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group_4_presentation_1_-_weight_loss_supplements [2019/01/29 17:28]
dhaliwaa
group_4_presentation_1_-_weight_loss_supplements [2019/02/01 23:05] (current)
dhaliwaa [References]
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 ===== History ===== ===== History =====
 {{ :​weight_loss_supplements.jpg?​300|}} {{ :​weight_loss_supplements.jpg?​300|}}
-The late 1800s patent medicine era was when the first availability of diet pills was seen. They were known as fat reducers, which increased the metabolic rate as they were centered on thyroid extract. Even though they were known to be an effective way of losing weight, the pills had many side effects that were not expected including weakness, an increase in heart rate, and even death. Even with all the risks becoming noticeable, the availability of these pills continued until the 1960s.+The late 1800s patent medicine era was when the first availability of diet pills was seen (Whittemore,​ 2019). They were known as fat reducers, which increased the metabolic rate as they were centered on thyroid extract ​(Whittemore,​ 2019). Even though they were known to be an effective way of losing weight, the pills had many side effects that were not expected including weakness, an increase in heart rate, and even death (Whittemore,​ 2019). Even with all the risks becoming noticeable, the availability of these pills continued until the 1960s (Whittemore,​ 2019).
    
-Then in the 1930s, dinitrophenol turned out to be a common medication for weight reduction. This drug led to several accidents that contributed to the Food and Drug Administration gaining more control and making new laws.+Moving onto the 1930s, dinitrophenol turned out to be a common medication for weight reduction ​(Whittemore,​ 2019). This drug led to several accidents that contributed to the Food and Drug Administration gaining more control and making new laws.
    
-In the 1950sthe drug, amphetamine,​ was the popular choice. Soldiers were given this drug to keep them attentive during World War II. Since one of the effects was suppression of appetite, it led to people using these pills for weight reduction.+Next, in the 1950s the drug, amphetamine,​ was the popular choice ​(Whittemore,​ 2019). Soldiers were given this drug to keep them attentive during World War II. Since one of the effects was suppression of appetite, it led to people using these pills for weight reduction ​(Whittemore,​ 2019).
    
-Ephedrine ​was used with caffeine in the 1970s to help patients that had asthma. People eventually started using this for weight loss. The Dietary Supplement Health and Education Act passed in 1994 in the United States. This act classified the herb, ephedra, which does not need FDA approval. This caused the spread in usage of ephedrine for obesity and also as an appetite suppressant.+Following the 1950s, ephedrine ​was used with caffeine in the 1970s to help patients that had asthma ​(Whittemore,​ 2019). People eventually started using this for weight loss (Whittemore,​ 2019). The Dietary Supplement Health and Education Act passed in 1994 in the United States ​(Whittemore,​ 2019). This act classified the herb, ephedra, which does not need FDA approval ​(Whittemore,​ 2019). This caused the spread in usage of ephedrine for obesity and also as an appetite suppressant(Whittemore,​ 2019).
    
-In 1973, fenfluramine was a drug used for the treatment of weight loss. This drug became really popular in the 1990s where this drug became prescribed over 180,000,000 times in one year.+Shortly after, in 1973, fenfluramine was a drug used for the treatment of weight loss (Whittemore,​ 2019). This drug became really popular in the 1990s where this drug became prescribed over 180,000,000 times in one year (Whittemore,​ 2019).
    
-Many herbal-based weight loss supplements boomed in the 21st century. Throughout the years, researchers continuously developed new supplements and learned through their mistakes through testing.+Lastly, many herbal-based weight loss supplements boomed in the 21st century ​(Whittemore,​ 2019). Throughout the years, researchers continuously developed new supplements and learned through their mistakes through testing ​(Whittemore,​ 2019).
  
