Nutritional medicine as mainstream in psychiatry

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1 Personal View Nutritional medicine as mainstream in psychiatry Jerome Sarris, Alan C Logan, Tasnime N Akbaraly, G Paul Amminger, Vicent Balanz-Martnez, Marlene P Freeman, Joseph Hibbeln, Yutaka Matsuoka, David Mischoulon, Tetsuya Mizoue, Akiko Nanri, Daisuke Nishi, Drew Ramsey, Julia J Rucklidge, Almudena Sanchez-Villegas, Andrew Scholey, Kuan-Pin Su, Felice N Jacka, on behalf of The International Society for Nutritional Psychiatry Research Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest Lancet Psychiatry 2015; benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are 2: 27174 complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence Published Online January 26, 2015 of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and http://dx.doi.org/10.1016/ gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional S2215-0366(14)00051-0 deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as The Melbourne Clinic monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (J Sarris PhD), and Royal (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and Melbourne Hospital (F N Jacka PhD), Department of overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate Psychiatry, The University of recognition of diet and nutrition as central determinants of both physical and mental health. Melbourne, Richmond, Melbourne, VIC, Australia; Introduction grains, lean meat, nuts, and legumes, with avoidance of Centre for Human Psychopharmacology, Pharmacologically focused approaches have achieved a processed foods, is more likely to provide the nutrients Swinburne University of moderate reduction in the worldwide burden of poor that aord resiliency against the pathogenesis of mental Technology, Hawthorn, VIC, mental health; however, indicators suggest that the disorders. The mechanisms by which nutrition might Australia (J Sarris, burden of disease attributable to mental disorders will aect mental health are, at least superficially, quite A Scholey PhD); Complementary Alternative continue to rise worldwide during the coming decades.1,2 obvious: the human brain operates at a very high Medicine and Nutrition Mental disorders in general, and major depression and metabolic rate, and uses a substantial proportion of total Research (CAMNR), Calabasas, anxiety disorders in particular, account for a large burden energy and nutrient intake; in both structure and CA, USA (A C Logan BA); of disability worldwide.2 Rapid urbanisation, and an function (including intracellular and intercellular com- INSERM U710 (Institut National de la Sant et de la overall transition from traditional lifestyles (concerning munication), it is reliant on aminoacids, fats, vitamins, Recherche mdicale), diet, physical activity, and social structures), which are and minerals or trace elements.3,8 Dietary habits modulate University of Montpellier, some of the most pressing global and environmental the functioning of the immune system, which also Montpellier, France issues of our time, have both been linked to increases in moderates the risk for depression.8 The antioxidant (T N Akbaraly PhD); Department of Epidemiology and Public depression and other mental disorders.3 Indisputably, defence system, which is also implicated in mental Health, University College depression and other common mental disorders are disorders, operates with the support of nutrient cofactors London, London, UK already, and will probably become increasingly, part of an and phytochemicals. Additionally, neurotrophic factors (T N Akbaraly); Orygen Youth epidemic of comorbidity between physical and mental ill- make essential contributions to neuronal plasticity and Health Research Centre, Parkville, VIC, Australia health, with diet being a crucial common determinant.4 repair mechanisms throughout life, and these too are (G P Amminger MD); Teaching The current state, wherein populations in both aected by nutritional factors.9 Unit of Psychiatry and developed and emerging economies preferentially The purpose of this Personal View is to provide a Psychological Medicine, La Fe consume nutrient-poor, energy-dense, highly processed platform for robust debate in the specialty, particularly University and Polytechnic Hospital, University of Valencia foods, is historically uniquemany people are both regarding the need to move towards a new integrated Medical School, Centro de overfed and undernourished. Although caloric intake framework in psychiatry, whereby consideration of Investigacin Biomdica En has increased, many individuals in auent, developed nutritional factors should be standard practice. To provide Red de Salud Mental nations do not meet the recommended intakes of several a well informed and respected consensus statement10 and (CIBERSAM), Valencia, Spain (V Balanz-Martnez MD); brain-essential nutrients, including B-group vitamins, viewpoint