"Micronutrient Treatment"

There are examples of "micronutrient treatments" being marketed to help various mental health problems.

These treatments may be marketed aggressively: there may be slick internet sites, perhaps with an enthusiastic following of people who believe strongly in the product.

If the manufacturer of such a product is quoting "research studies," I encourage you to look carefully at the studies referred to. If you are seriously considering products of this type, I would suggest looking at the articles in their entirety at a library.

I encourage anyone interested in pursuing treatments of this sort to ask the following questions:

1) What type of evidence exists regarding effectiveness & safety? Is the evidence from large, double-blinded, randomized, controlled studies conducted by researchers who do not have financial connections with the manufacturer?

2) Is the research pertaining to the product published in a journal with high scientific standards? (In order to answer this question for yourself, I would invite you to leaf through numerous issues of the journal, and compare this with an independent, peer-reviewed journal such as Lancet or The New England Journal of Medicine).

2) Is the evidence mainly from enthusiastic testimonial accounts or case studies? Is this type of evidence reliable enough for you?

3) How much money is required to purchase the treatment? Does the manufacturer encourage you to involve yourself in a long-term financial commitment?

4) After acquainting yourself with common sales and marketing tactics (for a primer on this subject, see Robert Cialdini's book, The Psychology of Persuasion), do you see evidence of highly persuasive or biased sales tactics being used in the marketing of the product? Are vulnerable people being taken advantage of in the marketing of the product?

Have a look at this link, which gives a brief history and overview of charlatanism--being familiar with this history may allow you to make more informed choices about your own medical care:
http://en.wikipedia.org/wiki/Quackery

I do not mean to single out alternative remedies in this post--I encourage the same critical standards to be applied regarding all types of therapy. Mainstream pharmaceutical manufacturers and other providers of mainstream therapies may often be guilty of devious marketing behaviours. In my opinion, though, mainstream pharmaceutical manufacturers have a much harder time getting away with overt charlatanism at this point, compared to many manufacturers of alternative remedies.

Also, I wholeheartedly acknowledge that there can be alternative remedies which are helpful, and which are marketed ethically.

Here in Canada, we live in a free society, with a strong emphasis on freedom of speech. Imposing more strict legal restrictions or regulations upon health choices would limit freedom. I support maintaining a free society, but the presence of charlatanism is one of the costs of this freedom.

Inositol

Inositol is chemically similar to glucose (the type of sugar required by the brain for energy). It is a precursor in a so-called "second messenger system," which cells require to communicate with each other. In the brain, these second messenger systems are activated by various neurotransmitters including serotonin. There is some evidence that brain levels of inositol are reduced in depression and anxiety disorders. Inositol is present in a typical diet, in amounts of about 1 gram per day. Doses of supplemental inositol are typically 10-20 grams per day.

A Cochrane review from 2004 concluded that there was no clear evidence of supplemental inositol being beneficial in the treatment of depression:
http://www.ncbi.nlm.nih.gov/pubmed/15106232

Here's a 2006 reference from Bipolar Disorders showing that supplemental inositol could help treat bipolar depression in some patients already taking lithium or valproate. In 4 out of 9 patients taking 6-20 grams per day of inositol, their depression substantially improved over 6 weeks, with continuing improvement over an additional 8 weeks. However, the other 5 out of 9 patients either did not improve, or actually had worse symptoms. The patients who got worse had more manic or irritable symptoms at the beginning of the trial. When the results were averaged, the inositol did not appear to help significantly--however, it is notable that a subgroup of patients appeared to benefit significantly.
http://www.ncbi.nlm.nih.gov/pubmed/16542187

This 2001 study from the Journal of Clinical Psychopharmacology compared 1 month of inositol (up to 18 grams per day) with fluvoxamine (up to 150 mg per day) in the treatment of panic disorder. Both groups improved similarly. The fluvoxamine group had more side effects of tiredness and nausea. The study is limited by its short duration.
http://www.ncbi.nlm.nih.gov/pubmed/11386498

This 1995 study from the American Journal of Psychiatry compared 12 grams per day of inositol with placebo, for one month, in the treatment of panic disorder. The authors conclude that inositol was effective with no significant side effects. Mind you, when eyeballing the chart of data from individual patients, the results did not look very impressive.
http://www.ncbi.nlm.nih.gov/pubmed/7793450

