Goldenseal

Overview

Many people consider the main active constituent in goldenseal to be berberine, and most of the clinical studies have been done on the single compound. Berberine is an alkaloid that also comes from several other plants including Coptis chinensis (goldenthread), Berberis aquifolium (Oregon grape), B. vulgaris (barberry), and B. aristata (tree tumereic), which has a long history in folk medicine for diarrhea. Since goldenseal has had an endangered status, many herb companies have substituted it with other berberine-containing plants in formulas. Most commonly, goldenseal is used in immune support formulas (usually along with Echinacea), or for its antioxidant, anti-cancer effects, or for urinary tract infections.

Although goldenseal has a long traditional medicinal history among the Native Americans and later with the settlers, no clinical studies have been performed with the single herb in humans. However, there exists animal and in-vitro studies on goldenseal and both preclinical and clinical data on berberine. Preliminary animal models have shown goldenseal root to be immunostimulatory and to decrease an enzyme involved with tumor growth in colon cancer. Preliminary studies have found berberine to be of possible value for diarrhea, and liver cirrhosis (Choudhry et al, 1972; Gupte, 1975; Watanabe et al, 1982).

Comments

Goldenseal is often piggy-backed in immune support formulas with Echinacea, but little clinical evidence yet confirms this use.

Scientific Support

In a randomized controlled study, the effect of berberine sulfate (BS) was tested in 165 adults who were suffering from acute diarrhea due to either Escherichia coli or Vibrio cholerae. At the dosage of 400 mg of BS, patients with E. coli experienced a significant reduction in mean stool volume during three consecutive 8-hr periods after treatment. At 24 hrs past treatment, a significant number of E. coli patients treated with the BS were cured of their diarrhea than compared to control. In the cholera group, however, 1200 mgs were administered and found to only slightly decrease the stool volume, but when compared to the tetracycline only group (BS+ tetracycline vs. tetracycline only) did not show a significant difference in stool volume (Rabbani et al., ).

Khin-Maung-U et al. (1985) studied the effect of berberine, tetracycline, and the combiniation of berberine + tetracycline in 400 adult patients with diarrhea. In the 185 patients that suffered from diarrhea induced by cholera, there was a significant reduction in the frequency and volume of diarrheal stools in both treatment groups involving tetracycline, but not in the berberine alone group. Factoral design equations were able to show a 1 liter reduction of diarrheal stools and a reduction of cAMP concentrations in the berberine groups. In the 215 patients with non-cholera diarrhea, neither tetracycline or berberine showed benefit over placebo.

Safety / Dosage

Goldenseal is generally thought to be safe, but should not be used during pregnancy or lactation. Goldenseal is contraindicated for people with high blood pressure or other cardiovascular diseases.

Berberine is considered safe at goldenseal’s recommended dosages, however, they are contraindicated for pregnancy and may interfere with vitamin B metabolism. The LD(50) in rats for berberine is greater than 1,000 milligrams per kilogram of boy weight, indicating a low toxicity. Topical application of berberine may cause photosensitivity (Inbara et al., 2001; Kowalewski et al., 1975).

The typical dosage of goldenseal is 4 to 6 grams of the powdered root daily, 250-500 mg of the extracted root (usually standardized to 5% berberine content) three times daily (McKenna et al., 2002).

References

1.Choudhry VP, Sabir M, Bhide VN. Berberine in giardiasis. Indian Pediatr. 1972 Mar;9(3):143-6.

2.Gupte S. Use of berberine in treatment of giardiasis. Am J Dis Child. 1975 Jul;129(7):866.

3.Inbaraj JJ, Kukielczak BM, Bilski P, Sandvik SL, Chignell CF. Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine. Chem Res Toxicol. 2001 Nov;14(11):1529-34.

4.Khin-Maung-U, Myo-Khin, Nyunt-Nyunt-Wai, Aye-Kyaw, Tin-U. Clinical trial of berberine in acute watery diarrhoea. Br Med J (Clin Res Ed). 1985 Dec 7;291(6509):1601-5.

5.Kowalewski Z, Mrozikiewicz A, Bobkiewicz T, Drost K, Hladon B. [Toxicity of berberine sulfate] Acta Pol Pharm. 1975;32(1):113-20.

6.McKenna D, Jones K, Hughes K, Humphrey S. Botanical Medicines: The Desk Reference for Major Herbal Supplements, 2nd Ed. 2002 Haworth Press; Binghamton, NY

7.Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae.