 ===== Myths ===== ===== Myths =====
  
 1)   ​Weight loss being a linear process 1)   ​Weight loss being a linear process
-A common misconception is that losing weight is a linear process. Everyone has days or even weeks where his or her body weights fluctuate. An example for women is that during their menstrual cycle, water weight fluctuates a lot. No matter how much the weight is fluctuating,​ as long as the weight is generally going down over time, the individual will achieve weight loss in the long term 
  
-2)   ​Supplements help with weight loss +A common misconception is that losing weight is a linear process (Gunnars, 2019). Everyone has days or even weeks where his or her body weights fluctuate (White, 2011). An example for women is that during their menstrual cycle, water weight fluctuates a lot (White, 2011). No matter how much the weight is fluctuating,​ as long as the weight is generally going down over time, the individual will achieve weight loss in the long term. 
-A lot of supplements claim they have huge effects, but once they are studied, they are observed not to be very effective. There are a few that have modest effects and help weight loss through several months. One of the main reasons weight loss occurs for people that take supplements is the placebo effect of people wanting these supplements to work and end up being more conscious of their eating habits.+ 
 +2)   ​Supplements ​always ​help in managing ​weight loss 
 + 
 +A lot of supplements claim they have huge effects, but once they are studied, they are observed not to be very effective ​(Gunnars, 2019). There are a few that have modest effects and help weight loss through several months. One of the main reasons weight loss occurs for people that take supplements is the placebo effect of people wanting these supplements to work and end up being more conscious of their eating habits ​(Gunnars, 2019).
  
 ===== Regulations ===== ===== Regulations =====
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 There are two main methods by which Garcinia Cambogia can facilitate weight loss. It can either block fat production or reduce appetite. ​ There are two main methods by which Garcinia Cambogia can facilitate weight loss. It can either block fat production or reduce appetite. ​
  
-Hydroxcytric ​acid, the principal ingredient in Garcinia supplements,​ is a significant inhibitor of ATP. It specifically acts on ATP citrate lyase which is the primary enzyme that generates acetyl CoA from citrate in the cytosol of mammalian cells (Watson et al., 1969). Additionally,​ studies show that Hydroxcytric ​acid inhibits fatty acid synthesis in the liver through a series of biomechanical pathways. In summary, HCA inhibits lipogenesis by inhibiting ACLY, SREBP-1c and FAS expression, and accelerates lipolysis through amplifying HL activity and PPARα expression (Han, 2016). The following figure summarizes the methods by which hydroxycytric ​acid can reduce fat accumulation.+Hydroxycitric ​acid, the principal ingredient in Garcinia supplements,​ is a significant inhibitor of ATP. It specifically acts on ATP citrate lyase which is the primary enzyme that generates acetyl CoA from citrate in the cytosol of mammalian cells (Watson et al., 1969). Additionally,​ studies show that hydroxycitric ​acid inhibits fatty acid synthesis in the liver through a series of biomechanical pathways. In summary, HCA inhibits lipogenesis by inhibiting ACLY, SREBP-1c and FAS expression, and accelerates lipolysis through amplifying HL activity and PPARα expression (Han, 2016). The following figure summarizes the methods by which hydroxycitric ​acid can reduce fat accumulation.
  
-The exact mechanism by which hydroxcytric ​acid suppresses appetite is unclear, however, rat studies suggest that Garcinia Cambodia can raise levels of serotonin, an appetite suppressant (Ohia et al., 2001). Researchers have shown that hydroxcytric ​acid can increase the release and availability of serotonin in the synaptic cleft in cells of the rat cortex. Serotonin is known to regulate eating behavior and appetite control by which higher levels tend to reduce appetite (Ohia et al., 2001). ​+The exact mechanism by which hydroxycitric ​acid suppresses appetite is unclear, however, rat studies suggest that Garcinia Cambodia can raise levels of serotonin, an appetite suppressant (Ohia et al., 2001). Researchers have shown that hydroxycitric ​acid can increase the release and availability of serotonin in the synaptic cleft in cells of the rat cortex. Serotonin is known to regulate eating behavior and appetite control by which higher levels tend to reduce appetite (Ohia et al., 2001). ​
  
 ===== Clinical Studies ===== ===== Clinical Studies =====
 Various studies in animals support the use of hydroxcitrate as a supplement (Rao & Sakariah, 1988). In a particular study, Albino rats were fed a lipogenic diet with and without the addition of (−) hydroxycitrate for 15 days. After sacrificing the rats, the blood, liver and epididymal fat contents were measured and subsequently analyzed. Results indicated that rats who consumed hydroxycitrate had a significant reduction in food consumption,​ epididymal fat, serum triglyceride and an overall decrease in the feed efficiency ratio (Rao & Sakariah, 1988). ​ Various studies in animals support the use of hydroxcitrate as a supplement (Rao & Sakariah, 1988). In a particular study, Albino rats were fed a lipogenic diet with and without the addition of (−) hydroxycitrate for 15 days. After sacrificing the rats, the blood, liver and epididymal fat contents were measured and subsequently analyzed. Results indicated that rats who consumed hydroxycitrate had a significant reduction in food consumption,​ epididymal fat, serum triglyceride and an overall decrease in the feed efficiency ratio (Rao & Sakariah, 1988). ​
  
