If your doctor agrees, try improving bipolar symptoms with fish oil capsules delivering 9.6 grams of omega-3 fatty acids per day along with your medications
Discuss exercise with your medical provider to see if it might be beneficial for you
Bipolar disorder is a mood disorder characterized by alternating states of depression and mania that follow each other in a repeating cycle.
People with bipolar disorder may cycle through these states quickly or may experience long periods of depression or mania. Often one mood state predominates, while the other occurs only infrequently or briefly. The cause of bipolar disorder is unknown.
Symptoms of the elevated mood stage of bipolar disorder include an exaggerated sense of confidence and well-being, racing thoughts, excessive talking, distractibility, increased desire for pleasurable activity, decreased need for sleep, impulsivity, irritability, and impairment in judgment. The depressed phase includes symptoms of sadness, fatigue, pessimism, feelings of helplessness, low self-esteem, and loss of interest in life, possibly with thoughts of suicide.
Exercise influences the production and use of neurotransmitters and hormones in the body, and its antidepressant effect is well known.1 A preliminary study of the effects of vigorous exercise on the body chemistry of patients with bipolar disorder found that exercise increased a specific chemical associated with better mood.2 However, exercise may adversely influence the effectiveness of some medications used for bipolar disorder. Many people with bipolar disorder take lithium, and because lithium is lost in sweat, exercise that involves significant sweating may change blood levels of lithium. Such a change has been reported in one person;3 therefore, people taking lithium who intend to start a vigorous exercise program should be monitored by their doctor.
Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.
For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.
3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.
Daily omega-3 fatty acids: 9.6 grams for adults, 1,290 to 4,300 mg for children
People with depression may have lower blood levels of omega-3s. Taking fish oil, in addition to prescribed medication, improved symptoms in one study.
People diagnosed with depression may have lower blood levels of omega-3 fatty acids.4 , 5 A double-blind trial found that bipolar patients taking 9.6 grams of omega-3 fatty acids from fish oil per day in addition to their conventional medications had significant improvements compared with those taking placebo.6 Similar benefits were reported in a preliminary trial that used 1.5 to 2 grams per day of pure eicosapentaenoic acid, a component of fish oil.7 In a preliminary trial, children with bipolar disorder saw benefits from omega-3 fatty acids (1,290 to 4,300 mg per day) from fish oil given for eight weeks.8
Vitamin-Mineral-Amino Acid Formula
Follow label instructions
A proprietary vitamin-mineral-amino acid formula showed promising results in a preliminary trial. More research is needed to confirm these findings.
In a preliminary trial, 11 patients with bipolar disorder were treated for six months with a moderate-potency vitamin-mineral formula (E.M. Power+ manufactured by Evince International, of Farmington, Utah) that also contained a proprietary blend of amino acids and other nutrients. The severity of depression decreased on average by 71% and the severity of mania decreased by 60% during the study.9 A double-blind study is needed to confirm these promising results.
Refer to label instructions
Supplementing with 5-HTP has had antidepressant effects in people with bipolar disorder; the effect was greater when combined with an antidepressant drug (doctor's supervision recommended)
L-tryptophan is the amino acid used by the body to produce serotonin, a chemical messenger important for proper brain function. Supplementation with L-tryptophan has led to improvement in depression in many studies,10 , 11 but information is limited about its effect on bipolar disorder. Case reports on two bipolar patients treated with lithium or an antidepressant drug described marked improvements when they were given 12 grams daily of L-tryptophan.12 , 13 Two trials using 6 grams of L-tryptophan daily for acute mania in patients with bipolar disorder found little or no improvement,14 , 15 but another double-blind, controlled study using 9.6 grams daily reported better results.16
L-tryptophan is converted to 5-HTP (5-hydroxytryptophan) before it becomes serotonin in the body. In a controlled trial, 200 mg daily of supplemental 5-HTP had antidepressant effects in bipolar patients, though it was not as effective as lithium.17 In a double-blind trial, patients with bipolar disorder had greater improvement with a combination of 5-HTP at 300 mg daily plus an antidepressant drug than with 5-HTP alone.18
Refer to label instructions
Folic acid deficiency is associated with both mania and depression. Getting enough folic acid helps the body manufacture serotonin and other neurotransmitters.
