Vitamins that may be helpful
Iron deficiency is known to affect mood and can exacerbate depression, but it can only be diagnosed and treated by a doctor. While iron deficiency is easy to fix with iron supplements, people who have not been diagnosed with iron deficiency should not supplement iron.
Deficiency of vitamin B12 can create disturbances in mood that respond to B12 supplementation.20 Significant vitamin B12 deficiency is associated with a doubled risk of severe depression, according to a study of physically disabled older women.21 Depression caused by vitamin B12 deficiency can occur even if there is no B12 deficiency-related anemia.22
Mood has been reported to sometimes improve with high amounts of vitamin B12 (given by injection), even in the absence of a B12 deficiency.23 Supplying the body with high amounts of vitamin B12 can only be done by injection. However, in the case of overcoming a diagnosed B12 deficiency, one can follow an initial injection with oral maintenance supplementation (1 mg per day), even when the cause of the deficiency is a malabsorption problem such as pernicious anemia.
A deficiency of the B vitamin folic acid can also disturb mood. A large percentage of depressed people have low folic acid levels.24 Folic acid supplements appear to improve the effects of lithium in treating manic-depressives.25 Depressed alcoholics report feeling better with large amounts of a modified form of folic acid.26 Anyone suffering from chronic depression should be evaluated for possible folic acid deficiency by a doctor. Those with abnormally low levels of folic acid are sometimes given short-term, high amounts of folic acid (10 mg per day).
Preliminary evidence indicates that people with depression may have lower levels of inositol.27 Supplementation with large amounts of inositol can increase the body’s stores by as much as 70%.28 In a double-blind trial, depressed people who received 12 grams of inositol per day for four weeks had a significant improvement in symptoms compared to those who took placebo.29 In a double-blind follow-up to this trial, the antidepressant effects of inositol were replicated. Half of those who responded to inositol supplementation relapsed rapidly when inositol was discontinued.30
Oral contraceptives can deplete the body of vitamin B6, a nutrient needed for maintenance of normal mental functioning. Double-blind research shows that women who are depressed and who have become depleted of vitamin B6 while taking oral contraceptives typically respond to vitamin B6 supplementation.31 In one trial, 20 mg of vitamin B6 were taken twice per day. Some evidence suggests that people who are depressed—even when not taking the oral contraceptive—are still more likely to be B6 deficient than people who are not depressed.32
Several clinical trials also indicate that vitamin B6 supplementation helps alleviate depression associated with premenstrual syndrome (PMS),33 although the research remains inconsistent.34 Many doctors suggest that women who have depression associated with PMS take 100–300 mg of vitamin B6 per day—a level of intake that requires supervision by a doctor.
Less than optimal intake of selenium may have adverse effects on psychological function, even in the absence of signs of frank selenium deficiency. In a preliminary trial of healthy young men, consumption of a high-selenium diet (226.5 mcg selenium per day) was associated with improved mood (i.e., decreased confusion, depression, anxiety, and uncertainty), compared to consumption of a low-selenium diet (62.6 mcg selenium per day.)35 In a double-blind trial, people who had a low selenium intake experienced greater improvement in depression symptoms after selenium supplementation (100 mcg per day) than did people with adequate selenium intake, suggesting that low-level selenium deficiency may contribute to depression.36
Vitamin D supplementation may be associated with elevations in mood. In a double-blind trial, healthy people were given 400–800 IU per day of vitamin D3, or no vitamin D3, for five days during late winter. Results showed that vitamin D3 significantly enhanced positive mood and there was some evidence of a reduction in negative mood compared to a placebo.37 In another double-blind trial, people without depression took 600 IU of vitamin D along with 1,000 mg of calcium, or a placebo, twice daily for four weeks.38 Compared to the placebo, combined vitamin D and calcium supplementation produced significant elevations in mood that persisted at least one week after supplementation was discontinued.
Omega-3 fatty acids found in fish oil, particularly DHA, are needed for normal nervous system function. Depressed people have been reported to have lower omega-3 fatty acid levels (e.g., DHA) than people who are not depressed.39 40 41 42 Low levels of the other omega-3 fatty acid from fish, EPA, have correlated with increased severity of depression.43 In a double-blind trial, people with manic depression were given a very high intake of supplemental omega-3 fatty acids (enough fish oil to contain 9.6 grams of omega-3 fatty acids per day) for four months.44 Ten of 16 people in the placebo group eventually were forced to discontinue the trial due to worsening depression compared with only 3 of 14 taking omega-3 fatty acids. Some scores of depression levels fell as much as 48% in the omega-3 fatty acids group.
EPA alone has also been reported to be beneficial. There is one case report of a man with a long history of severe depression who showed clear improvement within one month of starting a purified EPA supplement (4 grams per day of the ethyl ester of eicosapentaenoic acid [E-EPA]).45 In a double-blind study, supplementation with E-EPA for 12 weeks was significantly more effective than a placebo at relieving symptoms of depression.46 E-EPA was beneficial, even though the participants in the study had failed to respond adequately to conventional antidepressant drugs. The conventional medications were continued during treatment with E-EPA or placebo. An effective level of intake was 1 gram per day, whereas larger amounts of E-EPA resulted in little or no benefit. The authors of the study suggested that taking too much E-EPA might cause an imbalance with other essential fatty acids, which could reduce the effectiveness of the treatment.
The amino acid L-tyrosine can be converted into norepinephrine, a neurotransmitter that affects mood. Women taking oral contraceptives have lower levels of tyrosine, and some researchers think this might be related to depression caused by birth control pills.47 L-tyrosine metabolism may also be abnormal in other depressed people48 and preliminary research suggests supplementation might help.49 50 Several doctors recommend a 12-week trial of L-tyrosine supplementation for people who are depressed. Published research has used a very high amount—100 mg per 2.2 pounds of body weight (or about 7 grams per day for an average adult). It is not known whether such high amounts are necessary to produce an antidepressant effect.
