, stroke subtype, or infarct size and location, but a higher percentage of mortality was shown in women [27,28,29,30,33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Petrea, 2009, Gender Differences in Stroke Incidence and Poststroke Disability in the Framingham Heart Study, Stroke source

      Not checked in the free run.

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    Premisecitation

    Depression is more frequently experienced by women compared to men, with a peak in prevalence in middle age.

    “Depression is more frequently experienced by women compared to men, with a peak in prevalence occurring in middle age.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] Krueger, 2010, Persistent pro-inflammatory cytokines following the initiation of pegylated IFN therapy in hepatitis C infection is associated with treatment-induced depression, J. Viral Hepat.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Premisecitation

    Women have better cognitive performance than men in the Symbol Digit Modalities Test and Scales for Outcomes of Parkinson's disease-cognition.

    “Women showed higher cognitive abilities than men.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Cabezas, 2018, Sex differences in Parkinson’s disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics, Front. Neuroendocr. source

      Not checked in the free run.

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    Interpretationreasoning

    The incidence of stroke in women gradually increases with age, and mortality rates in women are higher, possibly due to the longer lifespan of women.

    “However, possibly due to the longer lifespan of women, the incidence of stroke in women gradually increases with age, and as a result, mortality rates in women are higher.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Women live longer than men.

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

    Premisecitation

    A substantially larger number of women than men have AD worldwide.

    “A substantially larger number of women than men have AD worldwide.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Mielke, 2014, Clinical epidemiology of Alzheimer’s disease: Assessing sex and gender differences, Clin. Epidemiol. source

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    Premisecitation

    The activity of CYP2C16, CYP2C19, and CYP2D6 isozymes and glucuronidation activity involved in drug metabolism are higher in men than in women.

    “The activity of several other CYP (CYP2C16, CYP2C19, and CYP2D6) isozymes and the conjugation (glucuronidation) activity involved in drug metabolism are higher in men than in women [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Tanaka, 1999, Gender-related differences in pharmacokinetics and their clinical significance, J. Clin. Pharm. Ther. source

      Not checked in the free run.

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    Interpretationcitation

    Women have higher incidence and prevalence of dementia than men.

    “Overall, women showed higher incidence and prevalence of dementia than men, possibly due to various factors, such as longer life expectancy of women and different neuroanatomical function [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Elbaz, 2002, Risk tables for parkinsonism and Parkinson’s disease, J. Clin. Epidemiol. source

      Not checked in the free run.

    • Rests on an assumption: Women live longer than men.

  • May combine two claims.

    Premisecitation

    Motor improvement after deep brain stimulation is similar in men and women, but women are likely to show better improvement in daily living activities compared to men.

    “In addition, motor improvement after deep brain stimulation is similar in men and women, but women are likely to show better improvement in daily living activities compared to men [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Miller, 2010, Gender differences in Parkinson’s disease: Clinical characteristics and cognition, Mov. Disord. source

      Not checked in the free run.

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    Premisecitation

    On average, both the incidence and the prevalence of stroke are higher in men than in women, though there is high variance between age groups and countries.

    “In a systematic review by Appelros et. al, it was shown that there was high variance between age groups and countries, but on average, both the incidence and the prevalence of stroke were higher in men than in women [32].”
    • Also stated in: § 2.1. Stroke · plain
      “Stroke prevalence between ages of 65 and 85 is 41% higher in men than women, and the male/female prevalence ratio decreases with age.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Barrett, 2007, Sex Differences in Stroke Severity, Symptoms, and Deficits After First-ever Ischemic Stroke, J. Stroke Cerebrovasc. Dis. source

      Not checked in the free run.

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    Premisecitation

    The rate of progression from MCI to AD is similar in men and women aged 70-79, but higher in women than men after age 80.

    “According to a Mayo Clinic study on aging, the progression from mild cognitive impairment (MCI) to AD was similar in men and women in the ages of 70–79, but higher in women than men after 80 years of age.”
    • Also stated in: § 2.1. Stroke · plain
      “Rate of progression from MCI to AD was similar in men and women aged 70–79, but higher in women than men after age 80.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Seshadri, 1997, Lifetime risk of dementia and Alzheimer’s disease: The impact of mortality on risk estimates in the Framingham Study, Neurology source

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  • May combine two claims.

