Diet and Micronutrients

Li et al. (2018) studied the relationship between the total consumptions of zinc, iron, copper and selenium, with depression. This cross-sectional study extracted the data of 14,834 adults (18+ years, 7399 male: 7435 female) from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. In unadjusted model and age- and gender-adjusted models, total zinc, iron, copper and selenium intakes were inversely associated with depression; when the highest quartile of copper and selenium intakes were compared to the lowest quartile, the multivariate adjusted odds ratios (ORs) of depression was recorded as 0.68 and 0.46, respectively. In addition, when quartile 3 for total zinc and iron consumption was compared to the lowest quartile, the inverse associations of depression were statistically significant, with OR of 0.7 for zinc and 0.66 for iron. Furthermore, those adults who met the Recommended Dietary Allowances (RDAs) for zinc (OR: 0.74), copper (OR: 0.68) and selenium (OR: 0.52) had significantly lower odds of depression, compared to those below the RDA. These results suggest inverse associations between total zinc, iron, copper and selenium intakes with depression.

Kimball et al. (2018) investigated the impact of a nutrition intervention program aimed at optimizing people’s vitamin D levels, on depression and anxiety by collecting data from 16,020 participants. The self-reported health measures of depression and anxiety were evaluated [using European Quality of Life Five Dimensions (EQ-5D) and Targeted Symptoms List (TSL)] as part of a community-based program focused on optimizing overall health through nutritional supplementation, education and lifestyle advice. The EQ-5D revealed that elevated levels of depression and anxiety were reported at baseline by more than 56% of the sample, but 49.2% (n = 7878) of those who reported any degree of depression or anxiety at baseline improved upon the first year in the program. Moreover, 97.2% of the 829 individuals who reported severe or extreme depression at baseline also showed improvements after one year. The better outcomes for depression and anxiety were significantly linked with higher vitamin D status (>100 nmol/L) and more strenuous physical activity, as observed in the regression analyses. This study concludes that those who suffer from mood and anxiety issues may benefit from nutritional supplements.

Using the data from the Eating Habit and Well-being study in Japanese workers, Nakamura et al. (2019) analyzed the relationship between the intake of six minerals with mental disorders. Among the 2089 participants of the study, there was no history of depression but 6.9% developed mental disorders (detected by Kessler's six-item psychological distress scale using a cut-off score of 12/13). The subjects’ dietary mineral intakes were estimated with the validated food frequency questionnaires, revealing the association between mental disorders with the lowest quartiles of zinc, copper, and manganese consumption. Whereas, the lowest quartiles of calcium, magnesium, and iron intake did not correlate with mental disorders. Also, combination analysis of high (≥median) or low (

Since women undertaking multiple roles in today’s society are increasingly experiencing psychological stress, this 2017 systematic review was designed to determine the effects of specific dietary supplements such as essential fatty acids (EFAs), B vitamins, vitamin C, magnesium and/or zinc in managing stress and anxiety in ladies. The search was for studies that recruited women aged 18 or above and that assessed stress and anxiety, including randomized controlled and pseudo-randomized trials. Due to the heterogeneity of the 14 included studies, narrative synthesis was performed. Essential fatty acids were found to be effective in various scenarios: alleviating anxiety in both premenstruation and during menopause in the absence of depression (ineffective after removing depression status); and reducing perceived stress and salivary cortisol levels during pregnancy. Also if disregarding the hormonal phase, EFAs were ineffective in reducing stress or anxiety in four groups of women. When magnesium supplementation was combined with vitamin B6, a reduction in premenstrual anxiety was seen but no effect was found with single supplementations, and when combined or not no impact was observed for stress in women suffering from dysmenorrhea. Other findings included older women experienced anxiety reduction using vitamin B6, but not folate or vitamin B12, while high-dose sustained-release vitamin C reduced anxiety and blood pressure in response to stress. To summarize, EFAs may be effective in reducing prenatal stress and salivary cortisol and may reduce anxiety during premenstrual syndrome and during menopause in the absence of depression; magnesium and vitamin B6 may be effective in combination in reducing premenstrual stress; vitamin B6 alone may reduce anxiety effectively in older women; and high-dose sustained-release vitamin C may reduce anxiety and mitigate increased blood pressure in response to stress. McCabe et al. (2017) called for longer term studies to investigate supplementation and to include compliance testing, use inert substances as controls and reliable outcome measures.

