What is Hydroxycitrate?

Hydroxycitrate: Controversial Weight-Loss Ingredient


Hydroxycitrate is a generic name for any salt of (-)-hydroxycitric acid (HCA), which occurs naturally in fruits from the genus Garcinia. HCA is found in particularly high concentrations in Garcinia cambogia, commonly called brindleberry or Malabar tamarind.

Hydroxycitrate is the active ingredient in a number of over-the-counter weight-loss products. Among the many dietary supplements that are advertised to aid in weight management, hydroxycitrate is distinguished by the large body of research examining its effectiveness, safety and mechanism of action. However, hydroxycitrate is also distinguishable by the conflicting and inconsistent nature of the studies, and by the controversy generated by these studies.

HCA is a competitive inhibitor of the enzyme ATP citrate lyase, which has a major role in synthesizing fatty acids in the body. HCA is also believed to reduce malonyl-CoA concentrations, leading to increased fatty acid oxidation. Therefore, it is believed that HCA promotes weight loss by interfering with fatty acid synthesis, promoting fat oxidation and reducing appetite.

A recent systematic review and meta-analysis showed a small but statistically significant weight-loss effect of HCA compared to placebo. However, gastrointestinal adverse effects were also twice as common in subjects taking HCA than in those taking placebo.

Several animal and human studies have supported the effectiveness of HCA for weight loss. Of these, the vast majority were funded or conducted by pharmaceutical companies, with one or more authors affiliated with a major supplier of HCA-based products.

Other studies have shown no effects of HCA on weight loss parameters (such as body weight reduction, blood/serum profiles, or satiety). One study, conducted at Columbia University and published in 1998 in the leading medical publication Journal of the American Medical Association, is considered to be strong evidence against the effectiveness of hydroxycitrate or HCA for weight loss.

However, proponents of HCA say that the high-fiber, low-calorie diet that was used in this study may have prevented the anti-obesity effects of hydroxycitrate.

Animal studies have shown that HCA may have toxic effects, such as testicular shrinkage and toxicity. However, the HCA used some of these studies reportedly contained large amounts of HCA lactone. In the free acid or lactone forms, HCA can potentially cause have negative effects on testicular development by chelating zinc, which can lead to zinc deficiency. Many commercial HCA products contain fully reacted calcium or potassium salts of HCA, so should have little or no free HCA acid or HCA lactone. Hydroxycitrate has been determined to be safe in several studies, and has been determined to be GRAS by an independent team of experts for use as a flavoring agent. Acidic conditions may promote lactone formation, even of fully reacted acid salts. Therefore, it should be cautioned that free HCA acid or HCA lactone may accumulate over time in acidic products.

Taken together, the research thus far does not provide conclusive evidence that hydroxycitrate effectively promotes weight loss, either through metabolic processes or by inducing satiety. More research is needed to determine the safety and effectiveness of HCA-containing products.

For more information about HCA, please visit Natural Standard's Foods, Herbs & Supplements database.

References

1.Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com

2.An herbal weight-loss drug fails in rigorous testing. Harv Heart Lett. 1999 Mar;9(7):6. View Abstract

3.Asghar M, Monjok E, Kouamou G, et al. Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats. Mol Cell Biochem. 2007 Oct;304(1-2):93-9. View Abstract

4.Badmaev V, Majeed M, Conte AA. Garcinia cambogia for weight loss. JAMA. 1999 Jul 21;282(3):233-4; author reply 235. View Abstract

5.Behne D, Kyriakopoulos A, Gessner H, et al. Sex-related effects of zinc deficiency on the selenium metabolism in rats. J Trace Elem Electrolytes Health Dis. 1992 Mar;6(1):21-5. View Abstract

6.Brandt K, Langhans W, Geary N, Leonhardt M. Beneficial and deleterious effects of hydroxycitrate in rats fed a high-fructose diet. Nutrition. 2006 Sep;22(9):905-12. View Abstract

