A Review of the Clinical Effects of Green Tea: Up-to-date Reasons to Imbibe
A Review of the Clinical Effects of Green Tea: Up-to-date Reasons to Imbibe
By David Kiefer, MD, Dr. Kiefer is Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona, Tucson; Adjuct Facutly, Bastyr University, Seattle; he reports no financial relationships relevant to this field of study.
We all know that we should be drinking more green tea; every few days, either the media or medical journals are touting a new use for the Asian staple. Can it really cure breast cancer while preventing liver disease, simultaneously increasing knee range of motion in people suffering from osteroarthritis? The answer is "possibly, yes," but an evidence-based review refines the glowing reports with some clinical pearls, dosing specifics, and hopeful avenues of future research, as detailed below.
Botany and Pharmacology
Green tea is one of several forms of tea made from the tea plant, Camellia sinensis, Family Theaceae. Two varieties are used for most tea production: Camellia sinensis var. sinensis and Camellia sinensis var. assamica, the former accounting for most green tea production. Variety assamica has a higher content of polyphenols, which makes green tea taste excessively bitter.1
The tea plant is an evergreen shrub or small tree and reaches a height of up to 35 feet, but is often trimmed to 6 feet when cultivated for the tea production. The alternate leaves are blade elliptic or oblong, measuring approximately 14 cm in length and 7.5 cm in width. Their surface is dark green, leathery, and shiny while the bottom side is pale green. The white blossoms appear from October to February solitarily or up to three in a cluster. The fruits ripen from August through October and contain two brown round seeds.2
Camellia sinensis is known for a high content of polyphenols, including the well-known epigallocatechin-3-gallate (EGCG); polyphenols are a family of phytochemicals with numerous physiological effects as detailed below.1 On average, green tea contains 20-45% polyphenols by weight; a subset of polyphenols, catechins, comprises 60-80% of the polyphenol composition.3 In addition, green tea contains a variety of vitamins, minerals, and other phytochemicals, such as the flavonol quercetin, in varying amounts depending on location and processing. Two methylxanthine compounds, caffeine and theophylline, are responsible for tea's stimulating effect.4
The relative polyphenol content depends on how the leaves are processed before drying; fermentation and heating of the leaves can affect the catechin content and resultant properties.4 For example, black and oolong tea contain less EGCG than green tea. Also, instant preparations and iced teas contain fewer catechins.1
Other factors influencing the phytochemical composition of tea are the geographical location, growing conditions, the preparation of the infusion, and the age of the leaves. Young leaves contain more methylxanthines, but less EGCG compared to older leaves. Methylxanthine content varies only slightly between green, black, and oolong teas.5,6
Mechanisms of Action and Clinical Effects
There is a long list of clinical conditions purportedly affected by the therapeutic use of green tea (see Table 1).1,3 It is beyond the scope of this article to address them all in detail, but the conditions with the greatest quantity and quality of data are reviewed below.
Table 1: Clinical Conditions with Varying Evidence for Efficacy of Treatment with Green Tea
- Cancer prevention
- Obesity
- Hyperlipidemia
- Hypertension
- Cardiovascular event prevention
- Sustaining weight loss
- Skin aging and counteracting photo-oxidation
- Anogenital warts
- Oral health
Cancer Prevention
During the last few decades, a large number of studies examined the cancer preventive effects of whole green tea and isolated EGCG, mostly through in vitro and animal research. Animal studies have shown the potential of green tea to inhibit carcinogenesis of the lung, esophagus, skin, liver, prostate, kidney, and stomach.7,8 EGCG seems to act by targeting cycle proteins, apoptotic proteins, growth factors, anti-apoptotic proteins, transcriptions factors, and protein kinases.7,8 Epidemiological research has looked at the cancer preventive effects of green tea on numerous types of cancer, though gastrointestinal cancers have been studied more than other cancers.1 A range of green tea consumption has been examined, from 1-2 cups daily to more than 10 cups daily. Overall, there has been little to no effect on the relative risk of cancer, an accurate assessment or one confounded by the structure of the study, the demographics of the population being studied, and the particular type of cancer involved. A recent Cochrane review on green tea and cancer found some evidence for lower prostate cancer risk in men consuming "higher amounts" of green tea; slight evidence was found for the prevention of liver, lung, pancreatic, and colorectal cancers; no or conflicting evidence was seen for other types of cancer.9
This is an area of great interest in research circles; expect a refinement of these results in coming years as new and more well-designed studies are published. For example, one recent paper suggests that the 2-3 cups of green tea analyzed in most human research provides about about 0.5 µM of EGCG daily, much less than the 20-200 µM used in basic science research, and may account for the equivocal research results of some studies; clearly a variable that could be improved upon.10 Also, EGCG has poor bioavailability when ingested with calcium and magnesium such as in hard water or milk, another confounding variable that, when corrected, may provide a better glimpse into the true cancer prevention effects of green tea.
