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Micronutrients, Phytonutrients, and Mental Health

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National statistics indicate that several nutrient shortfalls are common in the United States, including potassium, dietary fiber, choline, magnesium, calcium, and vitamins A, D, E, and C.1 Risk of selenium, zinc, folate, and B12 deficiency may also be found among select populations. Multiple factors may play a role in nutrient deficiency, including the prevalence of highly processed Western-style diets with low vegetable, fruit, and whole grain intake, topsoil erosion and a decline of nutrient levels in the soil, and food insecurity or limited access to healthy foods and variety.

Micronutrient malnutrition, or deficiencies in one or more crucial vitamins or minerals, may negatively impact both physical and mental health and potentially lead to chronic illness. To compound the issue, chronic psychological and environmental stress may negatively impact micronutrient concentrations in the body, leading to micronutrient depletion.2 In a time when stress-related statistics indicate significantly higher symptoms of anxiety and depression in the US due to the pandemic,3 a nutrient-dense diet made up of foods full of vitamins, minerals, and phytonutrients can be a powerful tool in promoting mental wellness and combating chronic disease.

From Magnesium to B Vitamins: Impacts on Anxiety and Depression

Magnesium is one micronutrient commonly under-consumed in the US, yet it is present in a variety of foods, from greens to whole grains. Although there is some conflicting evidence,4 low levels of magnesium intake have been associated with depression.5,6 Most recently, a 2019 cross-sectional analysis of medical records from 3,604 adults found a positive correlation between lower serum magnesium levels and depressive symptoms.7

Beneficial effects of magnesium supplementation on anxiety and stress-related symptoms have been suggested, though further trials may be required to confirm efficacy in all populations.8 For example, a 2017 randomized controlled trial (RCT) found that magnesium and zinc supplementation (320 mg magnesium sulfate and 27 mg zinc sulfate/day) did not reduce depression and anxiety symptoms in postpartum women after an eight-week intervention.9 However, a 2018 RCT found that magnesium intake (300 mg/day) alleviated stress symptoms in men and women with low magnesemia.10 Further, for participants who reported severe stress, a combination of magnesium (300 mg/day) and vitamin B6 (30 mg/day) demonstrated greater improvements.10

Some B vitamin deficiencies have been linked to an increased risk of depression, and consistent and sufficient intake of those nutrients, specifically folate and vitamin B12, may potentially decrease the risk of depression relapse and the onset of symptoms in an at-risk population.11 A 2019 systematic review and meta-analysis of 18 research articles suggested that B vitamin supplementation benefited both at-risk (poor nutrient and mood status) and healthy populations specific to improving their reported stress symptoms and overall mood.12

Phytonutrients & Antioxidants

A diet that incorporates a varied and colorful rainbow of fruits, vegetables, whole grains, spices, and herbs provides essential minerals and vitamins, including antioxidants. In addition, the bountiful phytochemicals that contribute to the color, taste, and smell of plants provide both physical and mental health benefits. A 12-week RCT in 2018 specifically studied curcumin and found that an increasing dose (from 500 to 1,500 mg/day) as an adjunctive treatment for major depressive disorder had significant antidepressant effects.13 Another 12-week RCT in 2017 with similar curcumin doses also indicated similar effects, benefiting depressive symptoms as well as reducing anxiety in depressed adults.14

Research suggests that acute and chronic psychological stress is associated with increased inflammatory activity in the body, contributing to the adverse mental health symptoms and furthering inflammatory processes.15 The anti-inflammatory properties of dietary phytonutrients and antioxidants may provide direct benefit. A 2018 RCT evaluated the effects of carotenoids (13 mg or 27 mg/day) on 59 young, healthy participants and found that carotenoid intake reduced psychological stress and improved emotional and physical health compared to placebo.16 Other antioxidants such as vitamins A, C, and E may also play a role in the development and alleviation of anxiety and depressive symptoms. An observational study of 80 patients found that those with generalized anxiety disorder had lower initial levels of those vitamins in their blood serum compared to healthy controls.17 After a six-week treatment of vitamins A, C, and E, a significant increase in blood levels of antioxidants and a significant reduction in anxiety and depression were reported.17

Research also suggests that omega-3 polyunsaturated fatty acids are protective against depression and reduce depressive symptoms.18-20 A 2018 RCT evaluated omega-3 supplementation as an adjuvant therapy to standard antidepressant medication for patients with major depressive disorders.21 After a 12-week treatment, compared to placebo, those participants in the omega-3 treatment group reported less symptoms of depression, anxiety sensitivity, and sleep disturbances and improved regulation of their emotions.21

Clinical Considerations

Nutrition is a cornerstone of functional medicine care. Diet quality is a crucial consideration when evaluating chronic physical and mental health conditions and when implementing personalized interventions that address imbalances in order to optimize a patient’s overall wellness. Dietary patterns that include adequate and varied consumption of foods that are rich in essential micronutrients, including antioxidants and phytonutrients, positively impact mental health. In addition, helping patients manage chronic psychological stress may not only decrease the risk of micronutrient depletion2 but also promote mental and physical wellness

For a deeper understanding of micronutrient imbalances and how tools such as IFM’s nutrition-oriented physical exam can help identify nutrient insufficiencies, hear from the functional medicine experts at IFM’s Applying Functional Medicine in Clinical Practice (AFMCP).