8.Watanabe A, Obata T, Nagashima H. Berberine therapy of hypertyraminemia in patients with liver cirrhosis. Acta Med Okayama. 1982 Aug;36(4):277-81.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Shark Cartilage / Bovine Cartilage

Overview

Cartilage extracts are just what you think they are – from sharks (the fins are typically used), while cartilage from the trachea (windpipe) of cows is used in bovine cartilage supplements. The cartilage is then pulverized, powdered and packed into capsules with various claims made for preventing/treating cancer, promoting wound healing, and relieving the pain and stiffness of arthritis.

Cartilage consumption has been linked to healing of connective tissue injuries since the middle part of the century (much as HCP/gelatin, glucosamine and chondroitin are today). In the early 1980s, cartilage extracts became a popular alternative treatment for reducing the pain and stiffness associated with arthritis (although gelatin, SAMe and glucosamine all appear to be more effective in this regard). Today, the most common use of cartilage supplements is as a cancer treatment. As the theory goes, cartilage supplements inhibit tumor growth by inhibiting angiogenesis (growth of new blood vessels) and “choking off” the blood supply that the tumor needs to survive and grow. This popular, but unproven, theory generated a wave of media attention in the 1980s following publication of a popular pseudo-scientific book entitled, “Why Sharks Don’t Get Cancer” (but they actually do).

Comments

At this time, cartilage extracts do not appear to provide significant value as a dietary supplement. As research into this area progresses, perhaps new findings will provide evidence of cartilage extracts in preventing angiogenesis in cancer patients (an experimental new drug derived from shark cartilage, Neovastat, is under investigation as an anti-tumor agent). Until then, consider other supplements with proven benefits in joint health/wound healing (HCP/Gelatin, SAMe, glucosamine and chondroitin) and cancer prevention (green tea and soy isoflavones).

Scientific Support

Cancer tumors generally need new blood vessels to grow, and some researchers have theorized that cartilage, which does not have blood vessels, might be a cancer preventive. Shark cartilage is known to harbor certain compounds that seem to slow down the growth of the new blood vessels needed for tumors to grow and spread. Several processes are thought to be involved. First, shark cartilage interferes with a group of enzymes known as matrix metalloproteases (MMPs), which are thought to be secreted by tumors to break down surrounding tissue and allowing the tumors to spread. Vascular endothelial growth factor activity (which promotes the formation of new blood vessels) is low shark cartilage. Some rodent studies have used injected shark cartilage extracts and have shown promising initial results (Horsman et al. 1998) – but when shark cartilage is taken by mouth, not enough of the active ingredients may be absorbed from the gastrointestinal tract to be very effective. Controlled studies of either oral or injected products in patients with advanced cancer that had been treated with conventional drugs, however, did not demonstrate effectiveness from shark cartilage in producing complete or partial responses (Miller et al. 1998). No studies involving patients with less advanced or previously untreated cancer have been published, but clinical research is ongoing.

Although there is certainly no shortage of testimonials for “miracle” cartilage products that “cure” cancer, the scientific evidence for such effects is lacking. Despite shark and bovine cartilage supplements being touted as cancer cures, careful scientific study in people with advanced tumors have shown these claims to be wildly optimistic at best and completely bogus in many cases. It is interesting to note, however, that for all the outlandish and unsubstantiated claims for shark cartilage to “cure” cancer, a growing number of laboratory and early-stage clinical studies (Davis et al. 1997) indicate that shark cartilage does indeed contain compounds which can inhibit tumor angiogenesis (growth of new blood vessels to feed the tumor). This means that something in cartilage prevents the growth of new blood vessels toward tumors, thereby restricting tumor growth. The inhibitor is probably not a typical protein, but may be a heat-stable form of proteoglycans (long chains of sugars and amino acids). Whatever this factor happens to be, it turns out that there is quite a lot of it in shark cartilage compared to cartilage from mammalian sources (such as cows). A major problem with the shark cartilage theory of tumor prevention, however, has always been the lack of clinical proof that this anti-angiogenesis factor could even get into the body when consumed as a dietary supplement.

