Association between serum gamma-glutamyltransferase and dietary factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1) Free full text
This 2004 research from the University of Minnesota, School of Public Health noted, "Diet may be involved in the strong dose-response relation of gamma-glutamyltransferase (GGT) concentration with incident diabetes." "Study subjects were 3,146 black and white men and women aged 17-35 y in 1985-1986. A diet history was taken at years 0 and 7. Food items were classified into alcohol; breaded, battered, or canned vegetables; fruit; fruit juice; refined grain; whole grain; dairy; legumes; meat; poultry; fish; fresh or frozen vegetables; nuts; and coffee" "GGT was positively associated with alcohol consumption and meat intake... and inversely associated with fruit intake." "Among possible meat constituents, dietary heme iron, but not saturated fat, was associated with GGT." "Dietary constituents typical of plant foods showed an inverse association. In contrast, vitamin supplements were positively associated with GGT." The investigators concluded, "Serum GGT activity increased in a dose-response manner as alcohol and meat consumption increased and fruit consumption decreased. Heme iron contained in meats and micronutrients contained in fruits may influence GGT metabolism. However, micronutrients taken as supplements had a positive association with GGT."
Effects of long-term antioxidant supplementation and association of serum antioxidant concentrations with risk of metabolic syndrome in adults (2) Free full text
This was a 2009 reported study undertaken in France. "The objective was to examine the effect of antioxidant supplementation for 7.5 y on the incidence of MetS and the epidemiologic association between baseline serum antioxidant concentrations and the prospective risk of MetS (metabolic syndrome)." "Adults (n = 5220) participating in the SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) primary prevention trial were randomly assigned to receive a supplement containing a combination of antioxidants (vitamins C and E, beta-carotene, zinc, and selenium) at nutritional doses or a placebo. Subjects were free of MetS at baseline and were followed for 7.5 y." "Antioxidant supplementation for 7.5 y did not affect the risk of MetS. Baseline serum antioxidant concentrations of beta-carotene and vitamin C, however, were negatively associated with the risk of MetS; the adjusted odds ratios (and 95% CIs) for the highest compared with the lowest tertile were 0.34 (0.21, 0.53; P for trend = 0.0002) and 0.53 (0.35, 0.80; P for trend = 0.01), respectively. Baseline serum zinc concentrations were positively associated with the risk of developing MetS; the adjusted odds ratio (and 95% CI) for the highest compared with the lowest tertile was 1.81 (1.20, 2.72; P for trend = 0.01)." The researchers concluded, "The experimental finding of no beneficial effects of antioxidant supplementation in a generally well-nourished population is consistent with recent reports of a lack of efficacy of antioxidant supplements. However, the relations observed between the risk of MetS and baseline serum antioxidant concentrations, which probably reflect associations with overall dietary patterns, do support the current recommendations to consume antioxidant-rich foods."
Dietary determinants of iron stores in a free-living elderly population: The Framingham Heart Study (3) Free full text
This 1998 report from the US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University noted, "Epidemiologic studies have found a relation between body iron stores and risk of chronic disease. Iron-absorption studies from single meals have shown that many dietary factors can influence nonheme-iron bioavailability. However, little is known about the association of these dietary factors with iron stores in free-living elderly populations." "...we investigated the consumption of various dietary components and iron stores in an elderly sample of The Framingham Heart Study participants. Serum ferritin was used as a measure of body iron stores in 634 free-living elderly (67-93 y of age), and dietary intake during the previous year was assessed by a food-frequency questionnaire." "After we controlled for sex, age, body mass index, total energy intake, smoking, and use of aspirin and other medications known to affect blood loss, we found five significant dietary factors associated with iron stores. Heme iron, supplemental iron, dietary vitamin C, and alcohol were positively associated with serum ferritin, whereas coffee intake had a negative association." The researchers concluded, "Our results suggest that in typical Western-style diets, a small number of dietary factors probably modulate the bio availability of dietary iron and influence the accumulation of iron stores."
