Nutritional Factors Affecting Mental Health

So Young Lim; Eun Jin Kim; Arang Kim; Hee Jae Lee; Hyun Jin Choi; Soo Jin Yang

doi:10.7762/cnr.2016.5.3.143

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Lim, Kim, Kim, Lee, Choi, and Yang: Nutritional Factors Affecting Mental Health

Review Article

Clinical Nutrition Research 2016; 5(3): 143-152.

Published online: 26 July 2016

DOI: https://doi.org/10.7762/cnr.2016.5.3.143

Nutritional Factors Affecting Mental Health

So Young Lim¹, Eun Jin Kim¹, Arang Kim¹, Hee Jae Lee², Hyun Jin Choi², Soo Jin Yang²

¹Department of Food and Nutrition, Chonnam National University, Gwangju 61186, Korea.

²Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea.

Correspondence to Soo Jin Yang. Department of Food and Nutrition, Seoul Women's University, 621 Hwarang-ro, Nowon-gu, Seoul 01797, Korea. Tel: +82-2-970-5643, Fax: +82-2-976-4049, sjyang89@swu.ac.kr

Received 12 July 2016 Revised 18 July 2016 Accepted 20 July 2016

The Korean Society of Clinical Nutrition

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dietary intake and nutritional status of individuals are important factors affecting mental health and the development of psychiatric disorders. Majority of scientific evidence relating to mental health focuses on depression, cognitive function, and dementia, and limited evidence is available about other psychiatric disorders including schizophrenia. As life span of human being is increasing, the more the prevalence of mental disorders is, the more attention rises. Lists of suggested nutritional components that may be beneficial for mental health are omega-3 fatty acids, phospholipids, cholesterol, niacin, folate, vitamin B6, and vitamin B12. Saturated fat and simple sugar are considered detrimental to cognitive function. Evidence on the effect of cholesterol is conflicting; however, in general, blood cholesterol levels are negatively associated with the risk of depression. Collectively, the aims of this review are to introduce known nutritional factors for mental health, and to discuss recent issues of the nutritional impact on cognitive function and healthy brain aging.

Keywords: Cognitive function, Dementia, Depression, Healthy brain aging, Mental health

INTRODUCTION

Mental well-being is a core component of optimal health, and is a status that individuals can manage stress from daily living and make positive achievements pursuing public interest and contribution to the community [1]. Maintaining individual's mental health is important to improve personal life values, to reduce medical cost and other social expenses to deal with mental disorders, and to enhance national competitiveness.

Mental disorders, which are the same as psychiatric disorders, are clusters of syndromes which disturb an individual's cognition, emotion regulation or behavior [2]. Common mental disorders include bipolar disorders (manic disorder, depression, and manic-depression), dementia, schizophrenia, and panic disorder [2]. Several factors affecting the development of mental disorders include genetic factors, stress, diet, physical inactivity, drugs, and other environmental factors [3 4 5]. Among these factors, dietary factors may aggravate or ameliorate symptoms and the progression of the disorders although those are not major etiologies. Nutritional factors having beneficial effect on mental health are polyunsaturated fatty acids (PUFAs), especially omega-3 FAs, phospholipids, cholesterol, niacin, folate, vitamin B6, vitamin B12, and vitamin D [6 7 8 9]. Conversely, saturated fat and simple sugar can be hazardous for brain health, increasing the risk for mental illnesses as well as other metabolic disorders including diabetes and cardiovascular diseases (CVD) [4]. The effects of nutritional factors on mental health have been investigated for a long time; however, strong evidence has not reported as enough to suggest specific nutritional strategy as a preventive means except omega-3 FAs. Previous intervention studies often reported contrasting results, and meta-analysis on those reports showed weak or no association between specific nutrients and indices of mental function [10 11 12]. Limitations in conducting nutrition-mental health study are as follows: 1) it has difficulties in subject recruit, collection of precise and reliable data from subjects on memory-based questionnaires, identification of the cause-effect relationship, and acquirement of compliance on intervention, 2) due to its heterogeneity, responses to intervention are complex and various, and 3) the study requires involvement of highly trained experts.