-Some human trials also support the efficacy of hydroxcytric ​acid in reducing weight and fat (Preuss et al., 2004). A double-blind,​ placebo-controlled,​ human trial was conducted in thirty obese individuals for eight weeks in India. Results indicate that body weight and body mass index decline by 6.3% in the HCA group. Furthermore,​ total cholesterol and triglyceride levels were reduced by 6.3% and 8.6% while food intake was reduced by 4%. Urine analysis revealed a 125-258% increase in excretion of fat metabolites such as acetaldehyde,​ formaldehyde and acetone. Thus, it is evident that fat accumulation and weight loss can indeed occur by consuming HCA. Additionally,​ the study also noted that test participants had a 40% increase in serotonin, an appetite suppressant,​ which further provides support for the reduction in appetite (Preuss et al., 2004). ​+Some human trials also support the efficacy of hydroxycitric ​acid in reducing weight and fat (Preuss et al., 2004). A double-blind,​ placebo-controlled,​ human trial was conducted in thirty obese individuals for eight weeks in India. Results indicate that body weight and body mass index decline by 6.3% in the HCA group. Furthermore,​ total cholesterol and triglyceride levels were reduced by 6.3% and 8.6% while food intake was reduced by 4%. Urine analysis revealed a 125-258% increase in excretion of fat metabolites such as acetaldehyde,​ formaldehyde and acetone. Thus, it is evident that fat accumulation and weight loss can indeed occur by consuming HCA. Additionally,​ the study also noted that test participants had a 40% increase in serotonin, an appetite suppressant,​ which further provides support for the reduction in appetite (Preuss et al., 2004). ​
  
 ===== Side effects & recommended dosage: ===== ===== Side effects & recommended dosage: =====
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 In a study conducted by Fong and colleagues (2010) hepatoxicity due to Hydroxycut was investigated. 24 cases from the FDA were obtained and out of the 24, 9 were chosen for further analysis. All patients previously were healthy but developed an acute hepatic injury due to Hydroxycut. It was assumed that participants in the study, all took the recommended dosage that the manufacturers of the supplement stated. All cases of the patients were then assessed to find the causality and damage of each patient via the Drug- Induced Liver Injury Network (DILIN) study (Fong et al., 2010). The results showed that 8 patients who had an acute liver injury, occurred after taking Hydroxycut, all patients were hospitalized. Three of the eight patients required a liver transplant (Fong et al., 2010). This study demonstrated the impact of Hydroxycut on the users. ​ In a study conducted by Fong and colleagues (2010) hepatoxicity due to Hydroxycut was investigated. 24 cases from the FDA were obtained and out of the 24, 9 were chosen for further analysis. All patients previously were healthy but developed an acute hepatic injury due to Hydroxycut. It was assumed that participants in the study, all took the recommended dosage that the manufacturers of the supplement stated. All cases of the patients were then assessed to find the causality and damage of each patient via the Drug- Induced Liver Injury Network (DILIN) study (Fong et al., 2010). The results showed that 8 patients who had an acute liver injury, occurred after taking Hydroxycut, all patients were hospitalized. Three of the eight patients required a liver transplant (Fong et al., 2010). This study demonstrated the impact of Hydroxycut on the users. ​
  
