This article has Open Peer Review reports available.
Effects of combined extract of cocoa, coffee, green tea and garcinia on lipid profiles, glycaemic markers and inflammatory responses in hamsters
© Chang et al. 2015
Received: 27 April 2015
Accepted: 6 August 2015
Published: 12 August 2015
Dyslipidaemia is highly associated with cardiovascular and cerebrovascular diseases, which have been ranked second and third place of leading causes of death in Taiwan. Some plant extracts have been proved effective against dyslipidaemia. However, the combination of plant extracts was rarely studied. The purpose of the present study is to understand the beneficial effects of a combined extract (comprising cocoa, coffee, green tea and garcinia; CCGG) on lipid profiles in serum, liver, and faeces as well as glycaemic markers and related proinflammatory cytokines by using an appropriate animal model, the golden Syrian hamster.
A total of 40 male hamsters were randomly assigned to five groups: (1) vehicle control, (2) high-cholesterol diet control, (3) high-cholesterol diet of 311 mg/kg/d of CCGG, (4) high-cholesterol diet of 622 mg/kg/d of CCGG and (5) high-cholesterol diet of 1555 mg/kg/d of CCGG. At the end of the experiment, blood, tissue and faecal samples were collected for further analysis.
After 6 weeks of treatment, CCGG supplementation significantly reduced serum lipid content (triglycerides, total cholesterol and LDL-C) and hepatic lipid content (triglycerides and cholesterol) with dose-dependent effects. In addition, an increase in excretion of faecal lipids (bile acids) was observed after supplementation. Furthermore, the homeostasis model assessment of insulin resistance (HOMA-IR) index and serum proinflammatory cytokine levels (TNF-α and IL-6) involved in dyslipidaemia was markedly improved. In addition, by monitoring biochemical parameters as well as histopathology of major tissues, no toxicity was observed after the consumption of CCGG.
Dietary CCGG supplementation may exert potential effects on ameliorating hyperlipidaemia, insulin resistance, liver steatosis and related inflammation.
As time has progressed and society advances, indulgent lifestyles have produced “lifestyle diseases”, particularly dyslipidaemia. Dyslipidaemia is a disease characterised by an abnormal amount of lipids in the blood, which can result in a predisposition to coronary, cerebrovascular and peripheral vascular arterial diseases. In addition, systemic inflammation has been proposed to be accompanied by dyslipidaemia, producing several proinflammatory factors (including tumour necrosis factor (TNF)-α and interleukin 6 (IL-6)) [1, 2]. Since 2000, cardiovascular and cerebrovascular diseases have been ranked second and third place of leading causes of death in Taiwan. According to the Industry & Technology Intelligence Service (Taiwan), dyslipidaemia prevalence has exceeded 10 % of the population (older than 15 y) in Taiwan. Moreover, dyslipidaemia is observed in the younger population. Dyslipidaemia severely threatens health and is associated with exorbitant medical expenses.
Current blood lipid-lowering drugs have a higher efficacy and potency than before; however, some adverse effects still occur when medication is taken. Minor gastrointestinal complaints including nausea, cramping and constipation occur when bile acid resins are taken . Niacin appears to cause cutaneous flushing and itching . Statins and fibric acids may be associated with increased serum aminotransferase levels, creatine kinase levels, myopathy and rhabdomyolysis . Diet control and increased physical activity are frequently encouraged to ameliorate dyslipidaemia . Studies [4–7] have revealed that consuming plant or natural extract supplements is beneficial. Plant polyphenols have recently gained increasing attention because of their potent properties against blood lipids and related inflammatory responses. Cocoa, coffee, green tea and garcinia (CCGG) contain abundant polyphenols, particularly proanthocyanidins, chlorogenic acids, catechins and xanthones, respectively [8–11]. Polyphenols potentially reduce blood lipids and have an antiinflammatory effect [12–17].
Regarding to CCGG, there were some obvious evidences for CCGG against dyslipidaemia stated in rodent and in vitro studies. Nwichi et al.  demonstrated an 8-weeks administration of cocoa extract exhibited hypolipidaemic effects in cholesterol-fed rats. Song et al.  demonstrated that an 11-week consumption of decaffeinated green coffee bean significantly reduced plasma lipids in high-fat diet fed mice. Yan et al.  studied the 6-weeks effect of green tea polysaccharides and polyphenols in high-fat diet fed rats, both of them showed effective reduction in serum lipids. Bumrungpert et al.  revealed the effects of mangosteen against inflammation and insulin resistance in human adipocytes. Despite of the fact that previous studies have stated the beneficial effects of diverse polyphenol-rich extracts in isolation, very few studies have examined the combination. However, combined ingredients may enhance the benefit and reduce the effective dose , also exert a synergistic effect .