    Premisecitation

    Individuals with reduced CYP2D6 activity due to mutated CYP2D6*4A genotype have a 2.5 times higher risk of PD than those with wild type, and this risk is higher in men.

    “Moreover, a recent study found that individuals with reduced CYP2D6 activity due to the mutated CYP2D6 * 4A (allelic variants of CYP2D6) genotype had a 2.5 times higher risk of PD than those with wild type, which was higher in men [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In the USA, insomnia diagnosis is double in women compared with men; insomnia symptoms for two nights or more per week occur in 30.5% of women and 24.5% of men; chronic insomnia incidence is 12.9% in women and 6.2% in men.

    “In the USA, insomnia diagnosis is double in women compared with that in men, and insomnia symptoms for two nights or more per week have been reported to occur in 30.5% of women and 24.5% of men. In the case of chronic insomnia, the incidence rate was higher in women (12.9%) than in men (6.2%) [36].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Morphy, 2007, Epidemiology of insomnia: A longitudinal study in a UK population, Sleep

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    Premisecitation

    Women over 65 have the highest risk for insomnia and have been reported to have an increasing risk with age.

    “In particular, women over 65 have the highest risk for insomnia and have been reported to have an increasing risk with age [35,38].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [35] Singareddy, 2012, Risk factors for incident chronic insomnia: A general population prospective study, Sleep Med. source

      Not checked in the free run.

    • cites [38] Ferretti, 2018, Sex differences in Alzheimer disease—The gateway to precision medicine, Nat. Rev. Neurol. source

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  • May combine two claims.

    Premisecitation

    CYP1A2 and CYP2E1 activities are higher in men than in women, while CYP3A activity is greater in women.

    “Recent studies demonstrate that CYP1A2 and CYP2E1 activities are higher in men than in women, while the activity of CYP3A, one of the most clinically relevant CYP isoforms, is greater in women [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Scandlyn, 2008, Sex-specific differences in CYP450 isoforms in humans, Expert Opin. Drug Metab. Toxicol. source

      Not checked in the free run.

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

    Premisecitation

    Drinking more than three cups of coffee a day reduces the risk of developing AD and PD.

    “Some studies have shown that by drinking more than three cups of coffee a day, caffeine reduces the risk of developing AD and PD [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Buijsse, 2006, Coffee consumption is inversely associated with cognitive decline in elderly European men: The FINE Study, Eur. J. Clin. Nutr.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a 2009 study of 1107 inpatients with neuro-ischemic stroke, there was no difference in prevalence of stroke between men and women, but women were older and more likely to have heart embolism.

    “In 2009, a study conducted by the Beth Israel Deaconess Medical Center in the USA analyzed 1107 inpatients aged 21 and older who were diagnosed with neuro-ischemic stroke [28]. This study revealed no difference in the prevalence of stroke between men and women, but when comparing the age of patients, women were older than men and were more likely to have heart embolism [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Wellenius, 2009, Gender differences in presenting and prodromal stroke symptoms, Stroke source

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  • May combine two claims.

    Premisereasoning

    Despite higher incidence of PD in men at all ages, the difference in PD risk between men and women is reduced with age.

    “Despite the higher incidence of PD in men at all ages, the difference in PD risk between men and women is reduced with age.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Augustine, E.F., Pérez, A., Dhall, R., Umeh, C.C., Videnovic, A., Cambi, F., Wills, A.-M.A., Elm, J.J., Zweig, R.M., and Shulman, L.M. (2015). Sex Differences in Clinical Features of Early, Treated Parkinson’s Disease. PLoS ONE, 10. source

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  • May combine two claims.

    Interpretationcitation

    Women have a higher incidence of anxiety disorders because they are more sensitive to lower levels of hormones that make up the stress response and because they experience residual anxiety from sexual abuse/violence more often than men.

    “Women have a higher incidence of anxiety disorders not only because they are more sensitive to the lower levels of hormones that make up the stress response, but also because women experience residual anxiety from sexual abuse/violence more often than men [84].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Burgess, 2016, Neuromuscular Disease Models and Analysis, Adv. Struct. Saf. Stud.

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    High caffeine intake is associated with a protective effect that suppresses PD incidence in men and women, significantly reduces PD risk in men, and only slightly reduces risk in women.