The purpose of this 2018 study was to explore the association between magnesium uptake from diet and psychiatric disorders among a large group of Iranian adults (n=3172; age 18-55). Dietary consumption was documented with a validated dish-based 106-item semi-quantitative food frequency questionnaire, while depression and anxiety, and psychological distress were evaluated using an Iranian validated version of the Hospital Anxiety and Depression Scale, and the General Health Questionnaire. The results demonstrated a significant inverse correlation between magnesium intake and depression among normal-weight men (OR 0·45) and overweight women (OR 0·45). Low Mg intake was also connected with higher prevalences of anxiety among all women (OR 1·80) and also normal-weight women (OR 1·73). While women in the highest quartile of Mg intake were 39% less likely to experience anxiety, compared with those in the lowest quartile. Even in unadjusted analyses, higher dietary Mg intake was associated with lower odds of anxiety among women (OR 0·61). Anjom-Shoae et al. (2018) were able to find evidence that dietary intake of magnesium was inversely associated with depression and anxiety but not with psychological distress.

Van der Burg and others (2019) conducted this systematic review of nutraceutical clinical trials in mood and psychotic disorders (major depression, bipolar disorder, schizophrenia) in the hope of discovering the most useful nutrient and genetic biomarkers for predicting nutraceutical response in people with these disorders. The team identified 35 studies (totalling 3836 participants) with baseline and endpoint blood nutrient markers and/or genetic polymorphisms. One of the most prominent findings was the strong association between polyunsaturated fatty acid concentrations (mostly EPA and DHA) and psychiatric outcomes observed in 10 out of 11 omega-3 studies, although the exact nature of the correlation varied between studies and diagnoses. No consistent evidence could be determined for levels of other nutrients (including Vitamin D, SAM/SAH ratios, carnitine, folate and vitamin B12) relating to treatment response, nor for the associations between one-carbon cycle genotypes (e.g. MTHFR C677 T, MTR and FOLH1) and treatment response. The available data therefore supported omega-3 indices as biomarkers of response to omega-3 treatments in mood disorders, although the researchers mention that larger population studies examining combinations of polymorphisms are required to determine if any genetic factors influence nutraceutical response in mood and psychotic disorders.

The association between dietary intake of magnesium and psychiatric disorders among Iranian adults: a cross-sectional study

This 2019 systematic review and meta-analysis was undertaken to examine and quantify the effects of B vitamin supplementation on mood in both healthy and 'at-risk' populations. The review accumulated 18 articles (2015 participants) including 16 randomized controlled trials involving daily supplementation with 3 or more B group vitamins with an intervention period of at least 4 weeks. Eleven of the 18 articles reported a positive effect for B vitamins over a placebo for overall mood or a facet of mood, while 5 out of the 8 studies in “at-risk” cohorts saw significant improvements in mood. B vitamin supplementation had a positive impact on stress, while it had no effect on anxiety and its beneficial effect on depression did not reach significance level. This review implies B vitamin supplementation can effect positive changes in healthy and at-risk populations for stress, but not for depressive symptoms or anxiety, and suggests its usefulness particularly in people who are at risk due to poor nutrient status or poor mood status.

Bakian et al. (2020) examined the association between dietary creatine and depression in U.S. adults, using the data dietary creatine intakes and patient health questionnaires obtained by the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES) on its 22,692 participants (aged ≥20 years). This study compared the depression prevalence in the subjects in the lowest quartile of dietary creatine intake (rate of 10.23/100) to occurrence in those in the highest quartile of creatine consumption (5.98/100 persons). While an inverse association was confirmed between dietary creatine and depression [adjusted odds ratio (AOR) = 0.68], the strongest correlations were seen in females (AOR = 0.62) and participants not taking antidepressant/anxiolytic medication (AOR = 0.58). These results highlighted a significant negative relationship between creatine intake and depression in a nationally representative cohort. This leaves the role that creatine plays in depression among women and across the lifespan to be investigated in the future.