Since the early 1980s, an animal model, the golden Syrian hamster, has been employed to assess diet-induced atherosclerosis . In general, using unmodified rats or mice as animal models is unsuitable for examining diet-induced changes in blood lipids because they do not develop aortic lesions or an atherogenic lipoprotein profile (nHDL-C > HDL-C) similar to human beings . Hamsters are a more appropriate animal model. Recently, numerous studies have adopted hamsters to investigate the effect of plant extracts on blood lipids [5, 26, 27]. Therefore, in the present study, we examined the potential effects and dose-response relationship of combined extract (composed of CCGG) on lipid profiles, glycaemic markers and inflammatory responses in hamsters. We monitored common toxicity markers that may be influenced after the intake of CCGG.
Diets and chemicals
The nutritional information of CCGG
An animal diet was LabDiet 5001 rodent diet (LabDiet, St. Louis, MO, USA) in a vehicle control group (vehicle), and an additional 0.2 % cholesterol and 10 % lard were added to the diet for a high-cholesterol diet group (HCD).
Animals and treatment
The animal use protocol was submitted to and had been approved by the Institutional Animal Care and Use Committee (IACUC) of National Taiwan Sport University (Taoyuan, Taiwan). The IACUC approval number of the present study was IACUC-10210 and was valid from 10/20/2013 to 12/31/2014. We declared all animal experiments were conducted according to the protocol. Male golden Syrian hamsters (4 weeks old) were purchased from the National Laboratory Animal Center (Taipei, Taiwan) and maintained in 12 h of light/dark at a temperature of 24 ± 2 °C and 65 ± 5 % humidity with access to food and water ad libitum. The hamsters were monitored daily for food intake. Body weight and water intake were recorded two times per week. The food efficiency was calculated at the end of the experiments. After 4 weeks of acclimatisation, the hamsters were randomised into five groups (n = 8 per group): (1) vehicle control (Vehicle), (2) high-cholesterol diet control (HCD), (3) high-cholesterol diet with 311 mg/kg/d of CCGG (CCGG-1X), (4) high-cholesterol diet with 622 mg/kg/d of CCGG (CCGG-2X) and (5) high-cholesterol diet with 1555 mg/kg/d of CCGG (CCGG-5X). The hamster CCGG dose (311 mg/kg/d) was converted from a human equivalent dose (HED) based on body surface area by the following formula from the US Food and Drug Administration: assuming a human weight of 60 kg, the HED for 2.5 (g/d) ÷ 60 (kg) = 0.042 × 7.4 = hamster dose of 311 mg/kg/d. The conversion coefficient 7.4 was used to account for differences in body surface area between a hamster and a human. CCGG was dissolved using deionised water and administered to the hamsters by gastric tube in a dose of 0.01 mL/g. At the end of week 6, the hamsters were anaesthetised with 5 % isoflurane at the rate of 0.5 L/min and euthanised by exsanguination after 12 h of food deprivation. Blood samples were collected from the abdominal aortas. The hearts, livers, kidneys, lungs and fat depots (epididymal fat) were collected and weighed. Serum samples were isolated using centrifugation at 2000 × g for 15 min. All of the samples were snap-frozen and stored at -80 °C until further analysis.
Biochemical analysis of serum samples
Liver lipid content
To determine liver cholesterol and triglycerides, 20 mg of liver tissue was homogenised in a 200-μL solvent (chloroform:isopropanol:NP40 = 7:11:0.1). Centrifuged at 12 000 × g for 10 min, an aliquot of 100 μL was extracted and dried. The pellet was reconstituted with a buffer (1 M of potassium phosphate, pH = 7.4, 500 mM of sodium chloride, 50 mM of cholic acid), and water bath sonication was employed to dissolve the precipitate. A Cholesterol Fluorometric Assay Kit (Cayman, Ann Arbor, MI, USA) and Triglyceride Colorimetric Assay Kit (Cayman, Ann Arbor, MI, USA) were used to analyse liver cholesterol and triglyceride contents.
