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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Immunity and Disease Prevention Research » Research » Publications at this Location » Publication #303910

Title: Citrus limonin glucoside supplementation decreased biomarkers of liver disease in overweight human subjects

Author
item KELLEY, DARSHAN
item Adkins, Yuriko
item ZUNINO, SUSAN
item WOODHOUSE, LESLIE - U.S. DEPARTMENT OF AGRICULTURE (USDA)
item BONNEL, ELLEN - U.S. DEPARTMENT OF AGRICULTURE (USDA)
item Breksa, Andrew
item MANNERS, GARY
item Mackey, Bruce

Submitted to: Journal of Functional Foods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/28/2015
Publication Date: 12/15/2014
Citation: Kelley, D.S., Adkins, Y.C., Zunino, S.J., Woodhouse, L., Bonnel, E., Breksa Iii, A.P., Manners, G.D., Mackey, B.E. 2014. Citrus limonin glucoside supplementation decreased biomarkers of liver disease in overweight human subjects. Journal of Functional Foods. 12:271-281. doi: 10.1016/jff.2014.11.026.

Interpretive Summary: Results from human epidemiological studies indicated inverse association between the intake of fruits and vegetables and the incidence of chronic inflammatory diseases including, metabolic syndrome (MS), diabetes, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), and cancer. Orange juice improved several biomarkers for these diseases in human studies, and the products prepared from citrus juice, peel, seeds, and pulp had similar effects in animal and cell culture models. Limonids are highly oxygenated triterpenoid citrus compounds which have been shown to have significant biological activity in animals models, but the risks and benefits of purified limonoids in human beings are not known. Aim of this study was to determine the safety and metabolic effects of purified limonin glucoside (LG) in human subjects. In a cross-over, placebo controlled, double blind study, we examined the safety of consuming purified LG and its effects on blood lipids, lipoproteins, liver enzymes, and risk factors for diabetes, CVD, and cancer in overweight/obese men and women. During the first 14 d, all subjects received 2 placebo drinks. For study d 15-70, one-half of the subjects continued to consume placebo drinks while the other half consumed drinks containing purified LG (250 mg/drink, 2 drinks/d). Drinks between the 2 groups were switched for study d 71-126. Twelve h fasting blood samples were collected on study d 15, 71, and 127, and results between placebo and LG treatments were compared. LG had no serious adverse effects in our study. It did not alter circulating concentrations of blood lipids, lipoproteins and their particle sizes, glucose, insulin, and hematological parameters. Also LG did not significantly alter concentrations of several conventional markers of inflammation except it decreased concentrations of two, MMP-9 by 38.7%, and TNF'alpha by10.7%. In addition, LG significantly decreased circulating concentrations of the liver proteins, gamma-glutamyl transferase (33.8%), alanine aminotransferase (13.1%), alkaline phosphatase 10.1%), and complement C3 (6.4%), and that of free prostate specific antigen (13.9%). Since elevated liver enzymes are associated with several chronic diseases including MS, diabetes, CVD, NAFLD, and cancer, LG may be useful in the prevention and/or treatment of those diseases. Future studies with LG are needed in human subjects who are at increased risk or at early stages of these diseases.

Technical Abstract: Orange juice and mixtures of citrus limonoid glucosides isolated from orange juice or its byproducts demonstrated health benefits in human and animal studies. However, the risks and benefits of purified limonin glucoside (LG) in humans are unknown. Aim of this study was to determine the safety and metabolic effects of purified LG in human subjects. In a cross-over, placebo controlled, double blind study, we examined the safety of consuming purified LG and its effects on blood lipids, lipoproteins, liver enzymes, and risk factors for diabetes, CVD, and cancer in overweight/obese men and women (5 each). During the first 14 d, all subjects received 2 placebo drinks. For study d 15-70, 5 subjects continued to consume placebo drinks while the other 5 consumed drinks containing purified LG (250 mg/drink, 2 drinks/d). Drinks between the 2 groups were switched for study d 71-126. Twelve h fasting blood samples were collected on d 15, 71, and 127, and results between placebo and LG treatments were compared using d 15 data as the covariate. LG had no serious adverse effects in our study. It did not alter circulating concentrations of blood lipids, lipoproteins and their particle sizes, glucose, insulin, and hematological parameters. Also LG did not significantly alter concentrations of conventional markers of inflammation except it decreased concentrations of MMP-9 (38.7%) and TNF'alpha (10.7%). In addition, LG significantly decreased circulating concentrations of the liver proteins, gamma-glutamyl transferase (33.8%), alanine aminotransferase (13.1%), alkaline phosphatase 10.1%), and complement C3 (6.4%), and that of free prostate specific antigen (13.9%). Since elevated liver enzymes are associated with several chronic diseases including metabolic syndrome, nonalcoholic fatty liver disease, diabetes, cardiovascular and kidney diseases, LG may be useful in the prevention and/or treatment of those diseases.