Garcinia cambogia for Weight Loss
 HCA: Prices and Ordering Information
Garcinia cambogia for Weight Loss
American Medical Association.
To the Editor: In their study evaluating the weight-loss potential of (-)hydroxycitric acid (HCA) derived from Garcinia cambogia, Dr Heymsfield and colleagues1 cite our HCA work. We wish to give a counterpoint to the conclusion expressed by the authors.
Based on their single clinical study, Heymsfield et al state that "These observations ... do not support a role as currently prescribed for the widely used herb G cambogia as a facilitator of weight loss." Aside from this strong statement, which contradicts the positive results reported in several earlier HCA clinical studies, the design of the trial indicates that the authors took little advantage of previously reported experiences involving HCA.2-4 In their own preclinical research, they report a prerequisite that suggests for HCA to effectively inhibit fat formation and body weight it needs to be administered with a simple carbohydrate-rich (lipogenic) diet.5
The study in question5 coadministered HCA with a high-fiber diet. This issue of a carbohydrate-rich diet vs a high-fiber diet was not mentioned by Heymsfield et al. Also lacking was mention of the fact that a high-fiber diet was not advocated in our previous HCA trials.2-4
The use of a high-fiber diet in combination with HCA may reduce gastrointestinal absorption of HCA, since high-fiber diets may reduce absorption of many nutrients and micronutrients. This issue becomes critical with HCA because its reported efficacy in inhibiting the intracellular enzyme adenosine triphosphate(ATP)–citrate-lyase depends entirely on the presence of HCA inside the target cell.
The significance of HCA availability in the cytosol of a target cell for inhibiting lipid synthesis or ATP–citrate-lyase was recently confirmed in 2 separate studies performed by Joanne Kelleher, PhD, at George Washington University (oral communication, November 24, 1998) and Joel Melnick, MD, at Northwestern University Medical School.6 The compound used in both of these studies was the same commercially available HCA used in the study by Heymsfield et al.
In view of the shortcomings of the study discussed above, the statement on HCA's lack of efficacy is unsupported, particularly in the absence of proof that HCA was absorbed from the gastrointestinal tract.
Vladimir Badmaev, MD, PhD
Muhammed Majeed, PhD
Anthony A. Conte, MD
Sabinsa Corporation
Piscataway, NJ
1. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA. 1998;280:1596-1600. MEDLINE
2. Conte AA. A non-prescription alternative in weight reduction therapy. Am J Bariatr Med. Summer 1993:17-19.
3. Conte AA. The effects of (-)-hydroxycitrate and chromium (GTF) on obesity. J Am Coll Nutr. 1994;13:535. Abstract 60.
4. Badmaev V, Majeed M. Open field, physician controlled, clinical evaluation of botanical weight loss formula Citrin. Presented at: Nutracon 1995: Nutraceuticals, Dietary Supplements and Functional Foods; July 11, 1995; Las Vegas, Nev.
5. Vasselli JR, Shane E, Boozer CN, Heymsfield SB. Garcinia cambogia extract inhibits body weight gain via increased energy expenditure (EE) in rats. FASEB J. 1998;12:A506.
6. Puttaparthi K, Rogers T, Elshourbagy NA, Levi M, Melnick JZ. Renal ATP citrate lyase (ATP CL) protein localizes throughout the nephron and increases only in the proximal tubule with chronic metabolic acidosis (CMA). Abstract presented at Pediatric Academic Societies' 1999 Annual Meeting. May 2, 1999; San Francisco, Calif.
Disclosure. Sabinsa Corporation is a manufacturer of hydroxycitric acid.
To the Editor: Dr Heymsfield and colleagues1 reported that "Garcinia cambogia failed to produce significant weight loss and fat mass loss [in humans] beyond that observed with a placebo," while previous reports indicate that G cambogia HCA decreases appetite, reduces food intake, and inhibits fat synthesis in animals,2, 3 and reduces body weight, triglycerides, and cholesterol levels in humans.4 Why the disparity?
First, the low-energy, 5040-kJ diet used in the study by Heymsfield et al negated the utility of HCA. This agent is a potent competitive inhibitor of ATP–citrate-lyase,5 an enzyme that converts citrate (a product of the Krebs citric acid cycle derived from carbohydrate metabolism) into acetyl–coenzyme A (CoA), the primary building block of fatty acid and cholesterol synthesis. However, the conversion of citrate to acetyl-CoA by ATP–citrate-lyase occurs only when the rate of glycolysis exceeds the energy requirements of the body.
