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.

Bilberry

Overview

Bilberry is a good example of an herbal medicine that is representative of a current trend in the interest in fruits with high anthocyanin content. Not only are these supplements and foods safe, but they are potent antioxidants, of a class that are just beginning to be understood and appreciated. The anthocyanin antioxidant compounds are also often helpful for maintaining vascular, cardiovascular and eye health. Bilberry’s main active components are the flavonoids called anthocyanidins, of which there are many in bilberry, and the carotenoids (zeaxanthin and lutein) (McKenna et al, 2001).

Bilberry has been used in several therapeutic applications due to its wide range of activities. Bilberry has been reported to be vasoprotective, antiedemic, antioxidant, anti-inflammatory, anti-ulcer, and astringent. The anthocyanosides in bilberry are known to exhibit many functions, including collagen-stabilizing and reinforcing activity, decreasing capillary permeability, relaxing smooth musculature, increasing urinary output, and increasing the contractile strength of the myocardium, a few of the key preclinical studies are listed below (McKenna et al., 2001):

•An extract of bilberry was tested for its effects on microvascular permeability in a hamster cheek pouch model of ischemia reperfusion injury. Bilberry caused a significant reduction in microvascular impairment, preservation of arteriolar tone, reduced number of leukocytes adhering to venular walls, preservation of capillary perfusion, and an increase in microvascular permeability (Bertuglia et al., 1995).

•Detre et al. (1986) tested the effect of bilberry on vascular permeability in rats with induced hypertension. Bilberry was found to bring the vascular permeability, which is increased in hypertensive states, back to normal levels in the hypertensive rat model.

•Bilberry has been shown to have an anti-aggregatory activity similar to acetylsalicylic acid, and in a study with 30 volunteers, it was shown to inhibit aggregation at the first 30 and 60 days, but return to normal after 120 days. This study was able to support the theory that bilberry’s action depends on an increase in cyclic AMP and/or platelet thromboxane A2 (Pulliero et al., 1989).

•Bilberry has been found to exhibit a protective effect on the capillary walls by stabilizing membrane phospholipids and by increasing connective tissue biosynthesis (Mian et al., 1977).

•Bilberry has exhibited antioxidant activity in a number of antioxidant models. An extract in mice with induced liver peroxidation showed significant antioxidant activity at doses of 250 and 500 mg/kg p.o (Martín-Aragón et al., 1999).

Comments

Bilberry seems to be a safe and efficacious preventative to degenerating vascular illnesses, and an excellent dietetic aid for diabetics for the prevention of macular degeneration. As the population in the U.S. ages, it is sure to need good, safe, preventatives of age-related degeneration such as bilberry.

Scientific Support

Bilberry extract (Tegens® at 160 mg, 240 mg, or 340 mg daily) administered to pregnant patients exhibiting venous insufficiency of the lower limbs or acute hemorrhoids caused a progressive amelioration of symptoms during the 3 month of treatment. The symptoms were reduced by: 94.6% for pruritus; 87.5% for paresthesias; 80.1% for cramps; 78.5% for pain; 60% exhaustion and the sensation of heaviness; and 75-83% for hemorrhoids. No side effects or adverse reactions were found for either mothers or the babies included in the study (Teglio et al., 1987).

Boniface et al. (1985) confirmed pharmacological evidence in experimental studies that bilberry’s anthocyanosides reduce the biosynthesis of polymeric collagen and glycoproteins (that are responsible for the vascular complications in diabetics), and compared this to a couple of clinical studies involving diabetics. The clinical studies administered bilberry anthocyanosides to diabetics, and found increases in vascular health; thus, confirming the pharmacological findings.

Bilberry anthocyanosides (Tegens® at 480 mg daily for 30 days) administered to patients with venous diseases characterized by phlebopathic stasis significantly improved measures of venous health compared to conventional treatments. Symptoms monitored were limb heaviness, pain levels, dyschromic and dystrophic skin phenomena, and limb edema (Ghiringhelli et al., 1978).

Patients with retinopathies were administered bilberry anthocyanosides (Tegens® at 160 mg daily) in a preliminary study. In the treatment phase of the study, 50% showed improvements vs. only 20% in the control group. In those patients with hard exudates in the back pole, 35% in the control phase worsened over the course of the study vs. 20% of the treatment group. In those with circinate disposition of the hard exudates, 15% worsened in the control group vs. 10% in the treatment group (Repossi et al., 1987).

Bravetti et al. (1987) examined the effects of anthocyanosides from bilberry extract administered with vitamin E (180 mg of a 25% standardized extract and 100 mg vitamin E) in patients with mild senile cortical cataracts. The treatment was found to reduce lens opacity in 97% of the cases examined.

A double-blind, placebo-controlled crossover study examined the effect of bilberry extract (Tegens® at 160 mg, twice daily) in 14 patients with diabetes or hypertension. An improvement of 77-90% in clinical symptomology was found for the patients after one month, and bilberry was concluded to be a safe and effective therapy (Perossini et al., 1987).

Anthocyanosides from bilberry (Tegens® at 480 mg three times daily) were administered to 10 patients with diabetic retinopathy in a pilot study. In the course of the study (6 months) improvements were seen in the retinal picture of all patients. The authors concluded bilberry to be of strong promise in the therapy of diabetic retinopathy (Orsucci et al., 1983).