However, studies reported recently suggest that oral administration of liquid cartilage extract delivers a similar anti-angiogenic effect in humans that has previously been observed in lab animals and test tube studies (Berbari et al. 1999). In one study, subjects (29 healthy males) received either a placebo or a liquid shark cartilage extract (7-21ml) each day for 3-4 weeks (Berbari et al. 1999). Midway through the supplementation period (day 12), a special sponge was inserted subcutaneously (under the skin of each subject’s arm) and removed on Day 23. Researchers then counted the number of cells which had grown into the sponge as an indirect measurement of angiogenesis. Results from the study found that cell density was significantly lower in subjects who had received the liquid cartilage extract compared to subjects who had received the placebo. These results are the first to show that the anti-angiogenic component of cartilage extracts is bioavailable in humans by oral administration and that oral intake of such extracts can actually reduce blood vessel growth in the body. The next step will be to conduct controlled clinical trials in cancer patients to see whether cartilage extracts can indeed “choke off” cancerous tumors (as those underway for the experimental drug, Neovastat are attempting to do) and live up to the claims made for many of the supplement currently on the market (Batist et al. 2002).

Safety/Dosage

Although no specific safety studies have been conducted on cartilage extracts, the doses commonly suggested are not expected to cause any significant side effects (or dramatic benefits). In some isolated cases, bovine tracheal cartilage has been associated with contamination by thyroid tissue (the trachea is located adjacent to the thyroid gland) and could potentially lead to thyroid hormone toxicity. For patients who do choose to supplement with cartilage extracts, typical dosage suggestions are likely to be in the range of 250-1000mg/day although significant differences may exist between products.

References

1.Batist G, Patenaude F, Champagne P, Croteau D, Levinton C, Hariton C, Escudier B, Dupont E. Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels. Ann Oncol. 2002 Aug;13(8):1259-63.

2.Berbari P, Thibodeau A, Germain L, Saint-Cyr M, Gaudreau P, Elkhouri S, Dupont E, Garrel DR, El-Khouri S. Antiangiogenic effects of the oral administration of liquid cartilage extract in humans. J Surg Res. 1999 Nov;87(1):108-13.

3.Blackadar CB. Skeptics of oral administration of shark cartilage. J Natl Cancer Inst. 1993 Dec 1;85(23):1961-2.

4.Chen JS, Chang CM, Wu JC, Wang SM. Shark cartilage extract interferes with cell adhesion and induces reorganization of focal adhesions in cultured endothelial cells. J Cell Biochem. 2000 Jun 6;78(3):417-28.

5.Davis PF, He Y, Furneaux RH, Johnston PS, Ruger BM, Slim GC. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res. 1997 Sep;54(2):178-82.

6.Dupont E, Savard PE, Jourdain C, Juneau C, Thibodeau A, Ross N, Marenus K, Maes DH, Pelletier G, Sauder DN. Antiangiogenic properties of a novel shark cartilage extract: potential role in the treatment of psoriasis. J Cutan Med Surg. 1998 Jan;2(3):146-52.

7.Ernst E. Shark cartilage for cancer? Lancet. 1998 Jan 24;351(9098):298.

8.Horsman MR, Alsner J, Overgaard J. The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. Acta Oncol. 1998;37(5):441-5.

9.Lee A, Langer R. Shark cartilage contains inhibitors of tumor angiogenesis. Science. 1983 Sep 16;221(4616):1185-7.

10.Liang JH, Wong KP. The characterization of angiogenesis inhibitor from shark cartilage. Adv Exp Med Biol. 2000;476:209-23.

11.McGuire TR, Kazakoff PW, Hoie EB, Fienhold MA. Antiproliferative activity of shark cartilage with and without tumor necrosis factor-alpha in human umbilical vein endothelium. Pharmacotherapy. 1996 Mar-Apr;16(2):237-44.

12.Miller DR, Anderson GT, Stark JJ, Granick JL, Richardson D. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol. 1998 Nov;16(11):3649-55.

13.Oikawa T, Ashino-Fuse H, Shimamura M, Koide U, Iwaguchi T. A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis. Cancer Lett. 1990 Jun 15;51(3):181-6.

14.Sauder DN, Dekoven J, Champagne P, Croteau D, Dupont E. Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. J Am Acad Dermatol. 2002 Oct;47(4):535-41.

15.Sheu JR, Fu CC, Tsai ML, Chung WJ. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res. 1998 Nov-Dec;18(6A):4435-41.