on this position, we formed an international Perinatal and Reproductive zinc, and magnesium.5 Although slight improvements collaboration of academic authors from members of the Psychiatry (M P Freeman MD), have been detected in the dietary intakes of sugar and International Society for Nutritional Psychiatry Research and Depression and Clincal fats between 200304 and 200910, documented intakes (ISNPR). In this Personal View, we outline the supportive Research Program (D Mischoulon MD), of nutrient-rich and fibre-rich vegetables and whole evidence underpinning the proposed paradigm shift, and Massachusetts General grains are far lower than recommended.6 These present our perspective about the future direction of Hospital, Boston, MA, USA; profound changes in dietary habits, along with tobacco nutritional medicine in psychiatry. National Institute on Alcohol Abuse and Alcoholism, use, insucient physical activity, and harmful alcohol National Institutes of Health, and recreational drug use, have resulted in an epidemic Current evidence Bethesda, MD, USA of ill health. The major non-communicable diseases, In the past several years, links have been established (J Hibbeln MD); Department of along with mental disorders, are expected to cost the between nutritional quality and mental health, and Clinical Epidemiology, Translational Medical Center worldwide economy US$47 trillion from 2014 to 2020, if scientifically rigorous studies have made important (Y Matsuoka MD), and no substantial and eective action is taken.7 contributions to the understanding of the role of Department of Mental Health A traditional whole-food diet, consisting of higher nutrition in mental health. Many epidemiological Policy and Evaluation, National intakes of foods such as vegetables, fruits, seafood, whole studies, including prospective studies, have shown Institute of Mental Health www.thelancet.com/psychiatry Vol 2 March 2015 271

2 Personal View (D Nishi MD), National Center associations between healthy dietary patterns and a glutamate modulatory eects, and anti-inflammatory, of Neurology and Psychiatry, reduced prevalence of, and risk for, depression11,12 and antioxidant, and neuroprotective activity.27 Zinc is an Kodaira, Tokyo, Japan; Department of Epidemiology suicide.13 Maternal and early-life nutrition is also abundant trace element that is involved in cytokine and Prevention, Center for emerging as a determinant of later mental health modulation and hippocampal neurogenesis via Clinical Sciences, National outcomes in children,14,15 and severe macronutrient upregulation of BDNF, and also modifies N-methyl-D- Center for Global Health and deficiencies during crucial developmental periods have aspartate and glutamate activity.28 Zinc deficiency has Medicine, Shijuku-ku, Tokyo, Japan (T Mizoue MD, long been implicated in the pathogenesis of both been linked to increased depressive symptoms, and A Nanri MD); Department of depressive and psychotic disorders.16,17 evidence is emerging that zinc supplementation Psychiatry, Columbia A recent systematic review has now confirmed a improves depressed mood, mainly as an adjunctive University College of Physicians relation between unhealthy dietary patterns and poorer intervention with antidepressants.28 and Surgeons, New York, NY, USA (D Ramsey MD); mental health in children and adolescents.18 In view of B vitamins are needed for proper neuronal function, Department of Psychology, the early age of onset for depression and anxiety, these and a deficiency of B9 (folate) has been reported in University of Canterbury, data suggest that diet is a key modifiable intervention depressed populations, and in poor responders to anti- Christchurch, New Zealand target for prevention of the initial incidence of common depressants.29 Several studies have assessed the (J J Rucklidge PhD); Department of Clinical Sciences, University mental disorders. Indeed, although not statistically antidepressant eect of folic acid with concomitant of Las Palmas de Gran Canaria, powered to assess the prevention of de-novo depression, antidepressant use, and results of most either showed an Las Palmas de Gran Canaria, results from the large European PREDIMED study19 increase in the proportion of participants who had an Spain (A Sanchez-Villegas PhD); showed a strong trend towards a reduced risk for incident antidepressant response, or improved the onset Department of Psychiatry & Mind-Body Interface depression for individuals randomly assigned to a of response. Vitamin D is a neurosteroid, with data Laboratory (MBI-Lab), China Mediterranean diet with nuts, and this protective eect suggesting that low maternal concentrations are Medical University Hospital, was particularly evident in those with type 2 diabetes. implicated in schizophrenia risk, and deficiency is and Graduate Institute of Similarly, results of an indicated prevention trial20 showed likewise linked to increased depressive