Nguyen et al. (2019) analyzed the mineral intake (sodium, potassium, calcium, magnesium, phosphorus, iron, zinc, copper and manganese) of 1423 Japanese elderly people (aged 65+) and examined its relationship with depressive symptoms. The mineral intake of the Japanese adults were reported through a validated and brief self-administered diet history questionnaire, while the Geriatric Depression Scale was employed to measure their depressive symptoms. Those subjects with depressive symptoms were found to have taken in less minerals than those without symptoms, considering all minerals except sodium and manganese. Among the males, the level of minerals in the diet did not vary between those showing depressive symptoms and those without signs of depression, but this did not hold true for the females. Mineral intake was significantly lower in female participants with depressive symptoms, compared to those without such symptoms; the minerals potassium, calcium, magnesium, phosphorus, iron, zinc, and copper were significantly and negatively correlated with depressive symptoms among the women, but not men. The results suggested that the deficiencies in mineral intake may be related to depressive symptoms, especially in women, among this Japanese elderly population.

This 2020 study explored the correlation between intake of vitamin B6 with depression and anxiety among 3362 adults. Kafashani et al. (2020) used a validated 106 item self-administered Willett-format dish-based semi quantitative food-frequency questionnaire (DFQ) and an Iranian validated version of the Hospital Anxiety and Depression Scale (HADS) questionnaire to obtain data on the participants’ diet and mental health. The results exposed the significantly lower consumption of vitamin B6 in anxious and depressed individuals, compared to healthy subjects. After making adjustments for potential confounders, less vitamin B6 in the diet of the women and of the whole sample population was associated with increased risk in developing depression (OR = 1.41, P < 0.001. OR = 1.33, P = 0.02, respectively) and higher odds of suffering from anxiety (OR = 2.30, P < 0. 001, OR = 2.30, P = 0.04). This data provides further evidence of the association between lower vitamin B6 intake and increased prevalence of depression and anxiety. Enhancing nutritional status is thought to help cut down on these disorders, but further research, particularly robust randomized controlled trials, are necessary to provide more proof.

Wang et al. (2018) reviewed the evidence on the association between the micronutrients zinc, magnesium and selenium, with depression, and also overviewed the potential mechanisms of action behind the interactions. Empirical data seems to strongly suggest the positive association between zinc deficiency with risk of depression, and the inverse dynamic between zinc supplementation and depressive symptoms. Research surrounding the relationship between low magnesium and selenium intake with depression was lacking and inconclusive. The mechanisms of action of these micronutrients could involve the HPA axis, glutamate homeostasis and inflammatory pathways. This review highly regards the importance of consuming adequate servings of micronutrients in supporting good mental health, and provides the readers with the most common dietary sources for zinc and various other micronutrients. The safety and efficacy of supplementation with these micronutrients, used to potentially treat depression, should be investigated more thoroughly, while prospective data on the relationship between micronutrient levels and depression remain desired.

This 2019 meta-review appraised all the meta-analyses conducted on randomized controlled trials (RCTs) investigating the efficacy and safety of nutrient supplements in common and severe mental disorders. The 33 meta-analyses identified by a systematic search produced outcome data of 10,951 participants. While early evidence suggests polyunsaturated fatty acids (PUFAs) may have positive impacts on attention-deficit/hyperactivity disorder, there is greater support for the use of PUFAs, and particularly eicosapentaenoic acid, in the treatment of depression. While folate-based supplementation in patients with depression and schizophrenia has been explored, high-dose methylfolate and its positive influence on major depressive disorder was highlighted. In addition, back-up for N-acetylcysteine as an adjunctive treatment in mood disorders and schizophrenia is increasing. All the nutrient supplements had good safety profiles, with no adverse effects or contraindications with psychiatric medication reported. It is therefore important that clinicians note the nutrients that are well established in their efficacy, and also be mindful of those lacking in evidence. Next research should look into the population that would benefit the most from these supplements, developing our understanding of the underlying mechanisms in the process.

