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Stress Management: Feeding the Brain


Our society is overburdened with stressors of all kinds: tension in the workplace and long commutes; family and relationship difficulties; financial challenges; and poor lifestyle habits including too much caffeine, too little sleep, and not enough leisure time. The consequences of chronic stress are depression, anxiety, and insomnia. While it stands to reason that we certainly ought to reduce our stressful situations as much as possible and develop better coping methods, we also need to optimize our physical health to limit the effects of chronic stress on our mind and body. Providing the body with key nutrients that have been shown to improve neurological and mental function plays an important role in helping manage ongoing stress. This article will discuss the effects of vitamin D, fish oil, B vitamins, and lavender on mental health.

     

Vitamin D

Vitamin D is a steroid hormone with activity in the brain, and is called a “neurosteroid” by some.[1] The vitamin D receptor (VDR) is widely distributed throughout the human brain, including the limbic system and prefrontal cortex, which are involved in regulation of mood and affect.[2] One of the mechanisms of depression is thought to involve inflammatory processes in the brain, and interestingly, vitamin D is also known to have anti-inflammatory effects.[2] Animal studies suggest that vitamin D may have a role in the production or maintenance of dopamine and serotonin levels in the brain.[2] Finally, vitamin D has also been shown to influence the hypothalamic–pituitary–adrenal (HPA) axis, which is the primary system responsible for adaptation to stress. Although the role of vitamin D on adrenal function is not well known, one study found that prenatal vitamin D deficiency leads to an increase in maternal corticosterone hormone.[3]

Clinical trials indicate that vitamin D supplementation is effective in treating depression and anxiety. A 2016 study of 158 girls with PMS-related mood symptoms and vitamin D deficiency found that vitamin D supplementation was associated with significantly decreased anxiety score, irritability score, and a decrease in symptoms of crying easily and sadness.[4] Another randomized study in 40 patients with major depressive disorder (MDD) found that vitamin D supplementation (50,000 IU per week for eight weeks) improved symptoms of depression on the Beck Depression Inventory (BDI) compared to placebo.[5]

Another study evaluated the effect of vitamin D when added to the antidepressant fluoxetine.[6] A total of 42 patients with a diagnosis of major depressive disorder were randomized to receive daily either 1,500 IU vitamin D3 plus 20 mg fluoxetine, or fluoxetine alone, for eight weeks. Researchers found that depression severity decreased significantly after intervention, with the vitamin D–plus-fluoxetine combination being significantly better than fluoxetine alone from the fourth week of treatment.

Among women at risk of depression in the perinatal (literally “around birth”) period, lower vitamin D levels were significantly associated with higher reports of depressive symptoms.[7]

     

Fish Oil

Fish-derived omega‑3 fatty acids include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA exerts well-documented anti-inflammatory effects: EPA competitively inhibits the production of proinflammatory cytokines such as prostaglandin E2 (PGE2) from arachidonic acid (AA), and leads to the production of anti-inflammatory cytokines by the cyclooxygenase (COX) enzymes. EPA may also influence cell signaling and neurotransmitter production in the brain. EPA has also been shown to lower cortisol levels in patients with major depression, equally to antidepressants (fluoxetine).[8]

An extensive body of research indicates that EPA exerts powerful antidepressant and mood-stabilizing effects. Data from many randomized trials and several meta-analyses show that EPA improves mood in patients with depression and bipolar disorder, as well as in patients with depressive symptoms but not necessarily meeting the criteria for major depression.[9][10] Notably, a meta-analysis found that supplements with EPA content greater or equal to 60% showed benefit on standardized mean depression scores, with an effect size of approximately 50%, while supplements with less EPA were ineffective.[11]

EPA has also been shown to improve the effectiveness of antidepressants. In one study, 42 subjects were randomized to receive 1,800 mg EPA and 400 mg DHA in addition to citalopram (antidepressant), compared to citalopram alone.[12] After nine weeks, patients receiving both citalopram and EPA demonstrated significantly greater improvement in Hamilton Depression Rating scale scores over time, starting at four weeks.

