Garcinia Cambogia: Medical Magic or Fat-Loss Fantasy?
Posted on March 22 2014
Garcinia Cambogia (GC) is a plant native to Indonesia that is also grown in India, regions of Africa and parts of Southeast Asia. It has long been used to increase the satiety effect of meals, as it suppresses the appetite via an effect on brain serotonin concentration. Another action of GC is reducing the storage of excess carbohydrate calories as fat by inhibiting an enzyme involved in the process known as de novo lipogenesis (the creation of new fat from excess sugar). It is likely that the traditional value of GC has more to do with suppressing the appetite (minimizing discomfort or suffering), rather than reducing fat creation, as the populations in its native regions deal with food scarcity rather than food excess as a rule.
The primary active ingredient in GC is a chemical called (-)-hydroxycitric acid (HCA). Those who shopped weight-loss products in the 1990s may recognize this as a frequent ingredient in fat-loss products, often combined with chromium picolinate and a “kitchen sink” of other ingredients. HCA-containing products did not acquire a dominant market presence until the potent combination of ephedrine and caffeine were pulled from the market; shortly after, phenylpropanolamine (Dexatrim) was also pulled, as well as pseudoephedrine products. Also, it was discovered that the mainstay prescription drug therapies, fenfluramine and dexfenfluramine, were causing pulmonary hypertension— including fatal cases. Despite all these market advantages, HCA-containing products did not achieve lasting sales. Yet, GC is reappearing in the weight-loss market.
Is there any validity to the claims that GC can aid in weight loss? There is a lot of published research, including both GC extract and HCA, to offer some clarity as to the potential and potency of GC for weight loss. During the period described above when HCA products were introduced to the supplement market, a study was published in the Journal of the American Medical Association that reported no additional weight loss was experienced by subjects taking 1,500 milligrams of HCA daily for 12 weeks. Both the HCA and control group lost a fair amount of weight by following a high-fiber, low energy (hypocaloric) diet during the 12 weeks. HCA did not increase fat loss or percent of weight lost as fat compared to the control group either. This study was criticized by advocates of GC/HCA extract— with three letters to the editor published in the July 21, 1999 issue of JAMA to question the conclusion and study design. These letters provide some of the first evidence as to the practical value of GC.
Research Is Questioned
Critics stated the study failed to generate a positive effect for GC due to the type of diet provided. The high-fiber, hypocaloric diet negated the value of GC by controlling for the factors that GC corrects. In other words, when the subjects were limited to a diet of roughly 1,200 calories per day, the appetite-suppressing effect of GC was masked because the control group that did not receive the GC was not allowed to eat more despite being hungry. Also, the high-fiber diet did not provide the sugar-rich food that gets converted to fat. HCA blocks the enzyme ATP-citrate lyase, which breaks sugar metabolites down to a form that can be used to create a fatty acid molecule. It is active only in conditions where there is excess sugar and calories, and the cellular mechanisms are switched to a lipogenic (fat creating) state. If the diet does not contain excess sugar and does not provide a large number of calories per meal, the enzyme that HCA blocks is not very active anyhow. Thus, the study did not provide conditions where GC/HCA could provide a benefit. Also, there was concern that the high-fiber diet may bind some of the HCA, the amount given was less than needed, and the form (calcium salt) was not as bioavailable as alternate forms.
It is interesting that a later study combining GC with glucomannan fiber also failed to show weight loss, perhaps supporting the claim that dietary fiber may bind GC/HCA and impede uptake from the gut.
While these may be valid reasons for explaining the failure of the 1998 JAMA study to repeat the weight-loss and fat-loss effect noted in earlier studies, it does not devalue the study findings. Instead, it clarifies the conditions that need to be present to realize benefit from GC— a carbohydrate-rich diet (called a lipogenic diet, meaning it promotes fat storage) that is not hypocaloric. Ironically, this is saying that GC works best when the person taking it does the least in terms of making healthy diet choices to promote weight loss. It is a challenge to accept this argument, as thus far it seems that one would have to ignore healthy weight-loss advice to see any benefit from GC.
Yet, it’s been reported that GC may double or triple the weight loss seen with diet and exercise. What evidence is there to support that claim? A study was published in 2000, reporting that mice who were provided HCA for 25 days burned more fat for calories and increased muscle glycogen (a storage form of sugar) compared to control mice. If this is also seen in humans, it would provide support for a greater fat-loss effect during exercise, though not necessarily greater weight loss. Well, indeed such an effect was noted in a small study on healthy, young adult men who performed two 60-minute sessions of intense exercise a week apart. After an hour of cycling, the men were given a high-carbohydrate meal (80% carbohydrate supplying 1.6 grams of carbohydrate per kilogram of bodyweight). One session, that was all they received; the other session, they also received 500 milligrams of HCA. Muscle biopsies and other measures were performed showing that despite a lower insulin concentration, muscle glycogen stores were restored at nearly twice the rate, and a greater percentage of fat was burned for calories— very similar to the mouse study. Neither study suggested that a greater number of calories were burned, but it suggests that HCA may increase post-exercise fat burning to preserve/restore muscle glycogen. The potential weight-loss benefit of a lower insulin response to the post-exercise meal needs to be further investigated.
The post-exercise, fat-based calorie burning has not been consistent in studies utilizing HCA in conjunction with exercise in trained athletes. The benefit is more evident in untrained individuals, suggesting that the enzyme(s) affected by GC/HCA are already altered by habitual endurance exercise.
