Can Nutrition Be a Factor in Bipolar Disorder?

Can Nutrition Be a Factor in Bipolar Disorder?

  • Doctors Best

Bipolar disorder, formerly known as manic depression, is a psychiatric disorder characterized byepisodes of energy and elation lasting a week or more followed by a period of depression.

Treatment is based on medications that include the mineral lithium, which has been a lifesaver for many patients. Little is known concerning the benefit of alternative therapies. Nevertheless, in a survey of 435 patients, 50% reported the use of herbs or vitamins.

Vitamins B and C

A report published in 1978 documented a positive effect for pyridoxine (vitamin B6) in a study that included 17 patients with bipolar disorder.2 The vitamin is a cofactor in enzymatic reactions that result in the synthesis of neurotransmitters that can be insufficient in depressive states.

An early double-blind trial found a benefit for patients in both manic and depressed states following a single dose of 3 grams vitamin C in comparison with a placebo.3

Having a lower plasma level of the B vitamin folate has been associated with increased affective morbidity in bipolar patients treated long-term with lithium compared with those whose folate levels were higher.4 Other research found significantly lower red blood cell folate levels averaging 193 nanomoles per liter (nmol/l) in patients with mania in comparison with 896 nmol/l in a matched control group.5 In a case-control study, 88 patients in the acute phase of mania treated with sodium valproate experienced improvement in mania severity with the addition of folic acid over the course of a three week study in comparison with those who received sodium valproate and a placebo.6

The authors of a study involving bipolar disorder patients and their first-degree relatives suggest that low folate and vitamin B12 and high homocysteine levels could be a risk factor for developing the disease.7 It was the conclusion of a recent review that folate augmentation could be effective for bipolar treatment and that biologically active forms of folate that do not require biochemical conversion could be beneficial for mood stabilizer-associated folate deficiency.8

Omega-3 and CoQ10

A pilot study of men and women with bipolar depression resulted in 67% of participants treated with 12 grams inositol per day experiencing a 50% or more decrease in Montgomery-Asberg Depression Rating Scale (MADRS) scores, compared to 33% of those who received a placebo.9 However, other research suggests that restricting dietary inositol is helpful for some bipolar patients.10 In a randomized, double-blind 12-week trial involving children with bipolar spectrum disorder who were given omega 3 fatty acids, inositol, or a combination of the two, those who received omega 3 fatty acids plus inositol experienced the greatest decrease in mania and depression symptoms.11 A review of long-chain polyunsaturated fatty acids in psychiatric disease observed that 4 out of 6 randomized trials of the omega 3 fatty acid eicosapentaenoic acid (EPA)) in patients with depression and bipolar disorder had favorable outcomes.12

Treatment with up to 800 mg coenzyme Q10 (CoQ10) over a period of 4 weeks was associated with a reduction in MADRS scores in a trial involving older men and women with bipolar disorder.13 The researchers noted a significant decline in symptoms of lassitude, inability to feel, sadness, and difficulty concentrating in CoQ10-treated patients. “A neuroprogressive hypothesis of bipolar disorder has developed that implicates the neurobiological mechanisms of inflammation, glutamatergic excitotoxity, oxidative stress and mitochondrial dysfunction in the pathophysiology of neuronal damage and cognitive impairment in bipolar disorder with advancing age,” writes Brent P. Forester, MD, MSc, and colleagues. “Previous treatment studies that included aging cohorts of individuals with bipolar depression were not designed to address these underlying neurobiological mechanisms. CoQ10 has both anti-oxidant and mitochondrial enhancing effects, providing a neurobiological rationale for adjunctive use of CoQ10 in clinical studies of bipolar depression.”