16.Simone CB, Simone NL, Simone CB 2nd. Shark cartilage for cancer. Lancet. 1998 May 9;351(9113):1440.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Beta-Carotene

Overview

Beta-carotene is part of a large family of compounds known as carotenoids (which includes over 600 members such as lycopene and lutein). Carotenoids are widely distributed in fruits and vegetables and are responsible, along with flavonoids, for contributing the color to many plants (a rule of thumb is the brighter the fruit/vegetable, then the higher the content of flavonoids and carotenoids). In terms of nutrition, beta-carotene’s primary role is as a precursor to vitamin A (the body can convert beta-carotene into vitamin A as it is needed). It is important to note that while beta-carotene and vitamin A are described together in many nutrition texts, they are not the same compound and they have vastly different effects in the body. Although beta-carotene can be converted to vitamin A in the body, there are important differences in terms of action and safety between the two compounds. Beta-carotene, like most carotenoids, is also a powerful antioxidant – so it has been recommended to protect against a variety of diseases such as cancer, cataracts and heart disease. The best food sources are brightly colored fruits and veggies such as cantaloupe, apricots, carrots, red peppers, sweet potatoes and dark leafy greens.

Evidence from population studies suggests that mixed sources of carotenoids from foods (eating lots of fruits and veggies) can help protect against many forms of cancer and heart disease as well as slow the progression of eye diseases such as cataracts and macular degeneration. As an antioxidant, it is logical (perhaps) to assume that beta-carotene (which is the primary carotenoid in the diet), may be responsible for a significant portion of the observed beneficial health effects of carotenoid-rich diets – but it is not logical to then assume that high doses of isolated beta-carotene supplements will deliver the same anti-cancer and cardioprotective effects observed with diets high in fruits and vegetables.

Comments

Beta-carotene supplements are relatively inexpensive and widely available. There are synthetic and natural sources of beta-carotene supplements. The natural forms typically come from algae (Dunaliella salina), fungi (Blakeslea trispora) or palm oil. In terms of conversion to vitamin A, the “trans-” form of beta-carotene has the maximum conversion rate. Synthetic beta-carotene is nearly all in the trans form (98%), while natural forms vary in the form of beta-carotene that they provide (the different forms are known as isomers). Among natural forms of beta-carotene, the fungal form provides the highest concentration of trans beta-carotene (94%) followed by algae sources (64%) and palm oil sources (34%) – so from the perspective of vitamin A conversion, either the synthetic form or the fungal form of beta-carotene will provide the highest conversion into active vitamin A. From a “mixed” carotenoid perspective, however, beta-carotene derived from algae also provides the “cis-” isomer of beta-carotene (about 31%) as well as alpha-carotene (3-4%) and other carotenoids (1-2%). Beta-carotene derived from palm oil provides the most “balanced” mixture of carotenoid isomers (34% trans-beta, 27% cis-beta, 30% alpha and 9% other carotenoids) – but it also has the lowest vitamin A conversion (because it only provides 34% as the trans form).

Based on the current scientific evidence, beta-carotene supplements should be utilized/recommended primarily as a way to supply adequate levels of vitamin A for proper nutrition – and not for prevention of cancer, heart disease or eye problems (although a “dietary” level of mixed carotenoids of up to 10mg/day probably poses no significant health risk). There may also be some benefit in consuming beta-carotene supplements for skin protection (reduced risk of sunburn) – but this effect may be more pronounced when taken in conjunction with other antioxidants such as lycopene, lutein, selenium, and vitamins C and E.

Scientific Support

It is important to note that the vast majority of the scientific evidence for the health benefits of beta-carotene comes from studies that looked at food sources of beta-carotene (and other carotenoids, often referred to as “mixed” carotenoids) – not supplements. From population (epidemiological) studies, we know that a high consumption of fruits and vegetables is associated with a significant reduction in many diseases – especially several forms of cancer (lung, stomach, colon, breast, prostate, and bladder). Because the data suggested that the “active” components in a plant-based diet may be carotenoids, and because beta-carotene is the chief carotenoid in our diets, it was widely believed (until about the mid-1990’s) that the majority of the health benefits attributable to fruits and vegetables may be due to beta-carotene.

One of the largest epidemiological studies, the Physicians’ Health Study (PHS - over 22,000 male physicians) found that while high levels of carotenoids obtained from the diet were associated with reduced cancer risk, beta-carotene from supplements (about 25mg/day) had no effect on cancer risk (Comstock et al. 1997). A possible explanation for this finding may be that while purified beta-carotene may contribute some antioxidant benefits, a “blend” of carotenoids (and/or other compounds in fruits and veggies) is probably even more important for preventing cancer. It may even be possible that isolated beta-carotene supplements could interfere with absorption or metabolism of other beneficial carotenoids from the diet.

