Tuesday, August 26, 2014

REVIEW: The Rise and Controversy of Garcinia Cambogia Extract for Weight Loss

In our society where almost nothing is impossible, scam is also present everywhere and almost in every product there is a scam and there are scammers.  The weight loss market has not escape from the scammer and fake products. In fact according to the Press Release of Federal Trade Commission posted in their website last January 7, 2014 about the Crackdown on Deceptive Advertising, has charged Sensa, L’Occitane HCG Diet Direct LeanSpa, LLC for used of deceptive advertising claims to peddle fad weight- loss products, from food additives and skin cream to dietary supplements.
  • L’Occitane, which claimed that its skin cream would slim users’ bodies but had no science to back up that claim, and
  • HCG Diet Direct, which marketed an unproven human hormone that has been touted by hucksters for more than half a century as a weight-loss treatment.
  • Sensa, deceptively advertised that the powdered food additive Sensa enhances food’s smell and taste, making users feel full faster, so they eat less and lose weight, without dieting, and without changing their exercise regime.  The defendants did not have competent and reliable scientific evidence to support these claims, according to the FTC’s complaint.
  • LeanSpa LLC, was also charged for deceptively promoting their product through a fake news website that openly promote the benefits of the product.
The four companies are just few of the many companies that have been charged for deceptive advertising of weight loss product. The common denominator of their charges was that, first, they have no scientific evidence of their claim about the effectiveness of the product; second, in some instances consumers were compensated for their endorsement of the product; third, they falsely cited clinical studies to promote the product. 

How about Garcinia Cambogia Extract? It is a known weight loss product in the market that started to pop-up in the market in the late 2012 and has 2.7 million monthly average searches according to Google for the last 12 months since 2013 until June 2014. 

Scroll down the page and together let’s examine the validity of the claim about Garcinia Cambogia and how effective it is for weight loss; and whether the claim about it also falls on one of the three common denominator of false advertising mention above.

We will also examine how to spot deceptive and fake weight loss product.

Happy Reading and Learning for a Safe and Effective Weight Loss. 

What is in Garcinia Cambogia?

Garcinia Cambogia is a scientific name of fruit tree that grows in the tropical countries of the Southeast Asia, particularly in Indonesia, Malaysia, India and the Philippines. The fruit of this tree looks like a small pumpkin and is green to pale yellow in color. It has recently received significant media attention because of its claimed effects on weight loss.

The main component that is in Garcinia Cambogia Extract (GCE) is the Hydroxycitric Acid (HCA), which becomes the centre of the claim that because of this natural acid content, it makes weight loss fast and easy. Even without the need of diet and exercise.

How did it all Started?

Garcinia Cambogia Extract never had a significant history in the Google Trends until September 2012. But in October 2012, the word Garcinia Cambogia has started to pop up in the Google Trends and has made it to the top with an average of 2.7 million searches per month according to Google for the last 12 months prior to July 2014. 

It all started with a TV Show, “The Dr Oz Show” hosted by Dr. Mehmet Oz. 

Dr Mehmet Oz is a known American cardiothoracic surgeon. He is an author of some medical books and a TV personality with show such as “The Dr Oz Show”, “NY Med”, “The Truth About Food”, “National Body Challenge” and “Your Life A to Z”. 

Dr. Oz is a respected medical practitioner having appeared in the popular TV shows of Oprah Winfrey and Larry King. 

In the Oct 29, 2012 episode of his show, Dr Oz repeatedly and with flowery words touted about the Holy Grail of weight loss, the GCE or the Garcinia Cambogia Extract. Who doesn’t like it? No Exercise, No Diet and No Effort weight loss product.

 What is Hydroxycitric Acid?

HCA is a derivative of citric acid and can be found in plants species native to South Asia such as Garcinia Cambogia, Garcinia Indica and Garcinia Atroviridis. HCA is usually marketed as a weight loss supplement either alone or in combination with other supplements. 

HCA has been shown to be a competitive inhibitor of ATP-citrate lyase, the enzyme catalysing the extramitochondrial cleavage of citrate to oxaloacetate the acetyl-CoA. This enzyme is important in maintaining the acetyl-CoA pool for fatty acid and cholesterol biosynthesis, particularly during the hyperlipogenic nutritional state produced by high carbohydrates feeding. 

