Fish Oil & Bipolar Disorder
Information provided by IcelandHealth.com

Bipolar disorder is a mood disorder characterized by alternating states of depression and mania that follow each other in a repeating cycle. The symptoms of a depressed state include sadness, hopelessness, lethargy, changes in appetite and sleep, agitation, and inability to concentrate. The symptoms of a manic state include an abnormally elevated mood (an emotional "high"), reduced need for sleep, racing thoughts, easy distractibility, a high state of alertness, and excessive mental and physical activity. People with bipolar disorder may cycle through these states quickly or may have long periods of depression or mania. Often one mood state predominates and the other occurs only infrequently or briefly. The cause of bipolar disorder is unknown.

Lifestyle changes that may be helpful: 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 rigorous 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 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 individual;3 therefore, people taking lithium who intend to start a vigorous exercise program should be monitored by their doctor.

Nutritional supplements that may be helpful: Both folic acid and vitamin B12 are used in the body to manufacture serotonin and other neurotransmitters. It is well known that deficiencies of either nutrient are associated with depression.4 5 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.6 Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.7 8 9 Some studies have found that people taking lithium long term, and also have high blood levels of folic acid, respond better to lithium.10 11 Not all studies have confirmed these findings, however.12 A double-blind study was conducted combining 200 mcg folic acid per day with lithium therapy.13 Even though the volunteers in this study were doing well on lithium alone before the study, addition of folic acid further improved their condition, whereas placebo did not. Based on the available evidence, it is suggested that people taking lithium also take at least 200 mcg of folic acid per day.

There have been case reports of both mania and depression associated with vitamin B12 deficiency, and these symptoms cleared after treatment with injections of B12.14 15 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.

Restriction of dietary calcium was reported to alleviate manic episodes in one bipolar patient and calcium supplementation (approximately 800 mg per day) increased mania symptoms slightly in six manic depressive patients, according to another uncontrolled report.16 Therefore, if calcium supplementation is desired by people with bipolar disorder, it should be taken with caution.

Lithium is a mineral contained in certain drugs used in the medical treatment of bipolar disorder. Lithium may be present in some trace mineral supplements, but the amount is too small to have any effect on bipolar disorder. See the Drug-Nutrient Interactions article on lithium for important information for people taking lithium medications.

Vanadium is a trace mineral nutrient that may influence bipolar disorder. Elevated blood and hair levels of vanadium have been reported in people with mania and depression, and one effect of the bipolar medication lithium is interruption of a biochemical action of vanadium in the body.17 Vanadium is therefore one suspect in the search for a cause of bipolar disorder.

Vitamin C helps the body to reduce its load of vanadium and has been studied for its possible role in treatment of bipolar disorder.18 A double-blind trial found that both manic and depressed bipolar patients were significantly better when given a single dose of 3 grams of vitamin C compared to those given a placebo.19 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 those experiencing mania.20 Until more is known, people with bipolar illness should avoid supplements containing vanadium and consider supplementing with vitamin C.

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.21 However, lithium reduces normal brain levels of inositol, and this may be one of the ways lithium helps people with bipolar disorder.22 23 24 Although inositol is known to have significant antidepressant properties in large amounts of 12 grams per day,25 26 case reports involving bipolar patients have reported either no benefit,27 some benefit,28 or worsening of symptoms from inositol supplementation.29 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.

People diagnosed with depression may have lower blood levels of omega-3 fatty acids.30 31 A recent double-blind trial evaluated the effect of omega-3 fatty acid supplementation on people with bipolar disorder. Patients in this study were given 9.6 grams of omega-3 fatty acids from Fish oil, or a placebo, in addition to their conventional medications. Those receiving this large amount of Fish oil had significant improvements compared to those taking placebo, including a longer period between relapses.32

