Oolong tea does not improve glucose metabolism in non-diabetic adults

Abstract

Background:

Studies of the influence of tea on glucose metabolism have produced inconsistent results, possibly because of the lack of dietary control and/or unclear characterization of tea products.

Methods:

Therefore, a double-blind crossover study was conducted in which healthy males (n=19) consumed each of three oolong tea products or a control beverage as part of a controlled diet. Treatment beverages (1.4 l/day) were consumed for 5 days, followed by assessment of fasting plasma glucose, fasting serum insulin and an oral glucose tolerance test. Tea products included oolong tea, oolong tea with added catechins and oolong tea with added oolong tea polyphenols, and control beverages included caffeinated water and unsupplemented water. On the fifth day of each treatment period, treatment beverages were consumed with a standardized meal, and glucose and insulin responses were assessed for 240 min.

Results:

No significant differences were detected for fasting plasma glucose, fasting serum insulin, incremental plasma glucose area under the concentration time curve (AUC), total plasma glucose AUC or total serum insulin AUC.

Conclusions:

Neither oolong tea nor oolong tea supplemented with catechins or other polyphenols produced improved glucose metabolism in healthy adult volunteers on the basis of this highly controlled dietary intervention trial.

Introduction

Diabetes mellitus is characterized by hyperglycemia and glucose intolerance as a result of insulin deficiency, impaired effectiveness of insulin action or both (Reaven, 1995). Diabetes leads to a number of problems, including kidney failure, retinopathy, vision loss, cardiovascular disease and stroke. Prevalence of diabetes has reached 246 million people worldwide, and is projected to reach 380 million by 2025 (Federation, 2006).

Type 2 diabetes accounts for 85–95% of diabetes cases in the United States and other developed countries, and may account for a higher percentage in developing countries (Federation, 2006). Because tea is a widely consumed polyphenol-rich food, tea has been studied for its potential to influence postprandial glucose response, insulin action and the incidence of diabetes. However, evidence surrounding the potential for tea to influence diabetes has been controversial.

Epidemiological studies have yielded seemingly contradictory results related to tea consumption and risk for diabetes. In a retrospective cohort study of 17 413 Japanese adults, green tea intake was associated with lower diabetes risk, whereas oolong and black tea were not (Iso et al., 2006). The Womens’ Health Study surveyed 84 276 US women to find reduced risk for diabetes amongst tea drinkers (Song et al., 2005). From the National Health and Nutrition Examination Survey (NHANES) follow-up Study, there was an inverse relationship between tea intake in general and diabetes risk, but only for adults under 60 years of age who had recently lost weight (Greenberg et al., 2005). Results from a food frequency questionnaire distributed to 40 011 participants of the European Prospective Investigation into Cancer and Nutrition suggested that tea consumption was inversely associated with type 2 diabetes (van Dieren et al., 2009). A small study of 542 men and women from Cyprus, Mitilini and Samothraki islands showed that tea intake was associated with lower glucose levels in non-obese (Polychronopoulos et al., 2008). As little as one cup of black tea per day was associated with decreased risk of diabetes in a study of 36 908 men and women in the Singapore Chinese Health Study (Odegaard et al., 2008). Jing et al. (2009) conducted a meta-analysis that considered many of these studies together and concluded that tea consumption of four or more cups per day ‘might have a role in prevention of type 2 diabetes.’ In contrast, a number of large survey studies do not support a relationship between tea intake and diabetes risk, including the Health Professionals’ Follow-up Study (Salazar-Martinez et al., 2004), the Nurses’ Health Study (Salazar-Martinez et al., 2004) and the Nurses’ Health Study II (van Dam et al., 2006).

Results from intervention studies are equally equivocal. Several studies have suggested that tea consumption improves parameters related to glucose metabolism (Hosoda et al., 2003; Bryans et al., 2007; Fukino et al., 2008; Venables et al., 2008; Nagao et al., 2009), whereas others have shown no effect (Ryu et al., 2006; MacKenzie et al., 2007b; Louie et al., 2008). In a study of 20 diabetic adults, fasting plasma glucose and fructosamine were lower after daily oolong tea consumption for 30 days (Hosoda et al., 2003). In another study (n=16 healthy adults), plasma glucose response after a 75 g glucose load was improved when 1 g black tea was ingested with the glucose (Bryans et al., 2007), whereas 3 g black tea had no effect. In a study of overweight Japanese with borderline diabetes, consumption of green tea extract with their regular diets resulted in a small reduction in hemoglobin A1c, whereas fasting glucose, insulin and homeostasis model assessment (HOMA) were not affected (Fukino et al., 2008). A study with 55 adults consuming green tea for 4 weeks showed no effects on fasting insulin, glucose or HOMA (Ryu et al., 2006). Finally, MacKenzie et al. (2007b) administered green and black tea extracts to diabetic adults for 3 months, with the primary endpoint being glycosylated hemoglobin. No hypoglycemic effect was detected.

