Gotu Kola

Gotu kola (Centella asiatica) is an Indian herb that has been used for centuries in Ayurvedic (Indian) and traditional Chinese medicine to alleviate symptoms of depression and anxiety. Several animal studies have shown that gotu kola enhances performance in maze tests (which assess memory and learning ability as well as degree of anxiety) and reduces various symptoms of stress. Findings from human studies also suggest a beneficial effect of gotu kola in reducing anxiety and responses to laboratory-induced stress. It is interesting to note that a number of laboratory studies have also shown gotu kola to bind to specialized cellular receptors in the gastrointestinal tract called cholecystokinin (CCK) receptors. CCK receptors help regulate appetite, food intake, and eating behavior, and the binding of gotu kola to them may help modulate hunger and food cravings throughout the day, especially those cravings and urges for bingeing that can be brought on by stress. It is important to keep in mind that gotu kola should not be confused with the kola nut, which is completely unrelated and is often used in weight-loss and energy supplements as a natural source of caffeine.

In one investigation of the anxiolytic (antianxiety) effects of gotu kola, twenty healthy volunteers were given either a single 12-gram dose of gotu kola or a look-alike placebo. Results showed that compared with placebo, gotu kola significantly reduced the response of the subjects to a series of laboratory stressors (loud noises and other startling events) administered over the subsequent thirty to sixty minutes. Now, 12 grams is a pretty large dose of gotu kola, but the effect was quite fast and very powerful. Smaller doses are known to be effective in reducing stress response during the presence of normal, everyday stressors of the sort that most of us would encounter on a regular basis.

The activity of gotu kola has also been studied in another form of stress: that of injury. In animal studies, gotu kola extracts have been shown to increase the production of hydroxyproline and collagen, the structural components needed for wound healing, by 50–60 percent. Other studies have shown gotu kola to possess antioxidant effects that can be beneficial in wound healing, skin protection, and immune-system support. In these studies, the antioxidant effects of gotu kola, given twice daily for seven days, improved antioxidant capacity of the tissue by 35–75 percent and reduced free-radical damage by nearly 70 percent.

Gotu kola is frequently found in topical skin preparations for its benefits in speeding wound healing; dietary forms of the herb are generally provided in capsule or tablet form. Dietary intake of gotu kola appears to be nontoxic, but there is some anecdotal evidence that gotu kola may result in elevated blood-sugar levels, an effect that could be of concern to individuals with diabetes. Typical dosage recommendations are in the range of 60–180 mg per day of an extract standardized to contain 30–40 percent of the active triterpene compounds (asiaticoside, asiatic acid, and related compounds).

St. John's Wort

St. John's wort (Hypericum perforatum) is typically recommended as an herbal alternative to antidepressant medications. It is effective in balancing mood and lifting spirits, and in many people it is also quite beneficial in relieving the fatigue that is often associated with mild to moderate depression and high stress. People who are depressed or under constant stress often lack the energy to even get themselves out of bed in the morning, and their day is a never-ending battle against fatigue. By correcting neurotransmitter imbalances in the brain, St. John's wort can bring energy levels back to normal and help alleviate the crushing fatigue that accompanies depressed mood and chronic stress.

The precise active ingredients in St. John's wort are unknown, but extracts standardized to contain 0.3 percent hypericin and 3 percent hyperforin, in doses of 900 mg per day, are known to be effective in alleviating mild to moderate depressive symptoms. St. John's wort is readily available as capsules containing the standardized extract. Using these hypericin/hyperforin extracts, numerous clinical studies have shown that people with mild or moderate depression tend to respond to St. John's wort to about the same degree as they would to some of the older prescription antidepressant medications, with fewer side effects. A number of well-controlled studies comparing the St. John's wort extract to prescription antidepressants such as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) have found St. John's wort to be comparable in effectiveness, but superior to prescription drugs with regard to tolerability. Overall, more than a dozen double-blind placebo-controlled studies have been conducted—albeit mostly small ones—and the majority support the case for the effectiveness of St. John's wort in alleviating mild to moderate depression, but not severe depression.

