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Hydroxycitric Acid- A weight Loss Aid

By Yousry Naguib, Ph.D.
Vitamin Retailer magazine, December 2001
Hydroxycitric acid is a popular dietary supplement purported to be energy enhancing, and fat burning. Hydroxycitric acid is an active ingredient that is extracted from the South Asian fruit Garcinia cambogia, which is about the size of an orange and looks similar to a small pumpkin.
Obesity is the number one nutritional problem in the U.S. An estimated one third of Americans are overweight, with an additional 25 percent being classified as obese.
Being overweight significantly increases a person’s risk of developing diabetes, heart disease, stroke, and other diseases that cause morbidity, mortality, and high health-care expenditure. Type II occurs when the body does not properly respond to insulin, a hormone that helps to regulate the blood level of glucose, or blood sugar.
Researchers at Harvard found that more than 90 percent of the 3,300 women who developed diabetes over a 16-year study period were overweight, inactive, and smokers. The researchers followed female nurses who were free of heart disease, diabetes, and cancer at the beginning of the study. The low risk group had a body-mass index (calculated as weight in kilograms divided by the square of height in meters) of less than 25 and a diet high in fibers and polyunsaturated fat and low in trans fat and glycemic load (which reflects the effect of diet on the blood glucose level). Being overweight or obese was the most important diabetes risk predictor, followed by lack of exercise [1]. The study suggests that most of diabetes can be prevented through diet and exercise. Maintaining a healthy weight is the most important way to reduce risk of Type II diabetes.
Effective methods for weight reduction are constantly being sought. No one approach, whether dietetic management, or commercial weight loss program, can alone solve the obesity problem. Most weight reduction treatment regimens involve caloric restriction, which is based on the principle that if intake of food is less than energy expenditure, stored calories, will be consumed, mainly in the form of fat. However, once the diet regimen is stopped, weight is quickly regained. 
Other treatment regimens are based on the principle of increasing metabolism. By increasing metabolism, calories are burned thereby decreasing body weight.

Mechanism of Action
Hydroxycitric acid reportedly promotes weight loss, in part, through suppression of appetite [2]. The conversion of carbohydrates into fat requires an enzyme called ATP-citrate lyase. ATP (adenosine triphosphate) is a nucleotide present in all living cells, which serves as an energy source for many metabolic processes and is required for ribonucleic acid synthesis. The enzyme catalyzes the cleavage of citrate into acetyl coenzyme A, which is responsible for cholesterol and fatty acid synthesis de novo. Prevention of converting excess calories into fat in turn slows the production of cholesterol and triglycerides. At the same time, the liver is able to synthesize more glycogen, amplifying the satiety signal to the brain and suppressing appetite and food carvings.
Animal studies with Hydroxycitric acid have demonstrated that inhibition of ATP citrate lyase enzyme leads to a decrease in the synthesis of both cholesterol and fatty acids [3], and an increase in low-density lipoprotein (LDL) receptor activity [4]
 McCarty suggested that Hydroxycitric acid somehow increases thermo-genesis, a metabolism of fat or other compounds to produce heat rather than metabolic energy in the form of ATP [5].