Patients with various retinopathies were administered bilberry (Difarel 100® at 200 mg, three times daily) and were found to have improvements in their conditions. The authors noted that improvements in the hemorrhagic tendency and vascular permeability, while being improved in all participants, were most evident in those with diabetic retinopathy (Scharrer and Ober, 1981).

Bilberry extract was administered to normal subjects at 300 mg daily in a placebo-controlled study. Significant improvements were found in measures of visual health: adaptive ability to light and dark, macular recuperation time, and chromatic discrimination (Sala et al., 1979).

An anthocyanoside rich extract of bilberry was administered to 40 normal subjects in a placebo-controlled trial to test its effect on various aspects of visual health. In the treatment group, improvements were found in all tested visual functions, including darkness adaptation, macular sensitivity, and adapto-cinematographic thresholds compared to placebo (Jayle and Aubert, 1964).

Under conditions of food rationing and little or no fruits, during WWII, the British Royal Air Force pilots were reported to use bilberry to improve their night vision. Subsequently, numerous clinical studies were performed to try to confirm this effect (McKenna et al., 2001). In one of these studies, the long-term administration of a bilberry extract (Difrarel 100®- 100 mg of anthocyanosides and 0.005 b-carotene; 4 tablets daily for 8 days) showed improvements in visual functions of 14 air traffic controllers. The results found decreased dazzling effect; decreased visual fatigue, and a quicker adaptation of scotopic vision (Belleoud et al., 1966).

Safety / Dosage

Bilberry dosages are usually recommended in the range of 240-640 mg daily for most uses (usually 500 mg), and less than 300 mg/daily for eye health. Bilberry extracts are usually based on anthocyanoside content, and a 25% standardized extract is the standard preparation (McKenna et al., 2001):

Bilberry is quite safe, as it is also a traditional food, and the only reported side effects of bilberry have been digestive disturbances. This has not yet been clearly investigated and it is possible that most of these reports were idiosyncratic. Furthermore, bilberry is often formulated with minerals, and these are well-known to cause some digestive disturbance when taken without food (McKenna et al., 2001).

Very high doses of bilberry have a blood thinning action, and should be avoided with use of warfarin or antiplatelet drugs (McKenna et al., 2001).

References

1.Belleoud L, Leluan D, Boyer Y. [Study on the effects of anthocyanin glucosides on the nocturnal vision of air traffic controllers]. Revue de Medecine Aeronautique et Spatiale 1966; 3:45.

2.Bertuglia S, Malandrino S, Colantuoni A Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in hamster cheek pouch microcirculation. Pharmacol Res. 1995 Mar-Apr;31(3-4):183-7.

3.Boniface R, Miskulin M, Robert L et al. Pharmacological properties of myrtillus anthocyanosides: correlation with results of treatment of diabetic microangiopathy, in: Farkas, L.; M. Gabor; and F. Kallay (eds.), Flavonoids and Bioflavonoids: Proceedings of the 7th Hungarian Bioflavonoid Symposium. 1985; Budapest, Hungary: Akademiai Kiado.

4.Bravetti GO, Fraboni E, Maccolini E. Preventive medical treatment of senile cataract with vitamin E and Vaccinium myrtillus anthocyanosides: clinical evaluation. Annali di Ottalmologia e Clinica Oculistica 1987; 115:109-116.

5.Detre Z, Jellinek H, Miskulin M, Robert AM. Studies on vascular permeability in hypertension: action of anthocyanosides. Clin Physiol Biochem. 1986;4(2):143-9.

6.Ghiringhelli C, Gregoratti L, Marastoni F. Capillarotropic action of anthocyanosides in high dosage in phlebopathic statis. Minerva Cardioangiol. 1978 Apr;26(4):255-76.

7.McKenna DJ, Jones K, Hughes K (eds). Botanical Medicines: A Desktop Reference for the Major Herbal Supplements. 2001 Haworth Press: New York

8.Martín-Aragón S, Basabe B, Benedi JM et al. In vitro and in vivo antioxidant properties of Vaccinium myrtillus. Pharmaceutical Biology1999; 37:109-113.

9.Mian E, Curri SB, Lietti A. et al. Anthocyanosides and microvessels wall:new findings on the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Medica 1977; 68:3565-3581.

10.Perossini M, Guidi G, Chiellini S. et al. [Diabetic and hypertensive retinopathy therapy with Vaccinium myrtillus anthocyanosides (Tegens): double-blind, placebo-controlled clinical trial. Annali di Ottalmologia e Clinica Oculistica 1987; 113:1173-1190.

11.Pulliero G, Montin S, Bettini V. et al. Ex vivo study of the inhibitory effects of Vaccinium myrtillus anthocyanosides on human platelet aggregation. Fitoterapia 1989; 55:69-74.

12.Repossi P, Malagola R, De Cadilhac C. The role of anthocyanosides on vascular permeability in diabetic retinopathy. Annali di Ottalmologia e Clinica Oculistica 1987; 113:357.

13.Scharrer A, Ober M. Anthocyanosides in the treatment of retinopathies. Klinische Monatsblatter für Augenheilkunde1981; 178:386-389.

14.Teglio L, Mazzanti C, Tronconi T et al. Vaccinium myrtillus anthocyanosides (Tegens) in the treatment of venous insufficiency of the lower limbs and acute hemorrhoids in pregnancy. Quaderni di Clinica Ostertrica e Ginecologica 1987; 42:221-231.

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.

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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.

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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.

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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.