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1、The effect of fructose consumption on plasma cholesterol in adults: a meta-analysis of controlled feeding trials1,2,3Tao An4,5, Rong Cheng Zhang4,5, Yu Hui Zhang4, Qiong Zhou4, Yan Huang4, Jian Zhang4, *.4 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovasc
2、ular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China5 Tao An and Rong Cheng Zhang contributed equally to this study.3 Supplemental Table 1 and supplemental Figures 1-4 are available as Online Supporting Material with the online posting of this paper at
3、http:/jn.nutrition.orgRUNNING TITLE: Fructose and cholesterolWORD COUNT: 5618; NUMBER OF FIGUREA: 3; NUMBER OF TABLES: 2SUPPLEMENTARY MATERIAL: Online Supporting Materials: 5AUTHOR LIST FOR INDEXING: An, Zhang, Zhang, Zhou, Huang, Zhang1 The study was supported by the Ministry of Science and Technol
4、ogy of China with grant of the National High-tech Research and Development Program of China to Dr Jian Zhang. 2 Author disclosures: T. An, R.C. Zhang, Y.H. Zhang, Q. Zhou, Y. Hung, J. Zhang have no conflicts of interest.* To whom correspondence should be addressed. Mailing address: Heart Failure Cen
5、ter, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishilu, Beijing, China; Zip code: 100000; Telephone number: 86-10-88396180; Fax number: 86-10-88396180; E-mail: Fwzhangjian62PROSPERO REGISTRATION NUMBERS: CRD42012003351AB
6、STRACTFructose is widely used as a sweetener in production of many foods, yet the relation between fructose intake and cholesterol remains uncertain. We performed a systematic review and meta-analysis of human controlled feeding trials of isocaloric fructose exchange for other carbohydrates to quant
7、ify the effects of fructose on total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in adult humans. Weighted mean differences were calculated for changes from baseline cholesterol concentrations by using generic inverse variance random-effects models. The Heyland Methodologi
8、cal Quality was used to assess study quality. Subgroup analyses and meta-regression were conducted to explore possible influence of study characteristics. Twenty-four trials (with a total of 474 subjects) were included in our meta-analysis. In an overall pooled estimate, fructose exerted no effect o
9、n TC, LDL-C and HDL-C. Meta-regression analysis indicated that fructose dose was positively correlated with the effect sizes of TC and LDL-C. Subgroup analyses showed that isocaloric fructose exchange for carbohydrates could significantly increase TC by 12.97 mg/dL (95%CI: 4.66, 21.29; P = 0.002) an
10、d LDL-C by 11.59 mg/dL (95%CI: 4.39, 18.78; P = 0.002) at 100g fructose/d but had no effect on TC and LDL-C when fructose intake was 100g/d. In conclusion, very high fructose intake (100g/d) could lead to significantly increase in serum LDL-C and TC. Larger, longer and higher-quality human controlle
11、d feeding trials are needed to confirm these results.Key words: fructose, cholesterol, meta-analysisINTRODUCTIONHyperlipidemia is a common risk factor for coronary heart disease (CHD), with 44.4% of adults in the United States having abnormal TC values and 32% having elevated LDL-C levels (1). Compa
12、red to subjects with normal blood lipid, those with hyperlipidemia have a 3-fold risk of heart attacks (2). Lifestyle modification should be initiated in conjunction both primary and secondary prevention of CHD. More consideration exists as to what constitutes healthy eating.Fructose is the most nat
13、urally occurring monosaccharide, and has become a major constituent of our modern diet. Fruit, vegetables, and other natural sources provide nearly one-third of dietary fructose, and two-thirds come from beverages and foods in the diets (eg, candies, jam, syrups, etc) (3). Fructose is preferred by m
14、any people, especially those with diabetes mellitus because of its low glycemic index (23% versus glucose 100%) (4). After intestinal uptake, fructose is mainly removed from the blood stream by the liver in an insulin-independent manner, and is used for intrahepatic production of glucose, fatty acid
15、s or lactate. Cross-sectional studies in human suggest that excessive fructose consumption can lead to adverse metabolic effects, such as dyslipidemia and increased visceral adiposity (5-7). The Dietary Guidelines for Americans, 2010, point out that it is lack of sufficient evidence to set a tolerab
16、le upper intake of carbohydrates for adults (8). Although The Candian Diabetes Association suggests consumption of no more than 60g of added fructose per day by people with diabetes for its triglyceride-raising effect (9), the threshold dose of fructose at which the adverse influence on cholesterol
17、is controversial.To determine the effect of fructose on cholesterol, a substantial number of clinical trials have been performed on adult humans with different health status (diabetic, obese, overweight, hyperinsulinemic, impaired glucose-tolerant and healthy). These trials used various intake level
18、s of fructose and different protocols. Thus, it is difficult to reach a consistent conclusion across these studies. Therefore, we conducted a systematic review of the scientific literature and meta-analysis of controlled feeding trials to evaluate the effect of isocaloric oral fructose exchange for
19、carbohydrates on cholesterol and to clarify the active factors of fructose.Materials and MethodsThis meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria (10).Search strategy. We searched PubMed (http:/www.ncbi.nlm.nih.gov/pubmed; from 1966
20、to December 2012), Embase (; from 1966 to December 2012) and the Cochrane Library database (http:/www.cochrane.org) by using the following search terms: fructose and (lipemia or lipaemia or lipids or cholesterol or “total cholesterol” or “LDL cholesterol” or “HDL cholesterol”) in English. We also se
21、arched China National Knowledge Infrastructure () and Wangfang database () in Chinese according to the search strategy. The search was restricted to reports of trials on humans.Study selection. All clinical trials using fructose and indexed within the above databases were collected. Two independent
22、reviewers (T.A., R.C.Z) screened the abstracts and titles for initial inclusion. If this was not sufficient, full texts articles were obtained and reviewed by at least two independent reviewers (T.A., R.C.Z, Q.Z., Y.H.). The reference lists of retrieved articles also used to supplement the database.
23、 Any disagreements were resolved through discussion. We included controlled feeding trials investigating the chronic effect of fructose on blood cholesterol, from both randomized and nonrandomized studies, if they met the following criteria: subjects must have been administered fructose for at least
24、 2 weeks; studies investigated the effect of oral free (unbound, monosaccharide) fructose when compared with isocaloric control diet with another carbohydrate in place of fructose; studies were performed in human adults with either a parallel or crossover design; subjects in both experimental groups
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