This 2019 study explored the potential correlation between dietary total antioxidant capacity (DTAC) and nutritional parameters with prevalence of depression among a female sample from Southern Brazil. The Beck Depression Inventory (BDI) helped analyze severity of depressive symptoms, while a 24-hour dietary recall allowed the monitoring of the women’s diet. The DTAC of the population ranged from 435.60 to 4502.62 mg VCE/day and depression was reported in 44% of all participants. Coffee was identified as the most consumed antioxidant food/beverage, while polyphenols were directly linked to the antioxidant capacity of fresh foods. Furthermore, women with depression were found to consume less polyphenols (p=0.022; Cohen's d=0.80), vitamin B6 (p=0.038; Cohen's d=0.65), vitamin A (p=0.044; Cohen's d =0.63), and vitamin C (p=0.050; Cohen's d =0.61). Lower BDI scores were also related with decreased polyphenol intake. This study hopefully provides helpful information on the recommended dietary antioxidant intake to support the prevention of depression among women.

This 2019 review summarizes the influence that polyphenols can have on the neural inflammation and mitochondrial dysfunction aspects of diet-induced hypothalamic dysfunction. Polyphenols were seen to help reduce oxidative stress and inflammation within the hypothalamus, enhancing leptin signaling and mitochondrial biogenesis in the process. The role of polyphenols in reducing the production of reactive oxygen species and in augmenting the natural oxidative defense systems also assists the prevention of neurodegeneration. Samodien et al. (2019) appreciate polyphenols as nutraceuticals with excellent potential as they have shown protective qualities against hypothalamic inflammation, mitochondrial dysfunction, and neurodegeneration. As hypothalamic inflammation spreads as an individual ages, polyphenol’s ability to possibly increase longevity should be studied, along with its therapeutic value in the management of mental health disorders since they are characterized too by advanced neuroinflammation.

This 2017 review summarizes the most valuable current evidence on the roles of zinc, magnesium, copper, lithium, iron, and manganese, and the deficiencies of these micronutrients, in the pathophysiology and treatment of anxiety.

This 2015 paper analyzes the micronutrients copper, selenium, manganese, iodine and vanadium and their roles in depression and anxiety. Młyniec et al. (2015) discuss potential mechanisms in which these elements may be linked with either depression or anxiety, including possible interactions between some of these micronutrients with enzymes that are involved in the pathophysiology of mental disorders. Furthermore, the authors inspect the dynamic between these elements and depression/anxiety, even the quantity of an element in the diet or in the blood associated with the symptoms of these disorders.

Rechenberg (2016) describes the lower quality of life, rise in comorbidity and increased mortality associated with depression, and the availability of a treatment option with a better safety profile than the well-established psychotherapy and pharmacotherapy used for clinical depression. Nutritional supplements are proposed as a means of reducing depressive symptoms and can be adopted as adjuvant therapy alongside pre-existing regimens, or as sole therapies. While there has been no shortage of interest in omega-3 fatty acids, B-vitamins (folate, vitamin B12, and vitamin B6), S-adenosylmethionine (SAMe), 5-hydroxytryptophan (5-HTP), and magnesium in the management of depression, this article explores the clinical data on these nutritional interventions and reviews its relevance to the pathophysiology and epidemiology of clinical depression.

This 2019 study assessed the correlation between dietary vitamin K intake (data collected through a semi-quantitative food frequency questionnaire) and depressive symptoms [diagnosed using the 20-item Center for Epidemiologic Studies-Depression (CES-D) ≥ 16] among 4,375 adult participants (aged 45-79) from North America. Around 10% (n=437) of the subjects exhibited symptoms of depression. After adjusting for potential confounders in the logistic regression analysis, those adults with the highest vitamin k intake were associated with lower incidences of depressive symptoms (OR = 0.58; 95%CI: 0.43–0.80), although this observation only applied to subjects not taking vitamin D supplements. Since this study provides evidence on the relevance of higher dietary vitamin K with lower appearance of depressive symptoms, further research is encouraged, especially to inspect the directionality of this association.