Unfortunately, intervention studies that have looked at purified beta-carotene supplements (not mixed carotenoids) have not cleared up any of the confusion. In 1994, the results from a large (almost 30,000 subjects) supplementation study (ATBC – the Alpha-Tocopherol and Beta-Carotene study) showed not only that beta-carotene supplements (20mg/day for 5-8 years) did not prevent lung cancer in high risk subjects (long-time male smokers), but actually caused an increase in lung cancer risk by almost 20% (Pietinen et al. 1997). This same study also found a 10% increase in heart disease and a 20% increase in strokes among the beta-carotene users. In 1996, another large study (CARET – the Beta-Carotene and Retinol Efficacy Trial) found virtually the same thing – with subjects receiving beta-carotene showing almost 50% more cases of lung cancer (Goodman et al. 1996). These results were so alarming that the National Cancer Institute decided to halt the $40 million study nearly 2 years early. The ATBC study examined long-time heavy smokers, while the CARET study looked at present and former smokers as well as workers exposed to asbestos – all of which can be considered “high-risk” populations for developing lung cancer (which may or may not have contributed to the surprising study results).

On the positive side, beta-carotene has been successfully used for nearly 20 years to treat photosensitivity diseases, such as erythropoietic protoporphyria (EPP) and other skin conditions (Malvy et al. 2001). As such, beta-carotene has found its way into a variety of topical and internally consumed products meant for skin protection. In Europe, one of the most popular uses for carotenoid supplements (primarily beta-carotene and lycopene) is for skin protection during the summer sunbathing months (for “inside-out” sun protection).

Overall, it is interesting to note that of the 3 large-scale clinical trials on beta-carotene supplementation and cancer risk (ATBC, CARET and PHS), all 3 concluded that beta-carotene provided no protection against lung cancer – while 2 of them found a higher risk for lung cancer. However, the association between eating a diet high in fruits and vegetables and a reduced risk for cancer and heart disease remains strong – and there is no current evidence that small amounts of supplemental beta-carotene (such as a multivitamin) is unsafe. A prudent approach to carotenoid supplementation for disease prevention may be to strive to obtain a balanced blend of mixed carotenoids from foods – while reserving purified beta-carotene supplements for skin protection and as a source of vitamin A (see dosage suggestions below).

Safety / Dosage

At recommended dosages, beta-carotene is thought to be quite safe – although at least two large studies have shown that high-dose beta-carotene (20-50mg/day) can increase the risk of heart disease and cancer in smokers. Other reported side effects from high dose beta-carotene supplements (100,000IU or 60mg per day) include nausea, diarrhea and a yellow/orange tinge to the skin (especially hands and feet), which fades at lower doses of beta-carotene. The safest way to get your beta-carotene and other carotenoids is from eating a wide variety of fruits and vegetables.

Beta-carotene (the “trans-“ form) can be converted to vitamin A (3mg of beta-carotene supplies 5,000IU of vitamin A). Although beta-carotene supplements are commonly available in doses of 25,000IU (15mg) per day, and many people consume as much as 100,000IU (60mg) per day, the current state of the scientific literature does not support doses of beta-carotene much higher than those levels recommended for supplying vitamin A precursors (about 5,000-10,000IU per day of beta-carotene = 3-6mg).

References

1.Collins AR, Olmedilla B, Southon S, Granado F, Duthie SJ. Serum carotenoids and oxidative DNA damage in human lymphocytes. Carcinogenesis. 1998 Dec;19(12):2159-62.

2.Comstock GW, Alberg AJ, Huang HY, Wu K, Burke AE, Hoffman SC, Norkus EP, Gross M, Cutler RG, Morris JS, Spate VL, Helzlsouer KJ. The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity. Cancer Epidemiol Biomarkers Prev. 1997 Nov;6(11):907-16.

3.Daviglus ML, Dyer AR, Persky V, Chavez N, Drum M, Goldberg J, Liu K, Morris DK, Shekelle RB, Stamler J. Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study. Epidemiology. 1996 Sep;7(5):472-7.

