Dietary creatine intake and depression risk among U.S. adults

Amanda V Bakian, Rebekah S Huber, Lindsay Scholl, Perry F Renshaw, Douglas Kondo, Amanda V Bakian, Rebekah S Huber, Lindsay Scholl, Perry F Renshaw, Douglas Kondo

Abstract

Creatine monohydrate is actively being researched for its antidepressant effects, yet little is known about the link between dietary creatine and depression risk. This study examines the association between dietary creatine and depression in U.S. adults, using data from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). Patient health questionnaire, dietary creatine intake and covariates were obtained on 22,692 NHANES participants ≥20 years of age. Depression prevalence was calculated within quartiles of dietary creatine intake. Adjusted logistic regression models were formulated to determine the relationship between dietary creatine intake and depression risk. Additional covariates included income to poverty ratio, race/ethnicity, sex, age, education level, body mass index, healthcare access, smoking status, physical activity, and antidepressant/anxiolytic medication use. Models were further stratified by sex, age group, and antidepressant/anxiolytic medication use. Depression prevalence was 10.23/100 persons (95% CI: 8.64-11.83) among NHANES participants in the lowest quartile of dietary creatine intake compared with 5.98/100 persons (95% CI: 4.97-6.98) among participants in the highest quartile (p < 0.001). An inverse association was measured between dietary creatine and depression (adjusted odds ratio (AOR) = 0.68, 95% CI: 0.52-0.88). Dietary creatine's negative association with depression was strongest in females (AOR = 0.62, 95% CI: 0.40-0.98), participants aged 20-39 years (AOR = 0.52, 95% CI: 0.34-0.79) and participants not taking antidepressant/anxiolytic medication (AOR = 0.58, 95% CI: 0.43-0.77). Study results indicate a significant negative relationship between dietary creatine and depression in a nationally representative adult cohort. Further research is warranted to investigate the role creatine plays in depression, particularly among women and across the lifespan.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Crude prevalence (weighted percentages are presented) and 95% confidence interval of depression (defined as a PHQ-9 score of ≥10) by quartile of 2-day average dietary creatine intake among NHANES 2005–2012 adult participants.
Fig. 2
Fig. 2
Relationship (adjusted odds ratio and 95% confidence interval) between quartile of dietary creatine intake and depression risk among NHANES 2005–2012 participants stratified by sex.

