An Evidence-based Approach to Phytochemicals and Other Dietary Factors

7 Tea

Tea is an infusion of the leaves of the Camellia sinensis plant and is the most widely consumed beverage in the world, aside from water.1 Herbal teas are infusions of herbs or plants other than Camellia sinensis and will not be discussed in this article. Although tea contains several bioactive chemicals, including caffeine and fluoride, scientists are particularly interested in the potential health benefits of a class of compounds in tea known as flavonoids. In many cultures, tea is an important source of dietary flavonoids.

Definitions

Types of Tea

All teas are derived from the leaves of Camellia sinensis, but different processing methods produce different types of tea. Fresh tea leaves are rich in flavonoids known as catechins (Fig. 7.1). Tea leaves also contain polyphenol oxidase enzymes in separate compartments from catechins. When tea leaves are intentionally broken or rolled during processing, contact with polyphenol oxidase causes catechins to join together, forming dimers and polymers known as theaflavins (Fig. 7.2) and thearubigins, respectively. This oxidation process is known (incorrectly) in the tea industry as “fermentation.” Steaming or firing tea leaves inactivates polyphenol oxidase and stops the oxidation process.² Although there are thousands of tea varieties, teas may be divided into three groups based on the amount of oxidation they undergo during processing.

Fig. 7.1 Chemical structures of the principal catechins in tea.

Fig. 7.2 Chemical structures of some theaflavins in tea.

Unfermented Teas (White and Green Teas)

White tea is made from buds and young leaves, which are steamed or fired to inactivate polyphenol oxidase, and then dried. Thus, due to minimal oxidation, white tea retains the high concentrations of catechins present in fresh tea leaves. Green tea is made from more mature tea leaves than white tea, and tea leaves may be withered prior to steaming or firing. Although they are also rich in catechins, green teas may have catechin profiles that are different from those of white teas, with slightly higher levels of oxidation products.3

Semifermented Teas (Oolong Teas)

Tea leaves destined to become oolong teas are “bruised” to allow the release of some of the polyphenol oxidase present in the leaves. Oolong teas are allowed to oxidize to a greater extent than white or green teas, but for less time than black teas, before they are heated and dried. Consequently, the catechin, theaflavin, and thearubigin levels in oolong teas are generally between those of green/white teas and completely oxidized black teas.²

Fully Fermented Teas (Black Teas)

Tea leaves that are destined to become black tea are fully rolled or broken to maximize the interaction between catechins and polyphenol oxidase. Because they are allowed to oxidize completely before drying, most black teas are rich in theaflavins and thearubigins, but relatively low in monomeric catechins, such as epigallocatechin gallate (EGCG).⁴

Cup Sizes

The definition of a cup of tea varies in different countries or regions. In Japan, a typical cup of green tea may contain only 100 mL (3.5 oz). A traditional European teacup holds approximately 125–150 mL (5 oz), while a mug of tea may contain 235 mL (8 oz) or more.

Table 7.1 Caffeine content of teas and coffee 5,6

Type of Tea/Coffee	Caffeine (mg/L)	Caffeine (mg/8 oz)
Green	40–211	9–50
Black	177–303	42–72
Coffee, brewed	306–553	72–130

Table 7.2 Fluoride content of teas 12

Type of Tea	Fluoride (mg/L)^a	Fluoride (mg/8 oz)
Green	1.2–1.7	0.3–0.4
Oolong	0.6–1.0	0.1–0.2
Black	1.0–1.9	0.2–0.5
Brick tea	2.2–7.3	0.5–1.7

^a Fluoride in 1% w/v tea prepared by continuous infusion from 5 to 360 minutes.

Bioactive Compounds in Tea

Flavonoids

Flavanols are the most abundant class of flavonoids in all types of tea. Flavanol monomers are also known as catechins. The principal catechins found in white and green tea are epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG) (Fig. 7.1).² In oolong and black teas, theaflavins (Fig. 7.2) and thearubigins are more abundant. Tea is also a good source of another class of flavonoids called flavonols. Flavonols found in tea include kaempferol, quercetin, and myricetin. The flavonol content of tea is minimally affected by processing, and flavonols are present in comparable quantities in all teas. Unlike flavanols, flavonols are usually present in tea as glycosides (bound to a sugar molecule).