-In another study conducted by Dehoney and Wellein (2009), rhabdomyolysis was diagnosed in patients that had taken the supplement. The researchers looked into a specific case study of an 18-year-old Caucasian man who was sent to the emergency room since he was suffering from bilateral leg pain and weakness (Dehoney & Wellein., 2009). ​ When he was asked by the practitioners,​ if he took any medications,​ he had stated that he had taken Hydroxycut, 4 tablets a month. It was determined from this information and further tests, that he had elevated levels of creatine kinase, serum creatinine and aspartate transaminase (Dehoney & Wellein., 2009). He was sent home the same day, and was told to not use Hydroxycut. Two weeks later, his creatine kinase and liver enzymes reached homeostasis (Dehoney & Wellein., 2009). Therefore, from this study, we can conclude that Hydroxycut does result in the symptoms of rhabdomyolysis and results in fluctuations in the body serum. ​+In another study conducted by Dehoney and Wellein (2009), rhabdomyolysis was diagnosed in patients that had taken the supplement. The researchers looked into a specific case study of an 18-year-old Caucasian man who was sent to the emergency room since he was suffering from bilateral leg pain and weakness (Dehoney & Wellein., 2009). ​ When he was asked by the practitioners,​ if he took any medications,​ he had stated that he had taken Hydroxycut, 4 tablets a day. It was determined from this information and further tests, that he had elevated levels of creatine kinase, serum creatinine and aspartate transaminase (Dehoney & Wellein., 2009). He was sent home the same day, and was told to not use Hydroxycut. Two weeks later, his creatine kinase and liver enzymes reached homeostasis (Dehoney & Wellein., 2009). Therefore, from this study, we can conclude that Hydroxycut does result in the symptoms of rhabdomyolysis and results in fluctuations in the body serum. ​
  
 ===== Side Effects & Recommended dosage ===== ===== Side Effects & Recommended dosage =====
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 ====== Conclusion ====== ====== Conclusion ======
-When selecting ​and determining the efficacy of fat loss supplements ​it is important to examine the various ingredients listed on the labelThe supplement industry ​is a for-profit business ​and oftentimesthere may be unsubstantiated and exaggerated claims of weight loss and it is therefore more crucial ​to look at relevant scientific studies to validate ​such statementsFurthermore,​ it is also imperative ​to critically analyze the studies that were performed and determine whether it the results ​can be applicable ​to human dosagesFor examplestudies done on raspberry ketones may show some promise ​in rodentsbut has no evidence ​of efficacy in humansMoreoverwhen converting rodent to human dosage, the required supplementation becomes astronomically highOther critical variables regarding dietary supplements ​also include safety ​and toxicityIt is strongly advised ​for individuals looking at fat loss supplements to do their own extensive research on individual compounds ​and risks involved+  
 +The best way to lose weight is to eat healthily ​and exercise! Although some weight ​loss supplements ​are successful, many of them can have detrimental side effects and injure your healthThere is a need for further research of these supplements as many new discoveries are made each year and links to new diseases are becoming more prevalent.  
 + 
 +Overall, weight loss supplements have not promised significant results in comparison ​to traditional conventions ​such as diet and exercisePeople often opt for weight loss supplements due to the desire for quick results, their availability without prescription,​ the lack of physical demand, and many more perceived benefits due to inflated advertisement claims 
 + 
 +In terms of the future of weight loss supplementsnew drugs such as Lorcaserin have come out on the market ​in recent yearsand have been considered safe for use (“A new drug,” 2018). This pill has not shown to increase the risk of cardiovascular disease as a side effect, and has demonstrated sustainable weight loss outcomes (Bohula et al., 2018). Whereas, popular supplements such as Garcinia Cambogia, Hydroxycut, and Synephrine, which have been available for years, have all demonstrated considerable side effects. However, with Lorcaserin, the average participant only lost about nine pounds over a four-year period, which has prompted health professionals to question whether it’s worth it (“A new drug,” 2018)It is also expensive, ​and can cost users almost $9,000 USD over this period of use (“A new drug,” 2018)Additionally,​ similar to other supplements on the market, there is not enough research to show that it won’t cause health problems in the future. The only drugs approved ​for weight-loss in Canada are Saxenda, Xenical, and Contrave, but these do not allow patients to learn the benefits of healthy habits ​and appropriate diets (“A new drug,” 2018). Therefore, the recommended,​ and most effective approach to weight loss is a combination of increased exercise and limited calorie intake (Boucher, Shafer, & Chaffin, 2001)
  
