Supplements for Depression

We’ve updated our info sheet on supplements and depression–see below. See the NYBC entries for further information on DHEA; 5-HTP; SAMe; St. John’s Wort;
Fish oil (Max DHA); Tryptophan.

In recent years there’s been a lot of well-designed scientific research about the effectiveness of dietary supplements for depression. The supplements studied have ranged from the herb St. John’s Wort, which has a long tradition of use, to molecules like SAMe, L-Tryptophan, and 5-HTP, which play a role in the body’s production of neurotransmitters (such as serotonin) connected with mood and cognitive function. Other developments in depression research involve the steroid DHEA and fish oil.

DHEA (Dehydroepiandrosterone). In a study sponsored by the National Institute of Mental Health, DHEA was found to be an effective therapy for mild to moderate or severe midlife depression, on a par with some prescription drug treatments. Moreover, the NIMH research showed that taking DHEA promoted both a significant lifting of depressive symptoms and an improvement in sexual functioning. (On the other hand, inhibition of sexual function remains one of the chief troublesome side effects of prescription anti-depressants). Note that dosing recommendations vary for men versus women, and DHEA is not recommended for those diagnosed with prostate problems or cancer.

SAMe (S-adenosyl-l-methionine). First studied by Italian researchers in the 1950s, SAMe is produced naturally in the body from the amino acid methionine. Supplementing with SAMe increases concentrations of the neurotransmitters serotonin and L-dopamine, which are related to mood. Several studies show SAMe having an anti-depressant effect comparable to that of some prescription drugs. A dose of 400-800mg/day has been studied for mild to moderate depression, and 800-1600mg/day for the moderate to severe condition. As of 2007, SAMe was being compared with the prescription drug Lexapro® in a 5-year NIH-funded study. SAMe generally has fewer side effects than prescription anti-depressants. However, it should be avoided in people with bipolar disorder, and should be used cautiously with other anti-depressants, because the combination may push serotonin levels too high. Taking a B-complex vitamin while using SAMe can counter build up of homocysteine, which is associated with heart disease. (It’s best to take them separately.) SAMe also supports joint health and liver function, so may have positive effects for overall health if taken over the long term.

St. John’s Wort is a widely used herb with clinically demonstrated (multiple, well-controlled studies, mostly in Europe) anti-depressant effects for mild to moderate depression – generally without the side effects of prescription antidepressants. High doses of the herb may cause a sensitivity to light (phototoxicity), so avoid direct sunlight or sunbathing while using. Do not take St. John’s Wort with 5-HTP, serotonin re-uptake inhibitors (like Prozac), or with protease inhibitors, as it my affect beneficial liver enzymes. St. John’s Wort may also have activity against Epstein-Barr and herpes infections.

L-Tryptophan and 5-HTP (5-hydroxy L-tryptophan): These closely-related supplements are converted in the body to serotonin and to melatonin. (Specifically, L-Tryptophan converts to 5-HTP, which then converts to serotonin or melatonin.) Their use as antidepressants has been studied, and they have also been found to aid sleep and suppress appetite. (To minimize appetite suppression, try taking the supplement an hour before bedtime.) Mild gastrointestinal side effects have been reported with both. For best absorption, take with water or juice, and separately from protein-containing foods and dietary supplements. Although L-Tryptophan and 5-HTP are close relatives, people may respond somewhat differently to them. Thus, if encountering unwanted side effects or lack of effect from one, it may still be worthwhile to try the other.

The suggested dosage for 5-HTP is wide, ranging from 50 and 500 mg daily. It can be used together with other anti-depressants, in which case an effective dose could be quite low. The best approach is to start at the low end of the range and increase as needed. Like 5-HTP, L-Tryptophan has been used in combination with other anti-depressants, and has also been employed with lithium for bipolar disorder. An added benefit: 5-HTP may also decrease symptoms of fibromyalgia and migraine headaches.

Fish Oil. Epidemiological studies have suggested that populations that eat fish regularly have low rates of depression. More recently, research has found fish oil supplements (omega-3 fatty acids being the significant component) of benefit in treating depression and bipolar disorder. It’s also worth noting that fish oil can be taken with other anti-depressants as an adjunct therapy. Doses found effective in treating depression are quite high, 3 to 9 grams per day, so be aware of potential problems related to the supplement’s blood-thinning properties. Added benefit: as has been widely reported, fish oil can have a beneficial impact on cholesterol regulation and in supporting cardiovascular health.
REFERENCES: Christian R. Dolder, “Depression,” in Natural Products: A Case-Based Approach for Health Care Professionals, ed. Karen Shapiro, published by the American Pharmacists Association, Washington, DC (2006), pp. 97-114.
Shaheen E Lakhan and Karen F Vieira. “Nutritional therapies for mental disorders” in Nutrition Journal (2008), 7:2doi:10.1186/1475-2891-7-2. Accessed 10/7/2009 at
Schmidt PJ, et al. “Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression,” Archives of General Psychiatry (February 2005): Vol. 62, No. 2, pp. 154–62.
Hyla Cass, “Prescriptions for Depression,” in Supplement Your Prescription: What Your Doctor Doesn’t Know About Nutrition. Basic Health Publications (2007), pp. 113-128.


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