Caffeine

All teas contain caffeine, unless they are deliberately decaffeinated during processing. The caffeine content of different varieties of tea may vary considerably and is influenced by factors like brewing time, the amount of tea and water used for brewing, and whether the tea is loose or in teabags. In general, a mug of tea contains about half as much caffeine as a mug of coffee.4 The caffeine contents of more than 20 green and black teas prepared according to package directions are presented in Table 7.1.⁵ The caffeine content of oolong teas is comparable to green teas.³ There is little information on the caffeine content of white teas, since they are often grouped together with green teas. Buds and young tea leaves have been found to contain higher levels of caffeine than older leaves,⁸ suggesting that the caffeine content of some white teas may be slightly higher than that of green teas.³ See Chapter 6 on Coffee for more information on caffeine.

Fluoride

Tea plants accumulate fluoride in their leaves. In general, the oldest tea leaves contain the most fluoride.9 Most high-quality teas are made from the bud or the first two to four leaves—the youngest leaves on the plant. Brick tea, a lower quality tea, is made from the oldest tea leaves and is often very high in fluoride. Symptoms of fluoride excess (i.e., dental and skeletal fluorosis) have been observed in Tibetan children and adults who consume large amounts of brick tea.^10,11 Unlike brick tea, fluoride levels in green, oolong, and black teas are generally comparable to those recommended for the prevention of dental caries (cavities). Thus, daily consumption of up to 1 L of green, oolong, or black tea would be unlikely to result in fluoride intakes higher than those recommended for dental health.^12,13 The fluoride content of white tea is likely to be less than that of other teas, since white teas are made from the buds and youngest leaves of the tea plant. The fluoride contents of 17 brands of green, oolong, and black teas are presented in Table 7.2.¹² These values do not include the fluoride content of the water used to make the tea.

Disease Prevention

Cardiovascular Disease

Epidemiological Studies

Many epidemiological studies have examined associations between tea consumption and manifestations of cardiovascular disease, including myocardial infarction (MI) and stroke. A meta-analysis that combined the results of ten prospective cohort studies and seven case–control studies found that a 24-oz increase in daily tea consumption was associated with an 11% decrease in the risk of MI.14 However, caution was urged in the interpretation of these results because of bias toward the publication of studies suggesting a protective effect. Since then, the results of several other prospective cohort studies have been mixed. A 6-year study of Dutch men and women found that those who drank at least three cups (approx. 13 oz) daily had a significantly lower risk of MI than those who did not drink tea.¹⁵ A 7-year study of US women found that the risk of important vascular events (MI, stroke, or death from cardiovascular disease) was significantly lower in a small number of women who drank at least four cups of black tea daily.¹⁶ However, the sample size in this group was very limited and thus the significance of this finding is unclear. A 15-year study of US men found no association between tea consumption and cardiovascular disease risk, but tea consumption in this population was relatively low, averaging one cup per day.¹⁷ Overall, the available research suggests that consumption of at least three cups per day of black tea may be associated with a modest decrease in the risk of MI. A recent prospective cohort study in 40 530 Japanese adults reported that green tea consumption was associated with reductions in all-cause mortality and cardiovascular-related mortality.¹⁸ Specifically, when compared with drinking less than one cup per day, consumption of up to five cups of green tea daily was associated with a 16% reduction in mortality from all causes and a 26% reduction in mortality from cardiovascular diseases. Both relationships were stronger in women than in men, and among types of cardiovascular diseases, the inverse association was strongest for stroke mortality.¹⁸ Thus, green tea may also protect against the development of cardiovascular diseases, but more research is necessary to draw any firm conclusions.