Faecal lipid content
Faeces were collected and dried in an oven at Week 6. Subsequently, 0.1 g of faeces were pulverised in 1 mL of phosphate buffered saline and extracted using a solvent (chloroform:methanol = 2:1). The organic phase was filtered using filter paper (Whatman NO.5). Afterwards, the residue was dried and reconstituted with 1 mL of dimethyl sulphoxide. Water bath sonication was used to dissolve the precipitate. A cholesterol liquid assay (Randox, Antrim, UK), Triglyceride Colorimetric Assay Kit (Cayman, Ann Arbor, MI, USA) and Total Bile Acids Assay Kit (Crystal Chem, Downers Grove, IL, USA) were adopted to analyse faecal cholesterol, triglyceride and bile acid contents.
Histopathology of tissues
Liver, fat, heart, kidney and lung tissues were removed at the end of the experiment, fixed in 10 % buffered formalin, and then embedded in paraffin. The paraffin-embedded samples were sectioned and underwent haematoxylin and eosin (H&E) staining under a light microscope equipped with a charge-coupled device camera (Olympus, Tokyo, Japan) by a clinical pathologist.
Data are expressed as mean ± standard error of the mean (SEM). One-way ANOVA with Tukey’s posttest and Pearson correlation for dose-dependent effect were used for all data comparisons. A P < 0.05 was statistically significant. Statistical analyses were conducted using the SPSS 19.0.
Effects of CCGG supplementation on body weight, organ weight, and diet intake
Final body weight and effects of CCGG supplementation on food intake, water intake and food efficiency ratio
Final body weight (g/hamster)
Food intake (g/hamster/week)
Water intake (g/hamster/week)
Food efficiency ratio (%)
Effects of CCGG supplementation on serum lipid profiles
Effects of CCGG supplementation on serum biochemical analysis
Effects of CCGG supplementation on serum glycaemic markers and insulin resistance
Effects of CCGG supplementation on serum cytokine levels
Effects of CCGG supplementation on serum biochemical parameters
The safety of consuming CCGG was monitored at the end of the study. As shown in Table 3, no significant changes in total protein among the groups were observed compared with the HCD group. As indicators of hepatotoxicity, AST, ALT, Alk-P, albumin, total bilirubin and TP showed no differences among the groups versus the HCD group (P > 0.05). As indicators of nephrotoxicity, UA and creatinine showed no differences among the groups versus the HCD group (P > 0.05), whereas BUN was lower in the HCD group than in the four other groups. Similarly, as an indicator of cytotoxicity, LDH showed no differences among the groups versus the HCD group (P > 0.05). However, for CPK, an attenuation by 55.8 % in the CCGG-5X group, compared with the HCD group, was observed (P < 0.05).
Effects of CCGG supplementation on hepatic and faecal lipid contents
Effects of CCGG supplementation on hepatic and faecal lipids
Effect of CCGG supplementation on the histopathology of tissues
Dyslipidaemia is characterised by an increase in total cholesterol, low-density lipoprotein cholesterol, triglycerides or a combination of these abnormalities. The eventual clinical outcomes may include angina, myocardial infarction, arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm and sudden death . Dyslipidaemia is one of the most severe metabolic diseases and a real problem currently encountered in the world. Instead of taking medicine, supplementation may be another approach to amelioration this chronic condition. In this study, we used golden Syrian hamsters fed a high-cholesterol diet (0.2 % cholesterol) and added an additional 10 % lard for our model. The animal model was shown to be appropriate because the major features of a lipid metabolism and atherosclerosis were similar between hamsters and human beings [24, 25]. This study was designed to investigate the beneficial effects of a CCGG supplement on lipid profiles, glycaemic markers, proinflammatory cytokines and related toxicity markers.
