Product Review of Supplements for Cancer Prevention (Green Tea, Lycopene, and Selenium) Initial Posting: 4/19/06 Some supplements may reduce the risk of developing certain types of cancers. Many of these potential "chemopreventive" ingredients act directly or indirectly as antioxidants, helping to neutralize dangerous free radicals. Others offer potential benefits through hormonal effects or other mechanisms. The evidence that specific compounds can help prevent cancer generally comes from observational studies, in which populations that consume higher amounts of a natural substance (typically from diet and not from supplements) are found to have lower cancer rates. Such studies don't show cause and effect and must be considered preliminary evidence. In some cases, additional supporting evidence comes from test tube and animal studies. Double-blind, placebo-controlled studies are the gold standard for determining effectiveness of a treatment. Only three ingredients have some direct clinical evidence (from double-blind clinical trials) to support their use in for cancer prevention: vitamin E, lycopene and selenium. However, even in these cases the evidence remains far from conclusive. Other ingredients with potential benefit include folate, garlic, green tea, soy isoflavones and other isoflavones, indole-3-carbinol (I3C), diindolylmethane (DIM), vitamin C and vitamin D. Those highlighted in blue are the subjects of other reviews from ConsumerLab.com (click on their names to get their reports). This review focuses on three ingredients — green tea, lycopene, and selenium. Green tea is made from the plant Camellia sinensis. It contains compounds called catechin polyphenols that in test tube studies show antioxidant, anticarcinogenic, antitumorigenic, and anti-microbial properties. Green tea is made from the same plant as black tea, but green tea is made by lightly steaming freshly cut leaves, while black tea is fermented and has lower amounts of polyphenols. The main catechin polyphenol found in green tea is epigallocatechin gallate (EGCG). Lycopene is a red pigment and powerful antioxidant found in tomatoes, pink grapefruit, watermelons, apricots, and pink guavas. On a per gram basis, lycopene is about twice as power an anti-oxidant as another well-know carotenoid, beta-carotene. Selenium is a trace mineral that our bodies use to produce glutathione peroxidase — part of the body's own antioxidant defense system. It works with vitamin E to protect cell membranes from damage caused by free radicals. Test tube and animal studies hint that tea constituents might help prevent cancers of the stomach, lung, esophagus, duodenum, pancreas, liver, breast, and colon. However, results from observational studies in humans have varied. One study found that Japanese women who drank more than ten cups of green tea daily had a delay in the onset of cancer and also a 43% lower total rate of cancer occurrence. An effect was also seen in men but it was not statistically significant. A study in China found that those who drank green tea had significantly less risk of developing cancers of the rectum and pancreas, but not colon cancer. Another Chinese study found that green tea drinkers were 29% less likely to get stomach cancer than nondrinkers, with those drinking the most tea having the least risk. However, observational studies in both Japan and Hawaii have found no reduction in stomach cancer. A small pilot study in humans found that oral green tea extracts might be able to reduce prostate cancer rates in men who already have pre-cancerous changes in the prostate. There is preliminary laboratory evidence suggesting that the green tea catechin, EGCG, may help prevent skin cancer if applied directly to the skin. However, a double-blind, placebo controlled study failed to find that a combination of oral and topical green tea extracts reduced signs of precancerous sun-damage in skin. There is evidence suggesting a cancer-preventing benefit for lycopene, but it is indirect and far from definitive. A large observational study of men found a reduced incidence of prostate cancer among those eating high levels of tomatoes, tomato sauce, and pizza — all of which contain lycopene. In addition, a study of elderly Americans was conducted and found a diet high in tomatoes was associated with a 50% reduction in cancer. People who ate at least seven servings of tomatoes weekly developed less stomach and colorectal cancers compared to those who ate only two servings weekly. These observational studies involved tomato-based foods and not lycopene supplements. One preliminary controlled (but not blinded) study in humans did test lycopene supplements; when taken at a dose of 4 mg twice daily they appeared to help prevent precancerous cells in the prostate from turning cancerous. Regarding other medical conditions, lycopene has shown some promise for treatment of asthma. It has been observed that in parts of China where the soil is depleted of selenium, the incidence of various types of cancer is much higher than in the