The conversion of carbohydrate to fat requires that pyruvate be oxidized to acetyl-CoA. This oxidative process occurs within the mitochondria. However, fatty acid synthesis occurs predominately in the cytosol.
Therefore, the acetyl group, which is the intermediate substrate for fatty acid synthesis, must be transported from inside the mitochondria to the cytosol before it can be incorporated into fatty acids.
The acetyl group is transported out of the mitochondria as citrate. Once outside, an enzyme, ATPcitrate lyase, catalyzes the reaction, which cleaves citrate into acetyl-CoA and oxaloacetate. The acetyl group then enters the biosynthetic pathway of fatty acid synthesis.
Garcinia Cambogia and Garcinia Indica
Hydroxycitric acid (HCA) is an inhibitor of the enzyme ATP-citrate lyase. Therefore, it prevents the conversion of carbohydrates into fatty acids by preventing the breakdown of citrate in the cytosol. Many products are currently on the market that contain HCA among other ingredients. HCA is obtained from the extracts of the herbs Garcinia cambogia and Garcinia indica, both native to India.
Animal studies have shown HCA to be effective in reducing fatty acid synthesis. However, there is a lack of well-controlled human studies.
Several well-controlled animal studies have investigated HCAs effect on fatty acid synthesis. In general, they have all shown that HCA-administered orally, intravenously, or by intraperitoneal injection-inhibits fatty acid biosynthesis in the liver and adipose tissue.
The degree of inhibition depends on the dosage and can range from 20% to 80%. The decrease in fatty acid biosynthesis resulted in significant reductions in epididymal fat stores and total body fat.
Another interesting aspect of HCA was the reduction in food intake during HCA administration. Curiously, the reduction in food intake could not completely account for the decrease in body weight. Also, cholesterol and triglyceride levels were lower following HCA administration.
As mentioned above, well-controlled human studies investigating the fat-loss potential of HCA are lacking. Most of the studies that have investigated HCAs effect on body composition have been performed using products containing other ingredients, which could also be active ingredients. Of the seven studies reviewed by Heymsfield et al. only two have been published in peer-reviewed journals. Heymsfield and coworkers are the only ones to use HCA by itself. The other studies have appeared only in abstract form and have investigated HCA in combination with other components that may also be considered to promote fat loss.
All but one of the studies have reported that HCA, combined with other fat-loss supplements, produced significantly greater losses in fat than a placebo. The single study to investigate HCA by itself as the active ingredient reported that HCA failed to produce weight loss and fat mass loss beyond that observed with a placebo in overweight men and women.
Based on the limited research, HCA could promote fat loss, but only when used in combination with other components of fat loss supplements. Further research needs to investigate HCA supplementation alone and when used in combination with other ingredients. The discrepancies between the animal and human studies are interesting. But, as we are learning from leptin research, the regulation of fat metabolism in rats appears to be much different than that in humans.
Safety and Toxicity
Neither animal nor human studies have reported any treatment-related adverse events. A few animal studies have included tests specifically to look at liver function. The human studies have simply used an adverse incident reporting form and have reported that adverse events were not significantly different between the treatment group and placebo group.