In this review, we will introduce known nutritional factors affecting mental health, and discuss recent issues of the nutritional impact on cognitive function and healthy brain aging.

NUTRITIONAL FACTORS AFFECTING MENTAL HEALTH

Nutritional factors relating to mental health have a common aspect in that those factors are associated with the risk of CVD [13]. Omega-3 FAs are famous for cardio-protective effects [14 15 16]. Folate, vitamin B6 and B12 are parts of homocysteine metabolism, and deficiencies of these nutrients result in increased blood levels of homocysteine, which aggravate mental health [9 17 18 19]. Niacin is an effective modulator to increase high-density lipoprotein cholesterol and to improve lipidomic profiles [20 21], and vitamin D is associated with the risks of CVD and metabolic syndrome [22 23]. These nutrients are beneficial for mental health. Conversely, excess intake of saturated fat and sugar, which are risk factors for CVD, is detrimental to brain function [4 24]. In addition, recent studies add a promising evidence that specific dietary patterns including Mediterranean diet can be applied as effective strategies to prevent mental disorders [25].

Omega-3 FAs

Omega-3 FAs have been extensively studied with regard to the brain health. Omega-3 FAs' action on brain is mainly as a structural and functional component of membrane phospholipids in brain and retina [26 27 28]. Alpha-linolenic acid, a plant-based omega-3 FA, is found in flaxseed oil and soybean oil, and main dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is fish oil. These omega-3 FAs are potent activators of transcription factors and inflammatory modulators [29 30]. Anti-inflammatory activities of omega-3 FAs are often related to the suppression of excess extents of pro-inflammatory actions of omega-6 FAs [29].

Among several mental disorders, prevalence of dementia is evidently increasing as the portion of aged population is growing. In subjects with dementia at stage 1a (age-associated memory impairment) and 1b (mild cognitive impairment), low blood levels of omega-3 FAs were observed [31]. As dementia progresses to stage 2 (early dementia) and stage 3 (dementia with behavioral symptoms), mild and moderate protein-energy malnutrition (PEM) often develops, which requires oral nutritional supplements with protein and energy supplementation rather than omega-3 FAs intervention [31]. In case of severe dementia (stage 4), enteral nutrition or parenteral nutrition is recommended tosubjects with severe PEM [31]. Omega-3 FAs (1.0-3.4 g) intervention improved symptoms of Alzheimer's disease (AD), depression and schizophrenia as shown in Table 1 [32 33 34 35 36 37 38 39]. Mechanisms underlying beneficial effects of omega-3 FAs' on symptoms of mental disorders are regulations of integrity and fluidity of membrane, neurite growth, neurotransmitters, endothelium, neuronal survival, neurodegeneration, transcription, and inflammation [40]. Although further investigations are needed to identify the ideal dose of omega-3 FAs and the ratio of EPA and DHA, in general, 1 g daily intake of EPA and DHA is recommended to maintain brain health.

Table 1

Double blind, randomized, placebo-controlled trials involving omega-3 fatty acids (FAs) supplementation and major mental disorders

Ref. No.	Study design	Daily amounts of omega-3 FAs	Main findings
[32]	33 mild AD patients, omega-3 FAs (n = 18) and placebo (n = 15) for 6 mon	2.3 g (0.6 g EPA + 1.7 g DHA)	Reduce CSF levels of AD biomarkers
[33]	295 mild to moderate AD patients, DHA (n = 171) and placebo (n = 124) for 18 mon	2 g DHA	No effect on cognitive function
[34]	46 depressed women aged 66–95 years, omega-3 FAs (n = 22) and placebo (n = 24) for 8 wk	2.5 g (1.67 g EPA + 0.83 g DHA)	Ameliorate depressive symptoms and improve quality of life
[35]	36 pregnant/depressive women, omega-3 FAs (n = 18) and placebo (n = 18) for 8 wk	3.4 g (2.2 g EPA + 1.2 g DHA)	Lower depressive symptom ratings on the EPDS and BDI
[36]	60 schizophrenia patients, omega-3 FAs (n = 30) and placebo (n = 30) for 8 wk	1.0 g	Reduce PANSS score, general psychopathologic and total scores
[37]	71 first-episode schizophrenia patients aged 16-35 yr, 26 wk	2.2 g (1.32 g EPA + 0.88 g DHA)	Reduce the intensity of symptoms and improve the level of functioning