4.Goodman GE, Thornquist M, Kestin M, Metch B, Anderson G, Omenn GS. The association between participant characteristics and serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol among participants in the Carotene and Retinol Efficacy Trial (CARET) for prevention of lung cancer. Cancer Epidemiol Biomarkers Prev. 1996 Oct;5(10):815-21.

5.Hininger IA, Meyer-Wenger A, Moser U, Wright A, Southon S, Thurnham D, Chopra M, Van Den Berg H, Olmedilla B, Favier AE, Roussel AM. No significant effects of lutein, lycopene or beta-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects. J Am Coll Nutr. 2001 Jun;20(3):232-8.

6.Kiokias S, Gordon MH. Dietary supplementation with a natural carotenoid mixture decreases oxidative stress. Eur J Clin Nutr. 2003 Sep;57(9):1135-40.

7.Malila N, Virtamo J, Virtanen M, Pietinen P, Albanes D, Teppo L. Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers. Eur J Clin Nutr. 2002 Jul;56(7):615-21.

8.Malvy DJ, Favier A, Faure H, Preziosi P, Galan P, Arnaud J, Roussel AM, Briancon S, Hercberg S. Effect of two years' supplementation with natural antioxidants on vitamin and trace element status biomarkers: preliminary data of the SU.VI.MAX study. Cancer Detect Prev. 2001;25(5):479-85.

9.Nelson JL, Bernstein PS, Schmidt MC, Von Tress MS, Askew EW. Dietary modification and moderate antioxidant supplementation differentially affect serum carotenoids, antioxidant levels and markers of oxidative stress in older humans. J Nutr. 2003 Oct;133(10):3117-23.

10.Paolini M, Abdel-Rahman SZ, Sapone A, Pedulli GF, Perocco P, Cantelli-Forti G, Legator MS. Beta-carotene: a cancer chemopreventive agent or a co-carcinogen? Mutat Res. 2003 Jun;543(3):195-200.

11.Pietinen P, Ascherio A, Korhonen P, Hartman AM, Willett WC, Albanes D, Virtamo J. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol. 1997 May 15;145(10):876-87.

12.Pryor WA, Stahl W, Rock CL. Beta carotene: from biochemistry to clinical trials. Nutr Rev. 2000 Feb;58(2 Pt 1):39-53.

13.Vainio H. Chemoprevention of cancer: lessons to be learned from beta-carotene trials. Toxicol Lett. 2000 Mar 15;112-113:513-7.

14.van Poppel G. Epidemiological evidence for beta-carotene in prevention of cancer and cardiovascular disease. Eur J Clin Nutr. 1996 Jul;50 Suppl 3:S57-61.

15.Woodall AA, Britton G, Jackson MJ. Dietary supplementation with carotenoids: effects on alpha-tocopherol levels and susceptibility of tissues to oxidative stress. Br J Nutr. 1996 Aug;76(2):307-17.

16.Woutersen RA, Wolterbeek AP, Appel MJ, van den Berg H, Goldbohm RA, Feron VJ. Safety evaluation of synthetic beta-carotene. Crit Rev Toxicol. 1999 Nov;29(6):515-42.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Green Tea

Overview

Green tea (Camellia sinensis) is the second-most consumed beverage in the world (water is the first) and has been used medicinally for centuries in India and China. A number of beneficial health effects are attributed to regular consumption of green tea and dried/powdered extracts of green tea are available as dietary supplements. Green tea is prepared by picking, lightly steaming the leaves, and allowing them to dry. Black tea, the most popular type of tea in the U.S., is made by allowing the leaves to ferment before drying. Due to differences in the fermentation process, a portion of the active compounds are destroyed in black tea, but remain active in green tea. The active constituents in green tea are a family of polyphenols (catechins) with potent antioxidant activity. Tannins, large polyphenol molecules, form the bulk of the active compounds in green tea, with catechins comprising nearly 90%. Several catechins are present in significant quantities; epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG makes up about 10-50% of the total catechin content and appears to be the most powerful of the catechins – with antioxidant activity about 25-100 times more potent than vitamins C and E. A cup of green tea may provide 10-40mg of polyphenols and has antioxidant activity greater than a serving of broccoli, spinach, carrots or strawberries. A number of commercial green tea extracts are standardized to total polyphenol content and/or EGCG content and many are marketed with claims for preventing cancer, enhancing immune function, boosting antioxidant protection, reducing cholesterol, and stimulating weight loss.