    “In summary, high caffeine intake is associated with a protective effect that suppresses PD incidence in men and women, significantly reduces the risk of PD in men, and only slightly reduces the risk in women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Caffeine intake did not help improve cognitive abilities in either men or women, although steady caffeine intake seems to reduce dementia risk for both, with a greater effect in women.

    “Taken together, these studies show that caffeine intake did not help improve cognitive abilities in either men or women, although steady caffeine intake seems to reduce the risk of developing dementia for both men and women, with a greater effect in women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the Health Examinees study, coffee consumption was not significantly associated with stroke risk among men, but higher coffee consumption was inversely associated with stroke incidence in women.

    “A survey of about 15,000 men and women between 40 and 69 years of age did not show any significant association between coffee consumption and stroke risk among men. However, in the case of young women, the inverse relationship between coffee consumption and stroke risk was prominent. In other words, higher coffee consumption was found to be inversely proportional to the incidence rate of stroke in”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Mostofsky, 2010, Coffee and acute ischemic stroke onset: The Stroke Onset Study, Neurology source

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  • May combine two claims.

    Premisecitation

    Caffeine overdose can delay sleep onset, reduce total sleep time, change normal sleep stages, and reduce sleep quality.

    “Caffeine overdose can delay sleep onset, reduce total sleep time, change normal sleep stages, and reduce sleep quality. Caffeine-induced sleep disorder is known as a psychiatric disorder caused by excessive caffeine consumption [120].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [120] Benedetti, 2000, Smoking, alcohol, and coffee consumption preceding Parkinson’s disease: A case-control study, Neurology source

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  • May combine two claims.

    Premisecitation

    The highest prevalence of CMT disease occurs at ages 50-64, with men having a higher prevalence than women.

    “The highest prevalence of CMT disease occurs at ages 50–64, with men having a higher prevalence than women [53,88].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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  • May combine two claims.

    Premisecitation

    In women, PD risk was significantly reduced in the highest caffeine intake group (≥4 cups/day) compared to lowest (<1 cup/day), but the decrease was lower than in men.

    “In the case of women, the risk of PD was significantly reduced in the group with the highest caffeine intake (four or more cups per day) compared to the group with the lowest caffeine intake (less than one drink per day), but the decrease was lower than in men.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Knekt, 2007, Prospective study of coffee consumption and risk of Parkinson’s disease, Eur. J. Clin. Nutr.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Caffeine intake reduced sleep efficiency, sleep time, SWS, and REM sleep in both young and middle-aged groups, but during weekly recovery, middle-aged participants had significantly reduced sleep time and efficiency compared to younger participants.

    “In a study of 12 young and 12 middle-aged subjects who consumed one to three cups of coffee per day, caffeine intake was found to reduce sleep efficiency, sleep time, slow-wave sleep (SWS), and rapid eye movement (REM) sleep in both age groups. However, during the weekly recovery, middle-aged participants had significantly reduced sleep time and sleep efficiency compared to younger participants [”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Pollak, 2003, Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The onset of MG occurs at any age, but significantly earlier in women than men.

    “The onset of MG occurs at any age, but significantly earlier in women than men.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Jerath, 2016, Charcot-marie-tooth disease type 1X in women: Electrodiagnostic findings, Muscle Nerve source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Caffeine intake negatively affected the quality and amount of sleep with age, with no differences seen between men and women.

    “In summary, caffeine intake negatively affected the quality of sleep and the amount of sleep with age, with no differences seen between men and women.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Sex differences in PD are determined by the nigrostriatal dopamine system arising from genetic, environmental, and hormonal effects.

    “It has also been reported that sex differences in PD are determined by the nigrostriatal dopamine system arising from genetic, environmental, and hormonal effects.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Carmona, 2018, Sex differences in the mediators of functional disability in Major Depressive Disorder, J. Psychiatr. Res. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The effect of coffee intake on stroke risk is controversial, but more studies show women have a lower risk of stroke incidence from caffeine intake than men.

    “In summary, the effect of coffee intake on the risk for stroke showed controversial results, but more studies have shown that women have a lower risk of stroke incidence by caffeine intake, than men.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The incidence of MG is significantly higher in women under age 40, but higher in men over age 50.