AD, alzheimer's disease; BDI, beck depression inventory; CSF, cerebrospinal fluid; EPDS, edinburgh postnatal depression scale; PANSS, positive and negative syndrome scale.

Phospholipids and cholesterol

Phospholipid is a principal component to maintain integrity and functionality of neuronal membrane, and is recently suggested as a blood biomarker for mental health. Altered plasma phospholipids were observed in patients with mild cognitive impairment (MCI) and AD [41 42]. Metabolome analyses enabled to screen phospholipid profiles and to identify altered levels in response to specific conditions in a comprehensive way [43 44]. Ether phospholipids, phosphatidylcholines, sphingomyelins and sterols were low in AD patients, and three metabolites [2,4-dihydroxybutanoic acid, unidentified carboxylic acid, and phosphatidylcholine {PC (16:0/16:0)}] were identified as signature markers for the possible progression of MCI to AD [43]. Examples of altered phospholipids in subjects with AD are listed in Table 2 [41 43 44 45].

Table 2

Altered phospholipids in subjects with Alzheimer's disease (AD)

Ref. No.	Study design	Sample type	Altered phospholipids
[41]	Healthy control (n = 73), amnestic MCI/AD (n = 46), and converter (n = 28) aged 70 yr and older	Plasma	LysoPC a C18:2, PC aa C36:6, PC aa C38:0, PC aa C38:6, PC aa C40:1, PC aa C40:2, PC aa C40:6, and PC ae C40:6 were depleted in the plasma of the converter subjects
[43]	Healthy control (n = 46), MCI (n = 143), and AD (n = 47)	Serum	PC (18:0/20:4), PC (16:0/18:2), and PC (O-18:0/18:2) were decreased in AD
[44]	Healthy control (n = 17) and AD (n = 19)	Serum	PC (16:1/16:1), PC (16:1/16:0), PC (16:0/16:0), PC (16:1/18:3), PC (16:0/18:3), PC (16:0/18:2), PC (16:0/18:1), PC (16:0/18:0), PC (18:2/18:2), PC (18:2/18:1), PC (18:1/18:1), and PC (18:0/18:0) were increased in AD, while PC (16:0/20:5), PC (18:2/20:5), PC (16:0/22:6), PC (16:0/22:5), PC (18:1/20:4), PC (18:1/20:3), PC (18:0/20:3), and PC (18:0/22:6) were decreased in AD

MCI, mild cognitive impairment; PC, phosphatidylcholine; PC aa, diacyl form; PC ae, acyl-alkyl form.

Cholesterol also constitutes neuronal membrane to be responsible for fluidity, and acts as a signaling modulator for gene transcription, which is involved in nutrientsmetabolism and inflammation. In a large Korean Cancer Prevention Study cohort (n = 1,329,525), risk of depression was related to low levels of serum cholesterol concentration, suggesting the possible needs of cholesterol-raising regimen in subjects with depression [46]. However, a dietary intervention in increasing blood cholesterol has not been tried because the cholesterol-raising regimen such as high intakes of saturated fat, trans-fat, cholesterol, and total calories can cause increased the risk of other metabolic diseases (e.g. obesity, diabetes, and CVD).