As matcha tea gains popularity and has been found to contain higher amounts of green tea phytochemicals compared to regular green tea, this 2017 review focuses on the tea constituents caffeine, L-theanine, and epigallocatechin gallate (EGCG) and its widely reported beneficial impact on mood and cognitive performance. This review aimed to summarize the acute psychoactive effects of these tea components by evaluating 49 human intervention studies. Since a limited number of intervention studies on EGCG was discovered its effects were inconclusive. But enhanced alertness, arousal and vigor were reported with caffeine, as well as better performance on time-consuming and demanding cognitive tasks, even at doses as low as 40mg. Caffeine in combination with L-theanine especially increased alertness and raised performance levels in attention-switching tasks, but to a lesser extent than caffeine alone. Even L-theanine alone, starting at 200mg, improved relaxation, tension, and calmness. These studies demonstrate the positive influences of L-theanine and caffeine on avoiding distractions and maintaining attention and memory, and the relaxing effect of L-theanine (through reduction of caffeine-induced arousal).

This 2019 study focused on the possible relationship between dietary phytochemical index (DPI) and symptoms of depression, anxiety and psychological distress among 488 Iranian women (aged 20-50). The DPI was estimated using the formula: (daily energy derived from phytochemical-rich foods (kJ)/total daily energy intake (kJ))×100. Questionnaires were used to assess diet (validated and reliable FFQ) and symptoms of depression, anxiety and psychological distress (validated depression, anxiety, stress scales). The study participants were recruited from health centres in the south of Tehran, and averaged 31·9 (sd 7·7) years in age. Signs of depression, anxiety and psychological stress were seen in 34·6, 40·6 and 42·4 % (respectively) of the studied population. Results showed women in the highest tertile of DPI had 78%, 67% and 70% lower risks in developing depression, anxiety and psychological stress, respectively, compared with those in the lowest tertile. Although this study showcases the significant association between DPI and mental health in Iranian women, prospective studies are required for further confirmation.

This 2019 paper studied the relationship between frequency and duration of drinking tea with depressive symptoms among a set of Chinese seniors, assessing whether the interaction varies by gender or age. The data used was from 2005, 2008/2009, 2011/2012 and 2014 waves of Chinese Longitudinal Healthy Longevity Survey (CLHLS). There was a correlation between consistent and frequent tea drinking with significantly fewer prevalence of depressive symptoms, while socioeconomic status, health-related behavior, physical health, cognitive function, and social engagement mediated this relationship. Although this association was only significant for males and the oldest groups, and not among women or younger elders, these findings support the consistent and frequent tea-drinking may effectively reduce the Chinese elderly population’s chances of developing depressive symptoms. In China, continuing the tradition of drinking tea may promote healthy aging in a cost-effective way.

To assess the relationship between chocolate consumption and depressive symptoms, this 2019 study applied the data of 13,626 adults (≥20 years) participating in the National Health and Nutrition Examination Survey between 2007-08 and 2013-14, deriving daily chocolate intake (no chocolate, non-dark chocolate, dark chocolate) and quantity of chocolate consumed (g/day) from two 24-hr dietary recalls and using the Patient Health Questionnaire (PHQ-9) to determine clinically relevant depressive symptoms (scores ≥10). Following the exclusion of diabetics, the consumption of any chocolate was reported in 11.1% of the population, while 1.4% revealed eating dark chocolate. Although the intake of dark chocolate was not significantly associated with depressive symptoms (OR=0.30), those participants who consumed dark chocolate were found to have lower odds of developing clinically relevant depressive symptoms. Moreover, the subjects in the highest quartile for chocolate consumption (104-454 g/day) were 57% less likely to develop signs of depression when compared with those who did not eat any chocolate (OR = 0.43) and after adjusting for dark chocolate consumption. These results suggest the relevance of consuming chocolates, particularly dark chocolate, in enhancing the odds of avoiding depressive symptoms, although additional longitudinal studies and further long-term investigation of chocolate consumption will be required to explain the causality of this relationship and confirm these conclusions.

