The effect of Garcinia Cambogia as coadjuvant in the weight loss process

The World Health Organization (WHO) classifies obesity as an epidemic resulting from the imbalance between intake and energy expenditure, as a consequence of a sedentary lifestyle and poor eating habits1,2,3, as well as the socio demographic conditions4. This disease constitutes a significant global health problem that attacks adults and children and affects a worldwide, growing number of people5.

It is characterized as a chronic disease caused by excessive accumulation of body fat resulting in significant loss of quality of life and longevity. It occurs in developed and developing countries3,6, and it has the involvement of a complex interaction of environmental and genetic factors, besides being associated to morbidity and mortality related to heart attack, high blood pressure, diabetes and even cancer7,8.

Consequently, obesity is a public health problem that requires attention and multisectoral actions to promote a healthy lifestyle and improve the prevention and its control among population4,9.

The Ministry of Health (MoH), through Vigitel (Telephone-based Surveillance of Risk and Protective Factors for Chronic Diseases)10, in 2013, revealed overweight in 51% of the Brazilian population; men are the majority. In 2006, this percentage was 43%, a fact that shows that the obesity rate has been growing in the country. In 2012, ABESO (Brazilian Association for the Study of Obesity and Metabolic Syndrome)11 released the report “World Health Statistics 2012” of WHO revealing that obesity is the death cause of 2.8 million of people per year and that 12% of the world population is considered obese, and the American continent has the highest incidence of the disease.

Since obesity is reaching epidemic proportions, its effective management is an important clinical problem. Despite scientific efforts to understand the mechanisms that lead to overconsumption of food and overweight, at the moment, few weight management approaches are effective in a long-term12.

Therapeutic strategies to treat obesity include synthetic drugs and surgery, which can result in high costs and serious complications. Medicinal agents, herbal products, offer an alternative approach to manage weight, in combating obesity and co-morbidities associated resulting in a safer and more efficient treatment without risks to health2,13, due to their fewer side effects compared to synthetic drugs3. Thus, the phytotherapic represent a new potential coadjuvant or alternative therapy for the treatment of obesity14 and have frequently been used to promote weight loss15.

These agents act through five basic mechanisms, including the stimulation of thermogenesis, reduction of lipogenesis, increase of lipolysis, appetite suppression and decrease of lipids absorption13. Currently, the term “thermogenic fat burner” has been used to describe nutritional supplements that promote, somehow, the fat metabolism by increasing energy expenditure, fat burning, weight loss, lipid oxidation during the exercise16.

The probable reasons for obese people prefer herbal products for weight control include healthy weight loss without any side effects; lower demanding in lifestyle changes such as diet and exercise; ease of acquisition, available without a prescription; more easily accepted than a professional consultation with a doctor or a nutritionist; 100% natural with the perception that natural means safe7.

For these reasons, people in all countries have been using herbal medicines for weight control and treatment of obesity1,6,8. But despite these substances promise to improve or prevent the obesity, costs, effectiveness and side effects have to be considered and, for these reasons, they must be studied intensively1,2.

Among the natural supplements, herbals for the treatment of obesity, stands out the natural extract obtained from dried fruit of the tree Garcinia cambogia (GC), which is found in the forests of South India and South Asia, has been studied extensively and used as a supplement for weight loss1,2,6,8,17.

The hydroxyl citric acid or hydroxycitric acid (HCA) is extracted from the rind of the fruit. It is an organic acid considered the main active ingredient, which acts as a potential supplement to the weight control3,17,18,19 by causing the appetite suppression and reducing the body’s ability to form adipose tissue3. Besides acting as a phytotherapic coadjuvant for the treatment of obesity, the GC extract and its active component HCA have also been used to reduce cholesterol and triglycerides.

It is also available with addition of calcium, magnesium, potassium and mixtures thereof due to other effects, such as improvement of glucose tolerance and of blood pressure20,21.

Unlike chemical stimulants used for weight loss, it does not act on the central nervous system and does not cause insomnia, nervousness, changes in blood pressure or heart rate and its efficiency does not decrease along the time17,21. This way, the GC extract is quickly becoming a popular ingredient among many supplements for weight loss and has been used routinely for many centuries for not showing toxic effects3.

