Depression, characterized by unhappy feelings of hopelessness, can be a response to stressful events, hormonal imbalances, biochemical abnormalities, or other causes. Mild depression that passes quickly may not require any diagnosis or treatment. However, when depression becomes recurrent, constant, or severe, it should be diagnosed by a licensed counselor, psychologist, social worker, or psychiatrist. Diagnosis may be crucial for determining appropriate treatment. For example, depression caused by low thyroid function can be successfully treated with prescription thyroid medication. Suicidal depression often requires prescription antidepressants. Persistent mild-to-moderate depression triggered by stressful events is often best treated with counseling and not necessarily with medications.

When depression is not a function of external events, it is called endogenous. Endogenous depression can be due to biochemical abnormalities. Lifestyle changes and herbs may be used with people whose depression results from a variety of causes, but dietary and nutrient interventions are usually best geared to endogenous depression.

Restricting sugar and caffeine in people with depression has been reported to elevate mood in preliminary research.⁴ How much of this effect resulted from sugar and how much from caffeine remains unknown. Researchers have reported that psychiatric patients who are heavy coffee drinkers are more likely to be depressed than other such patients.⁵ However, it remains unclear whether caffeine-caused depression or whether depressed people were more likely to want the "lift" associated with drinking a cup of coffee. In fact, "improvement in mood" is considered an effect of long-term coffee consumption by some researchers, a concept supported by the fact that people who drink coffee have been reported to have a 58–66% decreased risk of committing suicide compared with non-coffee drinkers.⁶ Nonetheless, a symptom of caffeine addiction can be depression.⁷ Thus, consumption of caffeine (mostly from coffee) has paradoxically been linked with both improvement in mood and depression by different researchers. People with depression may want to avoid caffeine as well as sugar for one week to see how it affects their mood.

Nutritional supplements and other natural therapies that may be helpful: 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.¹⁰ 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.¹¹

Several studies also indicate that vitamin B6 supplementation helps alleviate depression associated with premenstrual syndrome (PMS),¹² although the research remains inconsistent.¹³ 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.

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.

Sub-optimal intake of selenium may have adverse effects on psychological function, even in the absence of signs of frank selenium deficiency. In a preliminary study 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.)¹⁴

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®).¹⁵ These case reports, while clearly limited and preliminary in scope, warrant a controlled trial to better understand the benefits, if any, of chromium supplementation in people with depression.

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 5 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 placebo.¹⁶ In another double-blind trial, people without depression took 600 IU of vitamin D along with 1000 mg of calcium, or placebo, twice daily for four weeks.¹⁷ Compared to placebo, combined vitamin D and calcium supplementation produced significant elevations in mood that persisted at least one week after supplementation was discontinued.

Deficiency of vitamin B12 can create disturbances in mood that respond to B12 supplementation.¹⁸ Depression caused by vitamin B12 deficiency can occur in the absence of anemia.¹⁹

Mood has been reported to sometimes improve with high amounts of vitamin B12 (given by injection), even in the absence of a B12 deficiency.²⁰ 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 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.²¹ Folic acid supplements appear to improve the effects of lithium in treating manic-depressives.²² Depressed alcoholics report feeling better with large amounts of a modified form of folic acid.²³ 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).

A deficiency of other B vitamins not discussed above (including B1, B2, 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.

The amino acid L-tyrosine can convert 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 the Pill.²⁷ L-tyrosine metabolism may also be abnormal in other depressed people²⁸ and preliminary research suggests supplementation might help.^{29 30} Several doctors recommend a twelve-week trial of 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 remains unclear whether such high levels are necessary for optimal effect.