A Significant Fat-Loss Agent?
An excellent review on the known and hypothesized effect of GC/HCA on fat loss-related mechanisms in the body was published in 2013 in the journal Evidence-based Complementary and Alternative Medicine detailing the mechanisms, pathways and even genomic effects of GC/HCA. Of interest were the findings exploring how GC/HCA turned off lipogenic and adipogenic genes. Upon review of the studies involving GC/HCA, the authors noted that the fat-loss effect of GC/HCA appears to be dependent upon a higher dose, whereas the cholesterol and triglyceride-lowering effect occurs with more moderate use. Unfortunately, the limit designated as “no observed adverse effect” (2,800 mg HCA per day) is below the dose used in the studies with the most significant weight loss (3,000-4,667 mg per day). The highest dosed study resulted in impressive weight loss (5.4% in eight weeks), with increase serum (blood) serotonin and HDL cholesterol (good cholesterol) while decreasing total cholesterol, LDL cholesterol (bad), triglycerides and food intake. Subjects in this study were using a treadmill five times per week and consumed a 2,000-calorie daily diet.
Though there are conflicting results in the many animal and human trials, and the medical community does not believe there to yet be enough evidence to support a claim of GC/HCA being a significant fat-loss agent, it is being discussed and consumed by many people. However, GC was one of the ingredients suspected to have caused liver damage as part of a combination product. It is difficult to know what role, if any, GC/HCA may have played in these injuries. A recent paper and mouse study refutes the suggestion that HCA is hepatotoxic (damages the liver). The safety and toxicity overview published in 2004, as well as the 2013 review, suggest GC/HCA is a safe ingredient.
To minimize risk, it may be safest to use GC/HCA as a stand-alone ingredient, rather than as part of a multi-ingredient combination capsule. It may also be wise to stay with an established brand, as the unprecedented demand has introduced questionable material into the supply chain of less legitimate distributors. Clinical data suggests that the fat-loss effect is most consistently noted when three grams are used daily (divided into three doses of one gram taken before meals). However, avoiding side effects has an upper threshold of 2,800 milligrams per day, just under three grams.
GC appears to be most relevant for the person who struggles with making good eating choices, has poor appetite control, binges on sweets, and has not included cardiovascular exercise in his/her weight loss efforts. It is the “training wheels” of weight loss, controlling appetite and the sabotaging effect of eating comfort foods. It may not be appropriate for the athlete or those with strong will power, but the general public may see benefit from the claimed effects of GC.
Pomeroy SR. Dr. Oz Has Found 16 Weight Loss ‘Miracles.’ So Why Is There Still an Obesity Epidemic? Forbes.com January 10, 2014. http://www.forbes.com/sites/rosspomeroy/2014/01/10/dr-oz-has-found-16-weight-loss-miracles-so-why-is-there-still-an-obesity-epidemic/, accessed February 10, 2014.
Egras AM, Hamilton WR, et al. An evidence-based review of fat modifying supplemental weight loss products. J Obes 2011;297315(7pp).
The Dr. Oz Show. November 5, 2012. http://www.doctoroz.com/videos/garcinia-cambogia-newest-fastest-fat-buster-pt-1, accessed February 12, 2014.
Heymsfield SB, Allison DB, et al. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA 1998;280:1596-600.
Vasques CA, Rossetto S, et al. Evaluation of the pharmacotherapeutic efficacy of Garcinia cambogia plus Amorphophallus konjac for the treatment of obesity. Phytother Res 2008;22:1135-40.
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.
Girola M, De Bernardi M, 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.
Ishihara K, Oyaizu S, et al. Chronic (-)-hydroxycitrate administration spares carbohydrate utilization and promotes lipid oxidation during exercise in mice. J Nutr 2000;130:2990-5.
Cheng IS, Huang SW, et al. Oral hydroxycitrate supplementation enhances glycogen synthesis in exercised human skeletal muscle. Br J Nutr 2012;107:1048-55.
van Loon LJ, van Rooijen JJ, et al. Effects of acute (-)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans. Am J Clin Nutr 2000;72:1445-50.
Lim K, Ryu S, et al. Short-term (-)-hydroxycitrate ingestion increases fat oxidation during exercise in athletes. J Nutr Sci Vitaminol 2002;48:128-33.
Tomita K, Okuhara Y, et al. (-)-hydroxycitrate ingestion increases fat oxidation during moderate intensity exercise in untrained men. Biosci Biotechnol Biochem 2003;67:1999-2001.
Lim K, Ryu S, et al. (-)-Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women. J Nutr Sci Vitaminol 2003;49:163-7.
Chuah LO, Ho WY, et al. Updates on Antiobesity Effect of Garcinia Origin (-)-HCA. Evid Based Complement Alternat Med 2013:751658(17pp).
Lau FC, Bagchi M, et al. Nutrigenomic analysis of diet-gene interactions on functional supplements for weight management. Curr Genomics 2008;9:239-51.
Preuss HG, Rao CV, et al. An overview of the safety and efficacy of a novel, natural(-)-hydroxycitric acid extract (HCA-SX) for weight management. J Med 2004;35:33-48.
Dara L, Hewett J, et al. Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol 2008;14:6999-7004.
Fong TL, Klontz KC, et al. Hepatotoxicity due to hydroxycut: a case series. Am J Gastroenterol 2010;105:1561-6.
Clouatre DL, Preuss HG. Hydroxycitric acid does not promote inflammation or liver toxicity. World J Gastroenterol 2013;19:8160-2.