The evaluation of its toxicity to the weight control is extremely important, as it requires a continuous consumption in the long term in order to maintain its effects8. Currently, the GC is being released by the National Health Surveillance Agency (ANVISA) and has been indicated as a coadjunct of overweight for participating in the regulation of appetite22, but the sale can only be made under a medical prescription.
The Resolution of the Federal Council of Nutritionists (FCN) of Brazil nr.390/200623 regulates the dietary prescription of nutritional supplements by the nutritionist and determines that it can be done based on the nutritional diagnosis in the following cases: I. specific physiological states; II. pathological conditions; III. metabolic changes, and the prescription of nutritional supplements should still be based on the following premises: I. food consumption adequacy; II. definition of the period of supplementation use; III. systematic re-evaluation of the nutritional status and of the dietary plan.

Due to the large supply in the market, marketing and popular use of herbal medicines, such as GC to act as a coadjuvant in treatments for obesity, this study aimed to deepen the scientific evidence on the effects of GC administration as a coadjuvant factor in the treatment of obesity regarding to its effectiveness, form of action, recommended daily dosage, side effects and contraindications, as a way of food and nutritional security for the population.

Literature review study for which there were consulted the LILACS-BIREME, MEDLINE and SciELO databases and selected scientific articles published in English, Portuguese and Spanish, between the period of 2007 and 2014 that conducted studies involving the administration of GC as a way of treatment for obesity. The descriptors used for research articles in the databases were the following: Garcínia Cambogia in Portuguese, and in English the terms used were “Garcinia cambogia”, “weight loss and obesity” and “Hydroxycitric Acid (HCA)”; this latter is not an indexed descriptor in the Health Science Descriptors (DeCS), but given the importance of this term for the search, it was adopted as a keyword. Thirty-four articles were identified, but only 21 were related to the objectives of this study. The first analysis of the articles was conducted by the title and then by the summary. In addition, 20 references were included because of their relevance to the study.
Table I shows the main results of non-randomized studies with supplementation of GC/HCA and table II presents the main results of randomized studies with supplementation of GC/HCA.
Due to the dramatic increase of the number of obesity cases in recent years, this disease has become one of the most important problems that public health has faced in several countries around the world, nowadays. In view of this, several methods to assist weight loss have arisen, like miracle diets and dietary supplements, but, often, little is known about the regular use and long-term of certain substances.
According to Kimet et al.24, GC is a popular supplement for weight loss. Studies suggest that the use of GC stimulates the burning of body fat, helps to inhibit appetite by reducing the desire to eat with a consequent reduction in food intake, and promotes satiety, and also acts in weight maintenance.

Being a study that aims the GC administration as a coadjuvant in the treatment of weight reduction, it can provide important information for both scientific uses as for the general population about the effects of its administration as a way to help in the treatment of obesity.

Table I



Effectiveness and way of acting
In the analysis of the effectiveness of GC, the study of Kovacs and Westertep-Plantenga28 concluded, in an experimental condition in humans, that the treatment with HCA during overfeeding with CHO can reduce the DNL. In rats, Kim et al.24 verified that the supplementation of this herbal medicine helped to reduce the body fat, but not to decrease weight or appetite.

Although, in humans, Kim et al.15 observed that the GC supplementation did not reduce the percentage of body fat, as it did not act on the decrease of appetite, BW, BMI and waist-hip ratio (WHR). Murer2 concluded that individuals with and without GC supplementation showed reduction of body fat and emphasized that the combination of diet and physical activity still remains the most suitable for positive changes of body composition.

The experiment of Anton et al.14 in humans also did not observe significant effects with the administration of GC dosages on food intake, satiety, weight loss, and oxidative stress levels. They highlighted that further research is needed to explore the promising effects of herbal medicines on food intake and satiety levels. However, they chose the compound derived from GC for their study because they noted in the literature its potential in acting in the reduction of food intake, in BW and in the levels of oxidative stress with safety, affecting the neuroendocrine pathways related to satiety.

Lira-García et al.29, in their review study with among sixteen assessed studies, found only one study that demonstrated significant weight loss between the control group and the experimental group with dosage of 1200 mg/day of GC and concluded that it was not possible to prove the effectiveness of the alternative products for weight loss because there is not enough GC protected against obesity induced [24] by HFD through the modulation of the synthesis of fatty acids and β-oxidation, but induced hepatic fibrosis, inflammation and oxidative stress.

The HFD and HSD groups showed [25] a significant increase in feed intake,
BW, BMI, TG, LDL, oxidative stress and renal disorder, while the groups supplemented with GC showed improvement of the harmful effects of HFD and HSD diets, with consequent reduction of feed intake, increase of the MDA level and decreased oxidative stress in renal tissue.