Both folic acid and vitamin B12 are used in the body to manufacture serotonin and other neurotransmitters. It is well known that deficiency of either nutrient is associated with depression.19 , 20 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.21 Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.22 , 23 , 24 Some studies have found that people who take lithium long term, and who also have high blood levels of folic acid, respond better to lithium.25 , 26 Not all studies have confirmed these findings, however.27 A double-blind study of patients receiving lithium therapy showed that the addition of 200 mcg of folic acid per day resulted in clinical improvement, whereas placebo did not.28
Refer to label instructions
Inositol may be useful for treating depression in people with bipolar disorder.
Inositol is a nutrient found in large amounts in the brain, but its possible role in mood disorders is unclear. Inositol levels may be reduced in certain parts of the brains of depressed and bipolar patients.29 However, lithium reduces normal brain levels of inositol, and this may be one of the ways lithium helps people with bipolar disorder.30 , 31 , 32 Although inositol is known to have significant antidepressant properties when administered in large amounts of 12 grams per day,33 , 34 case reports involving bipolar patients have reported either no benefit,35 some benefit,36 or worsening of symptoms from inositol supplementation.37 Until controlled research clarifies the effects of inositol in people with bipolar illness, it should only be used under the supervision of a qualified healthcare practitioner.
Refer to label instructions
In a preliminary trial, depression in patients with bipolar disorder significantly improved after NAC treatment.
In a preliminary trial, depression in patients with bipolar disorder significantly improved after N-acetyl cysteine treatment (1,000 mg twice a day for eight weeks).38 Double-blind trials are needed to confirm this benefit.
Refer to label instructions
SAMe is an amino acid that has an impact on serotonin levels, it has shown significant antidepressant effects in clinical trials.
SAMe (S-adenosylmethionine) is another amino acid that has an impact on serotonin levels, and it has demonstrated significant antidepressant effects in clinical trials.39 , 40 , 41 In both controlled and preliminary studies, SAMe has been shown to be helpful for the depressive symptoms of bipolar disorder. However, some patients have switched from depression to mania while using SAMe at 500 to 1,600 mg daily.42 , 43 This is a known side effect of other antidepressant medications.44 The mania induced by SAMe resolved when the supplement was discontinued, and in one case resolved spontaneously while the patient continued taking SAMe.45 Therefore, people with bipolar disorder should supplement with SAMe only under the supervision of a qualified healthcare practitioner.
Refer to label instructions
Vitamin B12 deficiency has been associated with both mania and depression. In one study, these symptoms cleared after treatment with B12 injections.
Both folic acid and vitamin B12 are used in the body to manufacture serotonin and other neurotransmitters. It is well known that deficiency of either nutrient is associated with depression.46 , 47 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.48 Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.49 , 50 , 51 Some studies have found that people who take lithium long term, and who also have high blood levels of folic acid, respond better to lithium.52 , 53 Not all studies have confirmed these findings, however.54 A double-blind study of patients receiving lithium therapy showed that the addition of 200 mcg of folic acid per day resulted in clinical improvement, whereas placebo did not.55
There have been case reports of both mania and depression associated with vitamin B12 deficiency, and these symptoms cleared after treatment with injections of B12.56 , 57 However, B12 deficiency has not been reported in bipolar disorder patients, and no studies have been published investigating the effects of vitamin B12 supplementation in people with bipolar disorder.
Refer to label instructions
Vitamin C helps the body reduce its load of vanadium, a mineral that adversely influences bipolar disorder. It has improved symptoms of depression and mania in some studies.
