Anxiety Disorders: Supplements Not Likely To Be Effective

It is not possible to review all compounds that, at one time or another, have been tried to treat symptoms of anxiety and have not shown to be effective, or lack sufficient rationale about how they may affect brain action to promote sleep. However, some of these compounds are sometimes marketed as anxiolytics, despite the lack of evidence of efficacy. Clinicians who seek to practice in the area of naturopathic psychopharmacology should be aware of compounds that continue to be propagated despite evidence to the contrary.


As discussed in site, GABA is a major neurotransmitter in the central nervous system that is ubiquitous and affects the firing of all neurons by increasing membrane polarization. Most GABA receptors are ionotropic and regulate the influx of chloride into the cell. As chloride levels increase in the cell, the negative charge also increases, and the cell becomes more and more difficult to stimulate.

A number of medications target GABA neurotransmission and have been shown to be effective in treating mood disturbance (especially mania and agitation), anxiety, and tics. Consequently, naturopaths sometimes recommend GABA supplementation, and various forms of GABA tablets and capsules are available on the market.

Unfortunately, these are of very limited value. GABA does not easily cross the blood-brain barrier (Foster & Kemp, 2006), and the majority of GABA becomes metabolized and/or excreted before it can enter the brain. Although some peripheral effects have been observed, like muscle relaxation, few psychogenic effects seem evident. When administered at high doses (at 1000 mg or higher), supplemental GABA does, in fact, appear to begin to cross the blood-brain barrier, but surprisingly, the effects are not the inhibition that is expected, and a mix of sedation as well as increased anxiety becomes evident. Thus, GABA supplements appear to show no benefits in treating symptoms of anxiety.


Ginkgo (Ginkgo biloba), sometimes also spelled ginko, and also known as the maidenhair tree or kew, is an ancient tree primarily endogenous to China but now widely grown in various parts of the world, usually under controlled conditions. Ginkgo has been used for thousands of years and was known in ancient China for its benefit in treating memory loss and breathing ailments. It is widely used in Europe, and ginkgo prescriptions account for up to 4 percent of all medication prescriptions in some countries. Over the past few decades, its use has been becoming more popular in the US. When used as a supplement, it is ingested in capsules or liquid extracts.

Ginko has many active ingredients, including various flavonoid glycosides, biflavones, and terpene lactones. Its psychoactive mechanisms primarily include an increase in acetylcholine activity, which it appears to accomplish by increasing the uptake of choline into the cells, and increasing the release of acetylcholine into the synapse. This action is probably responsible for ginkgo’s well-documented benefits in improving memory. However, some of ginkgo’s constituents may also inhibit MAO enzymes (both A and B types), as well as increases in serotonergic neurotransmission and elevating levels of GABA. Consequently, it has been presumed to have some anxiolytic properties.

Results of research studies, however, have not confirmed these effects. In animal models, some studies reported preliminary results, but these have never been replicated in humans. In addition, use of ginkgo may pose some risks. It potently inhibits platelets and cases of spontaneous bleeding have been reported with its use, including hemorrhaging and hematomas (Medical Economics, 2007). Use of ginkgo has also been associated with a decrease in seizure threshold. Even more importantly, use of ginkgo is associated with a risk of developing Stevens Johnson syndrome, a potentially fatal condition in which death of skin cells causes the epidermis to separate from the dermis, and children and adolescents are especially at risk for this disorder. All in all, weighing the lack of evidence of anxiolytic properties and the potential risks of using ginkgo, it seems clear ginkgo supplements should not be used in the pediatric population.


Serine is non-essential amino acid supplied from food or synthesized by the body from a number of metabolites, including glycine. Serine is found in soybeans, nuts (especially peanuts, almonds, and walnuts), eggs, chickpeas, lentils, meat, and fish (especially shellfish). Serine is produced by the body when insufficient amounts are ingested. It is metabolized from ketones and glycine, and retroconversion with glycine also occurs.

As with most amino acids, when food is ingested that contains serine, the molecule is extracted in the small intestine and absorbed into circulation. There, it travels through the body, crosses the blood-brain barrier, and enters neurons, where it gets metabolized into glycine and many other molecules. Thus, the amount of serine in cells is regulated through these metabolic processes. If too little is ingested, more serine is converted from various sources. When too much is ingested, only a portion is converted to glycine, and the remainder is metabolized into folate and many other proteins.

As with all precursors, only a limited amount of serine is converted to glycine, and supplementation seems to be of limited value. Although non-peer reviewed sources list it as effective in treatment of a variety of symptoms of psychological disorders (especially, depression and anxiety), there is no empirical research to support these claims. Thus, although supplementation with serine is not associated with significant adverse effects, benefits are unlikely, and therefore clinicians are advised to avoid using serine supplements.