Comments

Green tea consumed either as a beverage or as a daily dietary supplement is especially beneficial for individuals at high risk for cancer (e.g. family history) or those undergoing or recovering from chemotherapy or radiation treatment. Green tea is also beneficial as a general protective measure and dietary “insurance” of adequate polyphenol intake (which would otherwise be obtained from a diet high in fruits and vegetables). Recent data provides strong evidence that green tea may be effective in stimulating thermogenesis, increasing caloric expenditure, promoting fat oxidation and controlling body weight.

Scientific Support

Because the active compounds, the catechins, found in green tea are known to possess potent antioxidant activity, they may provide beneficial health effects by protecting the body from the damaging effects of oxidative damage from free radicals. A number of chronic disease states have been associated with free radical induced oxidative damage, including cancer, heart disease, suppressed immune function and accelerated aging.

Although numerous laboratory investigations have shown the powerful antioxidant activity of green tea and green tea extracts (August et al. 1999, Benzie et al. 1999), prospective clinical studies in humans are few (Hakim et al. 2003, Hakim et al. 2004). From the laboratory findings, it is clear that green tea is an effective antioxidant, that it provides clear protection from experimentally induced DNA damage and that it can slow or halt the initiation and progression of cancerous tumor growth (Ahn et al. 2003). There is also evidence from some studies that green tea provides significant immunoprotective qualities, particularly in the case of cancer patients undergoing radiation or chemotherapy (Elmets et al. 2001, Pisters et al. 2001). White blood cell count appears to be maintained more effectively in cancer patients consuming green tea compared to non-supplemented patients.

Several epidemiological studies show an association between consumption of total flavonoids in the diet and the risk for cancer and heart disease. Men with the highest consumption of flavonoids (from fruits and vegetables) have approximately half the risk of heart disease and cancer compared to those with the lowest intake. The primary catechin in green tea, EGCG, appears to inhibit the growth of cancer cells as well as play a role in stimulating apoptosis (programmed cell death), both of which are crucial aspects for cancer prevention (Pisters et al. 2001, Weisburger et al. 1998).

In terms of heart disease protection, the potent antioxidant properties of polyphenols would be expected to reduce free radical damage to cells and prevent the oxidation of LDL cholesterol – both of which would be expected to inhibit the formation of atherosclerotic plaques (Hodgson et al. 2000).

Aside from the clear benefits of green tea as an antioxidant, recent studies have suggested a role of catechins in promoting weight loss. Animal studies have shown green tea (and oolong tea) to suppress food intake, body weight gain, and fat tissue accumulation, while human studies have shown increases in metabolic rate and better weight maintenance following weight loss (Komatsu et al. 2003, Kovacs et al. 2004).

In some studies, green tea is associated with a mild increase in thermogenesis (increased caloric expenditure) – which is generally attributed to its caffeine content. However, a handful of studies have shown that green tea extract stimulates thermogenesis to an extent much greater than can be attributed directly to its caffeine content alone – meaning that the thermogenic properties of green tea may be due to an interaction between caffeine and its high content of catechin-polyphenols (Chantre and Lairon et al. 2002, Dulloo et al. 1999). A probable theory for the thermogenic effect of green tea is an increase in levels of norepinephrine – because catechin-polyphenols are known to inhibit catechol-O-methyl-transferase (the enzyme that degrades norepinephrine). One study examined this theory, and the effect of green tea extract on 24-hour energy expenditure, in 10 healthy men – who each consumed 3 treatments of green tea extract (50mg caffeine and 90mg epigallocatechin gallate), caffeine (50 mg), and placebo at breakfast, lunch, and dinner (Dulloo et al. 1999). The results of the study showed that, relative to placebo, the green tea extract resulted in a significant (4%) increase in 24-hour energy expenditure (approximately 80 calories per day) and a significant increase in the body’s use of fat as an energy source (24-h respiratory quotient). In addition, the 24-hour urinary norepinephrine excretion was 40% higher during treatment with the green tea extract than with the placebo. It is interesting to note that treatment with caffeine in amounts equivalent to those found in the green tea extract (50mg) had no effect on energy expenditure or fat oxidation – suggesting that the thermogenic properties of green tea are due to compounds other than its caffeine content alone (Komatsu et al. 2003, Kovacs et al. 2004).