L-phenylalanine is another amino acid that converts to mood-affecting substances (including phenylethylamine and norepinephrine). Preliminary research reported that L-phenylalanine improved mood in most of the depressed people studied.51 DLPA is a mixture of the essential amino acid L-phenylalanine and its synthetic mirror image, D-phenylalanine. DLPA (or the D- or L- form alone) reduced depression in 31 of 40 people in a preliminary trial.52 Some doctors suggest a one-month trial with 3–4 grams per day of phenylalanine for people with depression, although some researchers have found that even very low amounts—75–200 mg per day—were helpful in preliminary trials.53 In one double-blind trial, depressed people given 150–200 mg of DLPA per day experienced results comparable to that produced by an antidepressant drug.54
Acetyl-L-carnitine may be effective for depression experienced by the elderly. A preliminary trial found that acetyl-L-carnitine supplementation was effective at relieving depression in a group of elderly people, particularly those showing more serious clinical symptoms.55 These results were confirmed in another similar clinical trial.56 In that trial, participants received either 500 mg three times a day of acetyl-L-carnitine or a matching placebo. Those receiving acetyl-L-carnitine experienced significantly reduced symptoms of depression compared to those receiving placebo. At least two other clinical studies of acetyl-L-carnitine for depression in the elderly have reported similar results.57 58 The amount typically used is 500 mg three times daily, although one trial used twice that amount.
Some studies have reported lower DHEA levels in groups of depressed patients.59 However, this finding has not been consistent, and in one trial, severely depressed people were reported to show increases in blood levels of DHEA.60
Despite confusion regarding which depressed people might be DHEA-deficient, most double-blind trials lasting at least six weeks have reported some success in treating people with depression. After six months using 50 mg DHEA per day, “a remarkable increase in perceived physical and psychological well-being” was reported in both men and women in one double-blind trial.61 After only six weeks, taking DHEA in levels up to 90 mg per day led to at least a 50% reduction in depression in five of 11 patients in another double-blind trial.62
Other researchers have reported dramatic reductions in depression at extremely high amounts of DHEA (90–450 mg per day) given for six weeks to adults who first became depressed after age 40 (in men) or at the time of menopause (in women) in a double-blind trial.63 Other double-blind research has shown that limiting supplementation to only two weeks is inadequate in treating people with depression.64 Despite the somewhat dramatic results reported in clinical trials lasting at least six weeks, some experts claim that in clinical practice, DHEA appears to be effective for only a minority of depressed people.65 Moreover, due to fears of potential side effects, most healthcare professionals remain concerned about the use of DHEA. Depressed people considering taking DHEA should consult a doctor well versed in the use of DHEA.
Melatonin might help some people suffering from depression. Preliminary double-blind research suggests that supplementation with small amounts of melatonin (0.125 mg taken twice per day) may reduce winter depression.66 People with major depressive disorders sometimes have sleep disturbances. A timed-release preparation of melatonin (5–10 mg per day for four weeks) was shown to be effective at improving the quality of sleep in people with major depression who were taking fluoxetine (Prozac), but melatonin did not enhance its antidepressant effect.67 There is a possibility that melatonin could exacerbate depression, so it should only be used for this purpose under a doctor’s supervision.
SAMe (S-adenosyl methionine) is a substance synthesized in the body that has recently been made available as a supplement. SAMe appears to raise levels of dopamine, an important neurotransmitter in mood regulation. Higher SAMe levels in the brain are associated with successful drug treatment of depression, and oral SAMe has been demonstrated to be an effective treatment for depression in most,68 69 70 but not all,71 clinical trials. Most trials used 1,600 mg of SAMe per day. While it does not seem to be as powerful as full applications of antidepressant medications72 or St. John’s wort, SAMe’s effects are felt more rapidly, often within one week.73
Disruptions in emotional well-being, including depression, have been linked to serotonin imbalances in the brain.74 Supplementation with 5-HTP (5-hydroxytryptophan) may increase serotonin synthesis. Researchers are studying the possibility that 5-HTP might help people with depression. Some trials using 5-HTP with people suffering from depression have shown sign of efficacy.75 76 77 78 79 However, much of the research was either uncontrolled or used 5-HTP in combination with antidepressant drugs. Depressed people interested in considering this hormone precursor should consult a doctor.
There have been five case reports of chromium supplementation (200–400 mcg per day) significantly improving mood in people with a type of depression called dysthymic disorder who were also taking the antidepressant drug sertraline (Zoloft®).80 These case reports, while clearly limited and preliminary in scope, warrant further research to better understand the benefits, if any, of chromium supplementation in people with depression.
Phosphatidylserine (PS), a natural substance derived from the amino acid serine, affects the levels of neurotransmitters in the brain related to mood. In a preliminary trial, elderly women suffering from depression who were given 300 mg of PS per day for 30 days experienced, on average, a 70% reduction in the severity of their depression.81 Most research has been conducted with PS derived from bovine (cow) brain tissue. Due to concerns about the possibility of humans contracting infectious diseases (such as Creutzfeld-Jakob or “mad cow” disease), bovine PS is not available in the United States. The soy- and bovine-derived PS, are not structurally identical, and there is evidence that soy-derived PS may not have the same beneficial effects as bovine PS.82
An isolated preliminary trial suggests the supplement NADH may help people with depression.83 Controlled trials are needed, however, before any conclusions can be drawn.
A deficiency of other B vitamins not discussed above (including vitamin B1, vitamin B2, vitamin B3, pantothenic acid and biotin) can also lead to depression. However, the level of deficiency of these nutrients needed to induce depression is rarely found in Western societies.
Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.
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