Palmitoylethanolamide (PEA), known for its metabolic and neuroprotective effects, was investigated here by Lama et al. (2020) on its impact on the monoamine system and synaptic plasticity. In this preclinical study C57Bl/6J male mice were fed high-fat diet (HFD) for 12 weeks, before continuing in this trial being fed either 30 mg·kg-1 daily of ultra-micronized PEA or vehicle (control) for 7 weeks alongside a HFD. The study documented the depressive- and anhedonic-like behaviour, and cognitive performances of the mice, as well as performed monoamine analyses on the nucleus accumbens (Nac), prefrontal cortex (PFC), and hippocampus, and checked markers of synaptic plasticity and neurogenesis. The results showed few depressive- and anhedonic-like behaviour and reduced cognitive deficit induced by the HFD in the PEA-fed mice. Those given PEA also exhibited higher levels of 5-HT in the PFC, less dopamine and 5-HT replacement in the Nac and PFC, respectively, while their dopamine concentrations in the hippocampus and PFC also increased. Moreover, PEA seemed to improve synaptic plasticity, by restoring brain-derived neurotrophic factor signalling pathways in the hippocampus and PFC. The researchers highlighted PEA’s ability to promote neurogenesis, indicated by the reversal of the reduced glutamatergic synaptic density induced by HFD in the stratum radiatum of the CA1 of the hippocampus. PEA’s influence in monoamine homeostasis, synaptic plasticity and neurogenesis are evident, which imply its potential as an adjuvant therapy for suppressing depression-like behavior and reducing memory deficit.

Since the dyshomeostasis of copper and zinc is connected with neurodegeneration, Mravunac et al. (2019) set out to explore the relationship between copper and zinc serum levels, copper/zinc ratio, cognitive function, and signs of depression and anxiety among 139 Australian adults. Along with blood concentrations of zinc and copper, neurotrophic factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and insulin-like growth factor-1 were assessed, while the Hospital Anxiety and Depression Scale and the Cogstate battery and the Behavior Rating Inventory (BRI) of Executive Function (Adult version) allowed evaluation of the participants’ anxiety and depressive symptoms, respectively. Associations with lower depressive symptoms were found for copper and copper/zinc ratio but not for cognition. Also, plasma copper was positively correlated with BDNF while zinc was not associated with any of the outcomes. To summarize, higher blood copper levels and copper/zinc ratios were related to lower depressive symptoms, and copper was also positively associated with BDNF concentrations among an older population in Australia.

Since the association between low vitamin B6 levels and increased risk of depression has been documented but mostly in non-Hispanic white populations, Arévalo et al. (2019) recruited older adults of Puerto Rican descent, a population that has been previously reported to possess higher susceptibility to develop symptoms of depression, and tested the relationship between vitamin B6 status and depressive symptomatology longitudinally, at 3 different stages over ~ 5–7 years (baseline, after 2 years, and after 5 years). The participants’ plasma concentrations of pyridoxyl-5’-phosphate (PLP), which is a time-varying predictor of vitamin B6 levels, was determined to be significantly associated with depressive symptomatology. The data showed higher prevalence of depressive symptoms in the subjects deficient in PLP compared with those with highest levels, at baseline and over time also, even after controlling for multiple factors (age, sex, education, BMI, smoking and alcohol use, nutrition, perceived stress, stressful life events, allostatic load, use of antidepressants). But PLP levels were not linked with the rate of change in depressive symptomatology over time. The identification and treatment of people with vitamin B6 deficiency may be an effective preventative approach particularly among those of Puerto Rican descent since suboptimal concentrations of PLP was linked with higher depressive symptomatology among this study population and this relationship continued over time.