1. Sources and Composition of Garcinia Cambogia

1.1. Sources

Garcinia Cambogia (of the family Guttiferae), sometimes also referred to as Pazham Puzhi[4], Malabar tamarind,[5] or Bitter Kola[6] is a plant that bears small fruits (5cm diameter) and has traditionally been used as a food additive to both enhance the flavor of food products and to enhance satiety following consumption.[5] Very limited traditional medicine usage extends to gastrointestinal complications.[5]

1.2. Composition

The fruits of Garcinia Cambogia tend to contain:

  • Citric Acids (causative of taste and flavor) at 10-30% dry weight, of which a large segment consists of hydroxycitric acids (HCAs);[7] HCAs come in four isomers, (-)-Hydroxycitric acid, (+)-Hydroxycitric acid, (-)-Allo-HCA, and (+)-Allo-HCA[5]
  • Guttiferone I-K[8][9] and M-N[8]
  • The polyisoprenylated benzophenones Garcinol[9] and Isogarcinol[10]
  • Xanthochymol (highly variable between 113.66+/-0.75ng/mL fruit and undetectable) and Isoxamthochymol (23.26ng/mL or lower); about 2.52-2.56ng/mL of both in the leaves[11][12]
  • Cambogin, an isomer of isoxanthochymol[10] and Camboginol[13] (88.2mg/g of the fruit methanolic extract; undetectable in aqueous extracts, seeds, or stems)[10]
  • Isoxanthochymol (16.6mg/g methanolic extract; none in aqueous extract of the stems/seeds)[10]

It should be noted that currently marketed (-)-Hydroxycitric Acid supplements tend to be calcium/potassium salts of (-)-HCA containing about 60% (-)-HCA by weight.[5]

2. Pharmacology of Garcinia Cambogia

2.1. Serum

2g of (-)-HCA salts given to 4 human participants on an empty stomach resulting in plasma levels of 0.8μg/mL within 30 minutes leading up to plasma levels of 8.4μg/mL at two hours with a variable peak between 4.7 and 8.4μg/mL.[14] The authors hypothesized that if absorption was complete and evenly distributed, it would have resulted in a serum peak of 46μg/mL (based on the participant's body weight and 25% body fat), a preliminary guess at the bioavailbility of (-)-Hydroxycitric acid following oral administration would be 10-18%.[14]

The bioactive has been demonstrated to appear in the blood following oral administration, and may have bioactivity

3.1. Appetite

In freshly prepare rat brain slices, (-)-Hydroxycitric acid (salt form; 60% HCA by weight) was able to inhibit serotonin reuptake into rat corticol slices by 20% (300uM concentration), which was outperformed by fluoxetine (100uM) plus clomipramine (10uM) which inhibited 30% of uptake; oddly, no inhibition was noted with 1000uM (1mM) of (-)-Hydroxycitric acid.[15] The increased bioavailability of serotonin is thought to be related to appetite suppressing effects of supplemental (-)-Hydroxycitric acid.[15]

Another possible mechanism is the thought to be leptin related. One rat study (that failed to find reductions in food intake or weight after 4 weeks of 3.3% (-)-Hydroxycitric acid) noted that serum levels of insulin and leptin decreased, which was thought to be in response to leptin-mimetic actions (not established).[16]

May inhibit the reuptake of serotonin (not yet confirmed in a living model)

In rats who have had the reductions in feed intake quantified, it has been reported to be reduce by 13.7% (0.2% feed intake), 26.7% (2% feed intake) and 25.6% (5% feed intake) in male rats with similar reductions in female rats, with significant reductions of feed intake in this study only occurring 46 days after consumption (earliest) or 74 days (all tested doses).[17]

In rats, appears to suppress food intake

3.2. Neuroprotection

Garcinia Cambogia has once been associated with reduced brain oxidation and pathology of neurodegeneration, but was said to be working vicariously through reduced food intake and body weight (with the study concluding that the state of obesity and a high fat diet impairs neural function).[18]

4. Cardiovascular Health and Garcinia Cambogia

4.1. Lipoproteins and Cholesterol

A study in rates using 200-400mg/kg Garcinia Cambogia seeds (ethanolic extract) noted slight but statistically significant increases in LDL-C (the 'bad' cholesterol) with decreases in HDL-C, vLDL-C, and triglycerides.[6]

In obese humans given 2g of Garcinia Cambogia (60% Hydroxycitric acid) for 10 weeks, there were no significant alterations in ApoA1, ApoB, Phospholipids, Free Fatty acids, or the Artherogenic Index.[19]

4.2. Blood

One study on blood lipids also noted a small but significant increase in red blood cell count, indicative of erythropoeisis.[6] One review[5] suggests this may be due to the iron content of the seeds, or perhaps an increase in testosterone from the polyphenolic component.

5. Interactions with Fat Mass of Garcinia Cambogia

5.1. Mechanisms

(-)-Hydroxycitric acid appears to be a competitive inhibitor of the enzyme adenosine triphosphate-citrate (pro-3S)-lyase (a shorter designation is ATP Citrate Lysase),[20] which is an enzyme in the biosynthetic pathway of fatty acids (de novo lipogenesis) and its inhibition results in suppressed formation of Acetyl-CoA from Citrate and less substrate for fatty acid synthesis in vitro.[21] The (+)- isomer of Hydroxycitric acid does not have this same inhibitory potential, and is instead a substrate of the enzyme.

