Pomegranates: an update
Subject: An updated review of pomegranate research pertaining to cancer, cardiovascular and periodontal disease. Info on the pomegranate extract we prefer.
I first wrote about pomegranates in the summer of 2003. As you may recall (and if you don't, [ClickHere] to read that one first), there was exciting research on the role pomegranates might play in the prevention and treatment of heart disease and cancer. I recently took a few minutes to see what sort of new research had come out since this first letter.
Ephraim Lansky and a colleague of his in Japan showed that pomegranate extracts will cause differentiation in leukemia cells. Differentiation is the ability of cancer cells to revert back to their normal non-cancerous identities. Finding things that will cause differentiation is exceptionally desirable because it offers us a cancer therapy that isn't poisonous. Researchers are looking for ways to cause differentiation in breast, prostate, and other solid tumor cancers. Flavonoids are as a group differentiating chemicals. Vitamin A and the retinoids also cause differentiation but can be toxic. In the past Lansky has figured out a way to extract and ferment various pomegranate fractions and shown that they have antiproliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic action on breast and prostate cells and anti-angiogenic activity in vitro and in vivo. So now Lansky tested various fresh juice and fermented pomegranate juice fractions on human leukemia cells. The extract of pericarp and the fermented juice had the most striking effects. The fresh juice had only a weak effect. 
That the fermented and pericarp extracts have greater effect than the fresh juice on cancer cells is consistent with Lansky's earlier work that showed the same result. We now carry the pomegranate extract manufactured in Israel by Lansky's Lab in our office. Tom Reed of Slade and Reed Pomegranate Farms in California grows the pomegranates, makes a syrup and ships it to Israel for Lansky to ferment. The finished product, called Cardiogranate is then shipped back to the states. We are selling at the same price as advertised on the web. http://www.pomegranategold.com/cardiogranate.html
Lansky is behind another study that has come out since our first newsletter. In this study he worked with researchers in South Dakota and demonstrated that topical application of pomegranate oil lowers the incidence of skin cancer in mice exposed to cancer causing chemicals. Topical treatment with dilute pomegranate oil protected the mice, not entirely, but less mice got cancer and the ones that did had fewer tumors.  Pomegranate oil is available at an astronomic price so at this point don't get your hopes up about using it for suntan lotion. The more striking effect of the seed oil is that it works as an aromatase inhibitor. Aromatase inhibitors are the new family of chemicals being promoted as breast cancer treatments. Lansky with a group of Korean researchers in 2002 had already shown that his various pomegranate fractions could lower aromatse activity by 70-80%. 
Aromatase inhibitors suppress the production of estrogens. If you have hormone dependent breast cancer this is certainly a worthwhile goal. Preventing estrogen formation has its downside though. Without estrogen, bone density rapidly declines increasing the risk of osteoporosis and bone fractures. Pomegranates contain estrogen like chemicals and these may be enough to prevent osteoporosis. At least this is true in mice.
Just this month, May 2004, Japanese researchers published a study on mice in which they had surgically removed the ovaries. Treating them with pomegranate extracts increased their bone volumes and kept the mice from getting depressed (apparently there is some sort of swimming test that measures mouse depression, don't ask me to explain it.). The researchers theorize that pomegranate may prevent both bone loss and depression in menopausal women. 
Premarin and Hormone Replacement Therapy used to be promoted as preventing both osteoporosis and heart disease. This is no longer true for HRT but it may be true for pomegranate.
You will remember from our previous newsletter that much of the research focused on heart disease prevention. I won't repeat myself here but there is one important correction that needs to be made. In reviewing Aviram and Dornfeld's 2001 study on pomegranate juice I made a mistake. They showed that pomegranate juice inhibits angiotensin converting enzyme and significantly reduces systolic blood pressure. A 5% decrease in systolic blood pressure was reported over a 2 week period of consuming 50 ml of juice per day or as I said about two Tablespoons.  They were using juice from the “Wonderful” line of pomegranate trees but it turns out, not the PomWonderful pomegranate juice sold at King Soopers. They were using a concentrated extract instead. The equivalent dose would be 8 oz or a cup of the PomWonderful Juice. I must thank Dr. Shulman at PomWonderful for pointing out my misunderstanding. A concentrated unfermented pomegranate juice equivalent to what was used in the study is also available from Slade and Reed and is sold as Cardio Cleanser. We do not yet have this product at the clinic. Dr. Bloom only lets me order one new product at a time. I have to sell some before I'm allowed to order anything else new.
There are two other uses for pomegranate that I noticed in this literature review for the first time. The first has to do with oral and dental health. Researchers in Thailand think pomegranate may have a role in treating periodontal disease. They combined pomegranate extracts with extracts of another herb, Centella asiatica (commonly known as gotu kola) and formulated it into small “chips”. They inserted these chips into the gum pockets of people suffering from periodontal disease. Using these over a three month period caused significant improvement in pocket depth and adhesion of the gums. 
On the other side of the world, researchers in Brazil had made a gel solution of pomegranate extracts and shown it was useful in the treatment of candida overgrowth in the mouth associated with sores caused by wearing dentures. 
*To see the original Pomegranate newsletter [ClickHere]
*To read an article about Pomegranates and Lansky's research published in the Jerusalem Report, an Israeli English news magazine [Click Here]
 J Med Food. 2004 Spring;7(1):13-8 Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells. Kawaii S, Lansky EP.
 J Med Food. 2003 Fall;6(3):157-61. Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice. Hora JJ, Maydew ER, Lansky EP, Dwivedi C.
 Breast Cancer Res Treat. 2002 Feb;71(3):203-17. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, Poirier D, Nicholls P, Kirby A, Jiang W, Mansel R, Ramachandran C, Rabi T, Kaplan B, Lansky E.
 J Ethnopharmacol. 2004 May;92(1):93-101. Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice.
 Atherosclerosis. 2001 Sep;158(1):195-8. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Aviram M, Dornfeld L.
 J Int Acad Periodontol. 2003 Oct;5(4):106-15. Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts. A preliminary study. Sastravaha G, Yotnuengnit P, Booncong P, Sangtherapitikul P.
 Mycoses. 2003 Jun;46(5-6):192-6. Use of Punica granatum as an antifungal agent against candidosis associated with denture stomatitis. Vasconcelos LC, Sampaio MC, Sampaio FC, Higino JS.