    “The incidence of MG has been reported to be significantly higher in women under age 40, but higher in men over age 50 [52].”
    • Also stated in: § 2.1. Stroke · plain
      “The incidence of MG was significantly higher in women under age 40, but higher in men over age 50.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Jerath, 2016, Charcot-marie-tooth disease type 1X in women: Electrodiagnostic findings, Muscle Nerve source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Consuming less than three cups of coffee per day significantly reduced PD risk, while more than three cups did not significantly alter PD risk.

    “A meta-analysis of the Hui Qi research team found that consuming less than three cups of coffee per day significantly reduced the risk of PD, while consuming more than three cups of coffee per day did not significantly alter the risk for PD [107].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [107] Palacios, 2012, Caffeine and risk of Parkinson’s disease in a large cohort of men and women, Mov. Disord. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The reason for reduced PD risk difference with age is likely that women have a longer lifespan than men, and men are at greater risk of dying at a younger age.

    “The reason is likely that women have a longer lifespan than men, and men are at greater risk of dying at a younger age [43].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Baldereschi, 2000, Parkinson’s disease and parkinsonism in a longitudinal study: Two-fold higher incidence in men, Neurology source

      Not checked in the free run.

    • Rests on an assumption: Women live longer than men.

  • May combine two claims.

    Premisecitation

    Drinking moderate coffee (3-5 cups/day) lowers dementia incidence compared with not drinking coffee, and among coffee-drinkers, dementia incidence is lower in women than in men.

    “In addition, drinking a moderate amount of coffee (3~5 cups/day) lowers the incidence of dementia compared with not drinking coffee, and among coffee-drinkers, the incidence of dementia is lower in women than in men.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [104] Driscoll, 2016, Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women’s Health Initiative Memory Study, J. Gerontol. Ser. A Biol. Sci. Med. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a cohort of students aged 11-17, caffeine had no significant effect on anxiety in girls, but anxiety increased with caffeine intake in boys.

    “As a result from a cohort study of 3323 students aged 11–17 years (boys 48.5%, girl 51.5%), the effect of caffeine on anxiety was not significant in girls, but in boys, anxiety increased with caffeine intake [115].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [115] Botella, 2003, Coffee increases state anxiety in males but not in females, Hum. Psychopharmacol. Clin. Exp. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Men and women respond differently to caffeine administration, and these gender differences may be mediated by changes in circulating steroid hormones.

    “These results suggest that men and women respond differently to caffeine administration and that these gender differences may be mediated by changes in circulating steroid hormones [124].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [124] Park, 2016, Association between energy drink intake, sleep, stress, and suicidality in Korean adolescents: Energy drink use in isolation or in combination with junk food consumption, Nutr. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adequate caffeine intake has a positive effect on depression, but excessive caffeine intake can exacerbate depression by stimulating sympathetic nerves.

    “Adequate caffeine intake has a positive effect on depression, but excessive caffeine intake can exacerbate depression by stimulating sympathetic nerves [125].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Maron, 2018, Biological Markers of Generalized Anxiety Disorder, Focus source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    For anxiety, the risk is increased primarily in adult men but not in women, while during adolescence, the risk increases in both men and women, but to a much greater extent in men.

    “For anxiety, the risk seems to be increased primarily in adult men but not in women, while during adolescence, the risk increases in both men and women, but to a much greater extent in men.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Caffeine consumption has a positive effect of reducing risk of stroke, dementia, and depression in women and reducing risk of PD in men, and a negative effect of increasing sleep disorders and anxiety disorders in adolescence in both men and women.

    “In other words, caffeine consumption not only has a positive effect of reducing the risk of stroke, dementia, and depression in women and reducing the risk of PD in men, but also has a negative effect of increasing sleep disorders and anxiety disorders in adolescence in both men and women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    The risk of depression decreases in adult women but not in men, while in adolescence, women have a much higher risk of depression than men.

    “In fact, the risk of depression has shown to decrease in adult women but not in men, while in adolescence, women have a much higher risk of depression than men.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The risk of developing depression was decreased by caffeine intake to a greater extent in women than in men, and the effect varied by age of women.

    “In summary, the risk of developing depression was decreased by caffeine intake to a greater extent in women than in men, and the effect of caffeine intake on depression incidence was different according to the age of women.”
    Quote in the paperSubstantial claim
48 of 48

  • The paper relies on this without support.

    Women live longer than men.