Health Benefits
Animal studies have demonstrated that Hydroxycitric acid decreases weight gain by suppressing and reducing food intake. One animal study found that rats fed Hydroxycitric acid gained 80 percent less weight than rats who were not fed Hydroxycitric. And another animal study found that rats fed Hydroxycitric acid ate less food, gained less weight, and expended an average of 13 percent more energy than rats in a control group not taking Hydroxycitric acid [6].
In another animal study, lean and obese rats were fed Hydroxycitric acid in their diet for 39 days. In the lean rats, Hydroxycitric acid decreased body weight, reduced appetite, and body fat. In the obese rat, food intake and body weight were reduced, but body fat remained unchanged. The study indicated that treatment of obese rats resulted in a substantial reduction in the body weight [7]. 
The bioavailability of Hydroxycitric acid (HCA) was demonstrated in a study involving four subjects, who ingested 2 grams of HCA. Two hours later, analysis of  their plasma revealed the presence of HCA at a concentration 8.4 microgm /ml [8].
The efficacy of Hydroxycitric acid in weight loss management was also demonstrated in a double blind, placebo-controlled study involving eighty-nine mildly overweight females, who were randomly assigned to either 400mg caplets of Garcinia cambogia 30-60 min prior to meals for a total dose of 1.2g Hydroxycitric acid per day, or a placebo for 12 weeks. Both groups lost body weight with the active group achieving a significantly greater reduction (3.7 kg versus 2.4 kg) [9].
Hydroxycitric acid was also shown to provide protection against oxidation of carbohydrates in endurance-trained humans. Ten cyclists, 24 years of age, received either 3 mL per kg body weight of a hydroxycitrate solution (19 g / liter) or placebo about half an hour before and after exercise. Analysis of blood samples showed that the plasma Hydroxycitric acid concentration increased, but no significant change in total fat and carbohydrate oxidation at the end of the exercise period [10]
A recent study published in JAMA examined the efficacy of Garcinia cambogia for body weight and fat mass loss in overweight human subjects. In this double-blind, placebo-controlled trial, 135 overweight men and women subjects were randomly assigned to receive either 1.5g of Hydroxycitric acid per day or placebo, along with a high fiber diet, for twelve weeks. Hydroxycitric was taken 30 minutes before meals three times per day, for a total daily dose of 1500mg. The subjects were followed for 12 weeks. Both groups lost a significant amount of weight, 9 and 7 lb for placebo and Hydroxycitric acid-group, respectively. The study concluded that Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo [11]. All the patients in the study were prescribed a high-fiber, low calorie, low-energy diet.
Opponents have postulated that the high-fiber diet (low-energy) used in the study may have limited the gastrointestinal absorption of Hydroxycitric acid, thus rendering the study ineffective and leading to the disappointing results [12]. Hydroxycitric acid is believed to work by blocking the conversion of excess carbohydrates into fat, a simple carbohydrate-rich (high-energy) diet would have been more appropriate than the high-fiber diet used in the study, which does not provide the excess carbohydrates necessary for fatty acid synthesis. Similar results were obtained in a double blind, placebo controlled, randomized, crossover study involving 10 sedentary adult male subjects supplemented either Hydroxycitric acid (3g per day) or placebo for three days [13].
A study published in the journal of Medical Hypotheses [14,15] hypothesized that during aerobic exercise glucose uptake by working muscle increases, and as a result hepatic glucose output should increase. Failure of hepatic glucose output to keep pace with muscle uptake rapidly leads to hypoglycemia and exhaustion. Pre-administration of hydroxycitrate, a potent inhibitor of citrate lyase found in Garcinia is proposed to aid endurance during aerobic exercise by increasing glucose output. It was also proposed that Carnitine and chromium might potentiate the benefit of Garcinia.

Dosage / Safety         
            No serious side effects have been reported in human studies involving either fruit extracts or the concentrated chemical. Studies have shown that 4g daily of Hydroxycitric acid taken for four weeks produce no adverse effects. A typical dosage of Hydroxycitric acid is 250 to 1,000mg three times daily.

            Hydroxycitric acid derived from Garcinia cambogia works at the cellular level to keep carbohydrates from turning into fat, and to suppress appetite and to provide energy. Animal studies have shown that Hydroxycitric acid decrease weight gain by suppressing appetite and reducing food intake. Its use in weight loss is also supported by preliminary studies on humans.

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[2] Sergio W. A natural food, malabar tamarind, may be effective in the treatment of obesity. Medical Hypothesis 1988; 27:40
[3] Sullivan AC et al. Lipids 1977; 12:1; Triscari J and Sullivan AC. Comparative effects of hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo. Lipids 1977; 12:357
[4] Berkhout TA et al. Biochem J 1990; 272:181
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[6] Winifred Yu. Hydroxycitric acid. Natural Health, April 1999
[7] Greenwood MR et al. Effect of hydroxycitrate on development of obesity in the Zucker obese rat. Am J Physiol 1981; 240:E72
[8] Loe YC. et al. Gas chromatography/mass spectroscopy method to quantify blood hydroxycitrate. Anal Biochem 2001; 292:148
[9] Mattes RD et al. Effects of Hydroxycitric acid on appetitive variables. Physiol Behav 2000; 71:87
[10] Van Loon LJ. Effects of acute hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans. Am J Clin Nutr 2000; 72:1445
[11] Heymsfield SB et al. Garcinia cambogia (Hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA 1998; 280:1596
[12] Firenzuoli F, Gori L. Garcinia cambogia for weight loss. JAMA 1999; 282:234
[13] Kriketos AD et al. Hydroxycitric acid does not affect energy expenditure and substrate oxidation in adult males in a post-absorptive state. Int J Obes Relat Metab Disord 1999; 23:867
[14] McCarty MF. Optimizing exercise for fat loss. Medical Hypothesis 1995; 44:325
[15] McCarty MF. Inhibition of citrate lyase may aid aerobic endurance. Medical Hypothesis 1995; 45:247