Molecular and Cellular Biochemistry

, Volume 260, Issue 1, pp 171–186

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

  • Michael Shara
  • Sunny E. Ohia
  • Robert E. Schmidt
  • Taharat Yasmin
  • Andrea Zardetto-Smith
  • Anthony Kincaid
  • Manashi Bagchi
  • Archana Chatterjee
  • Debasis Bagchi
  • Sidney J. Stohs
Article
  • 311 Downloads

Abstract

Garcinia cambogia-derived (—)-hydroxycitric acid (HCA) is a popular and natural supplement for weight management. HCA is a competitive inhibitor of the enzyme ATP citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl CoA) in the cytosol. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides, and in the synthesis of acetylcholine in the central nervous system. Studies have demonstrated the efficacy of a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia(HCA-SX, Super CitriMax) in weight management. Results have shown that HCA-SX promotes fat oxidation, enhances serotonin release and availability in the brain cortex, normalizes lipid profiles, and lowers serum leptin levels in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity, as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of HCA-SX. However, no detailed long-term safety of HCA-SX or any other HCA extract has been previously assessed. We evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry over a period of 90 days. Furthermore, a 90-day histopathological evaluation was conducted. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX of feed intake and were sacrificed on 30, 60 or 90 days of treatment. The body weight and selected organ weights were assessed and correlated as a % of body weight and brain weight at 90 days of treatment. A significant reduction in body weight was observed in treated rats as compared to control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats, while no such difference in hepatic DNA fragmentation was observed as compared to the control animals. Furthermore, selected organ weights individually and as a % of body weight and brain weight at 90 days of treatment exhibited no significant difference between the groups. No difference was observed in hematology and clinical chemistry or the histopathological evaluation. Taken together, these results show that 90 day treatment of HCA-SX results in a reduction in body weight, and does not cause any changes in major organs or in hematology, clinical chemistry, and histopathology.