Here's a negative study, showing no difference between inositol and placebo, when added to antidepressant therapy for OCD:
http://www.ncbi.nlm.nih.gov/pubmed/11281989

The same author as above published a study in 1996 showing that inositol on its own was superior to placebo for OCD treatment. However, despite "statistical significance" being found, eyeballing the data from each patient (presented in the body of the paper) reveals doubtful clinical significance (that is, the amount of benefit looked quite unimpressive to me):
http://www.ncbi.nlm.nih.gov/pubmed/8780431

Here's a reference to a 2001 study showing that inositol was superior to placebo in treating binge eating and bulimic symptoms. In this case, I found the data to be clinically significant. However, the study was limited by its small size.
http://www.ncbi.nlm.nih.gov/pubmed/11262515

Here's a small 1995 study showing that 4weeks of inositol (12 grams per day) was superior to placebo in treating depressive symptoms. The data appeared clinically significant, though modest.
http://www.ncbi.nlm.nih.gov/pubmed/7726322

Here's a 2004 reference from a dermatology journal showing that inositol supplementation led to improvement of psoriasis in patients taking lithium:
http://www.ncbi.nlm.nih.gov/pubmed/15149510

In conclusion, inositol may be modestly effective for treating anxiety, eating disorder, and depressive symptoms. It may perhaps be quite variable in its effectiveness, i.e. some individuals might have much more benefit than others. It appears to be well-tolerated with few side-effects. I could not find good data on long-term safety though. The quality of the evidence is not very robust-- the studies have involved only small numbers of patients, for short periods of time. More research is needed.

Kava

Kava is a perennial shrub native to islands of the South Pacific. It has been ingested there as part of local culture. It has a relaxing effect.

Kava has been associated with liver toxicity: there have been cases of liver failure necessitating liver transplant, and there have been fatalities. As a result, the sale of kava is restricted in Canada.

Here is a reference about the liver toxicity issue:

http://www.ncbi.nlm.nih.gov/pubmed/15068826

In this 2008 article from a liver disease journal, cases of kava toxicity are reviewed. It is concluded that liver damage is a rare side effect of kava. It also found that many of those experiencing liver toxicity had used higher doses of kava, for longer periods of time, than recommended.

http://www.ncbi.nlm.nih.gov/pubmed/18989142

Effectiveness:

Here is a 2009 prospective, randomized, controlled study from Australia, in which 3 weeks of kava treatment (250 mg kava lactones per day) had minimal side-effects and led to substantial, clinically significant improvements compared to placebo in generalized anxiety symptoms and depressive symptoms:

http://www.ncbi.nlm.nih.gov/pubmed/19430766
As a critical commentary here, I think that 3 weeks is a VERY short study period, and therefore has limited clinical relevance. A great many approaches can relieve anxiety over a brief period of time (e.g. benzodiazepines); it's of much greater interest to see what happens after 3 months, or after 3 years!

Here is a 2003 Cochrane review, showing significant benefits in anxiety symptoms from kava treatment:

http://www.ncbi.nlm.nih.gov/pubmed/12535473

Here is a negative study from 2005, which showed that neither valerian nor kava differed from placebo in relieving anxiety or insomnia. The study participants were recruited on the internet, and were sent the blinded medication or placebo through the mail (another example of an interesting new study design):

http://www.ncbi.nlm.nih.gov/pubmed/16010204

In conclusion, kava seems promising as a treatment for anxiety. But there appears to be a small risk of very dangerous liver toxicity. It will require ongoing study to clarify risks vs. benefits, or to discover ways to minimize the risk of liver damage.

Valerian

Valerian is a perennial flowering plant native to Europe. Its sweetly-smelling flowers have been used to make perfume. Extracts from valerian root have been used as natural remedies in the treatment of insomnia and anxiety since ancient times.