To examine the serum levels of amino acids and non-enzymatic antioxidants in major depressive disorder (MDD) and study its interaction with depression, Islam et al. (2020) gathered 247 patients with MDD and 248 healthy controls (HCs) matched by age and sex, and employed the HPLC system (for amino acids, vitamin A and E), UV-spectrophotometer (to assess vitamin C) and Hamilton Depression Rating Scale (Ham-D, to measure severity of depression). It was revealed that subjects with MDD had significantly lower readings of the four amino acids (methionine, phenylalanine, tryptophan, and tyrosine) and of the three non-enzymatic antioxidants (vitamin A, E, and C), relative to healthy controls. In addition, lower methionine and tyrosine concentrations were linked with higher Ham-D scores. These findings suggest that lower methionine, phenylalanine, tryptophan, tyrosine, and non-enzymatic antioxidant levels in the blood are connected with depression, and may have been a contributing factor in the development of major depression among MDD patients.

While levels of magnesium are believed to be lower in patients with mental disorders, especially depression, this 2020 systematic review aimed to analyze the literature from 2010 to March of 2020 regarding the micronutrient in psychiatric disorders, in order to determine magnesium’s relationship with psychiatric pathology and its effectiveness as a therapeutic supplement. Thirty-two relevant articles were identified, consisting of 18 Depressive Disorders (DD), 4 Anxiety Disorders (AD), 4 Attention Deficit Hyperactivity Disorder (ADHD), 3 Autism Spectrum Disorder (ASD), 1 Obsessive–Compulsive Disorder (OCD), 1 Schizophrenia (SCZ) and 1 Eating Disorders (ED). Botturi et al. (2020) mainly found positive results with respect to depressive symptoms in 12 studies, with 7 indicating a significant association between lower serum magnesium levels and depression (measured with psychometric scales), 2 papers showing better depression-related outcomes following magnesium intake, and another 2 demonstrating the improvement of depressive symptoms in participants taking magnesium as an adjuvant treatment with antidepressants, all compared with control. Moreover, 2 more papers reported an association between low magnesium concentration with ADHD, while 2 other papers reported correlations of higher magnesium levels with lower Hamilton Anxiety Rating Scale (HAM-A) scores among depressed individuals and discovered the ideal levels in stressed patients. Magnesium was not significantly connected with panic or Generalized Anxiety Disorder (GAD), associations with ED and SCZ were inconsistent, and only one of three papers found lower levels in ASD. This review judges magnesium supplementation as having beneficial and potentially therapeutic effects, and believes there is reason to demand clinical trials investigating the efficacy of magnesium as single or adjuvant therapy to confirm its appropriate clinical use.

This 2019 study recruited 60 patients with MDD and 60 individuals for control, matched by age and gender, and investigated the relationship between trace elements and vitamins with depressive disorders. The participants were examined on Cu, Zn, Ni, Cr, Mn, Mg, and Al serum levels (determined by atomic absorption spectrometry) and vitamin (E & A) concentrations (using high-performance liquid chromatography). Cu, Cr, and Al readings were found to be significantly higher in MDD patients than control, while the levels of Zn, Ni, Mn, Mg, vitamin E, and vitamin A were significantly lower in individuals diagnosed with depression. Finally, the ratio of Cu/Zn was high among depressed patients, which may have an important role in diagnosing and monitoring MDD. The results also suggest that disturbances in the level of trace elements and vitamins (E and A) are significantly related with MDD, studying Cu and Zn may be crucial in accumulating knowledge on the pathogenesis of depressive disorders, and that vitamin E deficiency may heighten the risk of developing MDD. Apparently, further exploration into trace element supplementation is required.

The aim of this 2018 study was to evaluate the differences between 247 patients with major depressive disorder (MDD) and 248 healthy individuals (matched by age and sex) in their serum levels of the macro-minerals (MM) calcium and magnesium, and of the trace elements (TE) copper, iron, manganese, selenium, and zinc. Another objective was to assess the prevalence of depression associated with these MMs and TEs [both analyzed by atomic absorption spectroscopy (AAS)]. The data indicated significantly higher concentrations of copper and lower levels of calcium and magnesium, iron, manganese, selenium, and zinc in MDD patients compared with control subjects (both p-values  < 0.05). A disturbance in the element homeostasis was strongly suspected, possibly signifying that abnormal serum concentrations of MM and TE may contribute substantially to the pathogenesis of MDD and that measuring of these elements and minerals may be an effective tool for depression risk prognosis.

