Pomegranate Juice Reduces Cholesterol Synthesis in Macrophages in Cell Culture

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 9 No. 1 • October 2005

It does not take a majority to prevail … but rather an irate, tireless minority, keen on setting brushfires of freedom in the minds of men.
— Samuel Adams, American revolutionary
No one, no government agency has jurisdiction over the truth.
— Fox Mulder, The X-Files
In the end, more than they wanted freedom, they wanted security. When the Athenians finally wanted not to give to society, but for society to give to them, when the freedom they wished for was freedom from responsibility, then Athens ceased to be free.
— Edward Gibbon
We borrowed the profit motive [of the West] but not the entrepreneurial spirit. We borrowed the acquisitive appetites of capitalism, but not the creative risk-taking. We are at home with Western gadgets but are bewildered by Western workshops. We wear the wristwatch but refuse to watch it for the culture of punctuality. We have learned to parade in display, but not to drill in discipline. The West’s consumption patterns have arrived, but not necessarily the West’s technique of production.
— Ali A. Mazrui, State University of New York at Binghamton,
on the economic problems of Africa

Pomegranate Juice Reduces Cholesterol Synthesis in Macrophages in Cell Culture

Statins are widely used to decrease cholesterol synthesis in humans by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the rate-limiting step in the synthesis of mevalonate, from which cholesterol is synthesized. However, mevalonate is also the starting material for the production of other important biological chemicals, including CoQ10 and selenoproteins, such as glutathione peroxidase. The decreased production of CoQ10 and selenoproteins1, 2, 2a may be responsible for many side effects (potentially severe) of statin use. See more on this in the article that follows. In our view, the inhibition of the synthesis of mevalonate is a blunt instrument in the search for inhibitors of cholesterol synthesis and inhibits too many desirable products of mevalonate as an unwanted side effect.

That is one reason for our interest in pomegranate juice and other natural products that may decrease production of cholesterol without inhibiting HMG-CoA reductase. A recent paper3 reports that cholesterol biosynthesis by macrophages was inhibited by 50% after cell incubation with pomegranate juice. However, this inhibition did not take place at the HMG-CoA reductase level in the synthetic pathway. Thus, the synthesis of mevalonate was not itself inhibited, but the synthesis of cholesterol from mevalonate was. In an earlier study, the same authors report publishing a paper in which they demonstrated that “supplementation of pomegranate juice to atherosclerotic, apolipoprotein E-deficient mice, which already exhibit advanced atherosclerotic lesions, reduced macrophage lipid peroxides along with a reduction in macrophage cholesterol accumulation and foam cell formation.”

We hope that there will be follow-up on these findings, but it will all come to naught if the FDA (and FTC) can continue to prohibit the communication of truthful scientific information (including distributing peer-reviewed scientific papers) concerning dietary supplements and foods. (More on this in the FDA Update and Legislative Update below.) In the meantime, we are drinking a reduced-sugar (8 grams per 8-ounce cup) pomegranate juice diluted with water to 25% juice (Langers), which makes for a very tasty drink.


  1. Moosmann, Behl. Hypothesis: selenoprotein synthesis and side-effects of statins. Lancet 363:892-4 (2004).
  2. Warner et al. Inhibition of selenoprotein synthesis by selenocysteine tRNA[Ser]Sec lacking isopentyladenosine. J Biol Chem 275:28110-9 (2000).
    2a. Dale et al. Statins and cancer risk. JAMA 295:74-80 (2006).
  3. Fuhrman et al. Pomegranate juice inhibits oxidized LDL uptake and cholesterol biosynthesis in macrophages. J Nutr Biochem 16:570-6 (2005).

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