Because norepinephrine levels in humans are also associated with alertness, mental focus, attention, and overall mood – maintaining normal levels of this important neurotransmitter may have benefits for improving mood (reducing depression) and maintaining mental function (reducing attention deficit symptoms) through a mechanism of action similar to a number of pharmaceutical agents (Concerta, Strattera, Effexor).

Safety/Dosage

Green tea consumption of as much as 20 cups per day has not been associated with any significant side effects. In high doses, however, teas that contain caffeine may lead to restlessness, insomnia, heart palpitations and tachycardia (rapid heartbeat). Decaffeinated versions of green tea and green tea extracts are available – but due to differences in caffeine extraction methods, the amounts of phenolic/catechin compounds can vary between extracts. In addition, individuals taking aspirin or other anticoagulant agents (including vitamin E and ginkgo biloba) on a daily basis should be aware of the possible inhibition of platelet aggregation (blood clotting) associated with green tea (in some cases, green tea may prolong bleeding times). Typical dosage recommendations are for 100-500mg/day – preferably of an extract standardized to at least 40% polyphenols and/or EGCG as a marker compound (roughly equivalent to 4-10 cups of brewed green tea).

References

1.Ahn WS, Yoo J, Huh SW, Kim CK, Lee JM, Namkoong SE, Bae SM, Lee IP. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev. 2003 Oct;12(5):383-90.

2.August DA, Landau J, Caputo D, Hong J, Lee MJ, Yang CS. Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans. Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):709-13.

3.Benzie IF, Szeto YT, Strain JJ, Tomlinson B. Consumption of green tea causes rapid increase in plasma antioxidant power in humans. Nutr Cancer. 1999;34(1):83-7.

4.Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine. 2002 Jan;9(1):3-8.

5.Chow HH, Cai Y, Alberts DS, Hakim I, Dorr R, Shahi F, Crowell JA, Yang CS, Hara Y. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev. 2001 Jan;10(1):53-8.

6.Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999 Dec;70(6):1040-5.

7.Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord. 2000 Feb;24(2):252-8.

8.Elmets CA, Singh D, Tubesing K, Matsui M, Katiyar S, Mukhtar H. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J Am Acad Dermatol. 2001 Mar;44(3):425-32.

9.Gupta S, Ahmad N, Mohan RR, Husain MM, Mukhtar H. Prostate cancer chemoprevention by green tea: in vitro and in vivo inhibition of testosterone-mediated induction of ornithine decarboxylase. Cancer Res. 1999 May 1;59(9):2115-20.

10.Hakim IA, Harris RB, Brown S, Chow HH, Wiseman S, Agarwal S, Talbot W. Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study. J Nutr. 2003 Oct;133(10):3303S-3309S.

11.Hakim IA, Harris RB, Chow HH, Dean M, Brown S, Ali IU. Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: role of glutathione S-transferase genotypes. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):242-9.

12.Hodgson JM, Puddey IB, Croft KD, Burke V, Mori TA, Caccetta RA, Beilin LJ. Acute effects of ingestion of black and green tea on lipoprotein oxidation. Am J Clin Nutr. 2000 May;71(5):1103-7.

13.Komatsu T, Nakamori M, Komatsu K, Hosoda K, Okamura M, Toyama K, Ishikura Y, Sakai T, Kunii D, Yamamoto S. Oolong tea increases energy metabolism in Japanese females. J Med Invest. 2003 Aug;50(3-4):170-5.

14.Kovacs EM, Lejeune MP, Nijs I, Westerterp-Plantenga MS. Effects of green tea on weight maintenance after body-weight loss. Br J Nutr. 2004 Mar;91(3):431-7.

15.Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem Pharmacol. 1999 Sep 15;58(6):911-5.

16.Maron DJ, Lu GP, Cai NS, Wu ZG, Li YH, Chen H, Zhu JQ, Jin XJ, Wouters BC, Zhao J. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003 Jun 23;163(12):1448-53.

17.Pisters KM, Newman RA, Coldman B, Shin DM, Khuri FR, Hong WK, Glisson BS, Lee JS. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol. 2001 Mar 15;19(6):1830-8.

18.Weisburger JH, Rivenson A, Aliaga C, Reinhardt J, Kelloff GJ, Boone CW, Steele VE, Balentine DA, Pittman B, Zang E. Effect of tea extracts, polyphenols, and epigallocatechin gallate on azoxymethane-induced colon cancer. Proc Soc Exp Biol Med. 1998 Jan;217(1):104-8.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.