Endothelial Function

Vascular endothelial cells play an important role in maintaining cardiovascular health by producing nitric oxide, a compound that promotes arterial relaxation (vasodilation).¹⁹ Arterial vasodilation resulting from endothelial production of nitric oxide is termed endothelium-dependent vasodilation. Two controlled clinical trials found that the daily consumption of four to five cups (900–1250 mL) of black tea for four weeks significantly improved endothelium-dependent vasodilation in patients with coronary artery disease²⁰ and in patients with mildly elevated serum cholesterol levels²¹ compared with the equivalent amount of hot water. One of these studies noted that caffeine, provided at an equivalent dose to that of tea, had no short-term effects on endothelium-dependent vasodilation, suggesting that noncaffeine components of black tea may be responsible for the reported short-term vasodilatory effects. Indeed, flavonoids contained in tea may exert such effects.²² See Chapter 11 for more information on Flavonoids. Several small studies have suggested that green tea, or its major catechin, EGCG, may have similar vasodilatory effects.^23–25 The beneficial effect of tea consumption on vascular endothelial function could help explain the modest reduction in cardiovascular disease risk observed in some epidemiological studies.

Cancer

Animal Studies

Green and black tea have been found to have cancer-preventive activity in a variety of animal models of cancer, including cancer of the skin, lung, mouth, esophagus, stomach, colon, pancreas, bladder, and prostate.26,27 Additionally, white tea and green tea were shown to suppress intestinal polyps in mice. In most cases, flavonoids appear to contribute substantially to the cancer-preventing effects of tea, but caffeine has also been found to have cancer-preventing activity in some animal models of skin,²⁸ lung,²⁹ and colon³⁰ cancer. Although the beneficial effects of tea flavonoids were often attributed to their antioxidant activity, the overall contribution of tea flavonoids to plasma and tissue antioxidant activity in humans is now thought to be relatively minor.³¹ Currently, scientists are focusing their attention on the potential for tea flavonoids to modulate cell-signaling pathways that promote the transformation of healthy cells to cancerous cells.^32,33 See Chapter 11 for more information on flavonoids.

Epidemiological Studies

Despite promising results from animal studies, it is not clear whether increasing tea consumption will help prevent cancers in humans. The results of numerous epidemiological studies, focusing on many different types of cancers, do not provide any consistent evidence that consumption of green or black tea is associated with significant reductions in cancer risk.34 A recent prospective cohort study in 40 530 Japanese adults participating in the Ohsaki National Health Insurance Cohort Study reported that green tea consumption was not associated with total cancer mortality, or mortality from gastric, lung, or colorectal cancers.¹⁸ Because tea comes into direct contact with the gastrointestinal tract, scientists have been particularly interested in whether increased tea consumption may prevent cancers of the stomach and colon. Although a few case–control studies suggested that higher intakes of green tea were associated with decreased stomach cancer risk^35–37, prospective cohort studies do not support an inverse association between green tea consumption and stomach cancer risk in Japanese men and women.^38–42 Despite promising findings in animal models of colon cancer,⁴³ the majority of epidemiological studies have not found tea consumption to be associated with lower risk for colorectal cancer.^44,45 A meta-analysis of case–control and prospective studies concluded that currently available data do not suggest that either green or black tea is protective against colorectal cancer.⁴⁶ More recently, a systematic review of 51 studies, including more than 1.6 million participants, concluded that there is no convincing evidence that green tea consumption prevents various types of cancer.⁴⁷

There are several possible reasons for the discrepancies between findings from animal models of cancer and epidemiological studies in humans. Aside from potential species differences, it may be difficult for humans drinking tea to reach sufficient plasma and tissue levels of tea flavonoids to realize a protective effect. In general, flavonoids are rapidly metabolized and eliminated from the body, but there is considerable variation among individuals in this respect.⁴⁸ Catechol-O- methyltransferase (COMT) is one of the enzymes involved in flavonoid metabolism. There are two forms of the gene for COMT—a low-activity form and a high-activity form. A case–control study found that higher intakes of green tea were associated with lower breast cancer risk only in women who had inherited at least one copy of the low-activity form of COMT, suggesting that those who are less efficient at eliminating green tea flavonoids may be more likely to benefit from their consumption.⁴⁹ Relationships between tea consumption and cancer risk are likely to be complex, and further study is needed before specific recommendations can be made regarding tea consumption and cancer prevention.