Vitamin C helps the body to reduce its load of vanadium and this has been studied for its possible role in treatment of bipolar disorder.58 A double-blind trial found that both manic and depressed bipolar patients were significantly improved after one-time administration of 3 grams of vitamin C, compared with a placebo.59 The same study found that both manic and depressed patients did better on a reduced-vanadium diet compared to a normal diet. Another double-blind study reported that 4 grams per day of vitamin C in combination with a drug known as EDTA (which also helps remove elements such as vanadium from the body) was helpful to depressed bipolar patients but not to those experiencing mania.60 Until more is known, people with bipolar illness should avoid supplements containing vanadium and consider supplementing with vitamin C.
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2. Lykouras E, Garelis E, Varsou E, Stefanis CN. Physical activity and plasma cyclic adenosine monophosphate levels in manic-depressive patients and healthy adults. Am J Psychiatry 1979;136:540–2.
3. Norman TC, Mathews W, Yohe CD. A case study on the effects of strenuous exercise on serum lithium levels. Nebr Med J 1987;72:224–5.
4. Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996;31 Suppl:S157–61.
5. Maes M, Christophe A, Delanghe J, et al. Lowered omega 3 polyunsaturated fatty acids in serum phospholipids and cholesterol esters of depressed patients. Psychiatry Res 1999;85:275–91.
6. Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder. A preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatr 1999;56:407–12.
7. Osher Y, Bersudsky Y, Belmaker RH. Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study. J Clin Psychiatry 2005;66:726–9.
8. Wozniak J, Biederman J, Mick E, et al. Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial. Eur Neuropsychopharmacol 2007;17:440–7.
9. BJ, Simpson JSA, Ferre RC, et al. Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder. J Clin Psychiatry 2001;62:936–44.
10. Young SN. Behavioral effects of dietary neurotransmitter precursors: basic and clinical aspects. Neurosci Biobehav Rev 1996;20:313–23 [review].
11. Riemann D, Vorderholzer U. Treatment of depression and sleep disorders. Significance of serotonin and L-tryptophan in pathophysiology and therapy. Fortschr Med 1998;116:40–2 [review].
12. Chouinard G, Jones BD, Young SN, Annable L. Potentiation of lithium by tryptophan in a patient with bipolar illness. Am J Psychiatry 1979;136:719–20.
13. Hedaya RJ. Pharmacokinetic factors in the clinical use of tryptophan. J Clin Psychopharmacol 1984;4:347–8.
14. Prange AJ, Wilson IC, Lynn CW, et al. L-tryptophan in mania: contribution to a permissive hypothesis of affective disorders. Arch Gen Psychiatry 1974;30:56–62.
15. Chambers CA, Naylor GJ. A controlled trial of L-tryptophan in mania. Br J Psychiatry 1978;132:555–9.
16. Murphy DL, Maker M, Goodwin FK, et al. L-tryptophan in affective disorders: indoleamine changes and differential clinical effects. Psychopharmacologia 1974;34:11–20.
17. van Praag HM, de Haan S. Chemoprophylaxis of depressions. An attempt to compare lithium with 5-hydroxytryptophan. Acta Psychiatr Scand Suppl 1981;290:191–201.
18. Mendlewicz J, Youdim MB. Antidepressant potentiation of 5-hydroxytryptophan by L-deprenil in affective illness. J Affect Disord 1980;2:137–46.
19. Botiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996;54:382–90 [review].
20. Fine EJ, Soria ED. Myths about vitamin B12 deficiency. Southern Med J 1991;84:1475–81.
21. Hasanah CI, Khan UA, Musalmah M, Razali SM. Reduced red-cell folate in mania. J Affect Disord 1997;46:95–9.
22. McKeon P, Shelley R, O’Regan S, O’Broin J. Serum and red cell folate and affective morbidity in lithium prophylaxis. Acta Psychiatr Scand 1991;83:199–201.
23. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265–70.
24. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49–52.
25. Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982;141:87–9.
26. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265–70.
27. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49–52.
28. Coppen A, Chaudhry S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disord 1986;10:9–13.
29. Shimon H, Agam G, Belmaker RH, et al. Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder. Am J Psychiatry 1997;154:1148–50.