The supplementation of the GC HFD [26] failed to reduce the rising levels of serum lipids.
High intakes of HCA alone did not [20] lead to signs of inflammation or hepatotoxicity.

Table I

EGML and GCE did not promote [15] BW loss neither decreased the TC in overweight individuals consuming
usual diet. EGML increased levels of HDL-C. There were no serious adverse effects reported by the intake of EGML, GCE or placebo (starch).
No significant effects were observed [14] with the administration of the GC dosages or adverse effect level
(NOAEL) in humans at doses of

The supplementation of HCA [27] enhances the rate of glycogen synthesis in human skeletal muscle
and improves the postprandial insulin sensitivity.

The combination of diet and physical [2] activity remains the most suitable for positive changes in body composition.

The treatment with HCA during [28] overfeeding with carbohydrates can reduce DNL.

The study of Onakpoya et al.30, also of review, using data from randomized clinical trials (RCTs) in order to examine the effectiveness of GC/HCA extract as weight reducing agent, observed a small significant difference in loss weight, favoring the HCA over the placebo and they concluded that the ECR suggest that the GC/ HCA extracts can cause short term weight loss, confirming the review study of Astell et al.31, who concluded that the results of the RCT showed that the GC extract is effective in reducing body weight by suppressing appetite. The study of Amin, Kamel and Eltawab25, with rats, also concluded that the GC supplementation decreased the feed intake.

The theory behind the GC/HCA is that it works as anti-obesity agent by acting in the neuroendocrine pathways, related to the satiety, producing an anorectic effect, by promoting the inhibition of citrate lyase
enzyme that suppresses the appetite and increases the burning of body fat. Thus, it assists in regulating appetite, with consequent reduction of food intake, caloric restriction and weight loss. By inhibiting this enzyme, the body increases the oxidation of carbohydrates and inhibits the lipogenesis3,14,17,18,32,33. According to the ANVISA34, the register situation of GC in Brazil is classified in the category of appetite modulators and products for special diets, and it is indicated as a coadjuvant of overweight to participate in the regulation of appetite22.

Recently, there was found that the GC supplementation can be used as a metabolic regulator of obesity and lipid abnormalities in the system of mammals.19 Pandya et al.21, Sethi3, and Krishnamoorthy17 claim that GC/HCA reduces the lipid levels in blood, such as triglycerides and cholesterol, besides of increasing the thermogenesis. The HCA inhibits competitively the extramitochondrial citrate lyase enzyme that catalyzes the cleavage of citrate to acetyl-CoA and oxaloacetate, a key step in lipogenesis, necessary for the synthesis of fatty acids and cholesterol35,36.

However, in some studies, such as by Kim et al.24, in rats, there was found that the GC supplementation did not cause significant differences in the levels of TG, TC, HDL-c, phospholipids and free fatty acids. Similarly, the study of Ates et al.26 observed that the GC supplementation coupled with the high fat diet failed to reduce the increased serum levels of lipids in rats. In humans, Kim et al.15 also observed that after the supplementation of GC there were no significant differences in lipid levels (triglycerides and low-density lipoprotein LDL-c), or of adipocytokines (hormones of high adipocytes in obesity). A laboratory study performed by Simon et al.6 also concluded that there were not observed significant effects for the treatment of obesity and of other dyslipidemia with GC.

In contrast, the study of Amin et al.25 in rats, concluded that the GC supplementation improved the harmful effects caused by HFD or HSD, such as hypertriglyceridemia, increase of production of LDL, and of oxidative stress. Santos et al.36 reported in their review study that the administration GC showed inhibition of lipogenesis in the liver of rodents, adipose tissue, and small intestine but without confirmation in humans and claim that the only applicability of the HCA as anti-obesity agent seems to be the reduction of appetite, due to its anorectic effect.

Pandya et al.21 and Krishnamoorthy17 claim that the GC/HCA acts in the suppression of appetite by making glycogen synthesis in the liver and in other body tissues, increasing the energy levels.
The study done by Cheng et al.27 found that the HCA supplementation reinforced the glycogen synthesis rate in human skeletal muscle, improved the postmeal insulin sensitivity, and demanded higher energy expenditure in fat oxidation. Kim et al.2 observed that in rats the GC supplementation caused lower glucose levels, assuming that this could improve glucose tolerance by contributing to the reduction of visceral fat, since it is responsible for insulin resistance even in hyperlipidic diets.