L-tryptophan is the amino acid used by the body to produce serotonin. Supplementation with L-tryptophan has led to improvement in depression in many studies,33 34 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 tryptophan.35 36 Two trials using 6 grams of L-tryptophan daily for acute mania in patients with bipolar disorder found little or no improvement,37 38 but another double-blind placebo-controlled study using 9.6 grams daily reported more impressive results.39

L-tryptophan is converted to 5-hydroxytryptophan (5-HTP) 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.40 In a double-blind trial, patients with bipolar disorder had greater improvement with a combination of 5-HTP, 300 mg daily, plus an antidepressant drug than with 5-HTP alone.41

S-adenosylmethionine (SAMe) is another amino acid that has an impact on serotonin levels and it has demonstrated significant antidepressant effects in clinical trials.42 43 44 In both controlled and uncontrolled studies, benefits of SAMe for the depressive symptoms of bipolar disorder have been demonstrated as well, but some bipolar patients experienced a switch from depression to mania while using SAMe at 500–1,600 mg daily.45 46 This is a known side effect of other antidepressant medications.47 The mania induced by SAMe resolves when the supplement is discontinued, and in one case resolved spontaneously while the patient continued taking SAMe.48 Therefore, supplementation with SAMe by people with bipolar disorder should be done only under the supervision of a qualified healthcare practitioner.

Acetylcholine levels in the brain may affect mood disorders, and supplemental choline can increase acetylcholine levels. In a preliminary trial, six people with bipolar disorder were given one to two grams of choline twice per day (2-4 grams per day). Five of the six had a significant reduction in manic symptoms, and four of the six had a reduction in all mood symptoms.49 No properly controlled trials have yet investigated the effects of choline in treating people with bipolar disorder.

Are there any side effects or interactions? Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful: Although St. John’s wort (Hypericum perforatum) is well known for its antidepressant effects,50 its value in the treatment of bipolar disorder has not been studied. As with SAMe and other antidepressant substances, St. John’s wort has been reported to induce mania or a milder state known as hypomania in some depressed patients who did not have bipolar disorder.51 52 53 Whether St. John’s wort could bring on an episode of mania in a person with bipolar disorder is unknown. Nonetheless, the use of St. John’s wort by bipolar patients also requires careful monitoring by a qualified healthcare professional.

Are there any side effects or interactions? Refer to the individual herb for information about any side effects or interactions.

Checklist for Bipolar Disorder

Ranking

Nutritional Supplements

Herbs

Secondary

Fish oil

L-tryptophan

 

Other

5-HTP

Choline

Folic acid

Inositol

SAMe

Vitamin C

St. John’s wort

Information about the effects of a particular supplement or herb on a particular condition has been qualified in terms of the methodology or source of supporting data (for example: clinical, double blind, meta-analysis, or traditional use). For the convenience of the reader, the information in the table listing the supplements for particular conditions is also categorized. The criteria for the categorizations are: "Primary" indicates there are reliable and relatively consistent scientific data showing a health benefit. "Secondary" indicates there are conflicting, insufficient, or only preliminary studies suggesting a health benefit or that the health benefit is minimal. "Other" indicates that an herb is primarily supported by traditional use or that the herb or supplement has little scientific support and/or minimal proven health benefit.
[ Close Window ]

References:

1. Ransford CP. A role for amines in the antidepressant effect of exercise: a review. Med Sci Sports Exerc 1982;14:1–10 [review].

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. Botiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996;54:382–90 [review].

5. Fine EJ, Soria ED. Myths about vitamin B12 deficiency. Southern Med J 1991;84:1475–81.

6. Hasanah CI, Khan UA, Musalmah M, Razali SM. Reduced red-cell folate in mania. J Affect Disord 1997;46:95–9.

7. 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.

8. 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.

9. 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.

10. Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982;141:87–9.

11. 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.

12. 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.

13. Coppen A, Chaudhry S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disord 1986;10:9–13.

14. Goggans FC. A case of mania secondary to vitamin B12 deficiency. Am J Psychiatry 1984;141:300–1.

15. Verbanck PM, LeBon O. Changing psychiatric symptoms in a patient with vitamin B12 deficiency. J Clin Psychiatry 1991;52:182–3 [letter].