rest of the country. This observation has given rise to a theory that selenium deficiency is a common cause of cancer and selenium supplements can reduce this risk. In North America, however, selenium deficiency is uncommon. In people with adequate selenium intake, it is not clear whether or not additional selenium is helpful. One study indicated a 50% reduction in overall cancer deaths when additional selenium was taken — with significant decreases in cancer of the lung, colon, and prostate. However, results of this study have been tempered by further analysis indicating that most of the benefits were seen in study participants with somewhat lower levels of selenium to begin with. Selenium has not been shown to reduce the risk of skin cancer and selenium supplements do not appear to reduce the risk for colorectal cancer. However, early data suggests that there may be more effective and less toxic forms of organic selenium for preventing colorectal cancer than those used previously. In addition, animal trials have found anti-cancer benefits. Other potential benefits of selenium have been indicated. Low selenium levels have been associated with the development of rheumatoid arthritis — although selenium supplements don't seem to help rheumatoid arthritis once it has developed. There is preliminary evidence that selenium supplements may improve fertility in males who are selenium deficient. There is weak evidence that selenium might be helpful for diabetic neuropathy. Selenium does not appear to be helpful for preventing heart disease. One fairly large double-blind study failed to find that use of selenium improved general sense of well-being. Like other supplements, neither the FDA nor any other federal or state agency routinely tests supplements for quality prior to sale. However, quality issues can include the following: Labeled Amount — Does the product really contain the labeled amount of ingredient? Too little may not work. Too much may cause toxicity, particularly with selenium. Purity — Is the product free of lead — a contaminant found in many types of supplements. Ability to Break Apart for Absorption — Will the product break apart properly so that it can release its ingredient in the body? For a tablet to be most useful, it must fully disintegrate prior to leaving the stomach, delivering its contents for absorption in the gut. Some tablets are not properly made and can pass through your body completely or partially intact, depriving you of its ingredients. Remnants of such products are sometimes found in the stool. This happens, for example, when a tablet is too tightly compressed (too "hard") or is too thickly coated. ConsumerLab.com, as part of its mission to independently evaluate products that affect health, wellness, and nutrition, purchased green tea, lycopene, and selenium supplements sold in the U.S. and Canada and tested them to determine whether they 1) possessed the claimed amount of key ingredient, 2) were able to disintegrate fully to be available for absorption and 3) were free from unacceptable levels of lead (see Testing Methods and Passing Score). In green tea products, the amount of caffeine was also determined. Only one of the green tea products selected by CL passed testing, as did three products tested through CL's Voluntary Certification Program. Among products selected by CL, problems were found with the following: Futurebiotics Premium Standardized Green Tea Extract was contaminated with 4.5 mcg of lead per daily serving of three tablets. Herbal Select Standardized Green Tea Extract was contaminated with 3.3 to 6.6 mcg of lead per daily serving of one to two capsules. Food Science of Vermont Green Tea Extract was found to contain only 50 mg of EGCG per capsule — 71% of the 70 mg claimed. The State of California's "no significant risk level" for lead is 0.5 mcg of lead per day (see Passing Score). California requires products exceeding this level to provide a warning label — which these products did not. It has been reported that children can show signs of lead poisoning when exposed to more than 6 mcg or more of lead per day. Since children get approximately 1 to 2 mcg of lead each day from environmental exposure (water, food, air), additional exposure from this product could put some children at risk for lead toxicity and should be avoided. Although adults can tolerate higher amounts of lead (about 70 mcg per day), lead can build up in the body and such exposure should be avoided. Pregnant women should particularly avoid lead, as it can be transferred to the fetus. All five of the selected lycopene products passed testing, as did two products tested through CL's Voluntary Certification Program. One product, Canadian Sun Selenium, failed testing: It contained only 18.9 mcg of selenium — 38% of the 50 mcg claimed. Four other products selected by CL passed testing, as did three products tested through CL's Voluntary Certification Program. Listed below are the test results for twenty-two supplements. Products are grouped by key ingredient and listed