Vitamin B: niacin, folate, vitamin B6, and vitamin B12

Vitamin B is involved in energy metabolism as forms of cofactors, nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD). In a NAD-FAD-dependent and –independent ways, the B vitamins, especially niacin, folate, vitamin B6, and vitamin B12 affect mental health. Famous hypothesis for mental disorders is 'homocysteine hypothesis' that excess homocysteine causes the development of psychiatric symptoms. Particularly, folate, vitamin B6, and vitamin B12 are involved in homocysteine metabolism, and low levels of the B vitamins and high levels of homocysteine were observed in subjects with MCI, dementia, and depression [9 17 18 19 47 48]. Suggested mechanisms underlying homocysteine action on brain function are impairments in cerebral vasculature and function of neurotransmitters, and increases in neurotoxicity and oxidative stress [40 49 50]. Niacin's action on brain function is less studied compared with other vitamin B nutrients. A case-study reported that a subject with pellagra, a disease from niacin deficiency, showed psychiatric disorders, mainly behavioral deterioration and dementia, which were recovered by niacin intervention [51]. Recent studies on dietary intervention of niacin, especially nicotinamide riboside (NR), suggested that NR exerts neuroprotective effects, and restores cognitive decline by the regulation of beta-secretase 1 degradation and expressions of mitochondrial metabolism-related genes (aconitase, citrate synthase, glucose phosphate isomerase 1, phosphoglycerate kinase, and pyruvate dehydrogenase kinase) relating to the action of proliferator-activated receptor-γ coactivator 1α [52 53]. So far, vitamin B nutrients intervention relating to brain function showed equivocal results regarding their efficacy on cognitive function [54 55 56 57 58 59].

Antioxidants

The brain is vulnerable to oxidative stress because it has lipid-rich area especially in neuronal membrane and is metabolically active. Tight balance between oxidative stress and antioxidant system is required to maintain the structural integrity and optimal functions of brain [60]. Vitamins A, C, and E are major non-enzymatic antioxidants in foods, and there are emerging evidences that these antioxidant vitamins are protective against cognitive decline and mental disorders including anxiety disorders, attention-deficit/hyperactivity disorder, autism, bipolar disorder, depression, schizophrenia, and substance abuse [6 61 62 63]. Low blood levels of antioxidant vitamins are observed in subject with various mental disorders. Perinatal retinol deficiency shown as low levels of serum retinol concentrations is significantly associated with the increased risk (more than threefold) of schizophrenia and other schizophrenia spectrum disorders in the Prenatal Determinants of Schizophrenia study [64]. Subjects with high tertile of vitamins C and E intakes have lower risk of AD than subjects with lower intake tertiles of these antioxidant vitamins in the Rotterdam Study [65]. Especially, amyloid-beta deposition in brain relating to increased oxidative stress is one of the major causes of AD [66], and low levels of vitamins C and E in blood and/or cerebrospinal fluid were observed in AD patients [67 68]. Vitamin E intervention reduces amyloid-beta deposition, reactive oxygen species as well as nitric oxide synthesis, and prevents against cognitive impairment and the progression to AD [69]. Recently, a new approach to identify underlying mechanisms of neurodegenerative disorders and to investigate the intervention efficacy to improve the symptoms of mental disorders has applied. Application of redox proteomics approach enables to identity disease stage-specific modifications in oxidative stress-related molecules and to demonstrate a cluster of changes in protein oxidative modification by the specific nutritional intervention [70]. In general, existing intervention studies show beneficial effects of antioxidants on improving general symptoms of mental disorders, and the optimal combinations and the recommended duration of antioxidant vitamin intake need to be investigated.

Saturated fat and sugar

Because many factors affecting mental health are overlapped as those for CVD [13], dietary saturated fat and Western-style diet may impair cognitive function [71 72 73], and subjects with high BMI have low scores of a 37-item version of the Mini-Mental State Examination [74]. High levels of blood sugar due to excess sugar intake or uncontrolled blood sugar are main manifestations of diabetes. Recent findings consistently reported the positive association between diabetes and dementia [75 76], and diabetes induces AD in animal models [77 78]. Also, higher blood glucose and HbA1c concentrations were associated with reduced memory capacity and structural changes in hippocampus in cohort of healthy, older, nondiabetic individuals without dementia [79]. Intervention studies should focus on the development of practical dietary guidelines for each mental disorder and the identification of effective ways to compromise the negative effects of these saturated fat and simple sugars on mental disorders. Identifying the optimal dietary patterns such as Mediterranean diet is one of promising ways to find the effective dietary guidelines [25].

