A compound found in the peel of citrus fruit has the potential to lower cholesterol more effectively than some prescription drugs, and without side effects, according to a study by US and Canadian researchers.
A joint study by the US Department of Agriculture and KGK Synergize, a Canadian nutraceutical company, identified a class of compounds isolated from orange and tangerine peels and concentrated in citrus pectin that shows promise in animal studies as a potent, natural alternative for lowering LDL cholesterol (so-called 'bad' cholesterol), without the possible side effects, such as liver disease and muscle weakness, of conventional cholesterol-lowering drugs.
The findings, released in the April 2004 issue of the Journal of Agricultural and Food Chemistry, a peer-reviewed publication of the American Chemical Society, the world's largest scientific society, show that the compounds, called polymethoxylated flavones (PMFs), are similar to other plant pigments found in citrus fruits that have been increasingly linked to health benefits, including protection against cancer, heart disease and inflammation.
"Our study has shown that PMFs have the most potent cholesterol-lowering effect of any other citrus flavonoid," said Dr Elzbieta Kurowska, lead investigator of the study and vice president of research at KGK Synergize in Ontario, Canada. "We believe that PMFs have the potential to rival and even beat the cholesterol-lowering effect of some prescription drugs, without the risk of side effects."
PMFs are found in a variety of citrus fruits. The most common citrus PMFs, tangeretin and nobiletin, are found in the peels of tangerines and oranges. They are also found in smaller amounts in the juices of these fruits.
Using hamster models with diet-induced high cholesterol, the researchers showed that feeding them food containing 1 per cent PMFs lowered levels of LDL cholesterol by 32 to 40 per cent.
Previous animal studies by others have shown that similar flavonoids, particularly hesperidin from oranges and naringin from grapefruit, also may have the ability to lower cholesterol, although not as effectively as PMFs, according to Kurowska.
Treatment with PMFs did not appear to have any effect on levels of HDL cholesterol, or good cholesterol, the researcher said. No negative side effects were seen in the animals that were fed the compounds, she added.
The researchers are currently exploring the compound's mechanism of action on cholesterol metabolism. They now suspect, based on early results in cell and animal studies, that it works by inhibiting the synthesis of cholesterol and triglycerides inside the liver. A long-term human study of the effect of PMFs on high LDL cholesterol is now in progress. While drinking citrus fruits is full of health benefits, taking PMF supplements could be an easier way to lower cholesterol, since a person would have to drink 20 or more cups a day of orange or tangerine juice to have a therapeutic effect, Kurowska estimates.
KGK Synergize already has developed a nutrition supplement containing PMFs combined with a form of vitamin E that seems to enhance the compound's effect, according to Kurowska. Marketed as a cholesterol-lowering agent under the trade name Sytrinol, the supplement recently became available in the US.
Formulations containing citrus polymethoxylated flavones (PMFs), mainly tangeretin, or citrus flavanone glucosides, hesperidin and naringin, were evaluated for cholesterol-lowering potential in hamsters with diet-induced hypercholesterolemia. PMF metabolites were also investigated.
Diets containing 1% PMFs significantly reduced serum total cholesterol and very low-density lipoprotein (VLDL) + LDL cholesterol (by 19-27 and 32-40%, respectively) and either reduced or tended to reduce serum triacylglycerols. Comparable reductions were achieved by feeding a 3% mixture of hesperidin and naringin (1:1, w/w), implying lower hypolipidemic potency of the hesperidin/naringin vs PMFs. HPLC-MS analysis identified high serum, liver, and urine concentrations of tangeretin metabolites including dihydroxytrimethoxyflavone and monohydroxytetramethoxyflavone glucuronides and aglycones. Total liver concentrations of tangeretin derivatives corresponded to hypolipidemic concentrations of intact tangeretin in earlier experiments in vitro.
This suggests that PMFs are novel flavonoids with cholesterol- and triacylglycerol-lowering potential and that elevated levels of PMF metabolites in the liver might be directly responsible for their hypolipidemic effects in vivo.
Elzbieta M. Kurowska and John A. Manthey; Hypolipidemic Effects and Absorption of Citrus Polymethoxylated Flavones in Hamsters with Diet-Induced Hypercholesterolemia; J. Agric. Food Chem., 52 (10), 2879 -2886, 2004. 10.1021/jf035354z S0021-8561(03)05354-8
Web Release Date: April 21, 2004
Received for review November 17, 2003. Revised manuscript received March 9, 2004. Accepted March 16, 2004. This study was supported by KGK Synergize Inc. and by the USDA, Citrus and Subtropical Products Laboratory. The results were presented in part at the Experimental Biology 2003 Meeting in San Diego, CA (April 11-15, 2003).
KGK Synergize Inc., Suite 1030, One London Place, 255 Queens Avenue, London, Ontario, Canada N6A 5R8, and Citrus and Subtropical Products Laboratory, SAA, ARS, USDA, Winter Haven, Florida 33881