Here is a review of the evidence:


This is a reasonably-done randomized 2009 study showing no effect of valerian vs. placebo in arthritis patients with insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/19114414

This interesting 2007 study--in which subjects were recruited via a TV health program, randomly mailed placebo or valerian, with results collected on-line--showed a very slight improvement in symptoms with valerian, with no differences in side effects, compared to placebo. Subjects in the valerian group took 3600 mg of Valeriana officinalis one hour before bedtime, for 14 days. Perhaps the most significant bottom-line result from the study to report here is that 9.1% of the valerian subjects reported feeling "better or much better", compared to 3.7% of the placebo subjects, after the end of the study period.
http://www.ncbi.nlm.nih.gov/pubmed/17940604


Here is a 2007 review from a sleep medicine journal, concluding that valerian is safe but not effective in the treatment of insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/17517355


Here's a 2006 Cochrane review, showing no evidence of valerian helping with anxiety disorders (mind you, the amount of data is very small):
http://www.ncbi.nlm.nih.gov/pubmed/17054208

Here's one positive 2005 study from Sleep, showing a modest benefit in sleep parameters and quality of life, from 28 days of a valerian-hops combination, compared to placebo, in the treatment of mild insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/17054208

Here's an interesting reference suggesting that valerian could have been the first treatment for epilepsy: but its potential benefit would have been extremely inconsistent, and at this point it is certainly not a practical treatment for epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/15509234

There are some other articles of dubious quality, which I found in some of the herbal medicine journals.

There could be dangerous interactions between valerian and other medications:
This is a case report of side effects with valerian + lorazepam:
http://www.ncbi.nlm.nih.gov/pubmed/19441067


In conclusion, I am not impressed with the evidence about valerian. It does appear to be quite safe. Mind you, there does not appear to be a good evidence base about possible dangerous interactions with other compounds. I recommend avoiding it, or using it with extreme caution, if you are taking other psychotropic medications. It may have modest benefits for some people, but for the vast majority the evidence suggests that it does not differ from placebo.

Valerian-based perfumes or scented oils might be pleasant and safe to use as aromatherapy for insomnia or anxiety, in conjunction with other relaxing activities.

Herbal Supplements & Vitamins

I'm starting a series of posts based on some questions that were sent in by a visitor (A.E.).

Here's the first question:
1. Herbal supplements and vitamins: What are your views on therapeutic value of multivitamins, Valerian, Kava, Inositol, Passion Flower, and so on?

-I think the risk:benefit ratio of multivitamins is quite favorable. I've written a few other posts about vitamins. With respect to mood or brain function in general, there may be particular benefit from folic acid, thiamine, and higher doses of vitamin D. Standard dose vitamin-mineral supplements are probably harmless at worst (as long as you get a good-quality brand--there's some evidence of dangerous impurities such as lead, in some ). Many people have poor diets, and a supplement could at least help prevent deficiencies in vitamins and iron which may further obstruct recovery from mental health problems. Supplements should not be a substitute for improving the healthiness of one's overall diet (you still need to eat your vegetables even if you're taking vitamins!)

Selling supplements is a huge business: the world market has about $180 billion of annual sales, and is rapidly growing (reference: http://www.nutraceuticalsworld.com/articles/2008/04/dietary-supplements-the-latest-trends-issues).
This is comparable in size to the $440 billion annual market size of the pharmaceutical industry (reference: http://www.valuenotes.com/Prabhudas/pl_pharma_31Mar09.asp?ArtCd=143465&Cat=I&Id=12).

I think we need to be wary of the sales tactics that go on in the dietary supplement business, especially since the quality of research in this area is, for the most part, quite primitive. If you walk into the nutritional supplement area of a health food store or pharmacy, you may be bombarded with advertising, possibly a sales person offering you attention, concern, and apparent expertise--and all of this is in the context of all sorts of other obviously healthy things, perhaps organic vegetables, right next to you. It is a biased environment. Proximity to healthy food and healthy people does not constitute evidence of effectiveness! Yet, there are some supplements that could be helpful. Just be wary of the hype, pseudo-scientific claims, and sales jargon, etc.

I'll write separate posts about valerian, kava, passion flower, and inositol.

In the meantime, here's a reference to a 2006 review in The British Journal of Psychiatry about complementary medicines in psychiatry. I recommend having a look at the whole article at a library:
http://www.ncbi.nlm.nih.gov/pubmed/16449696