Another study examined the effects of EPA alone (1000 mg), fluoxetine alone (20 mg), or both combined for eight weeks on patients with major depression.[13] This study showed that EPA alone and fluoxetine alone were equally effective in managing the symptoms of depression; however, their combination resulted in the best improvement. The EPA-and-fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment. Response rates, defined as a 50% or greater decrease in baseline depression score, were 50%, 56%, and 81% in the fluoxetine, EPA, and combination groups, respectively.


B Vitamins

The family of B vitamins is important in the synthesis and metabolism of neurotransmitters and hormones such as estrogen. In addition, according to the homocysteine hypothesis of depression, elevations of the molecule homocysteine are implicated in the pathogenesis of depression.[14]

Homocysteine is an intermediate metabolite of methionine circulating in the bloodstream. If there are adequate levels of folate, vitamin B6, and vitamin B12 available, it is metabolized to cysteine, a harmless end-product. In the event of deficiency, homocysteine accumulates in the bloodstream, and has been associated with increased risk of stroke, and hypothetically, depression.[15][16]

One study evaluated supplementation with one capsule of activated B vitamins among 330 patients with genetic polymorphisms of folic-acid metabolism and major depressive disorder (MDD).[16] After eight weeks, 82.4% of patients showed a mean 25% reduction in homocysteine while on average, patients receiving placebo showed a small elevation in homocysteine. Patients receiving B vitamins also showed an average 12‑point reduction in depression symptoms by week eight, while 42% achieved full remission.

Numerous studies show that supplementation with various B vitamins including thiamin, folic acid, and vitamin B12 improve symptoms in patients with depression, in patients on antidepressant medications and not.[17][18][19][20]

   

Lavender

Finally, although not a nutrient, lavender is an herbal medicine with a high level of scientific evidence supporting its effectiveness in the treatment of anxiety and comorbid depression.[21][22] In Germany, an oral lavender preparation is approved for the treatment of anxiety. Studies show that it is equal to common anxiolytic medications such as paroxetine (Paxil) and lorazepam (Ativan) in the treatment of anxiety.[23][24]

In a study of 318 adults with mixed anxiety and depressive disorder (MADD) and at least moderately severe anxious and depressed mood, treatment with lavender 80 mg daily for 70 days improved symptoms significantly better than placebo. Patients taking lavender also showed more pronounced improvements of impaired daily living skills and health-related quality of life.[21] A similar study found improvements in sleep quality and anxiety ratings among patients with restlessness, insomnia, and anxiety.[22]

Natural health products have a role in supporting mood and stress management. Agents such as vitamin D, B vitamins, eicosapentaenoic acid, and lavender help provide fuel for optimal brain function, and show few side effects in comparison with some of the commonly available prescription medications.