alphabetically within each group. ConsumerLab.com selected fourteen of these products. Eight other products (each indicated with an asterisk) were tested at the request of their manufacturers/distributors through the Voluntary Certification Program and are included for having passed testing. Also listed are four products that are the same as ones that passed but sold under different brand names. Shown for each product are the claimed amount and form of the tested ingredient(s) and serving size recommended on its label. Products listed as "Approved" met their label claims and ConsumerLab.com's quality criteria (see Passing Score). For green tea products, the amount of caffeine found in a daily dose is also shown since caffeine occurs naturally in green tea. To put these amounts in perspective, a can of cola contains about 40 mg of caffeine and a cup of coffee has about 100 mg of caffeine. RESULTS OF CONSUMERLAB.COM TESTING OF GREEN TEA SUPPLEMENTS — TEST RESULTS — Food Science of Vermont Green Tea Extract (500 mg extract per vegetarian capsule, 2 per day) Ingredients Dist by Food Science of Vermont 140 mg EGCG NOT APPROVED Found only 99.1 mg EGCG (70.8% of claim) 5 mg Futurebiotics Premium Standardized Green Tea Extract (100 mg extract and 400 mg leaf per tablet, 2 per day) Ingredients Dist by Futurebiotics 40 mg polyphenol catechins from extract NOT APPROVED Found 50 mg EGCG 4.50 mcg of lead per daily serving 25 mg Herbal Select Standardized Green Tea Extract, 50% Polyphenols (500 mg extract per capsule, 1-2 per day) Ingredients Dist. by Herbal Select 250 - 500 mg polyphenols NOT APPROVED Found 43.5 - 87 mg EGCG 3.30-6.60 mcg of lead per daily serving NA 36-72 mg Life Extension Mega Green Tea Extract (725 mg extract per capsule, 1 per day) Ingredients Dist. by Quality Supplements and Vitamins, Inc 246.5 mg EGCG 427.75 mg polyphenols APPROVED NA 2 mg Nature's Bounty® Green Tea Extract (315 mg extract per capsule, 4 per day)* Ingredients Mfd. by Nature's Bounty, Inc. 190 mg polyphenols APPROVED Found 68.8 mg EGCG N/A 108 mg Pharmanex® Tegreen® 97 (250 mg per capsule, 1-4 per day)* Ingredients Dist. by Nu Skin Enterprises 95 - 380mg EGCG 242.5 - 970 mg polyphenols APPROVED NA 0.75-3.0 mg Puritan's Pride® Green Tea Extract 315 mg (315 mg per capsule, 4 per day)* Ingredients Mfd. by Puritan's Pride, Inc. 90 mg Polyphenols APPROVED Found 57.6 mg EGCG NA 77 mg *Tested through CL's Voluntary Certification Program prior to, at time of, or after initial posting of this Product Review. †Minimum amounts of catechins expected for green tea is 10% (wt/wt). Extracts may have more depending on concentration. See ConsumerTips™ for more information about catechins and dose. RESULTS OF CONSUMERLAB.COM TESTING OF LYCOPENE SUPPLEMENTS Bluebonnet Lycopene 20 mg (20mg per softgel, 1 per day) Ingredients Dist. by Bluebonnet Nutrition Corporation 20 mg APPROVED NA NA GNC Natural Brand™ Lycopene (10 mg per softgel, 1 per day) Ingredients Dist. by GNC 10 mg APPROVED NA NA Jarrow Formulas® Lyco-Sorb® (10 mg per softgel, 1-2 per day) Ingredients Mfd. by Jarrow Formulas 10 - 20 mg APPROVED NA NA KAL® Lycopene 10 mg (10 mg softgels, 1 per day) Ingredients Mfd. by Nutraceutical Corp. for Makers of KAL 10 mg APPROVED NA NA Nature's Answer® Lycopene (5 mg per mL, 1 mL per day) Ingredients Dist. by Nature's Answer® 5 mg APPROVED NA NA Nature's Bounty® Lycopene 5 mg (5 mg per softgel, 1 per day)* Ingredients Mfd. by Nature's Bounty, Inc. 5 mg APPROVED NA NA Puritan's Pride® Lycopene 10 mg (10 mg softgel, 1 per day)* Ingredients Dist. by Puritan's Pride, Inc. 10 mg APPROVED NA NA Similar to APPROVED Products:** Vitamin World® Lycopene 10 mg (10 mg per softgel, 1 per day) Ingredients Mfd. by Vitamin World, Inc *Tested through CL's Voluntary Certification Program prior to, at time of, or after initial posting of this Product Review. ** Product identical in formulation and manufacture to a product that has passed testing but sold under a different brand. For more information see CL's Multi-Label Testing Program. Canadian Sun Selenium 50 mcg (50 mcg per tablet, 1 per day) Ingredients Mfd. by Canadian Sun Health Products Ltd. 50 mcg NOT APPROVED Found only 18.9 mcg per tablet (37.8% of claim) Country Life® Vegetarian Selenium (100 mcg tablet, 1 per day) Ingredients Dist by Country Life 100 mcg APPROVED Metabolic Maintenance Selenium 200 mcg (200 mcg per capsule, 1 per day) Ingredients Mfd. by Metabolic Maintenance Products 200 mcg APPROVED NA Nature's Bounty® Natural Selenium 200 mcg (200 mcg per tablet, 1 per day)* Ingredients Mfd. by Nature's Bounty, Inc. 200 mcg APPROVED Puritan's Pride® Natural Selenium 50 mcg (50 mcg per tablet, 1-2 per day)* Ingredients Dist. by Puritan's Pride, Inc. 50 - 100 mcg APPROVED Puritan's Pride® Natural Selenium 100 mcg (100 mcg per tablet, 4 per day)* Ingredients Dist. by Puritan's Pride, Inc. 400 mcg APPROVED Schiff® Natural Selenium (200 mcg per tablet, 1 per day) Ingredients Dist. by Schiff Products 200 mcg APPROVED Whole Foods™ Selenium (100 mcg per tablet, 1-2 per day) Ingredients Dist