7.Burdock G, Soni M, Bagchi M, Bagchi D. Garcinia cambogia toxicity is misleading. Food Chem Toxicol. 2005 Nov;43(11):1683-4; author reply 1685-6. No abstract available. Erratum in: Food Chem Toxicol. 2007 Mar;45(3):515. View Abstract

8.Firenzuoli F, Gori L. Garcinia cambogia for weight loss. JAMA. 1999 Jul 21;282(3):234; author reply 235. View Abstract

9.Fukuoka M, Kobayashi T, Hayakawa T. Mechanism of testicular atrophy induced by di-n-butyl phthalate in rats. Part 5. Testicular iron depletion and levels of ferritin, haemoglobin and transferrin in the bone marrow, liver and spleen. J Appl Toxicol. 1995 Sep-Oct;15(5):379-86. View Abstract

10.Hayamizu K, Hirakawa H, Oikawa D, et al. Effect of Garcinia cambogia extract on serum leptin and insulin in mice. Fitoterapia. 2003 Apr;74(3):267-73. View Abstract

11.Heymsfield SB, Aronne LJ, Blackburn GL. HCA efficiency. Diabetes Obes Metab. 2004 Nov;6(6):458-9; author reply 460-1. View Abstract

12.Heymsfield SB, Allison DB, Vasselli JR, et al. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA. 1998 Nov 11;280(18):1596-600. View Abstract

13.Ishihara K, Oyaizu S, Onuki K, et al. Chronic (-)-hydroxycitrate administration spares carbohydrate utilization and promotes lipid oxidation during exercise in mice. J Nutr. 2000 Dec;130(12):2990-5. View Abstract

14.Kovacs EM, Westerterp-Plantenga MS, Saris WH. The effects of 2-week ingestion of (--)-hydroxycitrate and (--)-hydroxycitrate combined with medium-chain triglycerides on satiety, fat oxidation, energy expenditure and body weight. Int J Obes Relat Metab Disord. 2001a Jul;25(7):1087-94. View Abstract

15.Kovacs EM, Westerterp-Plantenga MS, de Vries M, et al. Effects of 2-week ingestion of (-)-hydroxycitrate and (-)-hydroxycitrate combined with medium-chain triglycerides on satiety and food intake. Physiol Behav. 2001b Nov-Dec;74(4-5):543-9. View Abstract

16.Kovacs EM, Westerterp-Plantenga MS. Effects of (-)-hydroxycitrate on net fat synthesis as de novo lipogenesis. Physiol Behav. 2006 Jul 30;88(4-5):371-81. View Abstract

17.Kriketos AD, Thompson HR, Greene H, Hill JO. (-)-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 Aug;23(8):867-73. View Abstract

18.Lee KH, Lee BM. Evaluation of the genotoxicity of (-)-hydroxycitric acid (HCA-SX) isolated from Garcinia cambogia. J Toxicol Environ Health A. 2007 Mar 1;70(5):388-92. View Abstract

19.Leonhardt M, Balkan B, Langhans W. Effect of hydroxycitrate on respiratory quotient, energy expenditure, and glucose tolerance in male rats after a period of restrictive feeding. Nutrition. 2004 Oct;20(10):911-5. View Abstract

20.Leonhardt M, Langhans W. Hydroxycitrate has long-term effects on feeding behavior, body weight regain and metabolism after body weight loss in male rats. J Nutr. 2002 Jul;132(7):1977-82. View Abstract

21.Leonhardt M, Hrupka B, Langhans W. Effect of hydroxycitrate on food intake and body weight regain after a period of restrictive feeding in male rats. Physiol Behav. 2001 Sep 1-15;74(1-2):191-6. View Abstract

22.Lim K, Ryu S, Nho HS, et al. (-)-Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women. J Nutr Sci Vitaminol (Tokyo). 2003 Jun;49(3):163-7. View Abstract

23.Lim K, Ryu S, Ohishi Y, et al. Short-term (-)-hydroxycitrate ingestion increases fat oxidation during exercise in athletes. J Nutr Sci Vitaminol (Tokyo). 2002 Apr;48(2):128-33. View Abstract