    “Age is a major risk factor for AD, and on average, women live longer than men.”

  • The paper relies on this without support.

    Few studies have been reported on sex differences in the effects of caffeine on neurological and psychiatric disorders.

    “However, few studies have been reported on sex differences in the effects of caffeine on neurological and psychiatric disorders.”

  • The paper relies on this without support.

    Few studies have been conducted on the incidence of anxiety in men and women by caffeine.

    “However, few studies have been conducted on the incidence of anxiety in men and women, by caffeine.”

  • The paper relies on this without support.

    There are not many research articles that analyzed individual sex/gender differences in the effect of caffeine on neurological disorders.

    “Moreover, there are not many research articles that analyzed individual sex/gender differences in the effect of caffeine on neurological disorders.”
4 of 4

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?

  • Although caffeine reduces the risk for AD in both men and women, the protective effect seems to be greater in women.

    “Although caffeine reduces the risk for AD [68, 69] in both men and women, the protective effect seems to be greater in women [70].”

    From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [70]

    Section 3.3 (Dementia) says steady caffeine intake seems to reduce dementia risk in both men and women, with a greater effect in women; the Conclusions repeat the greater reduction in women. The cited paper does not establish that this sex difference applies specifically to Alzheimer’s disease (AD), rather than dementia more broadly. Page numbers are not available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Caffeine increases sleep disorders and anxiety in both male and female adolescents.

    “caffeine has a negative effect of increasing sleep disorders and anxiety in both male and female adolescents [211].”

    From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [211]

  • Caffeine consumption reduces risk of stroke, dementia, and depression in women and of PD in men.

    “caffeine consumption reduces the risk of stroke, dementia, and depression in women and of PD in men.”

    From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [211]

  • Caffeine reduces endogenous nocturnal melatonin levels, with significant impact on duration and quality of sleep.

    “caffeine reduces endogenous nocturnal melatonin levels [238], with a significant impact on duration and quality of sleep [211].”

    From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [211]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Depression result reverses the table's caffeine threshold

    Major

    For study [115], the narrative associates increased depression in girls with less than 1000 mg per week, while Table 2 specifies more than 1000 mg per week.

  • Adolescent anxiety conclusion contradicts the reported result for girls

    Major

    The conclusion says adolescent anxiety risk increases in both sexes, but the anxiety section says the effect was not significant in girls.

  • Anxiety-study sample size conflicts with Table 2

    Minor

    The anxiety section gives 3323 students for study [115], whereas Table 2 gives 2307 for its anxiety result.

  • Claim about men's cognition conflicts with the cited reference title

    Minor

    The text says the beneficial association does not occur in aged men, but the cited reference [20] is explicitly about an inverse association between coffee consumption and cognitive decline in elderly men.

  • Stroke-study sample size differs sharply between text and table

    Minor

    The narrative describes about 15,000 participants in study [93], while Table 2 lists 173,357 cases for the same study.

5 of 5

Cites

Flagged first, then by citations

4 of the 133 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Institute of Medicine (2001). Caffeine for the Sustainment of Mental Task Performance, The National Academies Press.

Cited by

Sorted by citations

Related

Authors
Jee, H. J., Lee, S. G., Bormate, K. J., & Jung, Y.-S.
Affiliations
Ajou University (KR)
Corresponding author
Jung, Yi-Sook
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2020-10-09
Volume
12
Issue
10
Pages
3080
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu12103080
PMC
PMC7601837
OpenAlex
W3092318674
Semantic Scholar
9cf18b804a31de2b5b9e10005c8aed387e74b326
Cited by
111
References
133
Citations by year
2026: 10 · 2025: 16 · 2024: 27 · 2023: 25 · 2022: 25 · 2021: 6 · 2020: 2
FWCI
1.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Health and Welfare (HI18C0920)
  • Ministry of Science and ICT, South Korea (WISET202003GI01)
  • Ministry of Education (2018R1D1A1B07048729)
Topics
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
caffeine consumption, caffeine poisoning, neurological disorders, mental illness, sex differences, gender differences, protective factors, risk factors, personalized medicine, anxiety, insomnia
MeSH terms
Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Mental Disorders, Caffeine, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Nervous System Diseases, Risk Factors, Sex Characteristics, Risk Assessment, Young Adult

About these checks

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 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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