Methodology Study target Summary Advantages Disadvantages Benefits Pitfall of experiment In vitro cytotoxicity 3T3 fibroblast [ 21] G. indica was cytotoxic on 3T3 Rapid test Not fully representative compared to animal/human subject. First line screening Poor methodology, only Balb/c 3T3 was screened. In vitro genotoxicity ~Ames test ~Chromosomal aberration test ~ Salmonella typhimuriumi, ~Chinese hamster ovarian cell [ 22] HCA-SX did not induced mutagenic activity Rapid test Not fully representative compared to animal/human subject. First line screening In vivo genotoxicity Micronucleus test 8 weeks old ICR mice [ 22] Micronucleated polychromatic erythrocytes in bone marrow cell Better representation than in vitro cell line study Variation among animal. Preclinical screening i.p. injection with DMSO as vehicle not suitable; no prior i.p.
μmol/kg exceed the highest dose, poor statistic analysis [ 23]. In vivo acute toxicity Albino rat [ 12] HCA SX
> 5 g/kg body weight
High dosage (233X higher than maximum dose of 1.5 g/day in human) Single administration. Understand acute toxic effect at high concentration Only
, gross necropsy and body weight were recorded. No blood biochemical profiling and full blood count.
In vivo subchronic Rat [ 24, 25] HCA-SX reduced body weight, feed intake but no effect on other parameters. Experiment was design to represent actual recommended dosage. — Good reference to support the entry of clinical studies. — In vivo skin irritation Albino rabbit [ 12] HCA-SX was none irritating with primary irritation index = 0. More representative than in vitro test. Single exposure. This study only tested the irritative potential with single exposure. In vivo eye irritation Albino rabbit [ 12] HCA-SX was mild irritant on eye. More representative than in vitro test. — HCA-SX is an oral supplement. Results for in vivo skin and eye irritation can help to strengthen the MSDS. — In vivo reproduction toxicity Rat [ 36, 40] HCA-SX did not affect the postnatal maturation, reproductive capacity. “No observed adverse effect level” of HCA-SX higher than 1.5 mg/kg/day was determined in both parental, offspring generation and HCA-SX was not teratogenic. — Good reference to support that HCA was none toxic effect against reproductive system. — In vivo reproduction toxicity Zucker obese rats [ 26, 27] G. cambogia powder (containing 41.2 wt% of (−)-HCA, the ratio of free to lactone form is 36.6 to 63.4) impaired spermatogenesis — — — Zucker rat is not suitable in this study since it has a defect in testicular testosterone production. HCA used in this experiment contains high lactone that may contributed to it the impairment of spermatogenesis [ 31] Clinical studies (as stated in Table 1) 873 subjects Garcinia/HCA is generally none toxic with NOAEL > 4 g HCA Garcinia/HCA was recorded as none toxic up to 12 weeks consumption. None of the studies recorded the use of Garcinia/HCA for more than 12 weeks. Garcinia/HCA is generally safe to consume up to 3 months. Continue monitoring on the consumers who take Garcinia/HCA for more than 3 months can strengthen the knowledge of long term safety assessment of Garcinia/HCA.