St. John's wort is quite safe in terms of observed side effects, the most common of which are mild gastrointestinal upset, mild allergic reactions (skin rash), and insomnia/restlessness, usually when taken close to bedtime. There have been no published reports of serious adverse side effects from taking the herb alone, and animal studies using large doses of St. John's wort have not shown any serious problems. The most commonly studied adverse effect of St. John's wort is its ability to cause photosensitivity in fair-skinned individuals, increasing their risk of sunburn.

Although direct side effects from consuming St. John's wort appear to be quite rare, several recent reports have raised the possibility that the herb may interact with and decrease the effectiveness of various medications, including HIV drugs (protease inhibitors), immunosuppressants (such as cyclosporin for organ transplants), digoxin (for congestive heart failure), blood thinners (Coumadin/warfarin), chemotherapy drugs (olanzapine/clozapine), and asthma medications (theophylline). If you are currently taking any of these drugs or other prescription medications, discontinue taking or do not begin taking St. John's wort without first consulting your personal physician. Abrupt withdrawal of the herb could increase blood levels of various medications, which could be dangerous in certain cases.

St. John's wort appears to be helpful in about 50 to 60 percent of cases, but as with prescription antidepressants, the full effect takes about four to six weeks to develop. It is important to note that St. John's wort should never be used for the treatment of severe depression (feelings of suicide, extreme inability to cope with daily life, severe anxiety, or extreme fatigue); in such cases, physician-directed drug therapy may mean the difference between life and death.


5-HTP (5-hydroxytryptophan) is a derivative of the amino acid tryptophan. In the body, tryptophan is converted into 5-HTP, which can then be converted into serotonin, a potent neurotransmitter in the brain. Although 5-HTP is not found at any significant level in a normal diet, tryptophan is found in a wide variety of protein foods. The 5-HTP used in dietary supplements is derived from the seeds of an African plant, Griffonia simplicifolia, and is typically used as a treatment for relieving mild depression, counteracting insomnia, promoting weight loss, and reducing overall sensations of stress and pain, such as migraine headaches, fibromyalgia, and general muscle pain.

5-HTP is typically used to treat mild depression and to combat stress, and this is done based on the theory that as a precursor to serotonin, supplements of 5-HTP can increase serotonin levels and influence mood, sleep patterns, and pain control. In a few small studies, 5-HTP has been shown to be as effective as prescription antidepressant medications—and with fewer side effects. In other studies, doses of 5-HTP in the range of 300–900 mg per day have resulted in benefits in reducing pain associated with migraines and fibromyalgia, reducing appetite, and promoting sleep, possibly by increasing blood and brain levels of serotonin. It appears that there are "responders," individuals who experience an elevation in 5-HTP levels in the blood, as well as "nonresponders," who see no such increase.

The most significant safety concern related to 5-HTP supplements is the remote possibility for contamination with a compound linked to a disorder known as eosinophilic myalgia syndrome (EMS), which results in muscle pain and weakness, vomiting, headache, and, in rare cases, death. In 1989 an outbreak of EMS was linked to contaminated tryptophan supplements—not to the tryptophan per se, but to a contaminant in the supplements. As a result, the FDA banned the sale of all tryptophan supplements, a move that has been widely criticized by people on both sides of the supplement debate. The banned tryptophan supplements were manufactured from a bacterial source in a fermentation process, whereas 5-HTP is extracted from the seeds of a plant—so it is less likely (though not impossible) that the contaminant associated with EMS, commonly known as peak X, is present in 5-HTP supplements. Some supplement manufacturers and raw-material suppliers conduct quality-control tests to confirm the absence of peak X in their 5-HTP supplements. If you decide to try 5-HTP, it is suggested that you contact the manufacturer of your supplement for confirmation that their products have passed this type of analysis. Supplemental forms of 5-HTP are available in capsule or tablet form, as extracts from griffonia seeds (providing 15–20 percent 5-HTP), and in synthetic form (99 percent pure).