symptoms.30 A Neural and Cognitive Sciences, China Medical University, that dietary counselling was as eective as psychotherapy combination of nutrients that match the natural Taichung, Taiwan (K P Su MD); at prevention of transition to case-level depression in physiological needs of the body, and also better represent School of Medicine, Deakin older adults. A randomised controlled trial designed to the broad range of nutrients present in food, might University, IMPACT Strategic test the ecacy of dietary improvement as a treatment prove even more eective than isolated nutrients alone.31 Research Centre, Geelong, VIC, Australia (F N Jacka); Murdoch for major depression is underway.21 Childrens Research Centre, Convincing data suggest that select nutrient-based Future direction Parkville, VIC, Australia supplements (in isolation, or in combination),22 might During the past several years, high-quality research into (F N Jacka); and Black Dog provide many neurochemical modulatory activities that nutrition and mental healtha specialty that has been Institute, Hospital Road Prince of Wales Hospital, Randwick, are beneficial in the management of mental disorders. neglectedhas grown rapidly and is finally starting to NSW, Australia (F N Jacka) Examples of these nutrient-based supplements include develop its potential. In view of the changes related to Correspondence to: omega-3 fatty acids, S-adenosyl methionine (SAMe), rapidly growing urbanicity and the globalisation of the Dr Jerome Sarris, The Melbourne N-acetyl cysteine (NAC), zinc, B vitamins (including food industry, resulting in profound shifts away from Clinic, 2 Salisbury Street, folic acid), and vitamin D. Various clinical investigations traditional dietary patterns, the ways in which overall diet Richmond, Melbourne, VIC 3121, Australia support the potential usefulness of omega-3 fatty acids and specific nutritional elements, multinutrient inter- [email protected] for disorders including, but not limited to, bipolar ventions, or both can aect mental health clearly need to depression, post-traumatic stress disorder, and major be identified. In view of the widespread use of nutrient depression, and they are indicated in the prevention of supplements by individuals with and without mental psychosis.23 Omega-3 fatty acids can provide a range of disorders, scientifically rigorous methods should be used neurochemical activities via the following mechanisms: to assess the ecacy of these supplements and to identify modulation of neurotransmitter (noradrenaline, dopa- what dose of a nutrient supplement is needed, by whom, mine, and serotonin) re-uptake, degradation, synthesis, when, and under what circumstances. From this resultant and receptor binding; anti-inflammatory and anti- research, the evidence needs to be communicated to apoptotic eects; and the enhancement of cell mem- clinicians via educational programmes, and to the wider brane fluidity and neurogenesis via upregulation of public via public health campaigns. Formal medical brain-derived neurotrophic factor (BDNF).23,24 education should include training that focuses on the role SAMe is an endogenous sulphur-containing com- of diet and nutrients in brain function and mental health. pound that is an important neurochemical component Recommendations for governments to take more involved in the one-carbon cycle responsible for the substantive actions to improve food quality and promote methylation of neurotransmitters that regulate mood. healthier dietary practices should be considered to Clinical trials have shown that SAMe is an eective address the substantial burden of disease that results antidepressant,25 and clinically significant augmentation from unhealthy diets. Importantly, the activities of the eects occur with antidepressants.26 NAC has evidence food industry need to be examined at a governmental of ecacy in bipolar depression, schizophrenia, level, and relevant policies need to be designed to reduce trichotillomania, and other compulsive and addictive the worldwide burden of physical and mental ill-health behaviours.27 This aminoacid-based compound has attributable to poor diet.4 Such policies are advised to 272 www.thelancet.com/psychiatry Vol 2 March 2015