CONCLUSION

As the world is aging rapidly, attention on aging-related mental disorders has increased. Increased R & D planning and investment relating to these illnesses aim to reduce medical cost burden and to improve mental health as well as quality of life. Based on current evidence, nutritional factors are important for mental well-being. Especially, eating balanced meals on a regular basis and consuming nutrients for mental health including omega-3 FAs, antioxidants, niacin, folate, vitamin B6, and vitamin B12 at recommended dietary intake levels are suggested. Development of dietary guideline that is specific to each type and stage of mental disorder, and the identification of nutritional biomarkers on cognitive functions are suggested to study in the future. Because mental disorders are heterogeneous in symptoms and etiologies, well-designed diet intervention study on large cohorts is guaranteed to identify effective nutritional strategy.

Notes

^{Conflict of Interest} The authors have no potential conflicts of interest to disclose.

^Funding This work was supported by a research grant from Seoul Women's University (2015).

References

1. Manwell LA, Barbic SP, Roberts K, Durisko Z, Lee C, Ware E, McKenzie K. What is mental health? Evidence towards a new definition from a mixed methods multidisciplinary international survey. BMJ Open. 2015; 5:e007079.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, D.C.: American Psychiatric Association;2013.

3. Pinto RQ, Soares I, Carvalho-Correia E, Mesquita AR. Gene-environment interactions in psychopathology throughout early childhood: a systematic review. Psychiatr Genet. 2015; 25:223–233.

4. Beilharz JE, Maniam J, Morris MJ. Diet-induced cognitive deficits: the role of fat and sugar, potential mechanisms and nutritional interventions. Nutrients. 2015; 7:6719–6738.

5. Helgadóttir B, Forsell Y, Ekblom Ö. Physical activity patterns of people affected by depressive and anxiety disorders as measured by accelerometers: a cross-sectional study. PLoS One. 2015; 10:e0115894.

6. Lakhan SE, Vieira KF. Nutritional therapies for mental disorders. Nutr J. 2008; 7:2.

7. Lauritzen L, Brambilla P, Mazzocchi A, Harsløf LB, Ciappolino V, Agostoni C. DHA effects in brain development and function. Nutrients. 2016; 8:E6.

8. Haan MN, Miller JW, Aiello AE, Whitmer RA, Jagust WJ, Mungas DM, Allen LH, Green R. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. Am J Clin Nutr. 2007; 85:511–517.

9. Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 2008; 29:S143–72.

10. Forbes SC, Holroyd-Leduc JM, Poulin MJ, Hogan DB. Effect of nutrients, dietary supplements and vitamins on cognition: a systematic review and meta-analysis of randomized controlled trials. Can Geriatr J. 2015; 18:231–245.

11. Gowda U, Mutowo MP, Smith BJ, Wluka AE, Renzaho AM. Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition. 2015; 31:421–429.

12. Farina N, Isaac MG, Clark AR, Rusted J, Tabet N. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2012; 11:CD002854.

13. Azad MC, Shoesmith WD, Al Mamun M, Abdullah AF, Naing DK, Phanindranath M, Turin TC. Cardiovascular diseases among patients with schizophrenia. Asian J Psychiatr. 2016; 19:28–36.

14. Abbas AM. Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats. J Physiol Biochem. Forthcoming. 2016.

15. Barrett SJ. The role of omega-3 polyunsaturated fatty acids in cardiovascular health. Altern Ther Health Med. 2013; 19:Suppl 1. 26–30.