In addition to the above safety considerations, 5-HTP supplements are not recommended for children or for women who are pregnant or lactating. People currently taking prescription antidepressants, weight-control medications, or herbal remedies for depression (such as St. John's wort) should not combine these treatments with 5-HTP supplements, except on the advice and guidance of a nutritionally oriented physician.


S-adenosylmethionine (SAM-e) is a form of the sulfur-containing amino acid methionine, combined with adenosine (part of the energy compound ATP). Like methionine, SAM-e is involved in numerous metabolic processes in the body that require sulfur—such as the methylation reactions. The body typically manufactures all the SAM-e it requires from methionine consumed in protein foods, but a defect in methylation or a deficiency in any of the cofactors required for SAM-e production (such as methionine, choline, or the B vitamins) is theorized to reduce the body's ability to produce SAM-e.

It has been hypothesized that a defect in the body's methylation process is central to the biochemical basis of certain neuropsychiatric disorders, and that chronic stress can interfere with the body's ability to conduct these methylation reactions. Tissue levels of SAM-e have been found to be low in the elderly and in patients suffering from depression and chronic stress. SAM-e has performed as well as conventional antidepressant drugs in studies of depression, probably due to an increase in brain levels of neurotransmitters such as serotonin and dopamine.

SAM-e is quite safe at recommended doses and has the distinct advantage over some other herbal medicines of being a naturally occurring compound in the body, which suggests that supplementation with SAM-e simply provides an additional dietary source of this nutrient. Other antidepressant compounds that are available as dietary supplements, such as St. John's wort, could be viewed as more of a pharmacological approach to relieving depression because they are not naturally found in the body. The problem with dietary supplements containing SAM-e is their cost—SAM-e is not an inexpensive ingredient. The good news, however, is that the mood benefits of SAM-e are more affordable (delivered at 200–600 mg per day) than the joint-health benefits of the supplement (for which you'd need 1,200–1,400 mg per day). Even at 200–600 mg per day, however, SAM-e tablets (the most stable form) generally cost $20 to $30 for a ten-day supply.

Summary: Relaxation Supplements

So where do these calming herbs fit in? They can certainly represent an effective approach to promoting relaxation and de-stressing a person during periods of particularly high stress. However, when it comes to designing your specific cortisol-control regimen, it may be helpful to take it step-by-step (see the boxed text XXX). As such, most of the supplements covered in this section should be thought of as secondary choices to be used in specific cases of depression, insomnia, or when something is needed to take the edge off after a particularly stressful day.

We've now covered the five most important steps for controlling stress and modulating cortisol levels with supplements:

1. Avoid excessive doses of supplements that can increase cortisol levels (stimulants such as ephedra and caffeine)…

2. Take a multivitamin/multimineral supplement as a cortisol-control foundation…

3. Focus on targeted modulation of cortisol, testosterone, and HSD, especially during periods of high stress…

4. Consider adding "reinforcement" supplements against stress in the form of adaptogens…

5. Use calming supplements to fight depression, insomnia, and frazzled nerves…

Stressed Jess will have to follow each of these five steps for optimal cortisol control, with particular emphasis on step 3.

Strained Jane may be able to get away with following only steps 1–3; she may never have a need to progress to steps 4 and 5.

Relaxed Jack, as laid-back as he appears, he can also benefit from following the first two steps on a regular basis, but he may need to progress to step 3 during his occasional high-stress periods.

Faced with all of these recommendations, it is logical that you may feel a bit confused about how to put them into practice—but don't stress out about it! The next, and final, chapter pulls all of the preceding chapters together into the simple plan, summarized in Chapter 7, called the SENSE Lifestyle Program.


Shawn Talbott

Supplement Watch

Wisdom of Balance