Several in vivo studies have contributed to the understanding of the anti-obesity effects of GC/HCA via the release of serotonin in the brain, which has been considered as the main mechanism to decrease appetite and absorption of glucose and also in the increase of oxidation of fat, reducing DNL29,33. In recent studies in female mouse, there has been observed the effect of HCA on the regulator genes of obesity29. However, studies related to the presence of enzymatic inhibitors in extracts of these plants that participate or are responsible for its anti-obesity properties are scarce in the literature. Since the research conducted to evaluate the effective and safe use of herbal medicines is incipient, the notifications of events help in the generation of new information, promoting its rational use32.

Santos et al.36 still claim that in order to qualify the HCA as an anti-obesity effective metabolic agent it should produce a stimulating effect on the skeletal muscle, on the total fat oxidation or on the calorie consumption, but this has not been proved yet. Studies with this herbal demonstrated its effectiveness in combating obesity; however, there miss further studies on its mechanism of action to generate more security in its therapeutic use.

Tucci12 also states that the GC can contribute to the appetite suppression, but it still should be better demonstrated. In his review study, he noted that some phytochemicals show promising effects on weight control, however, more data is needed to define the real magnitude of effects and ideal doses. For Chandrasekaran7, an ideal anti-obesity herbal has to reduce the weight by 10% in relation to the placebo during the period of treatment, showing evidence of improvement of biochemical tests, like in the levels of lipids and glucose, without any side effects.

Daily Recommended Amount
The study of Amin et al.25 observed positive effects, such as decreased appetite and improve of the harmful effects caused by high fat and sucrose diets in rats that received supplementation of 50 mg/day of GC. The study of Cheng et al. 27 highlighted that the HCA supplementation enhanced the rate of glycogen synthesis in human skeletal muscle and improved the post-meal insulin sensitivity in the amount of 500 mg/day combined with a meal high in CHO (80% CHO, 8% LIP, 12% PROT) after 60 minutes of bicycle. Kovacs and Westertep-plantenga28 observed that the treatment with three capsules of 500 mg/day (1500mg/day) of HCA during the overfeeding with carbohydrate can reduce the DNL.

Ates et al.26 observed in rats that the GC supplementation combined with the hyperlipidic diet was not able to reduce the increase of the serum lipid levels in a dose of 2.390 mg/day of GC and suggest that higher dosages of GC extract should be investigated. Kim et al.15, noticed that for humans the intake of 2000 mg/ day of GC did not promote weight loss neither decreased the total cholesterol in overweight individuals consuming their usual diet. Anton et al.14 also did not observe significant effects in individuals with the administration of higher dosages of GC, 2800 mg/day and 5600 mg/day.

Murer2 concluded in his study that the combination of diet and physical activity remain the most suitable for positive changes in body composition by observing the combination of normocaloric diet associated with the intake of two capsules of 500 mg/day of GC (1000 mg/day), since the supplemented group and the unsupplemented group, fed only with normocaloric diet reduced body fat.
Although Onakpoya et al.30, in their review article with ECR have concluded that the dosage of HCA

The effect of Garcinia Cambogia as Nutr Hosp. 2015;32(6):2400-2408 2405 coadjuvant in the weight loss process used among the studies ranged from 1000 mg/day to 2800 mg/day, which resulted in a small weight loss, and they said that the magnitude of the effect is small and the clinical relevance is uncertain; so, future clinical trials should be stricter and better reported and that the ideal dose of HCA is currently unknown.
GC supplements are available in various forms, including pills, capsules and powders. The herbal medicine is usually standardized to contain fixed percentage of HCA, and the usual dosage from 300 mg to 500 mg should be administered three times a day and ingested half an hour before meals with water3.

Side effects and contraindications
About the side effects and contraindications of the GC usage, there was observed in the study of Kim et al.24 that the prolonged use of GC in the administered dose in rats can cause hepatotoxic effects and even develop non-alcoholic hepatic steatosis because of the accumulation of collagen in the liver, independently of being caused by hyperlipidic diet.