30. Fauroux CM, Freeman S. Inhibitors of inositol monophosphatase. J Enzyme Inhib 1999;14:97–108 [review].
31. Belmaker RH, Agam G, van Calker D, et al. Behavioral reversal of lithium effects by four inositol isomers correlates perfectly with biochemical effects on the PI cycle: depletion by chronic lithium of brain inositol is specific to hypothalamus, and inositol levels may be abnormal in postmortem brain from bipolar patients. Neuropsychopharmacology 1998;19:220–32 [review].
32. Belmaker RH, Bersudsky Y, Agam G, et al. How does lithium work on manic depression? Clinical and psychological correlates of the inositol theory. Annu Rev Med 1996;47:47–56 [review].
33. Levine J, Barak Y, Gonzalves M, et al. Double-blind, controlled trial of inositol treatment of depression. Am J Psychiatry 1995;152:792–4.
34. Levine J, Barak Y, Kofman O, Belmaker RH. Follow-up and relapse analysis of an inositol study of depression. Isr J Psychiatry Relat Sci 1995;32:14–21.
35. Souza FG, Mander AJ, Foggo M, et al. The effects of lithium discontinuation and the non-effect of oral inositol upon thyroid hormones and cortisol in patients with bipolar affective disorder. J Affect Disord 1991;22:165–70.
36. Grisaru N, Belmaker RH. Lithium dosage and inositol levels. Br J Psychiatry 1994;164:133–4 [letter].
37. Levine J, Witztum E, Greenberg BD, Barak Y. Inositol-induced mania? Am J Psychiatry 1996;153:839 [letter].
38. Berk M, Dean O, Cotton SM, et al. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 2011;135:389–94.
39. Rosenbaum JF, Fava M, Faulk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432–6.
40. Friedel HA, Goa KL, Benfield P. S-Adenosyl-l-methionine: A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389–417 [review].
41. Carney MWP, Chary TKN, Bottiglieri T. The switch mechanism in affective illness and oral S-adenosylmethionine (SAM). Br J Psychiatry 1987;150:724–5.
42. Carney MWP, Chary TKN, Bottiglieri T. The switch mechanism in affective illness and oral S-adenosylmethionine (SAM). Br J Psychiatry 1987;150:724–5.
43. Carney MWP, Chary TKN, Bottiglieri T, Reynolds EH. The switch mechanism and bipolar/unipolar dichotomy. Br J Psychiatry 1989;154:48–51.
44. Wehr TA, Goodwin FK. Can antidepressants cause mania and worsen the course of affective illness? Am J Psychiatry 1987;144:1403–11.
45. Rosenbaum JF, Fava M, Faulk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432–6.
46. Botiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996;54:382–90 [review].
47. Fine EJ, Soria ED. Myths about vitamin B12 deficiency. Southern Med J 1991;84:1475–81.
48. Hasanah CI, Khan UA, Musalmah M, Razali SM. Reduced red-cell folate in mania. J Affect Disord 1997;46:95–9.
49. McKeon P, Shelley R, O’Regan S, O’Broin J. Serum and red cell folate and affective morbidity in lithium prophylaxis. Acta Psychiatr Scand 1991;83:199–201.
50. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265–70.
51. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49–52.
52. Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982;141:87–9.
53. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265–70.
54. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49–52.
55. Coppen A, Chaudhry S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disord 1986;10:9–13.
56. Goggans FC. A case of mania secondary to vitamin B12 deficiency. Am J Psychiatry 1984;141:300–1.
57. Verbanck PM, LeBon O. Changing psychiatric symptoms in a patient with vitamin B12 deficiency. J Clin Psychiatry 1991;52:182–3 [letter].
58. Naylor GJ. Vanadium and manic depressive psychosis. Nutr Health 1984;3:79–85 [review].
59. Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med 1981;11:249–56.
60. Kay DS, Naylor GJ, Smith AH, Greenwood C. The therapeutic effect of ascorbic acid and EDTA in manic-depressive psychosis: double-blind comparisons with standard treatments. Psychol Med 1984;14:533–9.
Last Review: 05-01-2013
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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2014.
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