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Grapefruit extract shows anti-diabetes potential

An antioxidant extracted from grapefruit may help the liver break down fat and improve insulin sensitivity, according to new data from the Hebrew University of Jerusalem and Massachusetts General Hospital.

Naringenin, a compound derived from the bitter flavor of grapefruits and other citrus fruits, was found to mimic the actions of the established pharmaceuticals Fenofibrate (lipid-lowering action) and Rosiglitazone (anti-diabetic action), according to findings published in the online journal PLoS ONE.

If the results can be repeated in human studies, the dietary supplement may become a staple for people with elevated blood lipid levels (hyperlipidemia), type-2 diabetes, and perhaps metabolic syndrome.

Naringenin science

It is not the first time that naringenin has been reported to have potential for people suffering from the metabolic syndrome and related conditions. Indeed, last year scientists from the University of Western Ontario reported positive results in mice (Diabetes, Vol. 58, pp. 2198-2210), while the cholesterol lowering potential of grapefruits has also been reported (Journal of Agricultural and Food Chemistry, 2006, Vol. 54, pp 1887-1892).

"It is a fascinating find," said Yaakov Nahmias, PhD, from the Hebrew University of Jerusalem. "We show the mechanism by which naringenin increases two important pharmaceutical targets, PPAR-alpha and PPAR-gamma, while blocking a third, LXR-alpha. The results are similar to those induced by long periods of fasting".

According to the researchers, on eating a meal the blood is flushed with sugars, which activates LXR-alpha and causes the liver to create fatty acids for long-term storage. This processed is reversed during fasting, they note, and fatty acids are released by fat cells, thereby activating PPAR-alpha in the liver, and are broken down to ketones. A similar process, involving PPAR-gamma, increases sensitivity to insulin, they said.

"Dual PPAR-alpha and PPAR-gamma agonists, like naringenin, were long sought after by the pharmaceutical industry," added Nahmias, "but their development was plagued by safety concerns. Remarkably, naringenin is a dietary supplement with a clear safety record. Evidence suggests it might actually protect the liver from damage."

Study details

Nahmias and his co-workers studied the effects of naringenin in liver cells at concentrations ranging from zero to 240 micromoles. Results showed that the citrus compound activated both PPAR-alpha and PPAR-gamma, while also binding to LXR-alpha, which effectively blocked its activation.

“The potential of using a naturally occurring dietary supplement to regulate lipid metabolism is appealing as this by product of the grapefruit juice industry is non-toxic, cheap, and has demonstrated anti-inflammatory properties,” said the researchers.

“This is especially important in the context of the rising costs of cardiovascular care, estimated by the [American Heart Association] to rise above $500 billion this year.

“Naringenin ability to inhibit [a] target of statins, while upregulating PPAR-alpha, the target of fibrates, suggest it can naturally find its place in the routine treatment of hyperlipidemia,” they concluded.

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This article was published on Friday August 27, 2010.
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Source: PLoS ONE
Published and available online, http://dx.plos.org/10.1371/journal.pone.0012399
“Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPARa, PPARc and LXRa”
Authors: J. Goldwasser, P.Y. Cohen, E. Yang, P. Balaguer, M.L. Yarmush, et al.