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Hydroxycitric acid (HCA) is the prinicpal acid found in the fruit rind of Garcinia cambogia. This species also has other bioactive components, such as biflavanoids, xanthones and benzophenones, but these play only a minor role in its biological activity. Similar in structure to citric acid, the effects of HCA on metabolism were being researched as early as the 1970's. It is widely marketed as a fat loss aid, although there is little scientific evidence supporting the method of use and dosage that most supplement companies recommend. This article will explain possible reasons for discrepancies in the research, as well as the ideal way to utilize HCA.
2. How does HCA work?
There are a variety of ways in which HCA may aid in the improvement of body composition. HCA inhibits the extramitochondrial enzyme adenosine 5'-triphosphate (ATP) citrate-lyase, which catalyzes the cleavage of citrate to oxaloacetate and acetyl-CoA [1-3]. This leads to a reduction in the acetyl-CoA pool, which limits the availability of two-carbon units that are used for the synthesis of fatty acids and cholesterol [1, 3]. This makes HCA an effective inhibitor of de novo lipogenesis, the process which converts carbohydrates to fat. Secondly, HCA suppresses malonyl CoA (via inhibition of acetyl-CoA), which is an inhibitor of carnitine malpitoyl-transferase I [2-3]. Increased activity of this enzyme would increase fatty acid oxidation. In vitro, HCA increases oxidation of fatty acids in skeletal muscle cells and pancreatic beta cells [2], but the primary action of HCA in vivo is probably the liver, and increased hepatic fatty acid oxidation would also decrease appetite [2-4]. HCA also may stimulate glycogen synthesis in the liver, leading to increased sateity [2-3]. Finally, HCA inhibits uptake of serotonin in the brain in vitro, and if this also happens in vivo it may contribute to appetite suppression [5].
3. What is the evidence for and against HCA supplementation?
Many studies in rats have found that HCA suppresses food intake and inhibits body weight gain, both in young rats and in adult rats gaining weight after substantial body weight loss [2]. There are also many studies in humans on fat loss and appetite, with varying results. Unfortunately, most of the studies with positive results either used a small sample size or did not use a placebo group [6]. On the other hand, while many studies without methodological problems found no effect from HCA, they tested HCA on subjects on low calorie diets [6]. This is a nonsensical approach, because the mechanisms of action of HCA primarily favor the inhibition of fat regain after weight loss. During negative energy balance (e.g., on a low calorie diet), the conversion of citrate into acetyl-CoA by ATP-citrate-lyase does not occur, and glycogen levels in the liver are going to be low [3]. In contrast, during positive energy balance, HCA will inhibit de novo lipogenesis and increase the rate of liver glycogen repletion. Given the mechanism of action of HCA, it should not be very effective in contributing to fat loss, but should aid in the prevention of fat regain in the hypercaloric state. However, this has yet to be tested in a rigorous study in humans, and the role that de novo lipogenesis plays in fat regain in humans may be relatively minor. Future studies will need to be conducted to explore the full potential of HCA, and until then it should not be made a cornerstone of a fat loss strategy.
4. What are some other possible benefits of HCA supplementation?
Studies in mice and rats have found that HCA leads to an improvement in blood lipid profiles [1, 7] and that it prevents the development of ulcers in some models [8-9]. Some studies indicate that HCA may improve endurance performance in trained and untrained athletes by improving fat utilization [10-11], while others negate these findings [4]. In theory, HCA may improve insulin sensitivity in skeletal muscle by inhibiting malonyl-CoA [4].
5. How should one utilize HCA?
HCA is very safe, and is non-toxic in rats at up to 500 mg/kg daily and 5 g/kg acutely [5, 7]. Since the literature is inconsistent, dosage recommendations can vary greatly. HCA is probably not very useful if one is on a low calorie diet, but if one is implementing refeeds, a large dose (10-20 g) may inhibit lipogenesis and speed glycogen replenishment. This should be spread out among one dose 1-2 hours before the refeed and then every 2-3 hours during the refeed. For inhibiting fat gain while bulking, doses as low as 250 mg daily may have an effect, and some sources recommend 3-4 g daily.
If you have any questions or comments regarding this article, please email dvdtlsn@bulknutrition.com.
1. Fitoterapia. 2003 Apr;74(3):267-73. Effect of Garcinia cambogia extract on serum leptin and insulin in mice. Hayamizu K, Hirakawa H, Oikawa D, Nakanishi T, Takagi T, Tachibana T, Furuse M.
2. J Nutr. 2002 Jul;132(7):1977-82. Hydroxycitrate has long-term effects on feeding behavior, body weight regain and metabolism after body weight loss in male rats. Leonhardt M, Langhans W.
3. Physiol Behav. 2001 Nov-Dec;74(4-5):543-9. Effects of 2-week ingestion of (-)-hydroxycitrate and (-)-hydroxycitrate combined with medium-chain triglycerides on satiety and food intake. Kovacs EM, Westerterp-Plantenga MS, de Vries M, Brouns F, Saris WH.
4. Am J Clin Nutr. 2000 Dec;72(6):1445-50. Effects of acute (-)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans. van Loon LJ, van Rooijen JJ, Niesen B, Verhagen H, Saris WH, Wagenmakers AJ.
5. Mol Cell Biochem. 2002 Sep;238(1-2):89-103. Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Ohia SE, Opere CA, LeDay AM, Bagchi M, Bagchi D, Stohs SJ.
6. Anal Biochem. 2001 May 1;292(1):148-54. Gas chromatography/mass spectrometry method to quantify blood hydroxycitrate concentration. Loe YC, Bergeron N, Rodriguez N, Schwarz JM.
7. Phytother Res. 2001 Aug;15(5):395-400. Impact of certain flavonoids on lipid profiles--potential action of Garcinia cambogia flavonoids. Koshy AS, Vijayalakshmi NR.
8. Indian J Exp Biol. 2002 Jan;40(1):58-62. Prevention of HCl-ethanol induced gastric mucosal injury in rats by Garcinia cambogia extract and its possible mechanism of action. Mahendran P, Sabitha KE, Devi CS.
9. Phytother Res. 2002 Feb;16(1):80-3. The antiulcer activity of Garcinia cambogia extract against indomethacin-induced gastric ulcer in rats. Mahendran P, Vanisree AJ, Shyamala Devi CS.
10. J Nutr Sci Vitaminol (Tokyo). 2003 Jun;49(3):163-7. (-)-Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women. Lim K, Ryu S, Nho HS, Choi SK, Kwon T, Suh H, So J, Tomita K, Okuhara Y, Shigematsu N.
11. J Nutr Sci Vitaminol (Tokyo). 2002 Apr;48(2):128-33. Short-term (-)-hydroxycitrate ingestion increases fat oxidation during exercise in athletes. Lim K, Ryu S, Ohishi Y, Watanabe I, Tomi H, Suh H, Lee WK, Kwon T.
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