Garcinia cambogia (—)-Hydroxycitric acid 90-day toxicity study body and selected organ weights hepatic lipid peroxidation and DNA damage hematology and clinical chemistry histopathology 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Jequier E: Pathways to obesity. Int J Obes Relat Metab Disord 260: S12-S17, 2002CrossRefGoogle Scholar
  2. 2.
    Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL: Overweight and obesity in the United States: Prevalence and trends, 1960–1994. Int J Obes Relat Metab Disord 22: 39-47, 1998CrossRefPubMedGoogle Scholar
  3. 3.
    Colditz GA: Economic costs of obesity. Am J Clin Nutr 55: 503S-507S, 1992PubMedGoogle Scholar
  4. 4.
    Wolf AM, Colditz GA: Current estimates of the economic cost of obesity in the United States. Obes Res 6: 97-106, 1998PubMedGoogle Scholar
  5. 5.
    Haller CA, Benowitz NL: Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 343: 1833-1838, 2000CrossRefPubMedGoogle Scholar
  6. 6.
    Jena BS, Jayaprakasha GK, Singh RP, Sakariah KK: Chemistry and biochemistry of (−)-hydroxycitric acid from Garcinia. J Agric Food Chem 50: 10-22, 2002CrossRefPubMedGoogle Scholar
  7. 7.
    Sergio W: A natural food, the Malabar Tamarind, may be effective in the treatment of obesity. Med Hypotheses 29: 39-40, 1988CrossRefGoogle Scholar
  8. 8.
    Ramos RR, Saenz JLS, Agular RJA: Extract of Garcinia Cambogia in controlling obesity. Invest Med Int 22: 97-100, 1995Google Scholar
  9. 9.
    Lowenstein JM: Effect of (−)-hydroxycitrate on fatty acid synthesis by rat liver in vivo. J Biol Chem 246: 629-632, 1971PubMedGoogle Scholar
  10. 10.
    Sullivan AC, Triscari J, Hamilton JG, Miller ON, Wheatley VR: Effect of (−)-hydroxycitrate upon the accumulation of lipid in the rat. I. lipogenesis. Lipids 9: 121-128, 1974PubMedGoogle Scholar
  11. 11.
    Sullivan AC, Triscari J, Hamilton JG, Miller ON: Effect of (−)-hydroxycitrate upon the accumulation of lipid in the rat. II. Appetite. Lipids 9: 129-134, 1973Google Scholar
  12. 12.
    Triscari J, Sullivan AC: Anti-obesity activity of a novel lipid synthesis inhibitor. Int J Obes 8: 227-239, 1984PubMedGoogle Scholar
  13. 13.
    Ohia SE, Awe O, LeDay AM, Opere CA, Bagchi D: Effect of hydroxycitric acid on serotonin release from isolated rat brain cortex. Res Comm Mol Pathol Pharmacol 109: 210-216, 2001Google Scholar
  14. 14.
    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 238: 89-103, 2002CrossRefPubMedGoogle Scholar
  15. 15.
    Loe YC, Bergeron N, Rodriguez N, Schwarz J-M: Gas chromatography/mass spectrometry method to quantify blood hydroxycitrate concentration. Analytical Biochem 292: 148-154, 2001CrossRefGoogle Scholar
  16. 16.
    Conte, AA: A non-prescription alternative in weight reduction therapy. Am J Bariat Med (Summer): 17-19, 1993Google Scholar
  17. 17.
    Mattes DR, Bormann L: Effects of (−)-hydroxycitric acid on appetitive variables. Physiol Behav 71: 87-94, 2000CrossRefPubMedGoogle Scholar
  18. 18.
    Westerterp-Plantenga MS, Kovacs EMR: The effect of (−)-hydroxycitrate on energy intake and satiety in overweight humans. Int J Obes 26: 870-872, 2002CrossRefGoogle Scholar
  19. 19.
    Kovacs EM, Westerterp-Plantenga MS, de Vries M, Brouns F, Saris WH: Effects of 2-week ingestion of (−)-hydroxycitrate and (−)-hydroxycitrate combined with medium-chain triglycerides on satiety and food intake. Physiol Behav 74: 543-549, 2001CrossRefPubMedGoogle Scholar
  20. 20.
    Preuss HG, Bagchi D, Rao CVS, Echard BW, Satyanarayana S, Bagchi M: Effect of (−)-hydroxycitric acid on weight loss, body mass index and plasma leptin levels in human subjects. FASEB 16(abstr 742.16): A1020, 2002Google Scholar
  21. 21.
    Buege J, Aust S: Microsomal lipid peroxidation. Meth Enzymol 52: 302-310, 1978PubMedGoogle Scholar
  22. 22.
    Bagchi D, Carryl OR, Tran MX, Krohn RL, Bagchi DJ, Garg A, Bagchi M, Mitra S, Stohs SJ: Stress, diet and alcohol-induced oxidative gastrointestinal mucosal injury in rats and protection by bismuth subsalicylate. J Appl Toxicol 18: 3-13, 1998CrossRefPubMedGoogle Scholar
  23. 23.
    Largilliere C, Melancon SB: Free malondialdehyde determination in human plasma by high-performance liquid chromatography. Anal Biochem 170: 123-126, 1988CrossRefPubMedGoogle Scholar
  24. 24.
    Bagchi M, Balmoori J, Bagchi D, Ray SD, Kuszynski C, Stohs SJ: Smokeless tobacco, oxidative stress, apoptosis, and antioxidants in human oral keratinocytes. Free Rad Biol Med 26: 992-1000, 1999CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Michael Shara
    • 1
  • Sunny E. Ohia
    • 1
  • Robert E. Schmidt
    • 2
  • Taharat Yasmin
    • 1
  • Andrea Zardetto-Smith
    • 1
  • Anthony Kincaid
    • 1
  • Manashi Bagchi
    • 1
  • Archana Chatterjee
    • 1
  • Debasis Bagchi
    • 1
  • Sidney J. Stohs
    • 1
  1. 1.Department of Pharmacy Sciences, School of Pharmacy and Health ProfessionsCreighton University Medical CenterOmahaUSA
  2. 2.IDEXX Veterinary Services, Inc.West SacramentoUSA

Personalised recommendations