Conflicting results related to the potential role of tea in glucoregulation highlights the need for well-controlled dietary intervention studies with well-characterized tea products. In previous intervention studies, participants were instructed to consume tea with their usual diet. Therefore, diet was not controlled in any of the previous intervention studies, which may have contributed to the equivocal results. In addition, only one of the previous studies included a caffeine control, and none included treatments matched for all tea components except catechins or other polyphenols to isolate possible effects of those tea constituents. Thus, the present study was designed to test the acute effects of oolong tea, oolong tea supplemented with catechins or tea polyphenols and caffeine on glucoregulation when diet is controlled, thus removing a significant, confounding, previously uncontrolled variable. Oolong tea was selected for use in this study because of the intermediate nature of its processing compared with green and black teas and for the opportunity to independently increase the catechin and the polymerized polyphenol content in the context of a similar background oolong tea. In addition, Hosoda et al. (2003) found consumption of oolong tea for 30 days to be very effective in improving glucose metabolism.

Methods

A total of 20 men, aged 25–64 years, participated in a study of the potential effect of daily consumption of oolong tea on glucose and insulin response. Volunteers were nonsmokers, had a body mass index between 18–30 kg/m2, with no history of cancer, heart disease, hypertension, diabetes, liver or kidney disease, endocrine disorders or food allergies. All procedures were approved by the MedStar Research Institute Institutional Review Board, and volunteers gave written informed consent before participation.

Self-reported daily caffeine consumption was used as a selection criterion. The target population was men who, on a daily basis, consume caffeinated beverages with caffeine content equal to 2–4 cups of coffee (100–400 mg/day caffeine). Exclusion criteria included the following: (1) younger than 25 years or older than 65 years; (2) body weight greater than 135 kg or body mass index less than 25 or greater than 35 kg/m2; (3) fasting plasma glucose greater than 125 mg per 100 ml; (4) blood pressure greater than 160/100 mm Hg; (5) total cholesterol greater than 240 mg per 100 ml; (6) volunteers who do not drink beverages that contain caffeine; (7) history of bariatric or certain other surgeries related to weight control; (8) history or presence of type 2 diabetes, kidney disease, liver disease, certain cancers, gastrointestinal, pancreatic, other metabolic diseases or malabsorption syndromes; (9) smokers or other tobacco users (for at least 6 months before the beginning of the study); (10) history of eating disorders or other dietary patterns which are not consistent with the dietary intervention (for example, vegetarians, very low fat diets and high protein diets); (11) volunteers who have lost 10% of body weight within the last 12 months or who planned to initiate a weight loss program during the next 10 months; (12) volunteers who routinely participate in heavy exercise or volunteers who planned to initiate an exercise program during the study; (13) volunteers who have been on Atkins, South Beach or similar diet in 3 months before the beginning of the study; (14) use of prescription or over-the-counter antiobesity medications or supplements (for example, phenylpropanalamine, ephedrine and caffeine) during and for at least 6 months before the beginning of the study; (15) volunteers unable or unwilling to give informed consent or communicate with study staff; (16) self-report of alcohol or substance abuse within the past 12 months and/or current acute treatment or rehabilitation program for these problems; and (17) other medical, psychiatric or behavioral factors that in the judgment of the Principal Investigator may interfere with study participation or the ability to follow the intervention protocol.

Sample size was estimated using data from previous pilot studies of similar designs conducted at the Center. In these studies, the standard deviation of treatment differences for glucose area under the curve was 440 mg h per 100 ml. To detect a 30% change in glucose area under the curve with α=0.05 and power=80%, the estimated sample size was 19. SigmaStat for Windows (ver 3.5) was used for sample size estimations (Aspire Software International, Ashburn, VA, USA).

Volunteers consumed one of five treatment beverages during each of the five treatment phases in a balanced complete-block study design. Each subject was randomly assigned to one of 20 predetermined treatment sequences that were selected to be balanced for first order carryover effects of treatment sequence (Williams, 1949).