Cardiovascular Health and Hyperlipidemia
The consumption of green tea has positive effects on cardiovascular structures and function, including improving arterial compliance and endothelial function, and attenuating the development of atherosclerosis (possibly from decreased LDL oxidation), presumably from the antioxidant effects of the polyphenolic compounds.1,11 Whether these mechanisms of action translate into tangible improvement in cardiovascular conditions has been debated, with some researchers showing improvements in blood pressure, prevention of blood pressure increases, and decreased risk of myocardial infarction or cardiovascular mortality, while other researchers have failed to corroborate these effects.1,3,11,12 Again, dosing, demographics, and confounding variables are thought to account for the different research results. At a minimum, some of the trials have demonstrated that 5 or more cups daily is what has led to decreased cardiovascular disease mortality or incidence of stroke; it appears that green and black tea may have a similar magnitude of effect in this category.3,11
The effects on serum lipids also have been been variable. Some, but not all, clinical trials have found that green tea is able to lower total cholesterol and LDL-cholesterol, with minimal to no effects on HDL-cholesterol and triglycerides.3,11 The quantity of the effect, not surprisingly, depends on the green tea dose and form; four representative studies, chosen among the few that are available for their variety, are shown in Table 2.
Table 2: Green Tea Effect on Lipids as per Three Clinical Trials and One Review Article
Authors (year) Study type* Green tea form Effect on lipids
Maron (2003)13 DBRCT 375 mg once daily theaflavin- LDL decrease 16.4%; total cholesterol enriched green tea extract decrease 11.3%
Nantz (2009)14 DBRCT 100 mg L-theanine, Total and LDL cholesterol each 200 mg catechin green tea decreased by 9 mg/dL extract in a capsule: two capsules daily
Frank (2009)15 Placebo-controlled, 714 mg daily of green tea No change in total nor HDL parallel polyphenols in aqueous form cholesterol
Kim (2011)16 Review and 145-3000 mg daily green LDL decrease by 5.3 mg/dL; meta-analysis tea catechins total cholesterol decrease by 5.46 mg/dL
* DBRCT: double-blind, randomized controlled trial
Arthritis
There are both in vitro and in vivo research results demonstrating positive effects of green tea and EGCG on arthritis.17 The oral administration of EGCG in collagen-induced arthritis in mice leads to the inhibition of COX-2, IFN-g and TNF-a, decreasing the severity of the disease.18 EGCG can also regulate cytokines, chemokines, reactive oxygen species, and nitric oxide in the pathogenesis of osteoarthritis and rheumatoid arthritis, leading to cartilage protection, regulation of synovial fibroblast activity, and bone-preserving activity through osteoclast inhibition.19,20 The relevance of these mechanisms of action on humans remains to be seen; to date there have been no clinical trials examining the effect of green tea on people with arthritis.
Weight Loss
Barring the research on cancer, most of the clinical research on green tea has been done as a weight loss aid, as well as a maintenance treatment helping people to prevent weight gain after weight loss efforts. The catechins and methylxanthines in green tea likely synergize to cause an increase in overall metabolism, as well as a shift to fat oxidation in place of carbohydrate or protein metabolism.21 Green tea catechins, usually in a dose of 270-1200 mg daily, may lead to body weight loss of 1.31 kg over 3 months, according to one meta-analysis.22 The research is in its infancy; numerous factors, such as changes in fat metabolism (i.e., loss of fat mass vs body weight loss), demographics, and phytochemical ratio (catechins vs caffeine), are surfacing in trials that probably account for divergent research results.