Regarding cocoa, Khan et al.  evaluated the effects of chronic cocoa consumption on the lipid profiles of volunteers exhibiting a high risk of cardiovascular disease. After 4 weeks, HDL-C levels were higher compared with TC, TG and LDL-C levels. In addition, the LDL/HDL-C ratio showed no significant change. However, Jia et al.  examined the short-term effect of cocoa product consumption on the lipid profiles of eight trials. LDL-C and TC levels were lowered, but no change in HDL-C was observed. No evidence for a dose-response effect was obtained. Regarding coffee, the effect of coffee on blood lipids remains controversial. Panchal et al.  revealed that coffee extract supplementation for 8 weeks could not change the abdominal obesity or dyslipidaemia in high-carbohydrate, high-fat rats. A meta-analysis conducted by Cai et al.  suggested that the serum levels of TC, LDL-C and TG may significantly increase in Western people who consume coffee daily. By contrast, a single-dose of coffee polyphenols could drastically modulate postprandial hyperlipidaemia in mice . The effects of coffee beans are subsequently related to its phenol, oil and caffeine contents. Regarding green tea, the most effective polyphenol compounds against dyslipidaemia and other chronic diseases are known as catechins . Particularly through modulating PPAR expression, green tea leaf extract was shown to improve lipid homeostasis by decreasing plasma and hepatic lipids and increasing serum adiponectin in rodent models [4, 5]. In addition, relatively few studies have focused on the benefits of Garcinia mangostana on blood lipids and have primarily investigated its antioxidant, antitumoural, antiinflammatory, antiallergy, antibacterial, antifungal and antiviral properties . Xanthones (e.g. α-mangostin) are believed to be beneficial compounds. Nevertheless, Adiputro et al.  revealed a significant decrease in TC, LDL-C and TG as well as an increase in HDL-C in high-lipid fed rats after consuming mangosteen extract for 60 d.
We observed body weight and tissue weight. The liver, epididymal fat and heart were lower in the CCGG-5X group compared with the HCD group. These findings suggest that CCGG supplementation had potential effects on weight loss and organ protection. In addition, we observed that serum lipid levels were markedly increased in the HCD-fed hamsters compared with the normal chow-fed hamsters, and these increases were ablated by CCGG supplementation, even reversed to nearly baseline. Notably, simply dose-dependent reductions appeared in TC and LDL-C serum levels. Furthermore, hepatic lipid levels were increased in the HCD group. CCGG supplementation significantly decreased TG (by approximately 45 %) and cholesterol (dose-dependent) in the liver. In particular, hepatic steatosis improvement was observed in the histopathology. In addition, principally by the increase in the excretion of bile acid in faeces (by approximately 35 %), the absorption of a cholesterol diet was limited by CCGG supplementation.
Insulin resistance is a major underlying factor contributing to dyslipidaemia and hepatic steatosis . HOMA-IR was reported to primarily indicate hepatic insulin resistance . Improved HOMA-IR was revealed in previous studies after consuming 10-week flavan-3-ols-rich cocoa powder , 11-week 5-caffeoylquinic acid-rich coffee bean extract , and 8-weeks α-mangostin-rich mangosteen extract  in rodent models. However, the effect of green tea extract on insulin resistance remains controversial. Even increments in serum glucose and insulin levels were observed after 8-weeks EGCG-rich green tea extract intervention, leading to the development of diseases such as diabetes . In our study, we determined that CCGG supplementation significantly decreased serum insulin levels and ameliorated the HOMA-IR index, but did not affect fasting blood glucose levels. Similarly, a lack of blood glucose regulation after treatment with phenolic compounds in mice, despite a significant reduction in insulin production, was reported . It might take longer time either to induce or attenuate glucose level.
Inflammation leads to changes in lipid metabolism aimed at decreasing the harmful agents and promoting tissue repair involved in host defense . As the adipocytes of individuals enlarge, the adipose tissue undergoes physiological alterations that subsequently affect systemic metabolism. First, macrophages accumulate within adipose tissue, leading to local inflammation. Several proinflammatory factors (including TNF-α and IL-6) are produced [1, 2]. Importantly, inflammatory cytokines, which are protagonists in plaque formation throughout the atherosclerotic vessel, are produced. Therefore, chronic inflammation is a major contributing factor to atherosclerotic disease. Regarding cocoa, a previous study  suggested that cocoa rich in flavonoids has the dose-dependent effects of diminishing TNF-α and MCP-1. Gu et al.  reported that a dietary proanthocyanidin-rich cocoa supplement decreased plasma IL-6 and MCP-1 instead of TNF-α. Regarding coffee, Yamauchi et al. investigated 5-weeks coffee and caffeine consumption in diabetic KK-Ay mice. Inflammatory markers of serum IL-6 were improved, but not monocyte chemoattractant protein-1 (MCP-1) . However, a cross-sectional study revealed that coffee consumption does not affect serum TNF-α and IL-6 in Japanese workers . Similarly, green tea has the potential effect of preventing inflammation by inhibiting MCP-1  and TNF-α  expression. Regarding garcinia, α-mangostin plays a crucial role in antiinflammation. Both in vitro and in vivo studies have indicated the beneficial effects of suppressing the production of TNF-α [44, 45].