Experimental treatments were as follows: oolong tea, catechin-enriched oolong tea, tea polyphenol-enriched oolong tea, caffeine-enriched water and unsupplemented water. The oolong tea and treatment beverages were provided as individual servings in 350 ml cans. The manufacturer coded each treatment and provided the beverages to investigators without an accompanying key so that the study was conducted in a double blind manner. The oolong tea contained the amounts of catechins, polyphenols and caffeine normally found in one serving. The caffeine plus water and the water alone treatments were colored and artificially flavored to mimic the taste of the tea.

Daily intakes of caffeine, various catechins and polyphenols (fraction including polymerized flavanols and other flavonoids) are presented in Table 1. The analysis was provided by Suntory Limited and conducted as previously reported (Rumpler et al., 2001). Analyses of the treatments were conducted pre and post study and the levels were observed to be within 2% for all analytes. Caffeine levels were similar across treatments (except the water treatment) and averaged 200 mg/day.

Table 1 Daily intake of catechins, other polyphenols and caffeine from study treatments (mg/day)

Subjects consumed four 350 ml servings per day as a part of a controlled diet where all foods were provided. Servings were consumed throughout the day, with one serving each consumed at breakfast, lunch, mid-afternoon snack and dinner. Monday through Friday, subjects consumed breakfast and dinner at the Beltsville Human Nutrition Research Center, and lunch and a snack were provided to be consumed off-site. Meals for Saturday and Sunday were prepared at the Center, but consumed off-site. Treatment phases were separated by a 9-day break.

On the morning of the fifth day of each treatment period, an IV catheter was placed in an antecubital vein. Two 12 ml baseline blood samples were collected, separated by 15 min. Subjects then consumed a standard 2047 kJ breakfast meal consisting of 112 g waffles with 65 g syrup (containing 7 g protein, 87 g carbohydrate, 11 g fat and 2 g fiber), and their treatment product within 20 min. After consumption of the meal, 12 ml blood samples were collected at 30, 60, 90, 120, 150, 180 and 240 min. Plasma glucose concentrations were measured by standard automated enzymatic procedures (Dimension Xpand, Dade-Behring, Deerfield, IL, USA) and serum insulin concentrations were measured by enzyme-multiplied immunoassay methods (LINCOplex, Linco Research, St Charles, MO, USA). All analyses were performed in duplicate.

HOMA (homeostasis model assessment) was calculated as fasting insulin (μU/ml) × fasting glucose (mmol/l)/22.5 (Haffner et al., 1997). Incremental and total area under the concentration–time curve was calculated for plasma glucose, and total area under the serum concentration–time curve was calculated for serum insulin, by the trapezoid method using Microsoft Excel (2007).

Plasma glucose concentration and plasma insulin concentration were compared at each time point across treatments. Data were analyzed within a mixed linear models framework, with model parameters estimated using the Proc Mixed procedure in SAS (version 9.1, SAS Institute, Inc., Cary, NC, USA). Subject variation was modeled as a random effect. The model incorporated treatment (beverage) sequence and period as dependent variables. Repeated-measures analyses were conducted for glucose and insulin. Means reported are least-square means, standard errors represent the standard error of the estimate of main effect means and a binomial probability test (P-value) was used to test differences between means.

Results

A total of 19 men completed the intervention study. One subject discontinued participation because of a scheduling conflict (incomplete data from this subject were excluded from analyses). Another subject had two fasting insulin values that fell three standard deviations outside the mean, and those values were also eliminated from the analyses. Mean characteristics of the subject population completing the study were: 52±11 years of age, 95±13 kg in weight and 179±7 cm in height (Table 2). Body composition determined by dual energy X-ray absorptiometry averaged 62±8 kg lean body mass and 32±7% fat.

Table 2 Physical characteristics at baseline of subjects who completed the intervention (n=19)

Plasma glucose and serum insulin concentrations as a function of time during the meal-based oral glucose tolerance test are presented in Figures 1 and 2. All values were within expected concentrations for nondiabetic individuals. There was no effect of treatment on glucose or insulin concentration at any time point.

Figure 1
figure1

Plasma glucose concentrations following a meal challenge of men (n=19) consuming oolong tea, tea plus catechins, tea plus polyphenol, water plus caffeine and water.

Figure 2
figure2

Plasma insulin concentrations following a meal challenge of men (n=19) consuming oolong tea, tea plus catechins, tea plus polyphenol, water plus caffeine and water.

Fasting levels of plasma glucose, serum insulin and HOMA were not different after 5 days of consumption of the different tea beverages compared with control treatments (Table 3). Fasting plasma glucose and serum insulin levels confirmed that these subjects were nondiabetic. Similarly, values for area under the concentration time curves for plasma glucose and serum insulin were not different among treatments (Table 3).