16. Maehre HK, Jensen IJ, Elvevoll EO, Eilertsen KE. Omega-3 fatty acids and cardiovascular diseases: effects, mechanisms and dietary relevance. Int J Mol Sci. 2015; 16:22636–22661.

17. Hainsworth AH, Yeo NE, Weekman EM, Wilcock DM. Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID). Biochim Biophys Acta. 2016; 1862:1008–1017.

18. Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro A 3rd. High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am J Clin Nutr. 2005; 82:627–635.

19. Bhatia P, Singh N. Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression. Fundam Clin Pharmacol. 2015; 29:522–528.

20. Zambon A, Zhao XQ, Brown BG, Brunzell JD. Effects of niacin combination therapy with statin or bile acid resin on lipoproteins and cardiovascular disease. Am J Cardiol. 2014; 113:1494–1498.

21. Savinova OV, Fillaus K, Harris WS, Shearer GC. Effects of niacin and omega-3 fatty acids on the apolipoproteins in overweight patients with elevated triglycerides and reduced HDL cholesterol. Atherosclerosis. 2015; 240:520–525.

22. Prasad P, Kochhar A. Interplay of vitamin D and metabolic syndrome: a review. Diabetes Metab Syndr. 2016; 10:105–112.

23. Strange RC, Shipman KE, Ramachandran S. Metabolic syndrome: a review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes. 2015; 6:896–911.

24. DiNicolantonio JJ, Lucan SC, O'Keefe JH. The evidence for saturated fat and for sugar related to coronary heart disease. Prog Cardiovasc Dis. 2016; 58:464–472.

25. Huhn S, Kharabian Masouleh S, Stumvoll M, Villringer A, Witte AV. Components of a Mediterranean diet and their impact on cognitive functions in aging. Front Aging Neurosci. 2015; 7:132.

26. Sinclair AJ, Begg D, Mathai M, Weisinger RS. Omega 3 fatty acids and the brain: review of studies in depression. Asia Pac J Clin Nutr. 2007; 16:Suppl 1. 391–397.

27. Haag M. Essential fatty acids and the brain. Can J Psychiatry. 2003; 48:195–203.

28. Lauritzen L, Hansen HS, Jørgensen MH, Michaelsen KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res. 2001; 40:1–94.

29. Wang Y, Huang F.. N-3 Polyunsaturated fatty acids and inflammation in obesity: local effect and systemic benefit. Biomed Res Int. 2015; 2015:581469.

30. Zúñiga J, Cancino M, Medina F, Varela P, Vargas R, Tapia G, Videla LA, Fernández V. N-3 PUFA supplementation triggers PPAR-α activation and PPAR-α/NF-κB interaction: anti-inflammatory implications in liver ischemia-reperfusion injury. PLoS One. 2011; 6:e28502.

31. Kang HJ, Hong JW, Han JW, Yang SJ, Kim SW, Shin IS, Kim KW, Yoon JS, Kim JM. Nutritional biomaker in Alzheimer disease. J Korean Soc Biol Ther Psychiatry. 2014; 20:187–200.

32. Freund Levi Y, Vedin I, Cederholm T, Basun H, Faxén Irving G, Eriksdotter M, Hjorth E, Schultzberg M, Vessby B, Wahlund LO, Salem N Jr, Palmblad J. Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study. J Intern Med. 2014; 275:428–436.

33. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010; 304:1903–1911.

34. Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, Negroni M, Berra B, Politi P, Rizzo AM. Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J Am Coll Nutr. 2010; 29:55–64.

35. Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC, Pariante CM. Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2008; 69:644–651.

36. Jamilian H, Solhi H, Jamilian M. Randomized, placebo-controlled clinical trial of omega-3 as supplemental treatment in schizophrenia. Glob J Health Sci. 2014; 6:103–108.

37. Pawełczyk T, Grancow-Grabka M, Kotlicka-Antczak M, Trafalska E, Pawełczyk A. A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J Psychiatr Res. 2016; 73:34–44.