by Whole Foods Market 100 - 200 mcg APPROVED Similar to APPROVED Products:** Puritan's Pride® Selenium 200 mcg (200 mcg per tablet, 1 per day) Ingredients Dist. by Puritan's Pride, Inc Vitamin World® Selenium 200 mcg (200 mcg per tablet, 1 per day) Ingredients Dist. by Vitamin World, Inc Vitamin World® Natural Selenium 100 mcg (100 mcg per tablet, 2 per day) Ingredients Dist. by Vitamin World, Inc *Tested through CL's Voluntary Certification Program prior to, at time of, or after initial posting of this Product Review. ** Product identical in formulation and manufacture to a product that has passed testing but sold under a different brand. For more information see CL's Multi-Label Testing Program. Manufacturers may change ingredients and label information at any time. So be sure to check labels carefully when evaluating the products you use or buy. If a product's ingredients differ from what is listed above, it may not be the same as what was tested. CL cannot assure that results for other samples will be the same as those listed above because because there may be a lack of consistency both within and across lots. The information contained in this report is based on the compilation and review of information from product labeling and analytic testing. CL applies what it believes to be the most appropriate testing methods and standards. The information in this report does not reflect the opinion or recommendation of CL, its officers or employees. CL cannot assure the accuracy of information provided to it by third parties. Liability to any person for any loss or damage caused by errors, omissions, or inaccuracies in this report is hereby disclaimed. Copyright ConsumerLab.com, LLC, 2006. All rights reserved. This study is reproduced with the express written permission of ConsumerLab.com LLC. ConsumerTips™: Three cups of green tea per day is believed to contain 240 to 320 mg of polyphenols. It may be advisable to look for products that state the amount of "EGCG." More broadly, you may see the term "catechins" or "flavonols" — types of compounds that include EGCG. Catechins or flavonols are themselves part of a larger class of compounds called "polyphenols" — another term that you might see on labels. These compounds are anti-oxidants and may help explain the link between green tea consumption and reduced incidence of cancer. However, it is impossible to say how much of these compounds may be best. A dose sometimes suggested for green tea extract is 300 to 400 mg per day containing 80% total polyphenols and 55% epigallocatechin. This would yield about 150 to 200 mg of EGCG daily. As seen in this Review, the amount of EGCG in a recommended daily serving can vary considerably among products. The minimum suggested daily serving of a green tea extract ranged from 43.5 to 246.5 mg of EGCG. One product suggested as much as 380 mg of EGCG at the upper end of its suggested daily serving range of 1 to 4 capsules. The amount of EGCG in a serving is a function of the amount of extract in a dose and the concentration of EGCG in the extract. In this Review, EGCG concentrations ranged from 5% to 38%; less concentrated products tended to recommend higher doses. Possible weight loss benefit was shown in one study using a green tea extract standardized to contain 25% epigallocatechin gallate (EGCG). Lycopene exists naturally in fresh fruits and vegetables in the trans- configuration, which is poorly absorbed. Cooking tomatoes might make lycopene more bioavailable (more readily used by the body). Heat processing of raw foods into products such as tomato paste, juice, ketchup, changes lycopene from the trans- to the cis-configuration, which has better bioavailability. Tomatoes are the best source of lycopene. One cup (240 mL) of tomato juice, for example, provides about 23 mg of lycopene. Relatively high amounts of lycopene are also found in watermelon, guava, and pink grapefruit. Below are approximate amounts of lycopene in some foods. Tomato paste: 8 mg / ounce Tomato sauce: 9.6 mg / 1/4 cup Catsup: 2.9 mg / tbsp One medium tomato: 4.5 mg One pink grapefruit: 2.3 mg One sixteenth of a medium watermelon: 13.6 mg As a supplement: Lycopene supplements seem to have a similar bioavailability to foods; lycopene supplements can provide serum lycopene levels similar to those provided by tomato juice when ingested in equivalent amounts. Synthetic lycopene appears to be as well absorbed as natural-source lycopene. Most individuals in the U.S. and Canada are believed to consume more than enough selenium. Foods containing significant and reliable amounts of selenium include animal products like meat, seafood, and dairy foods, as well as whole grains and vegetables grown in selenium-rich soils. These include wheat germ, nuts (particularly Brazil nuts), oats, whole-wheat bread, bran, red Swiss chard, brown rice, turnips, garlic, barley, and orange juice. The selenium content of food varies depending on the selenium content of the soil in which it was grown. Studies suggest that many people in certain developed