Table 3 Parameters of glucose metabolism (least-square mean±s.e.m.)

Discussion

The four types of tea produced worldwide (white, black, green and oolong) are all from the plant Camellia sinensis. Because tea is the most widely consumed beverage worldwide (Higdon and Frei, 2003), and because numerous epidemiological studies have suggested tea may have a role in reducing risk of diabetes (Greenberg et al., 2005; Song et al., 2005; Iso et al., 2006; Odegaard et al., 2008; Polychronopoulos et al., 2008; Jing et al., 2009; van Dieren et al., 2009), controlled intervention studies are important for defining the potential for tea to maintain healthy glucose metabolism. Oolong tea processing involves fermenting the product more than green tea is fermented, but less than black tea. Although oolong tea, compared with green tea, is not as rich in catechins or polyphenols, the key compounds thought to convey health benefits, we explored oolong tea treatments that had been enriched in catechins or polymerized polyphenols to more effectively test the influence of these compounds on glucose metabolism.

Intervention studies of the effect of tea on glucoregulation have yielded ambiguous results. Several studies have suggested that tea consumption improves parameters related to glucose metabolism (Hosoda et al., 2003; Bryans et al., 2007; Fukino et al., 2008; Venables et al., 2008; Nagao et al., 2009), whereas others have shown no effect (Ryu et al., 2006; MacKenzie et al., 2007b; Louie et al., 2008). Differences in aspects of study design (subject population, intervention length and tea product tested) may contribute to the seemingly conflicting results.

It has been suggested that tea may be more effective in improving glucose metabolism in individuals with diabetes. However, studies of both diabetics and nondiabetics have produced inconsistent outcome measures. Fukino et al. (2008) administered green tea extract to diabetics for 2 months, resulting in a reduction in hemoglobin A1c. In another study, diabetics were provided 1.5 l oolong tea for 30 days, which resulted in a significant lowering of fasting plasma glucose and fructosamine. Nagao et al. (2009) found that green tea consumption for 12 weeks by diabetics resulted in reduced fasting serum insulin, but not fasting plasma glucose or hemoglobin A1c. In contrast, neither MacKenzie et al. (2007b) nor Ryu et al. (2006) found daily tea consumption by diabetics to improve parameters of glucose metabolism. Both Venables et al. (2008) and Bryans et al. (2007) showed that tea intake can influence response of nondiabetics to an oral glucose tolerance test. When nondiabetics consumed green tea extract for 24 h before an oral glucose tolerance test, subjects showed a mean reduction in insulin area under the serum concentration time curve of 15% (Venables et al., 2008). Similarly, when nondiabetics consumed 1 g black tea with 75 g glucose, plasma glucose concentration was lower at 120 min and plasma insulin was lower at 90 min, when compared those after a 75 g glucose load without tea. It should be noted that in the same study (Bryans et al., 2007), 3 g of tea consumed with 75 g glucose had no effect on glucose or insulin response. Louie et al. (2008) provided nondiabetic volunteers with 250 ml black tea 1 h after a potato-based meal to find no effect of tea on glucose metabolism. In total, these studies show that conflicting results have been observed with both diabetic populations and nondiabetic populations.

Intervention length is a variable that must be carefully considered when designing a nutrition study. Intervention times must be sufficient to allow physiological changes to take place to improve metabolic function. In addition, water soluble tea components display short half-times in plasma, thus the presence of tea polyphenols in plasma during the assessment of glucose metabolism has been speculated as an important variable (Stote and Baer, 2008). With respect to tea studies, interventions have ranged from single, acute bolus doses to 12 weeks of daily dosing. Of the longer term interventions (1–4 months), three showed an improvement in glucose metabolism with tea intake (Hosoda et al., 2003; Fukino et al., 2008; Nagao et al., 2009), whereas two did not (Ryu et al., 2006; MacKenzie et al., 2007b). Although our intervention of 5 days was relatively short, several previous studies have shown that short-term interventions with tea or tea components can produce significant changes in glucose metabolism and other parameters of health. Grassi et al. (2009) found that 1 week of black tea consumption by healthy men decreased flow-mediated dilation, as well as systolic and diastolic blood pressure. MacKenzie et al. (2007a) found that 7 days of caffeine intake by healthy adults was sufficient to reduce insulin sensitivity. Moreover a single day of green tea extract consumption improved glucose metabolism in 11 healthy men, as assessed by an oral glucose tolerance test (Venables et al., 2008). These studies suggest that 5 days of treatment should be sufficient to produce the biological effects investigated in this study.