 ====== References ====== ====== References ======
-[1] Dehoney, S., & Wellein, M. (2009). Rhabdomyolysis associated with the nutritional supplement Hydroxycut. American Journal of Health-System Pharmacy, 66(2), 142–148. https://​doi.org/​10.2146/​ajhp070640+[1] Alemzadeh, R., Karlstad, M. D., Tushaus, K., & Buchholz, M. (2008). Diazoxide enhances basal metabolic rate and fat oxidation in obese Zucker rats. Metabolism: Clini 
 + 
 +[2] Dehoney, S., & Wellein, M. (2009). Rhabdomyolysis associated with the nutritional supplement Hydroxycut. American Journal of Health-System Pharmacy, 66(2), 142–148. https://​doi.org/​10.2146/​ajhp070640 
 + 
 +[3] LiverTox. (2018). Hydroxycut. Retrieved January 27, 2019, from https://​livertox.nih.gov/​Hydroxycut.htm#​structure 
 + 
 +[4] Jill Corleone. (n.d.). How to Use Hydroxycut Effectively | Livestrong.com. Retrieved January 27, 2019, from https://​www.livestrong.com/​article/​375287-how-to-use-hydroxycut-effectively/​ 
 + 
 +[5] MedicineNet. (2009). FDA Warns to Stop Using Hydroxycut Products Information on MedicineNet.com. Retrieved January 27, 2019, from https://​www.medicinenet.com/​script/​main/​art.asp?​articlekey=99871 
 + 
 +[6] Fong, T.-L., Klontz, K. C., Canas-Coto, A., Casper, S. J., Durazo, F. A., Davern, T. J., … Seeff, L. B. (2010). Hepatotoxicity Due to Hydroxycut: A Case Series. The American Journal of Gastroenterology,​ 105(7), 1561–1566. https://​doi.org/​10.1038/​ajg.2010.5 
 + 
 +[7] Sharma, T., Wong, L., Tsai, N., & Wong, R. D. (2010). Hydroxycut(®) (herbal weight loss supplement) induced hepatotoxicity:​ a case report and review of literature. Hawaii Medical Journal, 69(8), 188–90. Retrieved from http://​www.ncbi.nlm.nih.gov/​pubmed/​20845283 
 + 
 +[8] Dara, L., Hewett, J., & Lim, J. K. (2008). Hydroxycut hepatotoxicity:​ a case series and review of liver toxicity from herbal weight loss supplements. World Journal of Gastroenterology,​ 14(45), 6999–7004. https://​doi.org/​10.3748/​WJG.14.6999 
 + 
 +[9] Chuah, L. O., Ho, W. Y., Beh, B. K., & Yeap, S. K. (2013). Updates on Antiobesity Effect of Garcinia Origin (-)-HCA. Evidence-Based Complementary and Alternative Medicine :​ ECAM, 2013, 751658. https://​doi.org/​10.1155/​2013/​751658 
 + 
 +[10] Chuah, L. O., Yeap, S. K., Ho, W. Y., Beh, B. K., & Alitheen, N. B. (2012). In Vitro and In Vivo Toxicity of Garcinia or Hydroxycitric Acid: A Review. Evidence-Based Complementary and Alternative Medicine, 2012, 1–12. https://​doi.org/​10.1155/​2012/​197920 
 + 
 +[11] Gutiérrez‐Hellín,​ J., & Coso, J. D. (2016). Acute p-synephrine ingestion increases fat oxidation rate during exercise. British Journal of Clinical Pharmacology,​ 82(2), 362–368. https://​doi.org/​10.1111/​bcp.12952 
 + 
 +[12] Han, J., Li, L., Wang, D., & Ma, H. (2016). (−)-Hydroxycitric acid reduced fat deposition via regulating lipid metabolism-related gene expression in broiler chickens. Lipids in Health and Disease, 15(1), 37. https://​doi.org/​10.1186/​s12944-016-0208-5
  
-[2LiverTox. (2018). HydroxycutRetrieved January 272019from https://livertox.nih.gov/Hydroxycut.htm#​structure+[13Lunsford, K. E., Bodzin, A. S., Reino, D. C., Wang, H. L., & Busuttil, R. W. (2016). Dangerous dietary supplements:​ Garcinia cambogia -associated hepatic failure requiring transplantationWorld Journal of Gastroenterology22(45)10071. ​https://doi.org/10.3748/wjg.v22.i45.10071
  