References

  1. Bertone-Johnson, E.R. “Vitamin D and the occurrence of depression: Causal association or circumstantial evidence?” Nutrition Reviews, Vol. 67, No. 8 (2009): 481–492.
  2. Okereke, O.I., and A. Singh. “The role of vitamin D in the prevention of late-life depression.” Journal of Affective Disorders, Vol. 198 (2016): 1–14.
  3. Tesic, D., et al. “Vitamin D deficiency in BALB/c mouse pregnancy increases placental transfer of glucocorticoids.” Endocrinology, Vol. 156, No. 10 (2015): 3673–3679.
  4. Tartagni, M., et al. “Vitamin D supplementation for premenstrual syndrome-related mood disorders in adolescents with severe hypovitaminosis D.” Journal of Pediatric and Adolescent Gynecology, Vol. 29, No. 4 (2016): 357–361.
  5. Sepehrmanesh, Z., et al. “Vitamin D supplementation affects the Beck depression inventory, insulin resistance, and biomarkers of oxidative stress in patients with major depressive disorder: A randomized, controlled clinical trial.” The Journal of Nutrition, Vol. 146, No. 2 (2016): 243–248.
  6. Khoraminya, N., et al. “Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder.” The Australian and New Zealand Journal of Psychiatry, Vol. 47, No. 3 (2013): 271–275.
  7. Williams, J.A., et al. “Vitamin D levels and perinatal depressive symptoms in women at risk: A secondary analysis of the mothers, omega‑3, and mental health study.” BMC Pregnancy and Childbirth, Vol. 16, No. 1 (2016): 203.
  8. Jazayeri, S., et al. “Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin‑1beta and interleukin‑6 concentrations in patients with major depressive disorder.” Psychiatry Research, Vol. 178, No. 1 (2010): 112–115.
  9. Mocking, R.J., et al. “Meta-analysis and meta-regression of omega‑3 polyunsaturated fatty acid supplementation for major depressive disorder.” Translational Psychiatry, Vol. 6 (2016): e756.
  10. Grosso, G., et al. “Role of omega‑3 fatty acids in the treatment of depressive disorders: A comprehensive meta-analysis of randomized clinical trials.” PLoS One, Vol. 9, No. 5 (2014): e96905.
  11. Sublette, M.E., et al. “Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression.” The Journal of Clinical Psychiatry, Vol. 72, No. 12 (2011): 1577–1584.
  12. Gertsik, L., et al. “Omega‑3 fatty acid augmentation of citalopram treatment for patients with major depressive disorder.” Journal of Clinical Psychopharmacology, Vol. 32, No. 1 (2012): 61–64.
  13. Jazayeri, S., et al. “Comparison of therapeutic effects of omega‑3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder.” The Australian and New Zealand Journal of Psychiatry, Vol. 42, No. 3 (2008): 192–198.
  14. Folstein, M., et al. “The homocysteine hypothesis of depression.” The American Journal of Psychiatry, Vol. 164, No. 6 (2007): 861–867. Review. Erratum in: The American Journal of Psychiatry, Vol. 164, No. 7 (2007): 1123—Buel, Jennifer [corrected to Buell, Jennifer].
  15. Zhao, M., et al. “Homocysteine and stroke risk: Modifying effect of methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention.” Stroke, Vol. 48, No. 5 (2017): 1183–1190.
  16. Mech, A.W., and A. Farah. “Correlation of clinical response with homocysteine reduction during therapy with reduced B vitamins in patients with MDD who are positive for MTHFR C677T or A1298C polymorphism: A randomized, double-blind, placebo-controlled study.” The Journal of Clinical Psychiatry, Vol. 77, No. 5 (2016): 668–671.
  17. Ghaleiha, A., et al. “Adjuvant thiamine improved standard treatment in patients with major depressive disorder: Results from a randomized, double-blind, and placebo-controlled clinical trial.” European Archives of Psychiatry and Clinical Neuroscience, Vol. 266, No. 8 (2016): 695–702.
  18. Almeida, O.P., et al. “B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: Results from the B‑VITAGE randomised, double-blind, placebo-controlled trial.” The British Journal of Psychiatry, Vol. 205, No. 6 (2014): 450–457.
  19. Papakostas, G.I., et al. “Effect of adjunctive l‑methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: Results from a randomized clinical trial.” The Journal of Clinical Psychiatry, Vol. 75, No. 8 (2014): 855–863.
  20. Venkatasubramanian, R., C.N. Kumar, and R.S. Pandey. “A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes.” Journal of Affective Disorders, Vol. 150, No. 2 (2013): 644–648.
  21. Kasper, S., et al. “Efficacy of silexan in mixed anxiety-depression: A randomized, placebo-controlled trial.” European Neuropsychopharmacology, Vol. 26, No. 2 (2016): 331–340.
  22. Kasper, S., I. Anghelescu, and A. Dienel. “Efficacy of orally administered silexan in patients with anxiety-related restlessness and disturbed sleep: A randomized, placebo-controlled trial.” European Neuropsychopharmacology, Vol. 25, No. 11 (2015): 1960–1967.
  23. Kasper, S., et al. “Lavender oil preparation silexan is effective in generalized anxiety disorder: A randomized, double-blind comparison to placebo and paroxetine.” The international Journal of Neuropsychopharmacology, Vol. 17, No. 6 (2014): 859–869.
  24. Woelk, H., and S. Schläfke. “A multi-center, double-blind, randomised study of the lavender oil preparation silexan in comparison to lorazepam for generalized anxiety disorder.” Phytomedicine, Vol. 17, No. 2 (2010): 94‑99.

 

Dr. Philip Rouchotas, MSc, ND

Well-known in the community as a naturopathic doctor,
associate professor, and editor-in-chief of Integrated
Healthcare Practitioners.





 

Dr. Heidi Fritz, MA, ND

A practicing naturopathic doctor since 2007, her areas of
focus include women's health, children's health, chronic
pain, and more.