If the body's energy needs are not met, the Krebs cycle converts carbohydrate calories into ATP for energy rather than citrate for fatty acid synthesis. Thus, a low-energy diet that does not exceed the energy requirements of the body would not provide the substrate (ie, citrate) necessary for fatty acid synthesis and thus would fail to demonstrate HCA's ability to inhibit fat production from excess carbohydrate consumption.
Second, HCA inhibits appetite and reduces food intake administered ad libitum in animals.2 However, the study by Heymsfield et al failed to evaluate HCA's ability to reduce food intake by virtue of its energy-restricted protocol. Although diet compliance was not quantitatively monitored during the study, subjective indices of patient compliance and feelings of satiety also were not assessed. In a similar study, Ramos et al4 reported that subjects taking HCA adhered to a recommended low-energy diet better than subjects receiving a placebo.
Third, the dose of HCA used in the study was low compared with that used in earlier successful animal trials.3 Bioavailability also may have been reduced. Excessive levels of calcium (used to stabilize the HCA molecule), high levels of naturally occurring pectin, and low solubility in water, factors that can reduce bioavailability, are know to exist in many, but not all, commercial HCA extracts. Since blood levels of HCA were not assessed, it is possible that the extract selected for this study had poor bioavailability and thus failed to deliver an effective dose.
James L. Schaller, MD
Birchrunville, Pa
1. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA. 1998;280:1596-1600. MEDLINE
2. Sullivan AC, Triscari J, Hamilton JG, Miller ON. Effect of (-)-hydroxycitrate upon the accumulation of lipid in the rat, II: appetite. Lipids. 1974;9:129-134. MEDLINE
3. Sullivan AC, Triscari J, Hamilton JG, Miller ON, Wheatley VR. Effect of (-)-hydroxycitrate upon the accumulation of lipid in the rat, I: lipogenesis. Lipids. 1974;9:121-128. MEDLINE
4. Ramos RR, Saenz JL, Aguilar CF. Extract of Garcinia cambogia in the control of obesity [in Spanish]. Invest Med Int. 1995;22:97-100.
5. Lowenstein JM. Experiments with (-)hydroxycitrate. In: Burtley W, Kornberg HL, Quayle JR, eds. Essays in Cell Metabolism. New York, NY: Wiley Interscience; 1970:153-166.
To the Editor: According to Dr Heymsfield and colleagues,1 "Garcinia cambogia [HCA] failed to produce significant weight loss and fat mass loss beyond that observed with a placebo"; "studies in humans are contradictory"; and ". . . at least 14 separate hydroxycitric acid–containing products are presently sold over-the-counter to consumers."
The main active component in the herbal extract of Garcinia compound is HCA. The earliest research, conducted in the 1970s, into the antiobesity effects of HCA was conducted by Hoffmann-La Roche Pharmaceuticals. Studies have shown the ability of HCA to inhibit the actions of citrate cleavage enzyme, suppress fatty acid synthesis, increase hepatic glycogen synthesis, suppress food intake, increase energy expenditure, curb appetite, reduce plasmatic cholesterol levels, and inhibit fat synthesis from excess carbohydrate calories.2, 3 The properties of Garcinia extract have been confirmed by clinical trials published in peer-reviewed literature.2-4
In the study by Heymsfield et al,1 only the amount of HCA, and not the chemical composition of the extract, was verified by chemical analysis. The bioavailability of the HCA product tested was not assessed, a quality factor that might significantly affect the results because many HCA products available on the market today have low bioavailability.
Excess calcium, common among many HCA products, reduces solubility and hinders bioavailability. Calcium-type powder is stable but not ideal for food products due to its insolubility in water.5 However, a compound complexed with calcium and potassium is nearly 100% soluble and creates a pH level that is favorable for maximum gastrointestinal absorption, 2 critical components of bioavailability. A soluble Garcinia powder and liquid extract containing a lactone form of HCA was compared with a calcium-type Garcinia powder administered in food to rats, and the liquid extract was proven more effective.5
Another problem of the study centers on the restricted diet used. Because all patients lost weight, including the placebo group, the study design eliminated any opportunity to demonstrate that HCA curbs appetite, reduces food intake, and inhibits fat synthesis in an unrestricted diet as the conversion of citrate into acetyl-CoA occurs only when the energy consumed exceed the energy requirements of the body.
Fabio Firenzuoli, MD
Luigi Gori, MD
St Joseph Hospital
Empoli, Italy
1. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA. 1998;280:1596-1600. MEDLINE
2. Ramos RR, Saenz FJ, Alarcon A. Extract of Garcinia cambogia in the control of obesity [in Spanish]. Invest Med Intern. 1996;22:97-100.