3 Personal View stimulate substantial public change in dietary habits Masterfoods, Martek, Naturex, Nestl, Neurobrands, Sanofi, Verdure back towards a traditional whole-food diet (dependent on Sciences, and Wrigley, and received speaker fees from Abbott Nutrition, Barilla, Bayer Healthcare, Danone, Flordis, GlaxoSmithKline Healthcare, the culture). Further, better education of the public and Kraft, Masterfoods, Martek, Novartis, Unilever, and Wrigley. K-PS has clinicians about the role of nutrients in the brain, and the received research grants from the National Science Council, National link to mental health, is crucially needed. Health Research Institute, and China Medical University in Taiwan, and joint research grants from the Royal Society (UK) and National Centre for Research and Development (Poland). FNJ has received grants and Conclusions research support from the Brain and Behaviour Research Institute Present treatment of psychiatric disorders can be (USA), the NHMRC, Australian Rotary Health, the Geelong Medical improved and greater attention can be given to preventive Research Foundation, the Ian Potter Foundation, Eli Lilly, the Meat and eorts. As a result of the immense burden of mental Livestock Board Australia, and The University of Melbourne, and has been a paid speaker for Sanofi-Synthelabo, Janssen Cilag, Servier, Pfizer, disorders, modifiable targets to reduce the incidence of Health Ed, Network Nutrition, Angelini Farmaceutica, and Eli Lilly. mental disorders are now urgently needed. Diet and References nutrition oer key modifiable targets for the prevention 1 Baxter AJ, Patton G, Scott KM, Degenhardt L, Whiteford HA. of mental disorders, having a fundamental role in the Global epidemiology of mental disorders: what are we missing? promotion of mental health. Now is time for the PLoS One 2013; 8: e65514. 2 Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease recognition of the importance of nutrition and nutrient attributable to mental and substance use disorders: findings from the supplementation in psychiatry. Nutritional medicine Global Burden of Disease Study 2010. Lancet 2013; 382: 157586. should now be considered as a mainstream element of 3 Logan AC, Jacka FN. Nutritional psychiatry research: an emerging discipline and its intersection with global urbanization, psychiatric practice, with research, education, policy, and environmental challenges and the evolutionary mismatch. health promotion supporting this new framework. J Physiol Anthropol 2014; 33: 22. Contributors 4 Jacka FN, Sacks G, Berk M, Allender S. Food policies for physical and mental health. BMC Psychiatry 2014; 14: 132. JS, ACL, and FNJ drafted the initial version of this manuscript. All authors contributed intellectual content to the manuscript, and read and 5 Parker E, Goldman J, Moshfegh A. Americas nutrition report card: comparing WWEIA, NHANES 20072010 usual nutrient intakes to approved the final manuscript. dietary reference intakes. FASEB J 2014; 28 (suppl): 384.2. Declaration of interests 6 Bowman S, Friday J, Thoerig R, Clemens J, Moshfegh A. Americans JS has received honoraria, research support, royalties, consultancy, or consume less added sugars and solid fats and consume more whole travel grant funding from Integria Health, Blackmores, Bioceuticals, grains and oils: changes from 200304 to 200910. FASEB J 2014; Taki Mai, Pepsico, HealthEd, Soho-Flordis, Pfizer, Elsevier, the Society for 28 (suppl): 369.2. Medicinal Plant and Natural Product Research, CR Roper Fellowship, 7 WHO. Global action plan for the prevention and control of and the National Health and Medical Research Council (NHMRC). noncommunicable diseases 20132020. Geneva: World Health ACL has received consulting fees from Genuine Health (Toronto, Organisation, 2013. Canada). VB-M has received grants, and served as consultant, adviser, or 8 Berk M, Williams LJ, Jacka FN, et al. So depression is an continuing medical education (CME) speaker during the past 3 years for inflammatory disease, but where does the inflammation come the following entities: Angelini, AstraZeneca, Bristol-Myers-Squibb, from? BMC Med 2013; 11: 200. Janssen, Juste, Lilly, Lundbeck, Otsuka, the Spanish Ministry of Science 9 Molendijk ML, Bus BA, Spinhoven P, et al. Serum levels of and Innovation, and Fundacin Alicia Koplowitz. MPF has received brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. funding for advisory board positions, or consulting, from: Takeda, Mol Psychiatry 2011; 16: 108895. Otsuka, Lundbeck, Genentech, Johnson & Johnson, and JDS 10 Sarris J, Logan A, Akbaraly T, et al. International Society for Therapeutics; pending research support from Takeda; and for medical Nutritional Psychiatry Research consensus position statement: editing for DSM Nutritionals and GOED Omega-3. YM has received nutritional medicine in modern psychiatry. World Psychiatry research support from the Japan Science and Technology Agency, (in press). National Center of Neurology and Psychiatry (Japan), the Ministry of 11 Lai JS, Hiles S, Bisquera A, Hure AJ, McEvoy M, Attia J. A systematic Health, Labour, and Welfare of Japan, and has been a paid speaker for review and meta-analysis of dietary patterns and depression in Mochida Pharmaceutical Co, Takeda Pharmaceutical Company, community-dwelling adults. Am J Clin Nutr 2014; 99: 18197. Suntory Wellness, Eli Lilly Japan KK, Otsuka Pharmaceutical Co, and 12 Psaltopoulou T, Sergentanis TN, Panagiotakos DB, Sergentanis IN, DHA & EPA Association. DM has received research support from the Kosti R, Scarmeas N. Mediterranean diet, stroke, cognitive Bowman Family Foundation, FisherWallace, Nordic Naturals, impairment, and