-[3Jill Corleone. (n.d.). ​How to Use Hydroxycut Effectively | Livestrong.comRetrieved January 272019, from https://www.livestrong.com/article/375287-how-to-use-hydroxycut-effectively/+[14Ohia, S. E., Awe, S. O., LeDay, A. M., Opere, C. A., & Bagchi, D. (n.d.). ​Effect of hydroxycitric acid on serotonin release from isolated rat brain cortexResearch Communications in Molecular Pathology and Pharmacology109(3–4)210–6. Retrieved ​from http://www.ncbi.nlm.nih.gov/pubmed/11758650
  
-[4MedicineNet. (2009). FDA Warns to Stop Using Hydroxycut Products Information on MedicineNet.com. Retrieved January 272019from https://www.medicinenet.com/script/main/​art.asp?​articlekey=99871+[15Onakpoya, I., Hung, S. K., Perry, R., Wider, B., & Ernst, E. (2011). The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical TrialsJournal of Obesity20111–9. ​https://doi.org/10.1155/2011/509038
  
-[5FongT.-L., KlontzK. C., Canas-CotoA., CasperSJ., Durazo, F. A., DavernT. J., … SeeffLB. (2010). Hepatotoxicity Due to HydroxycutA Case SeriesThe American Journal of Gastroenterology105(7), 15611566. https://​doi.org/​10.1038/ajg.2010.5+[16PreussHG., BagchiD., BagchiM., RaoCVS., SatyanarayanaS., & DeyDK. (2004). Efficacy of a novel, natural extract of (–)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX, niacin-bound chromium and Gymnema sylvestre extract in weight management in human volunteersa pilot studyNutrition Research24(1), 4558. https://​doi.org/​10.1016/J.NUTRES.2003.09.007
  
-[6SharmaT., Wong, L., Tsai, N., & WongRD. (2010). Hydroxycut(®(herbal weight loss supplement) induced hepatotoxicity:​ a case report and review of literatureHawaii Medical Journal69(8), 18890Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/​20845283+[17RaoR. N., & SakariahKK. (1988). Lipid-lowering and antiobesity effect of ()hydroxycitric acidNutrition Research, 8(2), 209212https://doi.org/10.1016/S0271-5317(88)80024-1
  
-[7Dara, L., HewettJ., & LimJK. (2008). Hydroxycut hepatotoxicitya case series and review of liver toxicity from herbal ​weight loss supplementsWorld Journal of Gastroenterology14(45), 69997004. https://​doi.org/​10.3748/WJG.14.6999+[18Rossato, L. G., CostaV. M., LimbergerRP., Bastos, M. de L., & Remião, F. (2011). SynephrineFrom trace concentrations to massive consumption in weight-loss. Food and Chemical Toxicology49(1), 816. https://​doi.org/​10.1016/j.fct.2010.11.007
  
-[8Chuah, L. O., Ho, W. Y., BehB. K., & Yeap, S. K. (2013). Updates on Antiobesity Effect of Garcinia Origin (-)-HCA. Evidence-Based Complementary and Alternative Medicine :​ ECAM2013, 751658https://doi.org/10.1155/2013/751658+[19Sergio, W. (1988)A natural foodthe Malabar Tamarindmay be effective in the treatment of obesityMedical Hypotheses27(1), 39–40Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/3205204
  
-[9ChuahL. O., Yeap, S. K., Ho, W. Y., Beh, B. K., & Alitheen, N. B. (2012). In Vitro and In Vivo Toxicity ​of Garcinia ​or Hydroxycitric Acid: A ReviewEvidence-Based Complementary and Alternative Medicine20121–12. https://​doi.org/​10.1155/2012/197920+[20SripradhaR., & Magadi, S. G. (2015). Efficacy ​of Garcinia ​Cambogia on Body Weight, Inflammation and Glucose Tolerance in High Fat Fed Male Wistar RatsJOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH9(2)BF01-4. https://​doi.org/​10.7860/JCDR/2015/​12045.5577
  
-[10Han, J., LiL., Wang, D., & MaH. (2016). ()-Hydroxycitric acid reduced fat deposition via regulating lipid metabolism-related gene expression in broiler chickensLipids in Health and Disease15(1), 37. https://​doi.org/​10.1186/s12944-016-0208-5+[21StohsS. J., PreussHG., & SharaM. (2011). The Safety of Citrus aurantium ​(Bitter Orangeand its Primary Protoalkaloid p-SynephrinePhytotherapy Research25(10), 1421–1428. https://​doi.org/​10.1002/ptr.3490
  