In our study, the results showed that serum TNF-α levels, but not IL-6, were increased in the HCD-fed hamsters. However, after the 6-weeks CCGG treatment, we observed that serum TNF-α levels were attenuated in three different-dosage-treated groups with a similar effect (approximately 30 % reduction). Furthermore, adiponectin is a secreted serum protein expressed exclusively in differentiated adipocytes. Adiponectin was shown to be highly correlated with metabolic syndrome and cardiovascular disease . Adiponectin regulation is coordinated by other factors, including body mass index and serum TG . A recent study  reported no change in serum adiponectin levels in 4-mo high-fat diet-induced obese rats. Thus, adiponectin levels might possibly be affected by some cooperative interaction because no differences occurred in serum adiponectin in our five groups. In addition, we observed that the CCGG supplement doses showed no sign of toxicity towards biochemical markers or histopathology and did not affect food or water intake.
On the whole, in CCGG, there were strong evidences that dyslipidaemia mediated by cocoa and green tea; insulin resistance mediated by cocoa, coffee and garcinia; inflammation mediated by cocoa, coffee, green tea and garcinia. Therefore, contributed by combined ingredients, we proposed that CCGG might exert a synergic effect. Accordingly, whether the combined ingredients indeed enhance the benefit and reduce the effective dose was crucial, since some studies [49–51] revealed their outcomes with disappointment after supplementation with multi-ingredient. However, our results are satisfactory. Based on conversion of animal doses to human equivalent doses from the US Food and Drug Administration, the doses of CCGG supplementation in hamster which are equivalent to 42, 84 and 210 mg/kg/d in human. Compared to single ingredient, less dose of CCGG supplementation might also be effective. Gu et al.  investigated the effect of cocoa powder supplementation on obesity-related inflammation in high fat fed obese mice. A 10-week 8 % unsweetened cocoa powder (approximately equivalent to 465 mg/kg/d in human) ameliorated obesity-related inflammation, insulin resistance and fatty liver disease. Panchal et al.  characterized the effects of coffee extract on a rat model of human metabolic syndrome. An 8-weeks 5 % aqueous coffee extract (approximately equivalent to 294 mg/kg/d in human) attenuated hypertension and impairment in glucose homeostasis without affecting abdominal fat deposition and plasma lipid profile. Luo et al.  investigated the effects of dietary supplementation with green tea on cholesterol and circulating immune complexes in SD rats fed with a high-cholesterol diet. A 30-d leaf powder of dose 1.0 or 2.0 g/kg body weight (approximately equivalent to 161 or 323 mg/kg/d in human) resulted in a significant decrease in plasma TC levels and circulating immune complexes and an increase in HDL-C. Adiputro et al.  evaluated the effect of mangosteen extract on lipid profile in rats fed a high lipid diet. A 60-d ethanolic extract of Garcinia mangostana pericarp at dosages of 400 or 800 mg/kg body weight (approximately equivalent to 65 or 129 mg/kg/d in human) significantly decreased cholesterol, TG and LDL-C levels. Concerning our results showed effective dose started at CCGG-1X group (equivalent to 42 mg/kg/d in human). Therefore, compared to previous studies focusing on single ingredient, the CCGG might have the synergic beneficial effects with relatively lower dose consumption. However, our limitation is that we cannot directly compare the effects of CCGG with each single ingredient. Additional studies are also required to assess the underlying mechanism that mediates the synergic effects of CCGG.
In conclusion, we demonstrated hypolipidaemic effects of a 6-weeks dietary supplementation by using a combined extract (consisting of CCGG) in HCD-fed hamsters. CCGG markedly attenuated serum lipid profiles (TG, TC, and LDL-C) and hepatic lipid profiles (TG and cholesterol) with dose-dependent effects, and increased faecal bile acid content. Furthermore, HOMA-IR index and serum cytokine levels (IL-6 and TNF-α) involved in dyslipidaemia were improved, and no toxicity appeared. Thus, we propose that CCGG may have potential effects of ameliorating hyperlipidaemia, insulin resistance, liver steatosis and related inflammation.
