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Pomegranates and vascular health

The juice of the pomegranate (Punica granatum) has been the focus of a number of investigations centering upon its vascular and antioxidant effects. The first line of human evidence revealed the effects of short-term juice ingestion. Thirteen men 20-35 years old drank 50ml for two weeks, while three men drank escalating doses (20-80ml/day) for a maximum of 10 weeks.1 The juice was produced via crushing of pomegranates (Wonderful variety), treating with pectinase, and then pasteurising and concentrating.

No changes in blood-lipid profiles were seen in the two-week study but after one week of 80ml/day, blood glucose, total cholesterol and triglycerides exhibited a 10-15 per cent increase. Modest improvements in plasma antioxidant activity and its resistance to chemically induced lipid peroxidation were seen after two weeks of 50ml/day. More impressive was the improvement in the resistance of LDL and HDL to ex vivo oxidation. HDL oxidation resistance was associated with an increase in serum paraoxonase (arylesterase) activity.

Paraoxonase1 (PON1) is a physically integrated component of HDL and is named after its ability to enzymatically degrade the insecticide paraoxon. A compelling body of evidence suggests that PON1 has an anti-atherosclerotic role.2

A recent study by the same investigative team reported on the long-term effects of pomegranate juice consumption on men and women with severe atherosclerosis, defined as 70-90 per cent narrowing of the internal carotid arteries.3 Ten patients consumed 50ml juice (diluted 1:5 with water each day) and nine received nothing. Among the group ingesting juice for up to one year, substantial improvements in carotid artery anatomy and function and systolic blood pressure were observed, while carotid narrowing progressed by nine per cent in the control group. Blood triglycerides and VLDL were significantly higher after one year of juice; body weight changes were not reported. PON1 activity was 83 per cent higher after one year of juice, accompanied by notable increases in LDL oxidation resistance and plasma antioxidant capacity.

Half of these subjects continued ingesting juice for up to two additional years, wherein all of the vascular and antioxidant effects persisted, while triglycerides (and VLDL) increased by more than 40 per cent (relative to baseline values) by year three.

These two studies are indeed provocative but warrant additional scrutiny. Compelling evidence with an engineered mouse model of atherosclerosis (apoE-deficiency) does create a plausible biological mechanism for pomegranate juice inhibiting atherosclerosis.4 However, the lack of placebo controls, small study sizes, and no measures of compliance in the two clinical trials — and the vast majority of the cardiovascular-relevant data emanating from a lead investigator with relevant patent inventorship and research funds received from marketers of the juice (POM Wonderful LLC, Los Angeles) — underscore the need for more rigorous, independent studies.

Moreover, the finding of the weak estrogens oestrone, alpha-estradiol and estriol as well as testosterone in pomegranate seeds and juice,6,7,8,9 in addition to genistein, daidzein and coumestrol,7 encourages monitoring of hormonal parameters during longer-term trials. Indeed, pomegranates enjoy a lore of being an anti-fertility fruit.10

Lastly, with preclinical evidence pointing to anti-angiogenic actions of pomegranate fractions (Wonderful cultivar)11 — being explored in breast and prostate cancer — the potential downside is an impairment in new blood vessel growth in states marked by ischemia, as seen in a number of cardiovascular conditions. The world waits to taste the fruits of research explorations and a more compelling body of human evidence.

Anthony Almada, MSc, is president and chief scientific officer of IMAGINutrition Inc. Respond:

1. Aviram M, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr 2000; 71:1062-76.
2. Durrington PN, et al. The hunt for nutritional and pharmacological modulators of paraoxonase. Arterioscler Thromb Vasc Biol 2002; 22:1248-50.
3. Aviram M, et al. Pomegranate juice consumption for three years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr 2004; 23:423-33.
4. Kaplan M, et al. Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr 2001; 131:2082-9.
5. Meir KS and Leitersdorf E. Atherosclerosis in the apolipoprotein E-deficient mouse. Arterioscler Thromb Vasc Biol 2004; 24:1006-14.
6. Heftmann E, et al. Identification of estrone in pomegranate seeds. Phytochemistry 1966; 5:1337-40.
7. Moneam NM, et al. Oestrogen content of pomegranate seeds. J Chromatogr 1988; 438:438-42.
8. Kim ND, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat 2002; 71:203-17.
9. Abd El Wahab, SM, et al. Characterization of certain steroid hormones in Punica granatum L. seeds. Bull Fac Pharm (Cairo University) 1998; 36:11-5.
10. Farnsworth NR, et al. Potential value of plants as sources of new antifertility agents. J Pharm Sci 1975; 64:717-54.
11. Toi M, et al. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis 2003; 6:121-8.

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