Can inhibit an enzyme in the de novo lipogenesis pathway that mediates fatty acid synthesis from non-fat sources, thought to inhibit the synthesis and deposition of fatty acids via this mechanism

The relevance of this pathway to humans may be in question, as human capacity for de novo lipogenesis does exist but tends to be less than that of rodents that are commonly used in research.[22]

In regards to this mechanism of action, there may be species-related differences

5.2. Adipokines 

2g of Garcinia Carmbogia for 10 weeks was associated with a reduction in the adipokine Adipsin (19%) without significantly influencing Adiponectin or Leptin.[19]

5.3. Weight Regain

There have been a few studies assessing weight regain. One in rats who were semi-starved (less than 10g of food daily for 10 days) who were subsequently randomized to receive normal diets of standard chow, sucrose loaded chow, glucose loaded chow or a high glucose fat diet with half of each group recieving 3% (-)-Hydroxycitric acid (85mmol/kg) and then followed for 10 days (so overall, 8 groups of which 4 had HCA supplementation).[23] 

This study noted that the inevitable weight regain in these rats was attenuated with HCA supplementation in all groups except normal chow, and only reached significance with glucose and glucose+fat diet groups; this was in part due to less food intake, and appeared to decrease the food efficiency ratio with all groups except standard chow.[23] This trial style was replicated with the glucose group, and it was noted that food intake was suppressed for a short time, and although there was indication that de novo lipogenesis may have been inhibited there was no significant suppressive effect on body weight regain.[24]

Two rat studies suggesting that Garcinia can reduce the amount of weight regained during a period of overfeeding after a period of low caloric intake 

5.4. Weight Gain

A rat trial in which rats were fed an obesogenic diet for 15 days with 2% added (-)-Hydroxycitric acid (as trisodium conjugate) noted that the food efficiency ratio decreased to 60% of control, and that body weight gain was suppressed to approximately half (49%) of control; food intake also decreased 17%, which would have contributed to the observed reduction in weight.[25]

One rat study suggesting that Garcinia can attenuate the rate of weight gain

5.5. Weight Loss

A study in human subjects using 2g Garcinia cambogia (60% Hydroxycitric acid) for 10 weeks in 86 overweight adults failed to find significant differences in weight loss or food intake.[19] One study using 2400mg of Garcinia cambogia daily divided before meals noted that while active treatment lost more weight from a low calorie diet than placebo over a period of 12 weeks (3.7+/-3.1kg weight loss rather than 2.4+/-2.9kg) that there were no reported differences in appetite.[26]

One of the larger and better controlled studies on the matter noted that, 1000mg of Garcinia Camboga (50% HCA by weight) taken before the three main meals of a low calorie diet given to overweight but otherwise healthy adults (of which placebo was also placed on) and then followed for 12 weeks failed to find any significant differences in dropout rates, weight loss, or adverse effects relative to placebo.[27]

Studies done in humans using isolated Garcinia Cambogia have mixed results on fat loss, with the one study reporting benefit showing relatively low magnitude of benefit (1.3kg more than placebo over 3 months, with very high variability)

In 40 persons with a BMI between 27.5-39 (mostly obese) given 100mg Garcinia Cambogia (confounded with inclusion of 400mg Inulin and 200mg White Kidney bean extract) before each of the three major meals for a period of 12 weeks, with both placebo and supplemental group being advised to diet (1200kcal), noted that weight loss in the diet and supplement group was greater (4% body weight over 12 weeks) than the diet and placebo group (not statistically significance).[1] Dropouts from the study were also greater in placebo (6) than supplement (1) groups.[1] One other study that uses Garcinia Cambogia but is highly confounded with other nutrients also noted beneficial effects on weight loss.[3]

The studies that are associated with both weight loss and Garcinia Camboga are confounded with many ingredients, and the observed effects on fat loss cannot be attributed to Garcinia itself.

Several reviews on the efficacy of Garcinia Cambogia suggest no significant benefit for weight loss in human interventions.[28][29][30][31][32] The rather frequent inclusion of Garcinia Cambogia in review articles relative to the lack of interventions may be related to the popularity of the supplement.