The present study was supported by the University-Industry Cooperation Fund no. S102019 (Kaohsiung Medical University, Kaohsiung, Taiwan). Sunrider International had no role in the design, analysis or writing of this article. We also thank Dr. Peir-In Liang, the pathologist of Department of Pathology, Kaohsiung Medical University Hospital (Kaohsiung, Taiwan) for pathological analysis.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998;83(3):847–50.PubMedGoogle Scholar
- Samad F, Yamamoto K, Pandey M, Loskutoff DJ. Elevated expression of transforming growth factor-beta in adipose tissue from obese mice. Mol Med. 1997;3(1):37–48.PubMedPubMed CentralGoogle Scholar
- Wells B, DiPiro J, Schwinghammer T, DiPiro C. Pharmacotherapy Handbook. 8th ed.: McGraw-Hill Global Education Holdings, LLC; 2012. p. 85–98.Google Scholar
- Luo XY, Li NN, Liang YR. Effects of Ilex latifolia and Camellia sinensis on cholesterol and circulating immune complexes in rats fed with a high-cholesterol diet. Phytother Res. 2013;27(1):62–5.View ArticlePubMedGoogle Scholar
- Li RW, Douglas TD, Maiyoh GK, Adeli K, Theriault AG. Green tea leaf extract improves lipid and glucose homeostasis in a fructose-fed insulin-resistant hamster model. J Ethnopharmacol. 2006;104(1-2):24–31.View ArticlePubMedGoogle Scholar
- Lin YL, Chang YY, Yang DJ, Tzang BS, Chen YC. Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters. Food chem. 2013;140(1-2):31–8.View ArticlePubMedGoogle Scholar
- Jung UJ, Park YB, Kim SR, Choi MS. Supplementation of persimmon leaf ameliorates hyperglycemia, dyslipidemia and hepatic fat accumulation in type 2 diabetic mice. PloS one. 2012;7(11):e49030.View ArticlePubMedPubMed CentralGoogle Scholar
- Wollgast J, Anklam E. Polyphenols in chocolate: is there a contribution to human health? Food Res Int. 2000;33(6):449–59.View ArticleGoogle Scholar
- Celik T, Iyisoy A, Amasyali B. The effects of coffee intake on coronary heart disease: ongoing controversy. Int J Cardiol. 2010;144(1):118.View ArticlePubMedGoogle Scholar
- Sae-tan S, Grove KA, Lambert JD. Weight control and prevention of metabolic syndrome by green tea. Pharmacol Res. 2011;64(2):146–54.View ArticlePubMedGoogle Scholar
- Pedraza-Chaverri J, Cardenas-Rodriguez N, Orozco-Ibarra M, Perez-Rojas JM. Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol. 2008;46(10):3227–39.View ArticlePubMedGoogle Scholar
- Gu Y, Yu S, Lambert JD. Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice. Eur J Nutr. 2014;53(1):149–58.View ArticlePubMedGoogle Scholar
- Jia L, Liu X, Bai YY, Li SH, Sun K, He C, et al. Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2010;92(1):218–25.View ArticlePubMedGoogle Scholar
- Kim A, Chiu A, Barone MK, Avino D, Wang F, Coleman CI, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. J Am Diet Assoc. 2011;111(11):1720–9.View ArticlePubMedGoogle Scholar
- Zheng XX, Xu YL, Li SH, Liu XX, Hui R, Huang XH. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. The Am J Clin Nutr. 2011;94(2):601–10.View ArticlePubMedGoogle Scholar
- Udani JK, Singh BB, Barrett ML, Singh VJ. Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study. Nutr J. 2009;8:48.View ArticlePubMedPubMed CentralGoogle Scholar
- Adiputro DL, Widodo MA, Romdoni R, Sargowo D. Extract of mangosteen increases high density lipoprotein levels in rats fed high lipid. Universa Medicina. 2013;32(1):37–43.Google Scholar
- Nwichi SO, Adewole EK, Dada AO, Ogidiama O, Mokobia OE, Farombi EO. Cocoa powder extracts exhibits hypolipidemic potential in cholesterol-fed rats. Afr J Med Med Sci. 2012;41(Suppl):39–49.PubMedGoogle Scholar
