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
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
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
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
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
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
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
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
S-adenosyl methionine (SAMe) 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-hydroxytryptophan (5-HTP) 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
Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.
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