With respect to the maintenance phase after weight loss, clinical trials have used a variety of doses in a variety of demographics. In one double-blind study, 46 women with an average body mass index (BMI) of 27.7 kg/m2 on a low-energy diet were given a green tea extract (1125 mg catechins and 225 mg caffeine daily) or placebo.23 The green tea group had less of a drop in resting energy expenditure, but no difference in body weight nor body composition compared to placebo. Another study randomized 104 moderately obese people, after 4 weeks on a very low energy diet (resulting in an average of 6.4 kg weight loss), to either 13 weeks of green tea extract (104 mg caffeine, 573 mg catechins daily) or placebo.24 The green tea group and the placebo group each gained weight in equal amounts during this maintenance phase. However, people who were used to drinking high amounts of caffeine regularly gained weight more than habitual low caffeine users. Related to this, another study found improved weight maintenance and higher resting energy expenditure in 76 people who were habitual low-caffeine users.25
Topical
Extracts of green tea are showing promise in several areas of topical treatment.1 An ointment standardized to 15% sinecatechins and a cream standardized to 10% inhibit viruses and stimulate the immune system, two effects that make it effective against external genital and perianal human papillomavirus (HPV).3,26 In addition, green tea extracts are used in combination to make conventional antibacterials more effective against methicillin-resistant Staphylococcus aureus,27 and there are dozens of research articles documenting the use of green tea as a photoprotectant, decreasing the adverse skin effects of ultraviolet radiation that may lead to aging or skin cancer.28 A variety of topical green tea products have been studied, ranging in concentration from 5-90% polyphenols.29
Dosing
One cup (250 mL) of brewed green tea (one teaspoon of dried leaves) has, on average, 30-40 mg of caffeine and 50-100 mg of catechins.22 "Typical" consumption varies, but it may be in the range of three cups daily, leading to 240-320 mg polyphenols ingested per day.3,5 However, some studies have looked at people ingesting greater than 10 cups daily, and one research group mentions a "desirable" green tea intake of 3-5 cups (approximately 1200 mL daily) providing at least 250 mg of polyphenols.9 Green tea extracts, some of which have been decaffeinated, are available as capsules or liquids ranging from 250-725 mg (230-290 mg EGCG) per capsule. The dosing range for green tea and green tea extracts varies widely depending on the clinical condition. Of note, green tea for weight loss and weight loss maintenance should remain caffeinated for optimal effects. Also, bioavailability may be enhanced through dry and cool storage, ingesting green tea during fasting, or co-administration of vitamin C or fish oil.10
Adverse Effects
When used in moderation, and especially as a hot water infusion, green tea is generally considered safe for most adults.3 Some people can feel stimulant effects (nervousness, restlessness, insomnia, palpitations) from the caffeine content of green tea or mild gastrointestinal upset.30 There have been cases of hepatotoxicity with the use of green tea and green tea products, prompting a review by the U.S. Phamacopeia (USP).31 Some of the cases were difficult to causally tie to green tea, but others seemed probable, especially when a challenge/re-challenge situation occurred. The USP concluded that concentrated green tea extracts might cause liver damage, especially when ingested under fasting conditions. However, it also emphasized "the wide usage of green tea as a beverage and the low incidence of a causal relationship to hepatotoxicity."31
Other possible adverse effects and interactions may exist. For example, some green tea extracts inhibit the cytochrome P450 system 3A4, a common point of metabolism for many pharmaceuticals and botanicals.31 Also, green tea catechins can inhibit the efficacy of sunitimib and bortezomib, two cancer pharmaceuticals; in high doses can counteract the effects of warfarin because of small amounts of vitamin K; again, in high doses, possibly may have anti-folate activity due to dihydrofolate reductase inhibition; and may cause allergic skin reactions with topical preparations.
Conclusion
From the long list of purported health effects for green tea, research is starting to refine the recommendations with both basic science and clinical research trials. Green tea contains both methylxanthines, such as caffeine and theophylline, and a family of compounds called polyphenols, one class of which are the catechins, such as EGCG. These medicinally active compounds vary in concentration in any given tea product, whether it be loose green tea or green tea extracts, and seem to have strong antioxidant, immunomodulatory, and antimicrobial effects. The most convincing data for clinical efficacy is for topical antiviral (HPV) effects. More modest results have been seen for weight loss, maintenance of weight loss, prevention of some but not all cancers, and lowering of total and LDL cholesterol. Dose recommendations vary, but the consumption of 3-5 cups of green tea daily meets many of the expert recommendations; more is probably needed for some weight loss effects (and it should be caffeinated), possibly for cancer prevention and cholesterol lowering. Caution is warranted in people with pre-existing liver disease, especially when ingesting more than 5 cups of green tea daily or taking green tea extracts. In addition, there are some drug interactions and other clinical scenarios to keep in mind, even though this plant is likely very safe for most of the population when used in moderation.