References

    1. Kessler RC, et al. The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R) JAMA. 2003;289:3095–3105.
    1. World Health Organization. Depression And Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization; 2017.
    1. Markou A. Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacology. 1998;18:135–174.
    1. Kessler RC. The effects of stressful life events on depression. Annu. Rev. Psychol. 1997;48:191–214.
    1. Dooley D, Catalano R, Wilson G. Depression and unemployment: panel findings from the Epidemiologic Catchment Area study. Am. J. Community Psychol. 1994;22:745–765.
    1. Strine TW, et al. Depression and anxiety in the United States: findings from the 2006 Behavioral Risk Factor Surveillance System. Psychiatr. Serv. 2008;59:1383–1390.
    1. Katon WJ. Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Biol. Psychiatry. 2003;54:216–226.
    1. Aneshensel CS, Stone JD. Stress and depression: a test of the buffering model of social support. Arch. Gen. Psychiatry. 1982;39:1392–1396.
    1. Jacka FN, et al. Association of western and traditional diets with depression and anxiety in women. Am. J. Psychiatry. 2010;167:1–7.
    1. Lai JS, et al. A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults. Am. J. Clin. Nutr. 2013;99:181–197.
    1. Guidelines on food fortification with micronutrients (2017): World Health Organization. World Health Organization. Retrieved 1 August 2018. .
    1. Sarris J, et al. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015;2:271–274.
    1. Sarris J, et al. Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Am. J. Psychiatry. 2016;173:575–587.
    1. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol. Rev. 2000;80:1107–1213.
    1. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem. J. 1992;281:21–40.
    1. Bender A, et al. Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology. 2006;67:1262–1264.
    1. Kondo DG, et al. Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study. J. Affect. Disord. 2011;135:354–361.
    1. Roitman S, Green T, Osher Y, Karni N, Levine J. Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord. 2007;9:754–758.
    1. Hellem TL, et al. Creatine as a novel treatment for depression in females using methamphetamine: a pilot study. J. Dual Diagn. 2015;11:189–202.
    1. Kious BM, Sabic H, Sung Y-H, Kondo DG, Renshaw P. An open-label pilot study of combined augmentation with creatine monohydrate and 5-hydroxytryptophan for selective serotonin reuptake inhibitor– or serotonin-norepinephrine reuptake inhibitor–resistant depression in adult women. J. Clin. Psychopharmacol. 2017;37:578–583.
    1. Kondo DG, et al. Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression. Amino Acids. 2016;48:1941–1954.
    1. Lyoo IK, et al. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am. J. Psychiatry. 2012;169:937–945.
    1. Nemets B, Levine J. A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression. Int. Clin. Psychopharmacol. 2013;28:127–133.
    1. Allen PJ, D’Anci KE, Kanarek RB, Renshaw PF. Chronic creatine supplementation alters depression-like behavior in rodents in a sex-dependent manner. Neuropsychopharmacology. 2010;35:534–546.
    1. Allen PJ, Danci KE, Kanarek RB, Renshaw PF. Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats. Pharm. Biochem. Behav. 2012;101:588–601.
    1. Renshaw PF, et al. Multinuclear magnetic resonance spectroscopy studies of brain purines in major depression. Am. J. Psychiatry. 2001;158:2048–2055.
    1. Hakkarainen R, et al. Is low dietary intake of omega-3 fatty acids associated with depression? Am. J. Psychiatry. 2004;161:567–569.
    1. Hoffmire CA, Block RC, Thevenet-Morrison K, Wijngaarden EV. Associations between omega-3 poly-unsaturated fatty acids from fish consumption and severity of depressive symptoms: an analysis of the 2005–2008 National Health and Nutrition Examination Survey. Prostaglandins Leukot. Essent. Fatty Acids. 2012;86:155–160.
    1. Murakami K, et al. Dietary intake of folate, other B vitamins, and ω-3 polyunsaturated fatty acids in relation to depressive symptoms in Japanese adults. Nutrition. 2008;24:140–147.
    1. Skarupski KA, et al. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Am. J. Clin. Nutr. 2010;92:330–335.
    1. Murakami K, Miyake Y, Sasaki S, Tanaka K, Arakawa M. Dietary folate, riboflavin, vitamin B-6, and vitamin B-12 and depressive symptoms in early adolescence: the Ryukyus Child Health Study. Psychosom. Med. 2010;72:763–768.