L-Phenylalanine is another amino acid that converts to mood-affecting substances (including phenylethylamine). Preliminary research reported that L-phenylalanine improved mood in most depressed people studied.³¹ 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 an uncontrolled study.³² 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 studies.³³ In one double-blind trial, depressed people given 150–200 mg of DLPA experienced results comparable to that of an antidepressant drug.³⁴

Phosphatidylserine (PS), a natural substance derived from the amino acid serine, affects neurotransmitter levels in the brain that affect mood. In a controlled trial, older women given 300 mg of PS had significantly less depression compared with placebo.³⁵ After forty-five days, the level of depression in the PS group was more than 60% lower than the level achieved with placebo.

Acetyl-L-carnitine may be effective for depression experienced by the elderly. An un-blinded study of 24 depressed people over 70 years of age found that acetyl-L-carnitine supplementation was highly effective in relieving depression after one month, particularly in those participants showing more serious clinical symptoms.³⁶ These results were confirmed in another clinical trial of 28 people aged 70–80 years. One group was treated with 500 mg three times a day of acetyl-L-carnitine in tablet form, while the other received placebo. Those receiving acetyl-L-carnitine experienced significantly reduced symptoms of depression compared to placebo.³⁷

Some studies have reported lower DHEA levels in groups of depressed patients.³⁸ However, this finding has not been consistent, and in one trial, severely depressed people were reported to show increases in blood levels of DHEA.³⁹

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.⁴⁰ 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 eleven patients in another double-blind trial.⁴¹

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 study.⁴² Other double-blind research has shown that limiting supplementation to only two weeks is inadequate in treating people with depression.⁴³ Despite the somewhat dramatic results reported in studies lasting at least six weeks, some experts claim that in clinical practice, DHEA appears to be effective for only a minority of depressed people.⁴⁴ Moreover, due to fears of potential side effects, most health care 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 low levels of melatonin (0.125 mg taken twice per day) may reduce winter depression.⁴⁵ People with major depressive disorders sometimes have sleep disturbances. A time-release preparation of melatonin (5–10 mg per day for 4 weeks) was shown to be effective at improving the quality of sleep of people with major depression who were taking fluoxetine (Prozac®), but melatonin did not enhance its antidepressant effect.⁴⁶ Further double-blind trials are required to confirm melatonin’s efficacy for depression.

Preliminary evidence indicates that individuals with depression may have lower levels of inositol.⁴⁷ Supplementation with large amounts of inositol can increase the body’s stores by as much as 70%.⁴⁸ 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.⁴⁹ In a double-blind follow-up to this study, the antidepressant effects of inositol were replicated, while half of those who responded to inositol supplementation relapsed rapidly when inositol was discontinued.⁵⁰

An isolated preliminary trial suggests the supplement NADH may help people with depression.⁵¹ Controlled trials are needed before any conclusions can be drawn.

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, and higher SAMe levels in the brain are associated with successful drug treatment of depression. Oral SAMe has been demonstrated to be an effective treatment for depression in most,^{52 53 54} but not all,⁵⁵ controlled studies. Most studies used 1,600 mg of SAMe per day. While it does not seem to be as powerful as full doses of antidepressant medications⁵⁶ or St. John’s wort, SAMe’s effects are felt more rapidly, often within one week.⁵⁷

Disruptions in emotional well-being, including depression, have been linked to serotonin imbalances in the brain.⁵⁸ Supplementation with 5-HTP may increase serotonin synthesis. Researchers are studying the possibility that 5-HTP might help people with depression. Some trials^{59 60} using 5-HTP with people suffering from depression have shown sign of efficacy.^{61 62 63} Depressed people interested in considering this hormone precursor should consult a doctor.