- Song SJ, Choi S, Park T. Decaffeinated green coffee bean extract attenuates diet-induced obesity and insulin resistance in mice. Evid-Based Compl Alt. 2014;2014:718379.Google Scholar
- Xu Y, Zhang M, Wu T, Dai S, Xu J, Zhou Z. The anti-obesity effect of green tea polysaccharides, polyphenols and caffeine in rats fed with a high-fat diet. Food Funct. 2015;6(1):297–304.View ArticlePubMedGoogle Scholar
- Bumrungpert A, Kalpravidh RW, Chuang CC, Overman A, Martinez K, Kennedy A, et al. Xanthones from mangosteen inhibit inflammation in human macrophages and in human adipocytes exposed to macrophage-conditioned media. J Nutr. 2010;140(4):842–7.View ArticlePubMedGoogle Scholar
- Yeh TS, Chan KH, Hsu MC, Liu JF. Supplementation with soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin complex improves endurance exercise capacity in humans. J Med Food. 2011;14(3):219–25.View ArticlePubMedGoogle Scholar
- Arias N, Macarulla MT, Aguirre L, Milton I, Portillo MP. The combination of resveratrol and quercetin enhances the individual effects of these molecules on triacylglycerol metabolism in white adipose tissue. Eur J Nutr. 2015. doi:10.1007/s00394-015-0854-9
- Nistor A, Bulla A, Filip DA, Radu A. The hyperlipidemic hamster as a model of experimental atherosclerosis. Atherosclerosis. 1987;68(1-2):159–73.View ArticlePubMedGoogle Scholar
- Dillard A, Matthan NR, Lichtenstein AH. Use of hamster as a model to study diet-induced atherosclerosis. Nutr Metab. 2010;7:89.View ArticleGoogle Scholar
- Zhang X, Wu C, Wu H, Sheng L, Su Y, Zhang X, et al. Anti-hyperlipidemic effects and potential mechanisms of action of the caffeoylquinic acid-rich Pandanus tectorius fruit extract in hamsters fed a high fat-diet. PloS one. 2013;8(4):e61922.View ArticlePubMedPubMed CentralGoogle Scholar
- Caimari A, del Bas JM, Crescenti A, Arola L. Low doses of grape seed procyanidins reduce adiposity and improve the plasma lipid profile in hamsters. Int J Obes. 2013;37(4):576–83.View ArticleGoogle Scholar
- Wu PW, Liu HY, Cheng YC, Tseng SH, Su SC, Chiueh LC. Determination of Catechins in Tea Drinks by High Performance Liquid Chromatography. Annu Rep Food Drug Res. 2011;2:90–6.Google Scholar
- Syamsudin F, Rahayu L. HPLC analysis and pharmacokinetic study of mangostin after orally administration in rats. Int J Pharma Bio Sci. 2010;1(1):1–7.Google Scholar
- Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes care. 1997;20(7):1087–92.View ArticlePubMedGoogle Scholar
- Khan N, Monagas M, Andres-Lacueva C, Casas R, Urpi-Sarda M, Lamuela-Raventos RM, et al. Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascular disease. Nutr Metab Cardiovasc Dis. 2012;22(12):1046–53.View ArticlePubMedGoogle Scholar
- Panchal SK, Poudyal H, Waanders J, Brown L. Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. J Nutr. 2012;142(4):690–7.View ArticlePubMedGoogle Scholar
- Cai L, Ma D, Zhang Y, Liu Z, Wang P. The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2012;66(8):872–7.View ArticlePubMedGoogle Scholar
- Murase T, Yokoi Y, Misawa K, Ominami H, Suzuki Y, Shibuya Y, et al. Coffee polyphenols modulate whole-body substrate oxidation and suppress postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. Brit J Nutr. 2012;107(12):1757–65.View ArticlePubMedGoogle Scholar
- Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes care. 2006;29(5):1130–9.View ArticlePubMedGoogle Scholar
- Jariyapongskul A, Areebambud C, Suksamrarn S, Mekseepralard C. Alpha-mangostin attenuation of hyperglycemia-induced ocular hypoperfusion and blood retinal barrier leakage in the early stage of type 2 diabetes rats. Biomed Res Int. 2015;2015:785826.View ArticlePubMedPubMed CentralGoogle Scholar