We tested whether co-consumption of oolong tea with the test meal would affect glucose metabolism. However, several studies have shown tea or tea components to influence glucose metabolism without co-consumption with the sugar source for an oral glucose tolerance test. A total of 7 days of caffeine intake by healthy adults reduced insulin sensitivity by HOMA (MacKenzie et al., 2007a) after an overnight fast. The study of Hosoda et al. (2003), which showed highly significant effects of oolong tea on glucose metabolism, was designed to test chronic effects of tea intake and post-treatment samples were collected under fasting condition. In yet another study, consumption of green tea extract during the previous 24-h period improved glucose sensitivity in 11 healthy men, as assessed by an oral glucose tolerance test after an overnight fast (Venables et al., 2008). The improvement of glucose metabolism uncovered in those studies did not depend on the tea beverage being co-consumed with the test meal or sugar source.

Intervention studies have been conducted with different types of tea (green, black and oolong), though again, examining studies by tea class yields conflicting results. A few studies with green tea have shown benefits with respect to glucose metabolism (Fukino et al., 2008; Venables et al., 2008; Nagao et al., 2009), whereas others have not (Ryu et al., 2006; MacKenzie et al., 2007b). One study with black tea showed glucoregulatory benefit (Bryans et al., 2007), whereas two did not (MacKenzie et al., 2007b; Louie et al., 2008). The study of Hosoda et al. (2003) suggested that oolong tea may provide beneficial effects, whereas the present study did not.

It has also been speculated that tea infusion time and polyphenol or catechin content may contribute to the disparity in results of intervention studies (Kyle et al., 2007). Previous studies have provided a wide range of polyphenols, reportedly from 300 mg (MacKenzie et al., 2007b) to 1490 mg/day (Hosoda et al., 2003). The highest reported polyphenol dose was that of Hosoda et al. (2003), providing 1490 mg polyphenols daily for 30 days, and this study resulted in a lowering of fasting plasma glucose and fructosamine. Venables et al. (2008) also provided a very high polyphenol dose of 890 mg, though for only 24 h before an oral glucose tolerance test, and insulin response was reduced after tea treatment. The present study provided the next highest polyphenol dose (676 mg/day), but no effect of tea treatment on glucose metabolism was observed. The tea treatments of MacKenzie et al. (2007b) provided a similar dose (600 mg) of polyphenols, yet again no effect of tea was observed. In contrast, Fukino et al. (2008) provided 544 mg polyphenols per day to observe a lowering of hemoglobin A1c. Bryans et al. (2007) fed two doses of polyphenols (350 and 1050 mg/day) to find that the lower dose of polyphenols lowered the 90 min serum insulin value and the 120 min plasma glucose value during an oral glucose tolerance test, whereas the larger polyphenol dose had no effect. Finally, the dose of 300 mg polyphenols by MacKenzie et al. (2007b) also had no influence on parameters of glucose metabolism. Thus, inconsistent results have been observed at both high and low levels of tea polyphenol intakes.

A critical factor that may contribute to the conflicting results related to tea and glucose metabolism is the lack of inclusion of a controlled diet for the duration of the dietary intervention. This study is the first of tea and glucose metabolism to include diet control in the design. Participants on this study were provided all foods consumed during the intervention. When diet is uncontrolled during an intervention period, there is no way to know what effect the rest of the diet is having on the major outcome variables, and it is difficult or impossible to be certain that the diets during different intervention periods are comparable or equivalent. Therefore, other dietary factors may have produced the positive results observed in some studies, or may have contributed variability and reduced ability to detect differences in others. Thus, a major strength of this study is that diet was controlled, thus removing a very important potential confounder.

In conclusion, neither oolong tea nor oolong tea supplemented with catechins or other polyphenols, produced improved glucose metabolism in healthy adult volunteers on the basis of this highly controlled dietary intervention trial. Previous studies of tea and glucose metabolism have been particularly equivocal, and these types of tightly controlled feeding studies are critical for revealing potential for dietary components to provide health benefits.

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Acknowledgements

Financial support for this study was from the US Department of Agriculture and Suntory Limited. Tea was provided by Suntory Limited.

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Correspondence to D J Baer.

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Baer, D., Novotny, J., Harris, G. et al. Oolong tea does not improve glucose metabolism in non-diabetic adults. Eur J Clin Nutr 65, 87–93 (2011). https://doi.org/10.1038/ejcn.2010.192

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Keywords

  • oolong tea
  • catechin
  • polyphenol
  • diabetes
  • insulin
  • glucose

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