Herbs that may be helpful: St. John’s wort extracts are among the leading medicines used in Germany by medical doctors for the treatment of mild to moderate depression. Using St. John’s wort extract can significantly relieve the symptoms of depression. People taking St. John’s wort show an improvement in mood and ability to carry out their daily routine. Symptoms such as sadness, hopelessness, worthlessness, exhaustion, and poor sleep also decrease.^{64 65}

The St. John’s wort extract LI 160 has been compared to the prescription antidepressants imipramine,⁶⁶ amitriptyline,⁶⁷ and maprotiline.⁶⁸ The improvement in symptoms of mild to moderate depression was similar, with notably fewer side effects, in people taking St. John’s wort. It is important to note, however, the above studies compared 900 mg per day of St. John’s wort extract with only 75 mg per day of the prescription antidepressants. Healthcare professionals consider this a very low amount. In a double-blind study using usual amounts of fluoxetine (Prozac®) - 20 mg per day - the St. John’s wort extract LoHyp-57 (5–7:1 dry extract) in the amount of 400 mg twice daily was equally effective at relieving depression in people aged 60–80 years.⁶⁹

A recent study compared a higher amount of the St. John’s wort extract LI 160 (1,800 mg per day) with a higher amount of imipramine (150 mg per day) in more severely depressed persons.⁷⁰ Again, the improvement was virtually the same for both groups with far fewer side effects for the St. John’s wort group. While this may point to St. John’s wort as a possible treatment for more severe cases of depression, this treatment should only be pursued under the guidance of a healthcare professional.

In the German Commission E monograph, the amount of St. John’s wort taken is typically based on hypericin concentration in the extract, which should be approximately 1 mg per day.⁷¹ For example, an extract standardized to contain 0.2% hypericin would require a daily intake of 500 mg (usually given in two divided dosages). Many European studies use higher intakes of 900 mg daily and this has become the accepted daily amount in modern herbal medicine. Recent research suggests, however, that hypericin is not the antidepressant compound in St. John’s wort and attention is starting to shift to the compound known as hyperforin.⁷² As an antidepressant, St. John’s wort should be monitored for four to six weeks to check effectiveness. If possible, St. John’s wort should be taken near mealtime.

Ginkgo biloba is supportive in the alleviation of depression for depressed elderly people not responding to antidepressant drugs.⁷³ It is unknown if ginkgo could alleviate depression in other age groups. A small, open study has shown that ginkgo can reduce sexual problems caused by antidepressants like fluoxetine (Prozac), bupropion (Wellbutrin®), venlafaxine (Effexor®), and nefazodone (Serzone®) in men and women.⁷⁴ Double-blind studies are now needed to determine if ginkgo is truly effective for this purpose.

Damiana has a tradition of being used to stimulate people with depression. Yohimbine (the active component of the herb yohimbe) inhibits monoamine oxidase (MAO) and therefore may be beneficial in depressive disorders. However, clinical research has not been conducted for its use in treating depression.

Pumpkin seeds contain L-tryptophan, and for this reason have been suggested to help remedy depression.⁷⁵ However, research is needed before pumpkin seeds can be considered for this purpose. It is unlikely the level of L-tryptophan in pumpkin seeds would be sufficient to relieve depression.

Vervain is a traditional herb for depression; however, there is no research to validate this use.

Other integrative therapies that may be helpful: Acupuncture may improve depression by affecting the synthesis of neurotransmitters that control mood.⁷⁶ Controlled studies^{77 78 79} have found electro-acupuncture equally effective as antidepressant drug therapy without causing side effects. However, a placebo-controlled trial found that both real and fake acupuncture improved depression equally well compared to no treatment.⁸⁰ It is well known that placebo effects are common in the treatment of depression,⁸¹ so more placebo-controlled trials are needed before accepting the usefulness of acupuncture for depression.

Many people who are depressed seek counseling with a psychologist, social worker, psychiatrist or other form of counselor. An analysis of four properly conducted trials of severely depressed patients comparing the effects of one form of counseling intervention, cognitive behavior therapy, with the effects of antidepressant drugs was published in 1999. In that report, cognitive behavior therapy was at least as effective as drug therapy.⁸² While the outcome of counseling may be more variable than outcomes from drug or natural substance interventions, many healthcare professionals consider counseling an important part of recovery for depression not due to identifiable biochemical causes.

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.

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