- Santana A, Santamarina A, Souza G, Mennitti L, Okuda M, Venancio D et al. Decaffeinated green tea extract rich in epigallocatechin-3-gallate improves insulin resistance and metabolic profiles in normolipidic diet-but not high-fat diet-fed mice. J Nutr Biochem. 2015. doi:10.1016/j.jnutbio.2015.03.001
- Esteve E, Ricart W, Fernandez-Real JM. Dyslipidemia and inflammation: an evolutionary conserved mechanism. Clin Nutr. 2005;24(1):16–31.View ArticlePubMedGoogle Scholar
- Ramiro E, Franch A, Castellote C, Perez-Cano F, Permanyer J, Izquierdo-Pulido M, et al. Flavonoids from Theobroma cacao down-regulate inflammatory mediators. J Agric Food Chem. 2005;53(22):8506–11.View ArticlePubMedGoogle Scholar
- Yamauchi R, Kobayashi M, Matsuda Y, Ojika M, Shigeoka S, Yamamoto Y, et al. Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice. J Agric Food Chem. 2010;58(9):5597–603.View ArticlePubMedGoogle Scholar
- Yamashita K, Yatsuya H, Muramatsu T, Toyoshima H, Murohara T, Tamakoshi K. Association of coffee consumption with serum adiponectin, leptin, inflammation and metabolic markers in Japanese workers: a cross-sectional study. Nutr Diabetes. 2012;2:e33.View ArticlePubMedPubMed CentralGoogle Scholar
- Heber D, Zhang Y, Yang J, Ma JE, Henning SM, Li Z. Green tea, black tea, and oolong tea polyphenols reduce visceral fat and inflammation in mice fed high-fat, high-sucrose obesogenic diets. J Nutr. 2014;144(9):1385–93.View ArticlePubMedGoogle Scholar
- Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R. Green tea prevents hyperglycemia-induced retinal oxidative stress and inflammation in streptozotocin-induced diabetic rats. Ophthalmic Res. 2012;47(2):103–8.View ArticlePubMedGoogle Scholar
- Liu SH, Lee LT, Hu NY, Huange KK, Shih YC, Munekazu I, et al. Effects of alpha-mangostin on the expression of anti-inflammatory genes in U937 cells. Chin Med. 2012;7(1):19.View ArticlePubMedPubMed CentralGoogle Scholar
- Sampath PD, Vijayaragavan K. Ameliorative prospective of alpha-mangostin, a xanthone derivative from Garcinia mangostana against beta-adrenergic cathecolamine-induced myocardial toxicity and anomalous cardiac TNF-alpha and COX-2 expressions in rats. Exp Toxicol Pathol. 2008;60(4-5):357–64.View ArticlePubMedGoogle Scholar
- Lee S, Kwak HB. Role of adiponectin in metabolic and cardiovascular disease. J Exerc Rehabil. 2014;10(2):54–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20(6):1595–9.View ArticlePubMedGoogle Scholar
- Shen CL, Cao JJ, Dagda RY, Chanjaplammootil S, Lu C, Chyu MC, et al. Green tea polyphenols benefits body composition and improves bone quality in long-term high-fat diet-induced obese rats. Nutr Res. 2012;32(6):448–57.View ArticlePubMedGoogle Scholar
- Soare A, Weiss EP, Holloszy JO, Fontana L. Multiple dietary supplements do not affect metabolic and cardio-vascular health. Aging. 2014;6(2):149–57.View ArticlePubMedGoogle Scholar
- Ormsbee MJ, Rawal SR, Baur DA, Kinsey AW, Elam ML, Spicer MT, et al. The effects of a multi-ingredient dietary supplement on body composition, adipokines, blood lipids, and metabolic health in overweight and obese men and women: a randomized controlled trial. J Int Soc Sport Nutr. 2014;11:37.View ArticleGoogle Scholar
- Wong RH, Garg ML, Wood LG, Howe PR. Antihypertensive potential of combined extracts of olive leaf, green coffee bean and beetroot: a randomized, double-blind, placebo-controlled crossover trial. Nutrients. 2014;6(11):4881–94.View ArticlePubMedPubMed CentralGoogle Scholar