16. Carman JS, Wyatt RJ. Calcium: bivalent cation in the bivalent psychoses. Biol Psychiatry 1979;14:295–336 [review].

17. Naylor GJ. Vanadium and manic depressive psychosis. Nutr Health 1984;3:79–85 [review].

18. Naylor GJ. Vanadium and manic depressive psychosis. Nutr Health 1984;3:79–85 [review].

19. Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med 1981;11:249–56.

20. 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.

21. 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.

22. Fauroux CM, Freeman S. Inhibitors of inositol monophosphatase. J Enzyme Inhib 1999;14:97–108 [review].

23. 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].

24. 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].

25. Levine J, Barak Y, Gonzalves M, et al. Double-blind, controlled trial of inositol treatment of depression. Am J Psychiatry 1995;152:792–4.

26. 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.

27. 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.

28. Grisaru N, Belmaker RH. Lithium dosage and inositol levels. Br J Psychiatry 1994;164:133–4 [letter].

29. Levine J, Witztum E, Greenberg BD, Barak Y. Inositol-induced mania? Am J Psychiatry 1996;153:839 [letter].

30. 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.

31. 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.

32. 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.

33. Young SN. Behavioral effects of dietary neurotransmitter precursors: basic and clinical aspects. Neurosci Biobehav Rev 1996;20:313–23 [review].

34. 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].

35. 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.

36. Hedaya RJ. Pharmacokinetic factors in the clinical use of tryptophan. J Clin Psychopharmacol 1984;4:347–8.

37. 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.

38. Chambers CA, Naylor GJ. A controlled trial of L-tryptophan in mania. Br J Psychiatry 1978;132:555–9.

39. Murphy DL, Maker M, Goodwin FK, et al. L-tryptophan in affective disorders: indoleamine changes and differential clinical effects. Psychopharmacologia 1974;34:11–20.

40. 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.

41. Mendlewicz J, Youdim MB. Antidepressant potentiation of 5-hydroxytryptophan by L-deprenil in affective illness. J Affect Disord 1980;2:137–46.

42. Rosenbaum JF, Fava M, Faulk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432–6.

43. Friedel HA, Goa KL, Benfield P. S-Adenosyl-l-methionine: A review of its pharmacological properties and therapeutic potential in liver disfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389–417 [review].

44. Carney MWP, Chary TKN, Bottiglieri T. The switch mechanism in affective illness and oral S-adenosylmethionine (SAM). Br J Psychiatry 1987;150:724–5.

45. Carney MWP, Chary TKN, Bottiglieri T. The switch mechanism in affective illness and oral S-adenosylmethionine (SAM). Br J Psychiatry 1987;150:724–5.

46. Carney MWP, Chary TKN, Bottiglieri T, Reynolds EH. The switch mechanism and bipolar/unipolar dichotomy. Br J Psychiatry 1989;154:48–51.

47. Wehr TA, Goodwin FK. Can antidepressants cause mania and worsen the course of affective illness? Am J Psychiatry 1987;144:1403–11.

48. Rosenbaum JF, Fava M, Faulk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432–6.

49. Stoll AL, Sachs GS, Cohen MB, et al. Biol Psychiatry 1996;40:382–8.

50. Kim HL, Streltzer J, Goebert D. St. John’s wort for depression: a meta-analysis of well-defined clinical trials. J Nerv Ment Dis 1999;187:532–8 [review].

51. Schneck C. St. John’s wort and hypomania. J Clin Psychiatry 1998;59:689 [letter].

52. O’Breasail AM, Argouarch S. Hypomania and St John’s wort. Can J Psychiatry 1998;43:746–7 [letter].

53. Neirenberg AA, Burt T, Matthews J, Weiss AP. Mania associated with St. John’s wort. Biol Psychiatry 1999;46:1707–8.

[ Close Window ]