Lobb37 claims that there are a growing number of reports of hepatotoxicity caused by supplements containing HCA. In his study, he approached six case reports: two women, of 33 and 40 years old, and four men of 19, 27, 28, and 30 years old; underestimating the incidence of hepatotoxicity associated with weight loss with the HCA. Each report showed similarities; in the screening of hepatic abnormalities and in the symptoms presented by patients, who were healthy and with normal hepatic functions. Among the laboratory findings and symptoms there were reported fatigue, nausea, vomiting, colic, fever, chills, anorexia, abdominal pain, jaundice in a period ranging from three days to three weeks; deregulated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin. Onakpoya et al.30, in their review study, observed, gastrointestinal adverse events twice more common in the HCA group in comparison to the placebo group.

In contrast, Clouatre and Preuss20 claim that the results obtained about the HCA safety and efficacy are different from a variety of studies performed with animals and humans, since they observed in rats that the HCA produced protective effect against the hepatic toxicity associated with ethanol and administration of dexamethasone, and kept levels of SGOT, SGPT, and alkaline phosphatase at almost normal levels. The compound was found to reduce the inflammatory response in the brain, intestine, kidney and serum, and they highlight that high intakes of HCA, by itself, did not lead to signs of inflammation or hepatotoxicity.

Sethi3 also affirms the protection capacity of the GC against external hepatotoxins such as alcohol, and a recent study showed its effect preventing liver cells becoming fibrocytes. Shivashankara et al.38, observed in their review study that pre-clinical studies conducted recently have shown that some herbal medicines, such as GC, protect against ethanol-induced hepatotoxicity, through the mechanism mediated by antioxidant action, elimination of free radicals, anti-inflammatory and antifibrotic, but they emphasized that future studies would be required to establish its applicability in humans.

In humans, Kim et al. 15 did not observe reports of serious adverse effects by the individuals who consumed GC supplements, corroborating the study of Anton et al.14 who also did not observe adverse effect (NOAEL) in humans with doses higher than 4000 mg/ dia. Lira-García et al.29, concluded in their review study that among the eight studies that were evaluated, in none of them were observed adverse effects on the use of GC.
The review studies conducted by Chuah et al.8, and Chuah et al.33, concluded that there was not observed adverse effect (NOAEL) in dosages of GC/HCA of up to 2800 mg/day, suggesting its safety for use. Most of the reports demonstrated the efficacy of GC/HCA, and there wasn’t found any toxicity.

Sethi3 concluded in his review study that the herbal medicines are more beneficial in the treatment of obesity due to its fewer side effects and also act on the prevention of diseases such as type 2 diabetes, heart disease, high blood pressure. Until now, there is no case study or report showing the direct adverse effect of HCA8, as well as there is no evidence that demonstrates hepatotoxicity associated with the HCA, and the true agents need to be firmly identified, along with the dose to which the negative effects are induced39.

Pandya et al.21 also claim that there aren’t any known side effects for the usage of this herb. However, it is not recommended for people diagnosed with diabetes or people suffering from any kind of dementia or syndrome, including Alzheimer disease as well as pregnant and lactating women and has contraindications regarding the concomitant use of certain drugs.

Egras et al.40 concluded in their review study that many obese people use food supplements for weight loss and that, so far, there is little clinical evidence to support their findings, but it is necessary to determine their efficacy and safety. Health professionals should be aware of the products available for weight loss to help their patients and to determine the risks and benefits of the supplement used to loss of weight. Yuliana et al.41 still claim that despite insufficient data regarding to its safety and efficacy, many herbal medicines are available for sale without a prescription, such as the GC, which reduces the appetite, and that the quality control of these herbal medicines also becomes important.
This review study has several limitations.

Although the research has involved studies in electronic media, there may not have identified all those available involving the use of GC/HCA as a supplement for weight loss. Furthermore, the methodological quality of most studies identified from this study is short. These factors hinder conclusive findings about the effects of GC/HCA on body weight.

Final considerations
Studies suggest positive results concerning the effectiveness of the GC in weight loss process, by reducing the appetite, the percentage of fat, the lipogenesis process, as well as the improvement of biochemical levels, such as triglycerides, cholesterol and glucose, muscle glycogen synthesis, and postmeal insulin sensitivity.

However, the ideal dose has not been well established yet; however the GC supplements are available in 300 mg and 500 mg dosages, with the intake direction of three times a day, with water, half an hour before the meals.

There is little evidence of adverse effects and signs of protective effect against the hepatotoxicity induced by ethanol. Therefore, it is necessary to carry out more randomized, controlled studies, clinical trials to evidence the efficacy of this herbal in the weight loss process, as well as the set of the posology, dosages, indications and contraindications.