Vitamins & other nutritional supplements

There are many people who believe that nutritional supplements can help with a variety of health problems. There is a field called "orthomolecular psychiatry", in which the practioners believe that vitamin supplements and other nutritional adjuncts can treat mental illnesses. I consider many of these beliefs to be spurious, and to be lacking a significant evidence base. I think many of those who benefit from these treatments are experiencing a combination of a placebo effect, and are perhaps benefiting from the psychotherapeutic care involved as well. Perhaps some of these individuals are also benefiting from not having the side-effects of other conventional therapies that were not working for them.

Here is a look at the evidence regarding vitamin supplementation; I restrict any references to journals that I consider to have a high professional standard:

1) Folic acid. There are a few studies which suggest that folic acid supplements may help augment the effectiveness of antidepressants. Here are a few references:
http://www.ncbi.nlm.nih.gov/pubmed/10967371
(in this study, adding 0.5 mg of folic acid daily to the antidepressant fluoxetine, improved depression severity, in women only)

http://www.ncbi.nlm.nih.gov/pubmed/15323594
and
http://www.ncbi.nlm.nih.gov/pubmed/15323595

(In these studies, low folic acid levels were strongly associated with resistance to fluoxetine treatment and more frequent depressive relapse. However, I am curious to know if this is merely an association--that is, whether the low-folic acid level group had other factors such as generalized poor nutrition or self-care, etc. that caused them to be more treatment-resistant.)


2) Thiamine (vitamin B1)
Thiamine can treat and prevent an extremely severe neurological syndrome called Wernicke-Korsakov encephalopathy; this syndrome occurs in nutritionally-deficient alcoholics, and causes devastating, permanent, sometimes total inability to form short-term memories. But there is not a lot of evidence about using thiamine to help other psychiatric disorders. Mind you, it hasn't been studied much. There are a few studies in the elderly, which suggest that thiamine supplementation helps with energy and well-being:
http://www.ncbi.nlm.nih.gov/pubmed/1986037

3) Other B vitamins:

Here's a study showing a relationship between folic acid levels--but not any other B vitamins or omega-3 fatty acid levels--and depressive symptoms in a group of Japanese adults.
http://www.ncbi.nlm.nih.gov/pubmed/18061404

Vitamin b-6: High doses may cause damage to sensory nerves, and I would not recommend taking more than 10 mg daily. Most daily multivitamins have about 3 mg. The toxicity is quite clear for doses over 100 mg/d.

http://www.ncbi.nlm.nih.gov/pubmed/16320662

http://www.ncbi.nlm.nih.gov/pubmed/14584010

Here is a reference to a new study including over 5000 women, over 7 years of follow-up, from Archives of Internal Medicine. It showed significantly reduced rates of macular degeneration in a large cohort of people taking high-dose b-vitamins (2.5 mg/d of folic acid; 50 mg/d of b-6; 1000 mcg/d of b12):
http://archinte.ama-assn.org/cgi/content/full/169/4/335

4) Vitamin D
There is accumulating evidence that higher doses of vitamin D are beneficial for a variety of health variables. Also, it is becoming apparent that many people are vitamin-D deficient, especially those who live in northern climates. Most supplements contain 400 IU, but probably a dose of at least 1000 IU daily could be recommended. Doses less than 10 000 IU have not been associated with toxicity, according to my review of the evidence, but we could conservatively say that doses up to 4000 IU daily are very likely to be safe, unless there is some medical disorder present (e.g. sarcoidosis) that causes a disturbance in calcium metabolism. Here is a very interesting and promising recent study suggesting beneficial mood effects from higher-dose vitamin D supplementation; the study is from a major, highly respected internal medicine journal:
http://www.ncbi.nlm.nih.gov/pubmed/18793245


It should be emphasized that more is not always better! Many vitamins cause toxicity if they are taken in excess. Also, some of the studies are showing that groups who took certain vitamin supplements (such as vitamin E and beta-carotene) actually fared more poorly, rather than better.
http://www.ncbi.nlm.nih.gov/pubmed/12876090

http://www.ncbi.nlm.nih.gov/pubmed/16645413

5) Omega-3 fatty acids
There is some evidence that omega-3 supplementation (containing the fatty acids EPA & DHA) can help reduce depressive symptoms, particularly in those with bipolar disorder. Omega-3 fatty acids can be found most abundantly in fish such as salmon. Plant sources include canola oil, flax, and walnuts (however, the plant sources only have one of the 3 types of omega-3 fatty acids). Here's a link to recent Cochrane Review abstract:
http://www.ncbi.nlm.nih.gov/pubmed/18425912
Here are some links to other reviews:
http://www.ncbi.nlm.nih.gov/pubmed/17685742med_RVDocSum

http://www.ncbi.nlm.nih.gov/pubmed/18370571
However the evidence appears to be fairly weak at this point, there may be some publication bias (i.e. studies showing no effect may not have been published) so more research really needs to be done. In the meantime, though, omega-3 supplementation (usually in the form of fish oil capsules) appears to be harmless, and potentially beneficial. The dose corresponding to what many of the studies used is about 3-6 grams of salmon oil daily (usually 3-6 capsules, each of which containing 1 gram).

Omega-3 supplementation may be beneficial in other ways--it may help protect against macular degeneration (vision deterioration during old age). Also there is some data showing that higher omega-3 intakes, or fish consumption, may slow the rate of cognitive decline in old age. Here's the best such study I could find showing this:

http://www.ncbi.nlm.nih.gov/pubmed/16216930

I suspect that some of the benefits from increasing omega-3 intake could be augmented by consuming a diet in which other unhealthy lipids are minimized--this would involve reducing omega-6 intake, eliminating trans fatty acids, and moderating the intake of saturated fats. I invite the interested reader to research this subject further.