Osteoporosis

Many factors can affect the development of osteoporosis, including nutrition, physical activity, and genetic factors. Components in tea, including caffeine, fluoride, and flavonoids, may influence bone mineral density (BMD).50 Although one cross-sectional study found that black tea consumption was associated with slightly lower BMD in US women,⁵¹ three other cross-sectional studies found that habitual tea consumption was associated with higher BMD in British⁵² and Canadian women⁵³ and in Taiwanese men and women.⁵⁰ A prospective study in 164 elderly women found that consumption of tea blunted the age-related loss in total-hip BMD.⁵⁴ Hip fracture is one of the most serious consequences of osteoporosis. A large case–control study in Mediterranean countries found that low tea consumption was associated with higher risk of hip fracture in men⁵⁵ and women.⁵⁶ However, two large prospective cohort studies of US women found no relationship between tea consumption and the risk of hip or wrist fracture over 4–6 years of follow-up.^57,58 The most recent of these two studies found that higher tea intakes were associated with slightly higher BMD in postmenopausal women, but this finding did not translate into a lower risk of hip or wrist fracture.⁵⁷ Further study is required to determine whether tea consumption affects the development of osteoporosis or the risk of osteoporotic fracture in a meaningful way.

Dental Caries

Fluoride concentrations in tea are comparable to those recommended for US water supplies to prevent dental caries (cavities).59 Green, black, and oolong tea extracts have been found to inhibit the growth and acid production of cavity-producing bacteria in the test tube.60–62 Although tea extracts reportedly prevent or decrease dental caries in animal models,⁶³ few published studies have examined the effect of tea consumption on dental caries in humans. A cross-sectional study of more than 6000 14-year old children in the United Kingdom found that those who drank tea had significantly fewer dental caries than nondrinkers; results were independent of whether sugar was added to tea.⁶⁴

Kidney Stones

Two large prospective studies found that the risk of developing symptomatic kidney stones decreased by 8% in women 65 and 14% in men⁶⁶ for each 8-oz (235 mL) mug of tea consumed daily. A study in rats concluded that the antioxidants in green tea may be involved in inhibiting calcium oxalate precipitation and thus kidney stone formation.⁶⁷ The implications of these findings for individuals with a previous history of calcium oxalate stone formation are unclear. High fluid intake, including tea intake, is generally considered the most effective and economical means of preventing kidney stones.⁶⁸ However, tea consumption has been found to increase urinary oxalate levels in healthy individuals,⁶⁹ and some experts continue to advise people with a history of calcium oxalate stones to limit tea consumption.⁷⁰

Weight Loss

Weight reduction can be achieved by long-term decreases in energy intake and/or increases in energy expenditure. Several small short-term trials have reported modest 3%–4% increases in energy expenditure after the consumption of oolong tea 71,72 or green tea extract.⁷³ However, none of these studies was specifically designed to assess weight loss. More recently, a clinical trial in overweight men and women, who had lost an average of 7.5% of their body weight by adhering to a very low-calorie diet for 4 weeks, found that green tea capsules (containing 573 mg/day of catechins and 104 mg/day of caffeine) were no better than placebo in preventing weight regain over the next 8 weeks.⁷⁴ A follow-up study by the same group of investigators reported that supplementation with green tea extract prevented weight regain after weight loss in subjects with low habitual caffeine intake (<300 mg/day) but not in those with high habitual caffeine intake (>300 mg/day).⁷⁵ A recent 12-week intervention trial in 35 overweight men reported that those given oolong tea enriched with green tea extract (690 mg catechins/day) experienced significant reductions in body weight, body mass index (BMI), waist circumference, body fat mass, and subcutaneous fat area compared with those administered oolong tea (33 mg catechins/day).⁷⁶ Large-scale intervention trials that control for energy intake and physical activity are needed to determine if tea or tea extracts promote weight loss or improve maintenance in humans. Interestingly, animal model studies showed a lowering of tissue fat levels in mice drinking green tea, black tea, or a caffeine-containing solution.²⁸

Safety

Adverse Effects

Tea

Tea is generally considered to be safe, even in large amounts. However, two cases of hypokalemia (abnormally low serum potassium levels) in the elderly have been attributed to excessive consumption of black and oolong tea (3–14 L/day).77,78 Hypokalemia is a potentially life-threatening condition that has been associated with caffeine toxicity.