Health-e-Iron note: we've included the following study as an example to demonstrate how a diet lacking in fruits and vegetables and therefore antioxidants can lead to severe visual disability due to excessive oxidative stress:
Oxidative stress-elevated high gamma glutamyltransferase levels, and aging ,intake of tropical food plants,migration and visual disability in Central Africans (4) Free full Text
This study was reported in 2012 by a team of scientists in Central Africa. The aim of the study was to, "To investigate the independent pathogenic role of high serum gamma-glutamyltransferase (GGT) levels, sociodemographic data, dietary and environmental risk factors for visual disability(VD)." "This was a case-control study, run in 200 black Congolese patients managed in Saint Joseph Hospital Ophthalmology Division from Kinshasa town. Logistic regression model was used to identify determinants of VD (n=58) among sex, age, cigarette smoking, alcohol abuse, rural-urban migration, education levels, aging ≥60 years, intake of red Beans, Safou fruit and Taro leaves, lipid profile, residence, socioeconomic status, and GGT." "After adjusting for confounding factors, we identified migration (OR=3.7 95% CI: 1.2-11.3; P=0.023), low education level (OR=3.1 95% CI 1.1-8.5; P=0.026), no intake of Safou fruit (OR=34.2 95% CI 11.5-102; P<0.0001), age ≥ 60 years (OR=2.5 95% CI 1.01-6.5; P=0.049), and serum GGT ≥10 U/L (OR=3.6 95% CI 1.3-9.6; P=0.012) as the significant and independent determinants of VD." The researchers concluded, "VD (visual disability) appears as a major public health problem in Central Africa to be prevented or delayed by control of migration, lifestyle changes, antioxidant supplements, appropriate diet, nutrition education, and blocking of oxidative stress." [Health-e-Iron note: Table 2 from this study appears below:]
Inhibition of food iron absorption by coffee (5) Free full text
This 1983 study reported, "Dual isotope studies were performed in iron replete human subjects to evaluate the effect of coffee on nonheme iron absorption. A cup of coffee reduced iron absorption from a hamburger meal by 39% as compared to a 64% decrease with tea, which is known to be a potent inhibitor of iron absorption. When a cup of drip coffee or instant coffee was ingested with a meal composed of semipurified ingredients, absorption was reduced from 5.88% to 1.64 and 0.97%, respectively, and when the strength of the instant coffee was doubled, percentage iron absorption fell to 0.53%. No decrease in iron absorption occurred when coffee was consumed 1 h before a meal, but the same degree of inhibition as with simultaneous ingestion was seen when coffee was taken 1 h later. In tests containing no food items, iron absorption from NaFeEDTA was diminished to the same extent as that from ferric chloride when each was added to a cup of coffee. These studies demonstrate that coffee inhibits iron absorption in a concentration-dependent fashion."
Health-e-Iron note: We have included a large number of coffee studies on this page. Coffee provides at least two important protective mechanisms. Coffee consumed with or shorty after meals inhibits the absorption of iron in people with sufficient iron stores; and coffee consumption has repeatedly been shown to be inversely related to GGT. In addition, coffee has been described to contain protective natural antioxidants in bio-available form.
Coffee consumption and decreased serum gamma-glutamyltransferase and aminotransferase activities among male alcohol drinkers (6) Free full text
This 1998 research was reported in Japan. The researchers noted the following respecting previous concerns about coffee consumption: "Attention has long been drawn to the potentially harmful effects of coffee on health, however recent epidemiological studies have suggested unexpected, possibly beneficial effects of coffee against the occurrence of alcoholic liver cirrhosis and upon serum liver enzyme levels." In a cross-sectional, controlled study of 12,682 individuals ("Those who had a history of liver disease and/or serum aminotransferases exceeding the normal range were excluded"), the researchers observed "Increased coffee consumption was strongly and independently associated with decreased GGT activity among males (P trend < 0.0001); the inverse association between coffee and serum GGT was more evident among heavier alcohol consumers (P < 0.0001), and was absent among non-alcohol drinkers. Among females, however, coffee was only weakly related to lower GGT level." The researchers concluded, "Our results suggest that coffee may inhibit the induction of GGT in the liver by alcohol consumption, and may possibly protect against liver cell damage due to alcohol."