As various studies have determined that the disturbances in the production, storage and utilization of brain energy are relevant in the development and maintenance of depression, Kious et al. (2019) proposes creatine as a nutritional supplement as it can possibly help correct this dyshomeostasis and has shown potential as an antidepressant in early clinical trials.

The aim of this 2020 study was to investigate the correlation between serum vitamin D concentrations and specific domains of depressive symptoms by each sex in the Korean general population. Rhee, Lee, and Ahn (2020) retrieved data from the Korea National Health and Nutrition Examination Survey of 2014 to gather their sample size of 820 men and 916 women (aged 19-76) who had completed health interviews and health examinations. These examinations provided data for serum 25-hydroxyvitamin [25(OH)D] concentrations, the Patient Health Questionnaire-9 (PHQ-9), and certain covariates. A statistically significant association between log-transformed serum 25(OH)D concentrations and total PHQ-9 scores in men (incidence rate ratio [IRR] = 0.74) was identified after multiple covariate adjustments. In men, log-transformed serum 25(OH)D concentrations were significantly associated with the PHQ-9 cognitive/affective subscore (IRR = 0.56). The findings show that serum vitamin D levels were inversely associated with cognitive/affective depressive symptoms in men.

Johnstone et al. (2020) conducted a systematic review on randomized controlled trials (RCTs) involving multinutrient interventions consisting of at least 4 vitamins and/or minerals in people with psychiatric symptoms, producing 16 RCTs (total 1719 participants) that met the inclusion criteria. The trials were related to various psychiatric categories including depression, post-disaster stress, antisocial behavior, behavioral deficits in dementia, attention-deficit/hyperactivity disorder, and autism. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assisted with the rating of evidence base, while significant clinical benefit was determined by using minimal clinically important differences (MIDs). The meta-analysis was performed on the trials in the Attention-Deficit/Hyperactivity Disorder (ADHD) category only because of the heterogeneity in participants, multinutrient formulas, outcome measures, and the absence of complete data. In samples with ADHD, the multinutrient intervention significantly improved (statistically and clinically) global functioning [mean difference (MD) −3.3, p = 0.001, MID −3.26; Standardized Mean Difference (SMD) −0.49 p = 0.001 MD −0.5), clinician ratings of global improvement (MD −0.58, p = 0.001, MID −0.5) and ADHD improvement (MD −0.54, p = 0.002, MID −0.5), and clinician (but not observer) measures of ADHD inattentive symptoms (MD −1.53, p = 0.05, MID −0.5)]. Narrative synthesis also revealed an improving trend of global measures among those subjects with autism and those with behavioral deficits in dementia. Furthermore, multinutrient interventions were associated with improvements in anxiety experienced post-natural disaster, and in the number of violent incidents among prisoners. According to this review, broad-spectrum formulas containing both vitamins and minerals had more substantial impacts than other formulas with fewer ingredients. Importantly, the reviewers have exposed the need for robust RCTs with full data (means and standard deviations for all outcomes) in order to find strong evidence for the role of multinutrients in psychiatric disorders.

Higher vitamin B 6 intake is associated with lower depression and anxiety risk in women but not in men: A large cross-sectional study

Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males

The effect of multivitamin supplementation on mood and stress in healthy older men

Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a meta-analysis

The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment

The effects of four-week multivitamin supplementation on mood in healthy older women: A randomized controlled trial

Effects of a multivitamin, mineral and herbal supplement on cognition and blood biomarkers in older men: a randomised, placebo-controlled trial

Influence of adjuvant Coenzyme Q10 on inflammatory and oxidative stress biomarkers in patients with bipolar disorders during the depressive episode

Assessment of dietary adequacy for important brain micronutrients in patients presenting to a traumatic brain injury clinic for evaluation

A randomised trial of nutrient supplements to minimise psychological stress after a natural disaster