-[11LunsfordKE., Bodzin, ​A. S., ReinoD. C., Wang, H. L., & BusuttilRW. (2016). Dangerous dietary supplementsGarcinia cambogia -associated hepatic failure requiring transplantationWorld Journal ​of Gastroenterology22(45)10071. https://​doi.org/​10.3748/wjg.v22.i45.10071+[22WatsonJ. A., FangM., & LowensteinJM. (1969). Tricarballylate and hydroxycitrateSubstrate and inhibitor of ATP: Citrate oxaloacetate lyaseArchives ​of Biochemistry and Biophysics135209–217. https://​doi.org/​10.1016/0003-9861(69)90532-3
  
-[12OhiaSE., AweSO., LeDayA. M., Opere, C. A., & Bagchi, D. (n.d.). Effect of hydroxycitric acid on serotonin release ​from isolated rat brain cortexResearch Communications in Molecular Pathology ​and Pharmacology109(3–4), 210–6. Retrieved from http://​www.ncbi.nlm.nih.gov/​pubmed/​11758650+[23WhiteCP., HitchcockCL., VignaY. M., & PriorJ. C. (2011). Fluid retention over the menstrual cycle: 1-year data from the prospective ovulation cohortObstetrics ​and gynecology international2011.
  
-[13OnakpoyaI., Hung, S. K., Perry, R., Wider, B., & Ernst, E. (2011). The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical TrialsJournal of Obesity, 2011, 1–9. https://doi.org/10.1155/2011/509038+[24WHITTEMOREF. (2019). The History ​of Diet Pills | Livestrong.comRetrieved from https://www.livestrong.com/article/​74336-history-diet-pills/
  
-[14PreussH. G., Bagchi, D., Bagchi, M., Rao, C. V. S., Satyanarayana,​ S., & Dey, D. K. (2004). Efficacy of a novel, natural extract of (–)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX, niacin-bound chromium and Gymnema sylvestre extract in weight management in human volunteers: a pilot study. Nutrition Research, 24(1), 45–58. https://doi.org/10.1016/J.NUTRES.2003.09.007+[25Gunnars, K. (2019). Top 12 Biggest Myths About Weight LossRetrieved from https://www.healthline.com/​nutrition/top-12-biggest-myths-about-weight-loss#​section11
  
-[15Rao, R. N., & Sakariah, K. K. (1988). Lipid-lowering and antiobesity effect ​of (−)hydroxycitric acidNutrition Research, 8(2), 209–212. https://doi.org/10.1016/​S0271-5317(88)80024-1+[26Beware ​of Products Promising Miracle Weight Loss. (2018). Retrieved from  
 +https://www.fda.gov/ForConsumers/​ConsumerUpdates/​ucm246742.htm
  
-[16SergioW(1988)A natural foodthe Malabar Tamarindmay be effective in the treatment of obesityMedical Hypotheses27(1)39–40Retrieved from http://www.ncbi.nlm.nih.gov/​pubmed/​3205204+[27SaperRB., EisenbergD. M., & PhillipsRS(2004)Common dietary supplements for 
 +weight lossAmerican family physician, 70, 1731-1740.
  
-[17SripradhaR., & MagadiSG. (2015). Efficacy of Garcinia Cambogia on Body Weight, ​Inflammation ​and Glucose Tolerance in High Fat Fed Male Wistar RatsJOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH9(2), BF01-4. https://​doi.org/​10.7860/​JCDR/​2015/​12045.5577+[28BoucherJ. L., Shafer, K. J., & ChaffinJA. (2001). Weight ​Loss, Diets, and Supplements:​ Does 
 +Anything Work?Diabetes Spectrum14(3), 169-175.
  
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-[19White, C. P., Hitchcock, C. L., Vigna, Y. M., & Prior, J. C. (2011). Fluid retention over the menstrual cycle1-year data from the prospective ovulation cohortObstetrics and gynecology international,​ 2011.+[30Dietary Supplements for Weight Loss. (2017). Retrieved from 
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-[20WHITTEMOREF. (2019). The History ​of Diet Pills | Livestrong.com. Retrieved from https://www.livestrong.com/​article/​74336-history-diet-pills/+[31PooyandjooM., Nouhi, M., Shab‐Bidar,​ S., Djafarian, K., & Olyaeemanesh,​ A. (2016). The 
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