People diagnosed with depression may have lower blood levels of omega-3 fatty acids.^1,2 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 medications had significant improvements compared with those taking placebo.³ 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.^[REF] However, in another double-blind trial, 8 grams per day of fish oil taken for 4 months was of no benefit for patients with bipolar disorder.^[REF] 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.⁴

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 preparation contained vitamin A (3,333 IU), vitamin C (250 mg), vitamin D (400 IU), vitamin E (100 IU), thiamine (5 mg), riboflavin (5.5 mg), niacinamide (25 mg), pyridoxine (7 mg), folic acid (400 µg), vitamin B12 (250 µg), biotin (25 µg), pantothenic acid (6 mg), calcium (550 mg), magnesium (250 mg), iron (6 mg), phosphorus (350 mg), iodine (75 µg), zinc (20 mg), copper (3 mg), selenium (100 µg), manganese (4 mg), chromium (250 µg), molybdenum (66 µg), potassium (100 mg), and a proprietary blend (doses not specified) of DL-phenylalanine, L-glutamine, citrus flavonoids, grape seeds, choline, inositol, Ginkgo biloba extract, L-methionine, germanium, boron, vanadium, and nickel. At baseline and periodically thereafter, patients were assessed with the Hamilton Rating Sclae for Depression (HAM-D), the Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS). The severity of depression decreased on average by 71% and the severity of mania decreased by 60% during the study.¹⁴ A double-blind study is needed to confirm these promising results.

(Gaby AR. Nutritional Medicine. Concord, NH: Fritz Perlberg Publishing, 2011:1028–1034.)

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,^15,16 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.^17,18 Two trials using 6 grams of L-tryptophan daily for acute mania in patients with bipolar disorder found little or no improvement,^19,20 but another double-blind, controlled study using 9.6 grams daily reported better results.²¹

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.²² 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.²³

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.^25,26 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.²⁷ Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.^28,29,30 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.^31,29 Not all studies have confirmed these findings, however.³⁰ 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.³⁴

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.³³ However, lithium reduces normal brain levels of inositol, and this may be one of the ways lithium helps people with bipolar disorder.^34,35,36 Although inositol is known to have significant antidepressant properties when administered in large amounts of 12 grams per day,^37,38 case reports involving bipolar patients have reported either no benefit,³⁹ some benefit,⁴⁰ or worsening of symptoms from inositol supplementation.⁴¹ 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.

SAMe (S-adenosylmethionine) is another amino acid that has an impact on serotonin levels, and it has demonstrated significant antidepressant effects in clinical trials.^43,44,45 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.^45,47 This is a known side effect of other antidepressant medications.⁴⁸ The mania induced by SAMe resolved when the supplement was discontinued, and in one case resolved spontaneously while the patient continued taking SAMe.⁴³ Therefore, people with bipolar disorder should supplement with SAMe only under the supervision of a qualified healthcare practitioner.

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.^48,49 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.⁵⁰ Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.^51,52,53 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.^54,52 Not all studies have confirmed these findings, however.⁵³ 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.⁵⁷

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.^58,59 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.

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.