Learn More About Functional Medicine

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Micronutrient Malnutrition: Not Limited to Developing Nations

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Adjunct Therapies for Depression

References

  1. US Department of Health and Human Services and US Department of Agriculture. 2015-2020 Dietary Guidelines for Americans.8th ed. Office of Disease Prevention and Health Promotion; 2015. http://health.gov/dietaryguidelines/2015/guidelines
  2. Lopresti AL. The effects of psychological and environmental stress on micronutrient concentrations in the body: a review of the evidence. Adv Nutr. 2020;11(1):103-112. doi:10.1093/advances/nmz082
  3. Czeisler MÉ, Lane RI, Petrosky E, et al. Mental health, substance use, and suicidal ideation during the COVID-19 pandemic – United States, June 24-30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1049-1057. doi:10.15585/mmwr.mm6932a1
  4. Wang J, Um P, Dickerman BA, Liu J. Zinc, magnesium, selenium and depression: a review of the evidence, potential mechanisms and implications. Nutrients. 2018;10(5):584. doi:10.3390/nu10050584
  5. Rosanoff A, Dai Q, Shapses SA. Essential nutrient interactions: does low or suboptimal magnesium status interact with vitamin D and/or calcium status? Adv Nutr. 2016;7(1):25-43. doi:10.3945/an.115.008631
  6. Tarleton EK, Littenberg B. Magnesium intake and depression in adults. J Am Board Fam Med. 2015;28(2):249-256. doi:10.3122/jabfm.2015.02.140176
  7. Tarleton EK, Kennedy AG, Rose GL, Crocker A, Littenberg B. The association between serum magnesium levels and depression in an adult primary care population. Nutrients. 2019;11(7):1475. doi:10.3390/nu11071475
  8. Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress—a systematic review. Nutrients. 2017;9(5):429. doi:10.3390/nu9050429
  9. Fard FE, Mirghafourvand M, Mohammad-Alizadeh Charandabi S, Farshbaf-Khalili A, Javadzadeh Y, Asgharian H. Effects of zinc and magnesium supplements on postpartum depression and anxiety: a randomized controlled clinical trial. Women Health. 2017;57(9):1115-1128. doi:10.1080/03630242.2016.1235074
  10. Pouteau E, Kabir-Ahmadi M, Noah L, et al. Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: a randomized, single-blind clinical trial. PLoS One. 2018;13(12):e0208454. doi:10.1371/journal.pone.0208454
  11. Almeida OP, Ford AH, Flicker L. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. Int Psychogeriatr. 2015;27(5):727-737. doi:10.1017/S1041610215000046
  12. Young LM, Pipingas A, White DJ, Gauci S, Scholey A. A systematic review and meta-analysis of B vitamin supplementation on depressive symptoms, anxiety, and stress: effects on healthy and ‘at-risk’ individuals. Nutrients. 2019;11(9):2232. doi:10.3390/nu11092232
  13. Kanchanatawan B, Tangwongchai S, Sughondhabhirom A, et al. Add-on treatment with curcumin has antidepressive effects in Thai patients with major depression: results of a randomized double-blind placebo-controlled study. Neurotox Res. 2018;33(3):621-633. doi:10.1007/s12640-017-9860-4
  14. Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: a randomised, double-blind, placebo-controlled study. J Affect Disord. 2017;207:188-196. doi:10.1016/j.jad.2016.09.047
  15. Maydych V. The interplay between stress, inflammation, and emotional attention: relevance for depression. Front Neurosci. 2019;13:384. doi:10.3389/fnins.2019.00384
  16. Stringham NT, Holmes PV, Stringham JM. Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults. Nutr Neurosci. 2018;21(4):286-296. doi:10.1080/1028415X.2017.1286445
  17. Gautam M, Agrawal M, Gautam M, Sharma P, Gautam AS, Gautam S. Role of antioxidants in generalised anxiety disorder and depression. Indian J Psychiatry. 2012;54(3):244-247. doi:10.4103/0019-5545.102424
  18. Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. 2011;72(12):1577-1584. doi:10.4088/JCP.10m06634
  19. Mozaffari-Khosravi H, Yassini-Ardakani M, Karamati M, Shariati-Bafghi SE. Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: a randomized, double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2013;23(7):636-644. doi:10.1016/j.euroneuro.2012.08.003
  20. Carney RM, Steinmeyer BC, Freedland KE, Rubin EH, Rich MW, Harris WS. Baseline blood levels of omega-3 and depression remission: a secondary analysis of data from a placebo-controlled trial of omega-3 supplements. J Clin Psychiatry. 2016;77(2):e138-e143. doi:10.4088/JCP.14m09660
  21. Jahangard L, Sadeghi A, Ahmadpanah M, et al. Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders – results from a double-blind, randomized and placebo-controlled clinical trial. J Psychiatr Res. 2018;107:48-56. doi:10.1016/j.jpsychires.2018.09.016

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