3. Rothacker DQ, Waitman BE. Effectiveness of a Garcinia cambogia and natural caffeine combination in weight loss: a double-blind placebo-controlled pilot study. Int J Obes. 1997;21(suppl 2):53.
4. Girola M, De Bernardi M, Contos S, et al. Dose effect in lipid-lowering activity of a new dietary integrator (chitosan, Garcinia cambogia extract, and chrome). Acta Toxicol Ther. 1996;17:25-40.
5. Sawada H, Tomi H, Tamura K, et al. Effects of liquid Garcinia extract and soluble Garcinia powder on body weight change: a possible material for suppressing fat accumulation. Nihon Yukagaku Kaishi. 1997;46:1467-1474.
In Reply: The increasing prevalence of obesity combined with the low efficacy of conventional treatments led us to examine the weight-loss effects of G cambogia, a natural source of the citrate-lyase enzyme inhibitor HCA. Our double-blind, randomized controlled trial was designed from the consumer's perspective: we administered either a placebo or widely available G cambogia preparation in suggested amounts along with dietary recommendations typical of that provided in package inserts.1 Our negative observations in the first adequately controlled and reported trial of this widely used herbal agent prompted several letters from readers.
The first group of issues raised by the respondents involves the low-fat, high-fiber hypocaloric diet recommended to our subjects in both placebo and active herb groups. Dr Badmaev and colleagues hypothesize that a high fiber intake may lead to gastrointestinal HCA binding with subsequent loss of enzyme inhibitor bioavailability. Dr Schaller's concern is that the citrate cleavage enzyme is relatively inactive when the subject is in negative energy balance, as would occur with ingestion of a low-energy diet. Drs Firenzuoli and Gori also express a similar concern regarding use of G cambogia with an energy "restricted" diet. These suggestions provide a potential theoretical basis for why the product tested in our study was "ineffective as prescribed." Nevertheless, our investigation was based on typical product diet plans2 and similar to that prescribed in the Garcinia studies by Conte3 and Badmaev et al.4
The second important group of comments extends Badmaev and colleagues' bioavailability concern. Firenzuoli and Gori report that water solubility, and thus gastrointestinal absorption of HCA, depends on factors such as degree of calcium and potassium acid complexing and acid vs lactone forms. Schaller also invokes the low-bioavailability hypothesis by again suggesting that fibers such as pectin and calcium stabilization may conspire to reduce HCA absorption. Administered dosage, as mentioned by Schaller, was lower than that used in earlier successful animal experiments. Our dosage of HCA was, however, almost identical to that used in most commercial preparations, in Conte's human study,3 and in Badmaev and Majeed's study.4
As potential consumers, we may ask why it remains uncertain that HCA derived from an over-the-counter product reaches its cellular destination in amounts adequate to actively inhibit citrate cleavage enzyme. Why are diet plans suggested to consumers that may render Garcinia's active agent nonabsorbable or inadvertently switch off the target citrate cleavage enzyme? Critical tests pinpointing each step in HCA uptake, distribution, and biological effects in humans are long overdue.
The need now exists to build, piece by piece, a strong series of human studies that establish if any G cambogia preparations can be added to the list of safe and effective weight-loss or weight-gain–prevention agents. Until this scientific foundation is established, consumers must rely on appropriately designed studies, such as ours, to judge if herbal weight-loss products such as the evaluated G cambogia preparation offer effective therapy beyond that of well-established diet and exercise measures.
Steven B. Heymsfield, MD
David B. Allison, PhD
Joseph R. Vasselli, PhD
Angelo Pietrobelli, MD
Debra Greenfield, MS, RD
Christopher Nunez, MEd
St Luke's–Roosevelt Hospital Center
New York, NY
1. Thermogenic Ultra Lean [package insert]. Herbal weight loss plan with Garcinia cambogia. Salt Lake City, Utah: Great American Nutrition;1998.
2. Committee for Proprietary Medicinal Products. Note for Guidance on Clinical Investigation of Drugs Used in Weight Control. London, UK: The European Agency for the Evaluation of Medical Products; 1997.
3. Conte AA. A non-prescription alternative in weight reduction therapy. Am J Bariatr Med. Summer 1993:17-19.
4. Badmaev V, Majeed M. Open field, physician controlled, clinical evaluation of botanical weight loss formula Citrin. Presented at: Nutracon 1995: Nutriceuticals, Dietary Supplements and Functional Foods; July 11, 1995; Las Vegas, Nev.
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