38. Song C, Shieh CH, Wu YS, Kalueff A, Gaikwad S, Su KP. The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: acting separately or synergistically? Prog Lipid Res. 2016; 62:41–54.

39. Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, Caraci F.. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid Med Cell Longev. 2014; 2014:313570.

40. Parletta N, Milte CM, Meyer BJ. Nutritional modulation of cognitive function and mental health. J Nutr Biochem. 2013; 24:725–743.

41. Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, MacArthur LH, Hall WJ, Fisher SG, Peterson DR, Haley JM, Nazar MD, Rich SA, Berlau DJ, Peltz CB, Tan MT, Kawas CH, Federoff HJ. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014; 20:415–418.

42. Whiley L, Sen A, Heaton J, Proitsi P, García-Gómez D, Leung R, Smith N, Thambisetty M, Kloszewska I, Mecocci P, Soininen H, Tsolaki M, Vellas B, Lovestone S, Legido-Quigley C; AddNeuroMed Consortium. Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease. Neurobiol Aging. 2014; 35:271–278.

43. Orešič M, Hyötyläinen T, Herukka SK, Sysi-Aho M, Mattila I, Seppänan-Laakso T, Julkunen V, Gopalacharyulu PV, Hallikainen M, Koikkalainen J, Kivipelto M, Helisalmi S, Lötjönen J, Soininen H. Metabolome in progression to Alzheimer's disease. Transl Psychiatry. 2011; 1:e57.

44. González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Combination of metabolomic and phospholipid-profiling approaches for the study of Alzheimer's disease. J Proteomics. 2014; 104:37–47.

45. Hartmann T, van Wijk N, Wurtman RJ, Olde Rikkert MG, Sijben JW, Soininen H, Vellas B, Scheltens P. A nutritional approach to ameliorate altered phospholipid metabolism in Alzheimer's disease. J Alzheimers Dis. 2014; 41:715–717.

46. Jung KJ, Mok Y, Chang HY, Son D, Han EJ, Yun YD, Jee SH. The relationship between serum lipids and depression. J Lipid Atheroscler. 2014; 3:11–19.

47. Pascoe MC, Linden T. Folate and MMA predict cognitive impairment in elderly stroke survivors: A cross sectional study. Psychiatry Res. 2016; 243:49–52.

48. Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy--a review. Nutrients. 2016; 8:68.

49. Hogervorst E, Ribeiro HM, Molyneux A, Budge M, Smith AD. Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease. Arch Neurol. 2002; 59:787–793.

50. Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Mattson MP. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci. 2000; 20:6920–6926.

51. Wang W, Liang B. Case report of mental disorder induced by niacin deficiency. Shanghai Arch Psychiatry. 2012; 24:352–354.

52. Gong B, Pan Y, Vempati P, Zhao W, Knable L, Ho L, Wang J, Sastre M, Ono K, Sauve AA, Pasinetti GM. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models. Neurobiol Aging. 2013; 34:1581–1588.

53. Chi Y, Sauve AA. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 2013; 16:657–661.

54. Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis. 2012; 29:133–149.

55. Clarke R, Bennett D, Parish S, Lewington S, Skeaff M, Eussen SJ, Lewerin C, Stott DJ, Armitage J, Hankey GJ, Lonn E, Spence JD, Galan P, de Groot LC, Halsey J, Dangour AD, Collins R, Grodstein F; B-Vitamin Treatment Trialists' Collaboration. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr. 2014; 100:657–666.

56. Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008; (4):CD004514.

57. Dangour AD, Whitehouse PJ, Rafferty K, Mitchell SA, Smith L, Hawkesworth S, Vellas B. B-vitamins and fatty acids in the prevention and treatment of Alzheimer's disease and dementia: a systematic review. J Alzheimers Dis. 2010; 22:205–224.

58. Balk EM, Raman G, Tatsioni A, Chung M, Lau J, Rosenberg IH. Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med. 2007; 167:21–30.

59. Wald DS, Kasturiratne A, Simmonds M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med. 2010; 123:522–527.e2.

60. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012; 5:9–19.

61. Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008; 11:851–876.

62. Brown HE, Roffman JL. Vitamin supplementation in the treatment of schizophrenia. CNS Drugs. 2014; 28:611–622.

63. McNeill G, Jia X, Whalley LJ, Fox HC, Corley J, Gow AJ, Brett CE, Starr JM, Deary IJ. Antioxidant and B vitamin intake in relation to cognitive function in later life in the Lothian Birth Cohort 1936. Eur J Clin Nutr. 2011; 65:619–626.

64. Bao Y, Ibram G, Blaner WS, Quesenberry CP, Shen L, McKeague IW, Schaefer CA, Susser ES, Brown AS. Low maternal retinol as a risk factor for schizophrenia in adult offspring. Schizophr Res. 2012; 137:159–165.

65. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002; 287:3223–3229.

66. Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010; 345:91–104.

67. Butterfield D, Castegna A, Pocernich C, Drake J, Scapagnini G, Calabrese V. Nutritional approaches to combat oxidative stress in Alzheimer's disease. J Nutr Biochem. 2002; 13:444–461.

68. Lopes da Silva S, Vellas B, Elemans S, Luchsinger J, Kamphuis P, Yaffe K, Sijben J, Groenendijk M, Stijnen T. Plasma nutrient status of patients with Alzheimer's disease: systematic review and meta-analysis. Alzheimers Dement. 2014; 10:485–502.

69. Yang SG, Wang WY, Ling TJ, Feng Y, Du XT, Zhang X, Sun XX, Zhao M, Xue D, Yang Y, Liu RT. α-Tocopherol quinone inhibits β-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines. Neurochem Int. 2010; 57:914–922.

70. Tramutola A, Lanzillotta C, Perluigi M, Butterfield DA. Oxidative stress, protein modification and Alzheimer disease. Brain Res Bull. Forthcoming. 2016.

71. Francis HM, Stevenson RJ. Higher reported saturated fat and refined sugar intake is associated with reduced hippocampal-dependent memory and sensitivity to interoceptive signals. Behav Neurosci. 2011; 125:943–955.

72. Eskelinen MH, Ngandu T, Helkala EL, Tuomilehto J, Nissinen A, Soininen H, Kivipelto M. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry. 2008; 23:741–747.

73. Okereke OI, Rosner BA, Kim DH, Kang JH, Cook NR, Manson JE, Buring JE, Willett WC, Grodstein F. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neurol. 2012; 72:124–134.

74. Benito-León J, Mitchell AJ, Hernández-Gallego J, Bermejo-Pareja F. Obesity and impaired cognitive functioning in the elderly: a population-based cross-sectional study (NEDICES). Eur J Neurol. 2013; 20:899–906. e76–897.

75. Moreira PI. High-sugar diets, type 2 diabetes and Alzheimer's disease. Curr Opin Clin Nutr Metab Care. 2013; 16:440–445.

76. Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, Haneuse S, Craft S, Montine TJ, Kahn SE, McCormick W, McCurry SM, Bowen JD, Larson EB. Glucose levels and risk of dementia. N Engl J Med. 2013; 369:540–548.

77. Kimura N. Diabetes mellitus induces Alzheimer's disease pathology: histopathological evidence from animal models. Int J Mol Sci. 2016; 17:E503.

78. Okabayashi S, Shimozawa N, Yasutomi Y, Yanagisawa K, Kimura N. Diabetes mellitus accelerates Aβ pathology in brain accompanied by enhanced GAβ generation in nonhuman primates. PLoS One. 2015; 10:e0117362.

79. Kerti L, Witte AV, Winkler A, Grittner U, Rujescu D, Flöel A. Higher glucose levels associated with lower memory and reduced hippocampal microstructure. Neurology. 2013; 81:1746–1752.

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ORCID iDs: Soo Jin Yang
https://orcid.org/http://orcid.org/0000-0001-7892-7648
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