    1. Spitzer RL, Kroenke K, Williams JBW, the Patient Health Questionnaire Primary Care Study Group. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. JAMA. 1999;282:1737–1744.
    1. Uher R, Payne JL, Pavlova B, Perlis RH. Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV. Depress. Anxiety. 2013;31:459–471.
    1. Kroenke K, Spitzer RL. The PHQ-9: a new depression diagnostic and severity measure. Psychiatr. Ann. 2002;32:509–515.
    1. Bowman SA, Friday JE, Moshfegh A. MyPyramid Equivalents Database, 2.0 for USDA Survey Foods, 2003-2004 [Online]. Food Surveys Research Group. 2008. Beltsville, MD: Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture; 2016.
    1. Balsom PD, Söderlund K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med. 1994;18:268–280.
    1. Camara AA, Arn KD, Reimer A, Newburgh LH. The twenty-four hourly endogenous creatine clearance as a clinical measure of the functional state of the kidneys. J. Lab Clin. Med. 1951;37:743–763.
    1. Gibis M, Weiss J. Impact of precursors creatine, creatinine, and glucose on the formation of heterocyclic aromatic amines in grilled patties of various animal species. J. Food Sci. 2015;80:C2430–C2439.
    1. Hughes RB. Chemical studies on the herring (Clupea harengus). IV.—Creatine in herring flesh, and its behaviour during heat processing. J. Sci. Food Agric. 1960;11:700–705.
    1. Marsh NL, Iwaoka WT, Mower HF. Formation of mutagens during the frying of Hawaiian fish: correlation with creatine and creatinine content. Mutat. Res. 1990;242:181–186.
    1. Pais P, Salmon CP, Knize MG, Felton JS. Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats, and meat drippings. J. Agric. Food Chem. 1999;47:1098–1108.
    1. Kröckel L, Jira W, Kϋhne D, Mϋller W. Creatine blooms on the surface of prepacked fermented sausages. Eur. Food Res. Technol. 2003;217:1–3.
    1. Puangsombat K, Gadgil P, Houser TA, Hunt MC, Smith JS. Heterocyclic amine content in commercial ready to eat meat products. Meat Sci. 2011;88:227–233.
    1. Del Campo G, Gallego B, Berregi I, Casado J. Creatinine, creatine and protein in cooked meat products. Food Chem. 1998;63:187–190.
    1. Purchas R, Rutherfurd SM, Pearce PD, Vather R, Wilkinson BHP. Concentrations in beef and lamb of taurine, carnosine, coenzyme Q10, and creatine. Meat Sci. 2004;66:629–637.
    1. Schwartz T, Chen Q, Duan N. Studying Missing Data Patterns Using a SAS® Macro. Las Vegas, NV: SAS Global Forum; 2011.
    1. Azur MJ, Stuart EA, Frangakis C, Leaf PJ. Multiple imputation by chained equations: what is it and how does it work? Int. J. Methods Psychiatr. Res. 2011;20:40–49.
    1. Richter CK, Bowen KJ, Mozaffarian D, Kris-Etherton PM, Skulas-Ray AC. Total long-chain n-3 fatty acid intake and food sources in the United States compared to recommended intakes: NHANES 2003–2008. Lipids. 2017;52:917–927.
    1. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States. JAMA. 2002;287:337–344.
    1. Wang Y, Lopez JMS, Bolge SC, Zhu VJ, Stang PE. Depression among people with type 2 diabetes mellitus, US National Health and Nutrition Examination Survey (NHANES), 2005–2012. BMC Psychiatry. 2016;16:88.
    1. Harper DG, et al. Tissue type-specific bioenergetic abnormalities in adults with major depression. Neuropsychopharmacology. 2017;42:876–885.
    1. Cunha MP, et al. Antidepressant-like effect of creatine in mice involves dopaminergic activation. J. Psychopharmacol. 2012;26:1489–1501.
    1. Allen PJ, Debold JF, Rios M, Kanarek RB. Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats. Pharmacol. Biochem. Behav. 2015;130:22–33.
    1. Cunha MP, Pazini FL, Oliveira Á, Machado DG, Rodrigues ALS. Evidence for the involvement of 5-HT1A receptor in the acute antidepressant-like effect of creatine in mice. Brain Res. Bull. 2013;95:61–69.
    1. Cunha MP, et al. The modulation of NMDA receptors and l-arginine/nitric oxide pathway is implicated in the anti-immobility effect of creatine in the tail suspension test. Amino Acids. 2015;47:795–811.
    1. Pazini FL, et al. Creatine, similar to ketamine, counteracts depressive-like behavior induced by corticosterone via PI3K/Akt/mTOR pathway. Mol. Neurobiol. 2016;53:6818–6834.
    1. Ahn N, Leem YH, Kato M, Chang H. Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice. J. Exerc. Nutrition Biochem. 2016;20:24–31.
    1. Riehemann S, et al. Frontal lobe in vivo31P-MRS reveals gender differences in healthy controls, not in schizophrenics. NMR Biomed. 1999;12:483–489.