Combined effects of coffee consumption and serum γ-glutamyltransferase on serum C-reactive protein in middle-aged and elderly Japanese men and women (7)
In this 2011 study from Japan the authors noted that, "The association between coffee intake and circulating levels of C-reactive protein (CRP) may be modified by oxidative stress. The authors examined the relation of coffee consumption to serum CRP considering potential inter-actions of serum γ-glutamyltransferase (GGT) and bilirubin." "The subjects included 4,455 men and 5,942 women aged 49-76 years who participated in the baseline survey of a cohort study on lifestyle-related diseases in Fukuoka, Japan." "Serum CRP concentrations were progressively lower with higher intake of coffee in men with high serum GGT (p for trend=0.009), but not in those with low serum GGT (p for trend=0.73) and GGT modified the association (p for interaction=0.03). Women showed no association between coffee intake and CRP whether serum GGT was low or high." The researchers concluded, "These results support a protective effect of coffee intake against systematic inflammation in middle-aged and elderly Japanese men and imply that such an effect may be stronger in elevated oxidative stress."
Determinants of gamma-glutamyltransferase: positive interaction with alcohol and body mass index, negative association with coffee (8) Free full text
This 1997 study was reported by the national Public Health Institute of Finland. "The authors studied determinants of gamma-glutamyltransferase activity in a random sample (n = 6,010) drawn from the general population aged 25-64 years in Finland in 1992." "In regression analysis, coffee intake and drinking boiled coffee were significantly (p < 0.01) negatively related to gamma-glutamyltransferase, whereas age, male gender, the number of cigarettes per day, serum total cholesterol and high density lipoprotein cholesterol, heart rate, and diastolic blood pressure were significantly positively related to gamma-glutamyltransferase." "A significant (p = 0.02) positive interaction was observed between alcohol intake and body mass index." "Elevated y-glutamyltransferase activities were found significantly less often at coffee intake levels of both four to six cups a day and seven or more cups a day compared with nondrinkers of coffee." The researchers describe the interaction of coffee consumption, alcohol intake and obesity in both the abstract and full text. The researchers concluded, "Elevated gamma-glutamyltransferase activities appear to be related to heavy alcohol intake among the nonobese and to very light intake among obese subjects. Coffee appears to decrease gamma-glutamyltransferase activity."
Coffee consumption and decreased serum gamma-glutamyltransferase: a study of middle-aged Japanese men (9)
In this 2000 report from Japan, "The potential inverse association between coffee intake and serum gamma-glutamyltransferase (GGT) was examined in a cross-sectional study involving 1,353 Japanese male office workers aged 35-59 years in Osaka, Japan." After controlling for confounding variables the researchers determined,"From the linear regression analysis, coffee intake was inversely related to serum GGT levels independently of age, body mass index, alcohol intake, and cigarette smoking. All of the latter variables were also independently and positively associated with serum GGT levels." The research team concluded, "These findings suggest that coffee consumption is inversely related to serum GGT and that coffee may inhibit the inducing effects of aging and possibly of smoking on serum GGT in the liver."
Coffee consumption, serum γ-glutamyltransferase, and glucose tolerance status in middle-aged Japanese men (10)
The researxhers in this 2012-reported study from Japan noted, "Recently, coffee consumption has been related to decreased risk of type 2 diabetes mellitus (DM) among those with high levels of serum γ-glutamyltransferase (GGT). We examined the association between coffee and glucose tolerance, determined by a 75 g oral glucose tolerance test, and the effect modification of serum GGT on the association." "The study subjects were 5,320 men aged 46-60 years who received a health examination at two Self-Defense Forces hospitals from January 1997 to March 2004. Those medicated for DM were excluded. Coffee consumption was classified into <1, 1-2, 3-4, and ≥5 cups/day. Statistical adjustment was made for age, body mass index, smoking, alcohol use, leisure-time physical activity, green tea consumption, parental diabetes, hospital, and rank in the Self-Defense Forces. Results: Men with normal glucose tolerance, isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG/IGT, and type 2 DM numbered 3,384, 398, 790, 348, and 400, respectively. The prevalence odds of isolated IGT, combined IFG/IGT, and type 2 DM, but not of isolated IFG, decreased with increasing consumption of coffee. An inverse association with coffee was observed for isolated IGT in both low (≤40 IU/L) and high (>40 IU/L) GGT groups, and for combined IFG/IGT and type 2 DM in the latter group. Conclusions: Coffee drinking is protective against glucose intolerance. A possible effect modification of GGT on the coffee-DM association warrants further studies."
