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The effect of fructose consumption on plasma cholesterol in adults: a meta-analysis of controlled feeding trials1,2,3
Tao An4,5, Rong Cheng Zhang4,5, Yu Hui Zhang4, Qiong Zhou4, Yan Huang4, Jian Zhang4, *.
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State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National
Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Tao An and Rong Cheng Zhang contributed equally to this study.
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Supplemental Table 1 and supplemental Figures 1-4 are available as Online
Supporting Material with the online posting of this paper at http://jn.nutrition.org
RUNNING TITLE: Fructose and cholesterol
WORD COUNT: 5618; NUMBER OF FIGUREA: 3; NUMBER OF TABLES: 2 SUPPLEMENTARY MATERIAL: Online Supporting Materials: 5
AUTHOR LIST FOR INDEXING: An, Zhang, Zhang, Zhou, Huang, Zhang
1
The study was supported by the Ministry of Science and Technology 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 Center, 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: Fwzhangjian62@163.com
PROSPERO REGISTRATION NUMBERS: CRD42012003351
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ABSTRACT
Fructose 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 quantify 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 Methodological 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 on 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) and 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
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higher-quality human controlled feeding trials are needed to confirm these results.
Key words: fructose, cholesterol, meta-analysis
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INTRODUCTION
Hyperlipidemia 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). Compared 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 naturally 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 many 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 acids 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 tolerable upper intake of carbohydrates for adults (8). Although The