**3.9. Herbal laxatives**

**3.6. Glucomannan (***Amorphophallus konjac***)**

118 Drug Discovery

Glucomannan is a soluble but highly viscous dietary fiber derived from the root of the *Amorphophallus konjac* (elephant yam) plant that grows native to Asia [27]. Although tradi‐ tionally used as a food, the plant has gained popularity as an additive in weight loss supple‐ ments since the dietary fiber absorbs water in the gastrointestinal tract, helping to promote a sense of satiety and act as a bulk laxative [226-228]. There is also evidence that fiber content of glucomannan helps to reduce cholesterol levels [67, 229-232]. In a double blind crossover study involving 63 healthy males, 3.9 grams of glucomannan administered daily for four weeks resulted in a 10% reduction in total cholesterol, 7.2% reduction in LDL cholesterol, and a 23% decrease in triglyceride levels [67]. A meta-analysis of clinical trials involving glucomannan reported overall decreases in the above markers as well as fasting blood glucose [230].

There are relatively few reported drug interactions with glucomannan, most of which are likely due to associated decreases in cholesterol and lipid levels as well as interference with absorp‐ tion of some drugs. Monitoring of patients taking antihypertensives, antilipemics, and other anti-obesity agents is warranted. Several studies note a significant decrease in fasting blood glucose levels following glucomannan administration while decreased absorption of the sulfonylurea drugs is possible [230, 231, 233-237]. Glucomannan can significantly decrease circulating levels of T3, T4, and FT3 in the treatment of thyrotoxicosis and therefore its use may be contraindicated in patients taking thyroid medications [238]. Glucomannan can potentially affect the absorption of certain drugs and supplements as demonstrated in one study in which absorption of the fat soluble Vitamin E was decreased potentially via the

*Hoodia gordonii*, a small succulent of the Apocynaceae family native to the Kalahari Desert, has been used traditionally by native tribes for its appetite and thirst suppressing proper‐ ties [240, 241]. The active constituent of Hoodia (P57 or P57AS3) is an oxypregnane steroi‐ dal glycoside which is purported to increase ATP production in the hypothalamus, resulting in a feeling of satiety [242]. There is little known regarding potential drug or herb interac‐ tions with *Hoodia*, although *in vitro* studies suggest a potential interaction with drugs

*Garcinia cambogia* is a plant native to Southeast Asia which yields a small purple fruit used in weight loss products for its hydroxycitric acid (HCA) content [27, 244]. The anorectic activity of HCA is due to the inhibition of the adenosine triphosphate-citrate (pro-3S)-lyase, which catalyzes the formation of acetyl-CoA, resulting in decreased fatty acid synthesis and lipo‐ genesis [245]. The evidence for HCA as an effective weight loss agent is contradictory. One randomized controlled trial reported a 5-6% reduction in weight and BMI following approx‐ imately a 4.5 gram daily dose of HCA, while two other studies reported no significant weight loss or effect on appetite at lower doses of 1.5 – 2.4 gram daily HCA doses [246-248]. There are

reduction of bile acids necessary for absorption of the vitamin [239].

**3.7.** *Hoodia gordonii*

metabolized by CYP 3A4 [243].

**3.8. Hydroxycitric acid (HCA,** *Garcinia cambogia***)**

Frequently laxatives and diuretics are used alone or in combination products to promote weight loss. However, there is little to no evidence supporting these supplements as antiobesity agents, although subgroups of this patient population may abuse laxatives and diuretics for the purpose of weight loss [250].