Interestingly, results from over 250 publications have concluded that people with bipolar disorder are more frequently born in winter and spring when women are likeliest to have the lowest plasma vitamin D levels in comparison with summer and fall.14 When tested in bipolar children exhibiting symptoms of mania, brain neurochemistry and mood improved after 8 weeks of vitamin D3 supplementation.15

Amino Acids, Minerals, and More

A study of 11 adults receiving drug treatment for bipolar disorder who were given a vitamin and chelated mineral supplement resulted in a benefit on all measures for those who completed the 6-month trial.16 Symptom reduction ranged from 55% to 66% and the need for psychotropic medications was reduced by more than half. In a review of clinical trials that evaluated the effects of nutraceuticals combined with pharmacotherapies in the treatment of bipolar mania and bipolar depression, positive effects were observed for L-tryptophan, branched chain amino acids, folic acid, magnesium and a chelated mineral formula in bipolar mania; and in bipolar depression, the amino acid N-acetylcysteine as well as a vitamin and chelated mineral formula had strong effects, while mainly positive evidence was found for omega-3 fatty acids.17

A study that compared blood samples from 55 bipolar disorder patients to samples collected from 55 age- and sex-matched healthy volunteers found significantly higher levels of malondialdehyde (a marker of oxidative stress) and lower levels of the antioxidant vitamins A, C and E, as well as the minerals calcium, iron, potassium, selenium, sodium and zinc among the bipolar group.18

In an article titled, “Bipolar disorder and cell membrane dysfunction. Progress toward integrative management,” published in Alternative Medicine Review, P. M. Kidd writes, “Controlled, double-blind trials show multinutrient combinations of vitamins, minerals, orthomolecules, herbals, and the omega-3 fatty acids EPA and DHA to be effective monotherapy. The molecular action of lithium and valproate converge with nutrients on the level of the cell membrane and its molecular signal transduction systems. This emergent, unified rationale presages effective integrative management of bipolar disorder.”19

Future research may provide more information concerning the potential of the above-mentioned nutrients to improve the well-being of bipolar disease patients treated with standard therapies. It is recommended to consult with a physician if you or a loved one is considering the addition of nutritional supplements to a treatment regimen.


  1. Kilbourne AM et al. Psychopharmacol Bull. 2007;40(3):104-15.
  2. Bukreev V. Zh Nevropatol Psikhiatr Im S S Korsakova. 1978;78(3):402-8.
  3. Naylor GJ et al. Psychol Med. 1981 May;11(2):249-56.
  4. Coppen A et al. Br J Psychiatry. 1982 Jul;141:87-9.
  5. Hasanah CI et al. J Affect Disord. 1997 Nov;46(2):95-9.
  6. Behzadi AH et al. Acta Psychiatr Scand. 2009 Dec;120(6):441-5.
  7. Ozbek Z et al. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jul 1;32(5):1331-7.
  8. Baek JH et al. Aust N Z J Psychiatry. 2013 Nov;47(11):1013-8.
  9. Chengappa KN et al. Bipolar Disord. 2000 Mar;2(1):47-55.
  10. Shaldubina A et al. Bipolar Disord. 2006 Apr;8(2):152-9.
  11. Wozniak J et al. J Clin Psychiatry. 2015 Nov;76(11):1548-55.
  12. Muskiet FA et al. J Nutr Biochem. 2006 Nov;17(11):717-27.
  13. Forester BP et al. J Clin Psychopharmacol. 2015 Jun;35(3):338-40.
  14. Ashkanian M et al. Ugeskr Laeger. 2010 Apr 26;172(17):1296-300.
  15. Sikoglu EM et al. J Child Adolesc Psychopharmacol. 2015 Jun;25(5):415-24.
  16. Kaplan BJ et al. J Clin Psychiatry. 2001 Dec;62(12):936-44.
  17. Sarris J et al. Bipolar Disord. 2011 Aug-Sep;13(5-6):454-65.
  18. Chowdhury MI et al. J Trace Elem Med Biol. 2017 Jan;39:162-168.
  19. Kidd PM. Altern Med Rev. 2004 Jun;9(2):107-35.

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