Numerous review articles assessing the evidence of Garcinia Cambogia conclude that there is no significant benefit of this compound in humans

6. Interactions with Glucose Metabolism of Garcinia Cambogia

6.1. Glycogen

When 500mg (-)-Hydroxycitric acid is consumed alongside 2g/kg carbohydrate post exercise in humans, a slight increase in the rate of glycogen resynthesis occurs.[33]

7. Interactions with Hormones of Garcinia Cambogia

7.1. Testosterone

1667.3mg of Garcinia Cambogia for 12 weeks (1000mg (-)-Hydroxycitric acid) failed to find significant influences on serum testosterone.[34]

7.2. Estrogen

1667.3mg of Garcinia Cambogia for 12 weeks (1000mg (-)-Hydroxycitric acid) failed to find significant influences on serum estrogens (estrone and estradiol).[34]

80% HCA Super Strength Garcinia Cambogia Extreme With No Calcium 180 Fast Acting Capsules. All Natural Appetite Suppressant and Weight Loss Supplement By Hamilton Healthcare up to 4500mg Per Day for Maximum Results

8. Interactions with Organ Systems of Garcinia Cambogia

8.1. Kidney and Bladder

While ingestion of a high-fat or high-sucrose diet is able to increase serum levels of urea and creatinine (thought to be indicative of kidney impairment), coingestion of Garcinia Cambogia at 50mg/kg is able to effectively normalize the increases in creatinine and urea.[35]

Oral ingestion of the leaves from Garcinia Cambogia at 100-200mg/kg of either the water extract or ethanolic extract was able to increase urine output in the range of 36-72% (ethanolic) or 17-39% (aqueous), both of which underperformed to 20mg/kg injections of the reference drug furosemide.[36]

The leaves of Garcinia may have weak diuretic properties

8.2. Testes

One study noted that oral consumption of 778-1244mg/kg bodyweight of (-)-Hydroxycitric acid to rats for up to 93 days was associated with testicular toxiciy with lower doses not associated with testicular toxicity.[37] This study has been critiqued,[38] where the lack of assurance on the salt form was questioned and the fact that the No Obervable Adverse Effect Limit (NOAEL) of 389mg/kg in rats is still 10-16 fold higher than the typical recommended serving for humans.[38]

A lone report on testicular toxicity with high dose (-)-Hydroxycitric acid consumption; may not be relevant to human supplementation doses


9. Safety and Toxicology of Garcinia Cambogia

9.1. General

Acute (14 day) administration of 5000mg/kg bodyweight (-)-Hydroxycitric Acid to albino rats of both genders (small sample size of 10) was not associated with any mortality or clinical signs of toxicology.[15]

Studies that do not inhernetly design themselves to assess toxicology but nevertheless use (-)-Hydroxycitric acid supplementation have also failed to find any toxicity associated with 3% of the rat diet for 5 days[24] or 10 days,[23] or up to 5% of the feed for 90 days.[39]

Currently, the human trials cited in Examine do not report any adverse effects that occur in the treatment groups (using Garcinia Camboga) to a greater degree than placebo.

No observable toxicity in rats or humans following oral ingestion at this moment in time.

9.2. Mutagenicity

A preliminary study assessing the mutagenicity of (-)-Hydroxycitric acid on five strains of Salmonella typhimurium (TA98, TA100, TA102, TA1535, and TA1537) up to 5000mcg/plate failed to find evidence of DNA damage or mutagenicity associated with (-)-Hydroxycitric Acid[40] and a lack of genotoxicity was repeatedly demonstrated elsewhere with the Ames test;[40][41] this latter study noted that (-)-HCA increased the amount of micronucleated polychromatic erythrocytes (MNPCEs) after intravenous administration, which is though to be genotoxic.[41] The conclusion of this has been criticized for being suggestive of genotoxicity while the study had some design flaws (used DSMO alongside (-)-HCA while control got water, DMSO not being recommended for this test[42]) and no LD50 test of the method of administration prior to genotoxicity testing.[43]

In rats given up to 5% (-)-Hydroxycitric acid in feed intake for a period of 90 days, there does not appear to be any significant DNA fragmentation in the liver or testicles.[17]

There does not appear to be any influence of the bioactive (-)-Hydroxycitric acid on DNA fragmentation or genomic damage; unlikely to be carcinogenic

9.3. Case Studies

There are numerous case reports of hepatoxicity associated with a supplement known as 'Hydroxycut' which touts Garcinia Cambogia as the main active ingredient,[44][45] although it has been argued that there is no evidence to suggest a link to (-)-Hydroxycitric acid due to inclusion of many ingredients.[46]

In a patient on chronic Monteluskat treatment who then consumed two supplements, fatality occurred; it was thought that Montelukast interacted advesely with one of the many compounds consumed but causative could not be linked.[47]

One reported case of Rhabdoyolysis associated with a dietary supplement of which contained Garcinia Cambogia has been noted, although Ma Huang (plant source of Ephedrine) is a large confound alongside Chromium and Guarana.[48]

Due to the usage of Garcinia in fat burners, there have been reported connections between Garcinia and adverse effects; there is currently no evidence to assume a direct link between the compounds