    1. Ellery SJ, Walker DW, Dickinson H. Creatine for women: a review of the relationship between creatine and the reproductive cycle and female-specific benefits of creatine therapy. Amino Acids. 2016;48:1807–1817.
    1. McEwen B. Estrogen actions throughout the brain. Recent Prog. Horm. Res. 2002;57:357–384.
    1. Anderson JC, Williams S, McGee R, Silva PA. DSM-III disorders in preadolescent children. Prevalence in a large sample from the general population. Arch. Gen. Psychiatry. 1987;44:69–76.
    1. Kuehner C. Gender differences in unipolar depression: an update of epidemiological findings and possible explanations. Acta Psychiatr. Scand. 2003;108:163–174.
    1. Morrison JH, Brinton RD, Schmidt PJ, Gore AC. Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J. Neurosci. 2006;26:10332–10348.
    1. Soares CN. Depression and menopause: current knowledge and clinical recommendations for a critical window. Psychiatr. Clin. North Am. 2017;40:239–254.
    1. Mohajeri M, Martín-Jiménez C, Barreto GE, Sahebkar A. Effects of estrogens and androgens on mitochondria under normal and pathological conditions. Prog. Neurobiol. 2019;176:54–72.
    1. Pazini FL, Cunha MP, Rodrigues ALS. The possible beneficial effects of creatine for the management of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2019;89:193–206.
    1. Hjelmervik H, et al. Sex- and sex hormone-related variations in energy-metabolic frontal brain asymmetries: a magnetic resonance spectroscopy study. Neuroimage. 2018;172:817–825.
    1. Rae CD, Brӧer S. Creatine as a booster for human brain function. How might it work? Neurochem. Int. 2015;89:249–259.
    1. Brosnan JT, Brosnan ME. Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu. Rev. Nutr. 2007;27:241–261.
    1. Burkert NT, Muckenhuber J, Großschädl F, Rásky É, Freidl W. Nutrition and health – the association between eating behavior and various health parameters: a matched sample study. PLoS ONE. 2014;9:e88278.
    1. Baines S, Powers J, Brown WJ. How does the health and well-being of young Australian vegetarian and semi-vegetarian women compare with non-vegetarians? Public Health Nutr. 2007;10:436–442.
    1. Michalak J, Zhang X, Jacobi F. Vegetarian diet and mental disorders: results from a representative community survey. Int. J. Behav. Nutr. Phys. Activity. 2012;9:67.
    1. Hibbeln JR, Northstone K, Evans J, Golding J. Vegetarian diets and depressive symptoms among men. J. Affect. Disord. 2018;225:13–17.
    1. Beezhold BL, Johnston CS, Daigle DR. Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults. Nutr. J. 2010;9:26.
    1. Beezhold BL, Johnston CS. Restriction of meat, fish, and poultry in omnivores improves mood: a pilot randomized controlled trial. Nutr. J. 2012;11:9.
    1. Cooper R, Naclerio F, Allgrove J, Jimenez A. Creatine supplementation with specific view to exercise/sports performance: an update. J. Int. Soc. Sports Nutr. 2012;9:33.
    1. Kley, R. A., Tarnopolsky, M. A., Vorgerd, M. Creatine for treating muscle disorders. Cochrane Database Syst. Rev. CD004760 (2013) 10.1002/14651858.CD004760.pub4.
    1. Bender A, Klopstock T. Creatine for neuroprotection in neurodegenerative disease: end of story? Amino Acids. 2016;48:1929–1940.
    1. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Retrieved 1 August 2018. .
    1. Dechent P, Pouwels PJW, Wilken B, Hanefeld F, Frahm J. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am. J. Physiol. 1999;277:R698–R704.
    1. Lyoo IK, et al. Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Res. 2003;123:87–100.
    1. Archer E, Hand GA, Blair SN. Validity of U.S. nutritional surveillance: National Health and Nutrition Examination Survey caloric energy intake data, 1971–2010. PLoS ONE. 2013;8:e76632.
    1. Hébert JR, et al. Considering the value of dietary assessment data in informing nutrition-related health policy. Adv. Nutr. 2014;5:447–455.
    1. Ahluwalia N, Dwyer J, Terry A, Moshfegh A, Johnson C. Update on NHANES dietary data: focus on collection, release, analytical considerations, and uses to inform public policy. Adv. Nutr. 2016;7:121–134.
    1. Brosnan JT, Silva RPD, Brosnan ME. The metabolic burden of creatine synthesis. Amino Acids. 2011;40:1325–1331.
    1. Daniel CR, Cross AJ, Koebnick C, Sinha R. Trends in meat consumption in the United States. Public Health Nutr. 2011;14:575–583.

Source: PubMed

3
Abonnere