Research into the biochemical treatment of bipolar disorder is not as prolific as it is for disorders such as depression and schizophrenia. Nevertheless, what there is gives cause for optimism.
Depressed people may have an impaired ability to metabolise certain essential fatty acids (Prostagl Leukotr Essent Fatty Acids, 1999; 60: 217-34), leading to lower blood levels of omega-3s (Lipids, 1996; 31 Suppl: S157-61; Psychiatr Res, 1999; 85: 275-91). For these individuals, the typical Western diet, which greatly favours omega-6 fatty acids, may be disastrous. Conventional medication may also worsen the problem (Eur Neuropsychopharmacol, 2003; 13: 99-103).
One double-blind trial discovered that people taking 9.6 g/day of omega-3s from fish oil in addition to their conventional medications had significantly improved bipolar symptoms compared with those taking a placebo (Arch Gen Psychiatry, 1999; 56: 407-12).
Both folic acid and vitamin B12 are used in the body to make serotonin and other neurotransmitters. A deficiency of either nutrient is associated with depression (Nutr Rev, 1996; 54: 382-90; South Med J, 1991; 84: 1475-81). Those diagnosed with mania also tend to have folate deficiencies (J Affect Disord, 1997; 46: 95-9), though some studies dispute this (Acta Psychiatr Scand, 1991; 83: 199- 201; J Affect Disord, 1992; 24: 265-70). There is evidence that increasing levels of folate can improve the response rate to lithium (J Affect Disord, 1986; 10: 9-13) but, again, there are also other data that dispute this claim (Int Clin Psychopharmacol, 1988; 3: 49-52).
On their own, both mania and depression are associated with vitamin-B12 deficiency, and injections of B12 can help clear these symptoms (Am J Psychiatry, 1984; 141: 300-1; J Clin Psychiatry, 1991; 52: 182-3). Although B12 deficiency is poorly researched in bipolar disorder, case reports suggest it may be a factor (West Ind Med J, 2000; 49: 347-8).
A double-blind trial found that, compared with a placebo, both manic and depressed bipolar patients significantly improved after a one-time-only administration of 3 g of vitamin C (Psychol Med, 1981; 11: 249-56). Vitamin C helps the body reduce its load of vanadium (Nutr Health, 1984; 3: 79-85), an excess of which may cause bipolar disorder, and 4 g/day combined with the chelator EDTA (which removes elements such as vanadium from the body) helped depressed bipolar patients, but not those with mania (Psychol Med, 1984; 14: 533-9).
The amino-acid L-tryptophan can improve depression (Fortschr Med, 1998; 116: 40-2), and high doses (9.6 g/day) may help bipolar patients with acute mania (Psychopharmacologia, 1974; 34: 11-20). Those taking lithium or an antidepressant markedly improved when L-tryptophan at 12 g/day was added to their treatment (Am J Psychiatry, 1979; 136: 719-20; J Clin Psychopharmacol, 1984; 4: 347-8).
Supplemental 5-HTP (a serotonin precursor) at 200 mg/day had antidepressant effects in bipolar patients, although it was not as effective as lithium (Acta Psychiatr Scand Suppl, 1981; 290: 191-201). 5-HTP may also enhance the effectiveness of antidepressants (J Affect Disord, 1980; 2: 137-46).
Yet another amino acid, S-adenosylmethionine (SAMe), has been proved in clinical trials to have significant antidepressant effects in bipolar patients (Acta Psychiatr Scand, 1990; 81: 432-6; Drugs, 1989; 38: 389-417).
However, in common with conventional antidepressants, some patients have swung from depression to mania with SAMe at 500-1600 mg/day (Br J Psychiatry, 1989; 154: 48-51). This mania can resolve spontaneously with continued supplementation (Acta Psychiatr Scand, 1990; 81: 432-6), but those with bipolar disorder should probably take SAMe only under the guidance of a qualified practitioner.