depression: a meta-analysis. Ann Neurol 2013; Methylation Sciences, and PharmoRx Therapeutics. He has received 74: 58091. honoraria for consulting, speaking, and writing from Pamlab, and the 13 Nanri A, Mizoue T, Poudel-Tandukar K, et al, and the Japan Public Massachusetts General Hospital Psychiatry Academy. He has received Health Center-based Prospective Study Group. Dietary patterns and royalties from Lippincott Williams & Wilkins for the published book suicide in Japanese adults: the Japan Public Health Center-based Natural medications for psychiatric disorders: considering the alternatives. Prospective Study. Br J Psychiatry 2013; 203: 42227. TM has received research grants from the Japan Society for the 14 Jacka FN, Ystrom E, Brantsaeter AL, et al. Maternal and early postnatal Promotion of Science, the National Center for Global Health and nutrition and mental health of ospring by age 5 years: a prospective Medicine (Japan), the National Cancer Center (Japan), the Ministry of cohort study. J Am Acad Child Adolesc Psychiatry 2013; 52: 103847. Health, Labour, and Welfare of Japan, the Industrial Health Foundation, 15 Steenweg-de Graa J, Tiemeier H, Steegers-Theunissen RP, et al. the Uehara Memorial Foundation, and Otsuka Pharmaceutical Co. Maternal dietary patterns during pregnancy and child internalising DN has received research support from the Japan Society for the and externalising problems. The Generation R Study. Clin Nutr 2014; 33: 11521. Promotion of Science and the Foundation for Total Health Promotion, and lecture fees from Qol Co, DHA & EPA Association, NTT DoCoMo, 16 Brown AS, Susser ES, Lin SP, Neugebauer R, Gorman JM. Increased risk of aective disorders in males after second trimester and Emotional Quotient Academy. AS has received funding from the prenatal exposure to the Dutch hunger winter of 194445. Biotechnology and Biological Sciences Research Council (UK), The Br J Psychiatry 1995; 166: 60106. Australian Research Council, the NHMRC, the British Psychological 17 Susser ES, Lin SP. Schizophrenia after prenatal exposure to the Society, the Australian Wine Research Institute, Abbott Nutrition, Dutch Hunger Winter of 19441945. Arch Gen Psychiatry 1992; Arla Foods, Bayer Healthcare, Cognis, Cyvex, GlaxoSmithKline Nutrition, 49: 98388. www.thelancet.com/psychiatry Vol 2 March 2015 273

4 Personal View 18 ONeil A, Quirk SE, Housden S, et al. Relationship between diet 26 Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. S-adenosyl and mental health in children and adolescents: a systematic review. methionine (SAMe) augmentation of serotonin reuptake inhibitors Am J Public Health 2014; 104: e3142. for antidepressant nonresponders with major depressive disorder: 19 Snchez-Villegas A, Martnez-Gonzlez MA, Estruch R, et al. a double-blind, randomized clinical trial. Am J Psychiatry 2010; Mediterranean dietary pattern and depression: the PREDIMED 167: 94248. randomized trial. BMC Med 2013; 11: 208. 27 Berk M, Malhi GS, Gray LJ, Dean OM. The promise of 20 Stahl ST, Albert SM, Dew MA, Lockovich MH, Reynolds CF 3rd. N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci 2013; Coaching in healthy dietary practices in at-risk older adults: a case of 34: 16777. indicated depression prevention. Am J Psychiatry 2014; 171: 499505. 28 Lai J, Moxey A, Nowak G, Vashum K, Bailey K, McEvoy M. The 21 ONeil A, Berk M, Itsiopoulos C, et al. A randomised, controlled ecacy of zinc supplementation in depression: systematic review of trial of a dietary intervention for adults with major depression randomised controlled trials. J Aect Disord 2012; 136: e3139. (the SMILES trial): study protocol. BMC Psychiatry 2013; 13: 114. 29 Fava M, Mischoulon D. Folate in depression: ecacy, safety, 22 Rucklidge JJ, Kaplan BJ. Broad-spectrum micronutrient formulas dierences in formulations, and clinical issues. J Clin Psychiatry for the treatment of psychiatric symptoms: a systematic review. 2009; 70 (suppl 5): 1217. Expert Rev Neurother 2013; 13: 4973. 30 Eyles DW, Burne TH, McGrath JJ. Vitamin D, eects on brain 23 Mischoulon D, Freeman MP. Omega-3 fatty acids in psychiatry. development, adult brain function and the links between low levels Psychiatr Clin North Am 2013; 36: 1523. of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 24 Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: 2013; 34: 4764. meta-analyses of use in mania and bipolar depression. 31 Rucklidge JJ, Johnstone J, Kaplan BJ. Magic bullet thinkingwhy J Clin Psychiatry 2012; 73: 8186. do we continue to perpetuate this fallacy? [letter]. Br J Psychiatry 25 Sarris J, Papakostas GI, Vitolo O, Fava M, Mischoulon D. S-adenosyl 2013; 203: 15455. methionine (SAMe) versus escitalopram and placebo in major depression RCT: ecacy and eects of histamine and carnitine as moderators of response. J Aect Disord 2014; 164: 7681. 274 www.thelancet.com/psychiatry Vol 2 March 2015

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