Recommendation
Prescribe green tea extracts topically for HPV, and counsel your patients interested in weight loss how to incorporate a moderate amount of green tea into their lives. For people with a family history of cancer, until research says otherwise, 3-5 cups of green tea daily may be a simple and tasty way to address that issue. Use cautiously, especially green tea supplements, in people with pre-existing liver disease.
References
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2. Zhengyi W, et al, eds. Flora of China. Volume 12. St Louis, MO: Botanical Garden; 1994.
3. Schneider C, Segre T. Green tea: Potential health benefits. Am Fam Physician 2009;79:591-594.
4. Lin YS, et al. Factors affecting the levels of tea polyphenols and caffeine in tea leaves. J Ag Food Chem 2003;51:1864-1873.
5. Shishikura Y, Khokhar S. Factors affecting the levels of catechins and caffeine in tea beverage: Estimated daily intakes and antioxidant activity. J Science Food Ag 2005;85:2125-2133.
6. Sang S, et al. The chemistry and bio- transformation of tea constituents. Pharm Res 2011;64(2,SI):87-99.
7. Singh BN, et al. Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochemical Pharmacology 2011;82: 1807-1821.
8. Yang CS, et al. Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance. Nature Rev Cancer 2009;9:429-439.
9. Boehm K, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No: CD005004.
10. Mereles D, Hunstein W. Epigallocatechin-3-gallate (EGCG) for clinical trials: More pitfalls than promises? Int J Mol Sciences 2011;12:5592-5603.
11. Hodgson JM, Croft KD. Tea flavonoids and cardiovascular health. Mol Aspects Med 2010;31:495-502.
12. Hasani-Ranjbar S, et al. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Curr Pharm Des 2010;16:2935-2347.
13. Maron DJ, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: A randomized controlled trial. Arch Intern Med 2003;163:1448-1453.
14. Nantz MP, et al. Standardized capsule of Camellia sinensis lowers cardiovascular risk factors in a randomized, double-blind, placebo-controlled study. Nutrition 2009;25:147-154.
15. Frank J, et al. Daily consumption of an aqueous green tea extract supplement does not impair liver function or alter cardiovascular disease risk biomarkers in healthy men. J Nutr 2009;139:58-62.
16. Kim A, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: A systematic review and meta-analysis. J Am Diet Assoc 2011;111:1720-1729.
17. Wu D, et al. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases. Mol Aspects Med 2011 Oct 14 [Epub ahead of print].
18. Haqqi TM, et al. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Nat Acad Sciences 1999;96:4524-4529.
19. Singh R, et al. Green tea polyphenol epigallocatechin-gallate: Inflammation and arthritis. Life Sciences 2010;86:907-918.
20. Ahmed S. Green tea polyphenol epigallocatechin 3-gallate in arthritis: Progress and promise. Arthritis Res Ther 2010;12:208.
21. Dulloo AG, et al. Efficacy of a green tea extract richin catechin polyphenols and caffeine in increasing 24h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999;70:1040-1045.
22. Rains TM, et al. Antiobesity effects of green tea catechins: A mechanistic review. J Nutr Biochem 2011;22:1-7.
23. Diepvens K, et al. Metabolic effects of green tea and of phases of weight loss. Physiol Behav 2006 30;87:185-191.
24. Kovacs EM, et al. Effects of green tea on weight maintenance after body-weight loss. Br J Nutr 2004;91:431-437.
25. Westerterp-Plantenga MS, et al. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res 2005;13:1195-1204.
26. Tzellos TG, et al. Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: A systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2011;25:345-353.
27. Cho YS, et al. Antibacterial effects of green tea polyphenols on clinical isolates of methicillin-resistant Staphylococcus aureus. Curr Microbiol 2008;57:542-546.
28. Hsu S. Green tea and the skin. J Am Acad Dermatol 2005;52:1049-1059.
29. Levin J, et al. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthetic Derm 2010;3:22-41.
30. Schönthal AH. Adverse effects of concentrated green tea extracts. Mol Nutr Food Res 2011;55:874-885.
31. Sarma DN, et al. Safety of green tea extracts: A systematic review by the U.S. Pharmacopeia. Drug Safety 2008;31:469-484.
We all know that we should be drinking more green tea; every few days, either the media or medical journals are touting a new use for the Asian staple. Can it really cure breast cancer while preventing liver disease, simultaneously increasing knee range of motion in people suffering from osteroarthritis? The answer is "possibly, yes," but an evidence-based review refines the glowing reports with some clinical pearls, dosing specifics, and hopeful avenues of future research, as detailed below.Subscribe Now for Access
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