Tea Extracts

In clinical trials employing caffeinated green tea extracts, cancer patients who took 6 g/day, in three to six divided doses, experienced mild to moderate gastrointestinal side effects, including nausea, vomiting, abdominal pain, and diarrhea.^79,80 Central nervous system symptoms, including agitation, restlessness, insomnia, tremors, dizziness, and confusion, have also been reported. In one case, confusion was severe enough to require hospitalization.⁷⁹ These side effects were likely related to the caffeine in the green tea extract.⁸⁰ In a 4-week clinical trial that assessed the safety of decaffeinated green tea extracts (800 mg/day of EGCG) in healthy individuals, a few of the participants reported mild nausea, stomach upset, dizziness, or muscle pain.⁸¹

Pregnancy and Lactation

The safety of tea extracts or supplements for pregnant or breast-feeding women has not been established. Some organizations advise pregnant women to limit their caffeine consumption to 300 mg/day, because higher caffeine intakes have been associated with increased risk of miscarriage and lower birth weight in some epidemiological studies. See Chapter 6 on coffee.

Drug Interactions

Green Tea

Excessive green tea consumption may decrease the therapeutic effects of the anticoagulant, warfarin (Coumadin). Such an effect was documented in one patient who began drinking one half gallon to one gallon of green tea daily.82 It is probably not necessary for people on warfarin therapy to avoid green tea entirely; however, large quantities of green tea may decrease warfarin's effectiveness.⁸³

Caffeine

Several drugs can impair the metabolism of caffeine, increasing the potential for adverse effects from caffeine.⁸⁴ Such drugs include cimetidine (Tagamet), disulfiram (Antabuse), estrogens, fluoroquinolone antibiotics (e.g., ciprofloxacin, enoxacin, norfloxacin), fluconazole (Diflucan), fluvoxamine (Luvox), mexiletine (Mexitil), riluzol (Rilutek), terbinafine (Lamisil), and verapamil (Calan). High caffeine intakes may increase the risk of toxicity of some drugs, including albuterol (Alupent), clozapine (Clozaril), ephedrine, epinephrine, monoamine oxidase inhibitors, phenylpropanolamine, and theophylline. Abrupt caffeine withdrawal has been found to increase serum lithium levels in people taking lithium, potentially increasing the risk of lithium toxicity. See Chapter 6 for more information on caffeine–drug interactions.

Nutrient Interactions

Nonheme Iron

Flavonoids in tea can bind nonheme iron, inhibiting its intestinal absorption. Nonheme iron is the principal form of iron in plant foods, dairy products, and iron supplements. The consumption of one cup of tea with a meal has been found to decrease the absorption of nonheme iron in that meal by approximately 70%.85,86 To maximize iron absorption from a meal or iron supplements, tea should not be consumed at the same time.

Summary

• Tea is an infusion of the leaves of the Camellia sinensis plant, which is not to be confused with so-called herbal teas.

• Some biologically active chemicals in tea include flavonoids, caffeine, and fluoride.

• Overall, observational studies in humans suggest that daily consumption of at least three cups of tea may be associated with a modest (11%) decrease in the risk of myocardial infarction (heart attack).

• Despite promising results from animal studies, it is not clear whether increasing tea consumption will help prevent cancers in humans.

• Although tea consumption has been positively associated with bone density in some studies, it is not clear whether tea consumption reduces the risk of fractures due to osteoporosis.

• Limited research suggests that tea consumption may be associated with fewer cavities and a slightly lower risk of kidney stones, but more research is needed to confirm these findings.

• It is currently unclear whether tea or tea extracts promote weight loss. Large-scale clinical trials that control for energy intake and expenditure are needed to answer this question.