24.Mattes RD, Bormann L. Effects of (-)-hydroxycitric acid on appetitive variables. Physiol Behav. 2000 Oct 1-15;71(1-2):87-94. View Abstract

25.Ohia SE, Opere CA, LeDay AM, Bagchi M, Bagchi D, Stohs SJ. Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Mol Cell Biochem. 2002 Sep;238(1-2):89-103. View Abstract

26.Ohia SE, Awe SO, LeDay AM, et al. Effect of hydroxycitric acid on serotonin release from isolated rat brain cortex. Res Commun Mol Pathol Pharmacol. 2001 Mar-Apr;109(3-4):210-6. View Abstract

27.Onakpoya I, Hung SK, Perry R, Wider B, Ernst E. The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials. J Obes. 2011;2011:509038. View Abstract

28.Preuss HG, Garis RI, Bramble JD, et al. Efficacy of a novel calcium/potassium salt of (-)-hydroxycitric acid in weight control. Int J Clin Pharmacol Res. 2005;25(3):133-44. View Abstract

29.Preuss HG, Bagchi D, Bagchi M, et al. Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss. Diabetes Obes Metab. 2004 May;6(3):171-80. View Abstract

30.Preuss HG, Rao CV, Garis R, et al. An overview of the safety and efficacy of a novel, natural(-)-hydroxycitric acid extract (HCA-SX) for weight management. J Med. 2004;35(1-6):33-48. View Abstract

31.Roy S, Shah H, Rink C, et al. Transcriptome of primary adipocytes from obese women in response to a novel hydroxycitric acid-based dietary supplement. DNA Cell Biol. 2007 Sep;26(9):627-39. View Abstract

32.Roy S, Rink C, Khanna S, et al. Body weight and abdominal fat gene expression profile in response to a novel hydroxycitric acid-based dietary supplement. Gene Expr. 2004;11(5-6):251-62. View Abstract

33.Saito M, Ueno M, Ogino S, et al. High dose of Garcinia cambogia is effective in suppressing fat accumulation in developing male Zucker obese rats, but highly toxic to the testis. Food Chem Toxicol. 2005 Mar;43(3):411-9. View Abstract

34.Schaller JL. Garcinia cambogia for weight loss. JAMA. 1999 Jul 21;282(3):234; author reply 235. View Abstract

35.Shara M, Ohia SE, Schmidt RE, et al. Physico-chemical properties of a novel (-)-hydroxycitric acid extract and its effect on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological changes over a period of 90 days. Mol Cell Biochem. 2004 May;260(1-2):171-86. View Abstract

36.Shara M, Ohia SE, Yasmin T, et al. Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and histopathological data over a period of 90 days. Mol Cell Biochem. 2003 Dec;254(1-2):339-46. View Abstract

37.Soni MG, Burdock GA, Preuss HG, et al. Safety assessment of (-)-hydroxycitric acid and Super CitriMax, a novel calcium/potassium salt. Food Chem Toxicol. 2004 Sep;42(9):1513-29. View Abstract

38.Talpur N, Echard BW, Yasmin T, et al. Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats. Mol Cell Biochem. 2003 Oct;252(1-2):369-77. View Abstract

39.Thom E. A randomized, double-blind, placebo-controlled trial of a new weight-reducing agent of natural origin. J Int Med Res. 2000 Sep-Oct;28(5):229-33. View Abstract

40.Tomita K, Okuhara Y, Shigematsu N, et al. (-)-hydroxycitrate ingestion increases fat oxidation during moderate intensity exercise in untrained men. Biosci Biotechnol Biochem. 2003 Sep;67(9):1999-2001. View Abstract

41.van Loon LJ, van Rooijen JJ, Niesen B, et al. Effects of acute (-)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans. Am J Clin Nutr. 2000 Dec;72(6):1445-50. View Abstract

42.Westerterp-Plantenga MS, Kovacs EM. The effect of (-)-hydroxycitrate on energy intake and satiety in overweight humans. Int J Obes Relat Metab Disord. 2002 Jun;26(6):870-2. View Abstract

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