countries, including New Zealand, Belgium, and Scandinavia, do not get enough selenium in their diets. Selenium supplements are available in organic and inorganic forms. Some research suggests that the inorganic form, selenite, is harder for the body to absorb than organic forms such as selenomethionine (selenium bound to methionine, an essential amino acid) or high-selenium yeast (which contains selenomethionine). A recent clinical trial found that selenomethionine had 19% better absorption than selenite; absorption from selenium yeast was about 10% better than selenite. Selenized yeast is brewer's yeast that has been grown in selenium rich broth and then used as a selenium supplement. Studies inconsistently suggest that 3 cups of green tea daily might provide protection against cancer. As discussed above, the dosage suggested by manufacturers varies widely from product to product. Whether these amounts are ideal or these extracts offer any benefit remains unknown. Most tend to provide about 75 mg of EGCG per day, but twice that amount has also been suggested, so you might consider adjusting the dose to get about 150 mg of EGCG. The optimum dosage for lycopene has not been established, but the amount found potentially helpful in studies generally fell in the range of 4 to 6.5 mg daily. For reducing the risk of prostate cancer, at least one study found potential benefit with 4 mg of lycopene supplement per day. A possible reduction in the risk of lung cancer in non-smokers has been seen with 12 mg of lycopene (from food) per day in men and about 6 mg per day in women. The Recommended Daily Allowance (RDA) for selenium is 20 mcg for children 1 to 3, 30 mcg for those 4 to 8, and 40 mcg for those 9 to 13. For individuals 14 and older the RDA is 55 mcg. However, the RDA for pregnant woman is 60 mcg and for nursing women it is 70 mcg per day. Since it is the deficiency of selenium that is potentially associated with cancer risk, getting the RDA should be sufficient to have benefit. However, a higher dose (200 mcg of selenium supplied as a 0.5 gram high-selenium brewer's yeast tablet daily) has also been used in studies. For patients infected with human immunodeficiency virus (HIV), 250 mcg of L-selenomethionine daily has been used for 12 months, although it is not clear that this provides any benefit. Bear in mind that certain digestive conditions, such as Crohn's disease, short-bowel syndrome and ulcerative colitis, might impair selenium absorption. Medications that reduce stomach acid might also reduce absorption of selenium. At very high doses selenium can cause hair loss and tissue damage (see Concerns and Cautions below). Green tea contains a significant amount of caffeine and can cause caffeine-related side effects and interfere with drugs that are MAO inhibitors. Even products listed as "decaffeinated" may contain up to 2% caffeine, and "caffeine free" products can contain small amounts. To help those sensitive to caffeine, we measured caffeine in the products and the results are shown in the results table. Liver toxicity has been associated with green tea supplements. There are recent reports of several cases of toxicity beginning from five days to four months after beginning use. Liver function returned to normal in most cases after discontinuation. However, one patient required liver transplant — the specific extract taken (Exolise from Arkopharma) is reported to have been removed from the market. Toxicity has not been reported with green tea beverage and it is possible that certain extraction processes, such as ethanolic extraction, may contribute toxic compounds. Green tea contains vitamin K, which directly counteracts Coumadin's blood-thinning action, but enormous quantities of green tea would be necessary to provide a significant amount of vitamin K. Preliminary research has raised concerns that lycopene might worsen established prostate cancer by increasing metastasis. However, lycopene is otherwise generally believed to be a safe supplement. Maximum safe dosages are not known. Maximum safe doses of selenium for individuals with severe liver or kidney disease have not been established. Excessive selenium intake, beginning at about 900 mcg daily, can cause selenium toxicity. Signs include depression, nervousness, emotional instability, nausea, vomiting, and brittleness or loss of hair and fingernails. At doses above the tolerable upper intake level (UL) of 400 mcg per day for adults and children 14 and older, hair and nail brittleness and loss occur. The UL is lower for younger individuals. The tolerable upper intake level (UL) for infants up to age 6 months is 45 mcg per day; for infants 7 to 12 months, 60 mcg per day; for children 1 to 3 years, 90 mcg per day; for children 4 to 8 years, 150 mcg per day; for children 9 to 13 years, 280 mcg per day. Note that these dosages apply to combined dietary and supplemental intake of selenium; when deciding how much selenium it's safe to take, keep in mind that most adults already receive about 100 mcg of selenium in the daily diet.