Coffee and serum gamma-glutamyltransferase: a study of self-defense officials in Japan (11) Free full text
In this earlier (1994) study from Japan also, "The relation of coffee drinking and other behavioral factors to serum gamma-glutamyltransferase (GGT) was examined in 2,494 male self-defense officials aged 48-56 years, who received a retirement health examination at the Self-Defense Forces Fukuoka Hospital between October 1986 and December 1990. Coffee, but not green tea, consumption was inversely related to serum GGT independently of body mass index, alcohol use, and smoking. All of the latter variables were also independently and positively associated with serum GGT. Lower levels of serum GGT associated with coffee drinking were more evident among heavier alcohol drinkers and also among heavier smokers. The findings suggest that coffee may inhibit the inducing effects of alcohol and possibly of smoking upon GGT in the liver."
Non-alcoholic beverage and caffeine consumption and mortality: The Leisure World Cohort Study (12) Free full text
This 2007 reported study was based on a large cohort of women and men residing at the Leisure World retirement community in California. "A baseline postal health survey included details on coffee, tea, milk, soft drink, and chocolate consumption. Participants were followed for 23 years (1981–2004). Risk ratios (RRs) of death were calculated using Cox regression for 8,644 women and 4,980 men (median age at entry, 74 years) and adjusted for age, gender and multiple potential confounders." The researchers noted that "Antioxidants may reduce mortality by decreasing the
incidence of cardiovascular disease, cancer and dementia." "Among nondrinkers of regular coffee, intake of decaffeinated coffee was unrelated to risk of death." "Moderate caffeine consumers had a significantly reduced risk of death (multivariable-adjusted RR=0.94, 95% CI: 0.90, 0.99 for 100–199 mg/day and RR=0.90, 95% CI: 0.85, 0.94 for 200–399 mg/day compared with those consuming <50 mg/day). Individuals who drank more than 1 can/week of artificially sweetened (but not sugar-sweetened) soft drink (cola and other) had a 8% increased risk (95% CI: 1.01–1.16). Neither milk nor tea had a significant effect on mortality after multivariable adjustment." The researchers concluded from the results of their study that, "association of caffeine intake (from coffee, tea, soft drinks, and chocolate) suggest a beneficial effect of moderate consumption. Individuals drinking 100–399 mg/day had the lowest risk. Those consuming more than 1 can/week of artificially-sweetened soft drinks had a small increased risk of death."
Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women (13) Free full text
In this 2004 "A prospective study from combined surveys conducted in 1982, 1987, and 1992 of 6.974 Finnish men and 7,655 women aged 35 to 64 years without history of stroke, coronary heart disease, or DM (diabetes mellitus) at baseline, with 175,682 person-years of follow-up. Coffee consumption and other study parameters were determined at baseline using standardized measurements." The hazard Ratios (HR) "associated with the amount of coffee consumed daily (0-2, 3-4, 5-6, 7-9, > or =10 cups) were 1.00, (95% confidence interval ..., 0.39 ..., 0.39..., and 0.21...(P for trend<.001) in women, and 1.00, 0.73..., 0.70 ..., 0.67..., and 0.45 ... (P for trend =.12) in men, respectively." "In both sexes combined, the multivariate-adjusted inverse association was significant (P for trend <.001) and persisted when stratified by younger and older than 50 years; smokers and never smokers; healthy weight, overweight, and obese participants; alcohol drinker and nondrinker; and participants drinking filtered and nonfiltered coffee." As of the date this research was published (2004), the researchers concluded, "Coffee drinking has a graded inverse association with the risk of type 2 DM; however, the reasons for this risk reduction associated with coffee remain unclear." [Health-e-Iron note: Research published after 2004 clarifies the reasons for the described risk reductions associated with coffee consumption]
Coffee and tea consumption and risk of type 2 diabetes (14) Free full text
This 2009 study reported in the Netherlands was aimed to "to examine the association of consumption of coffee and tea, separately and in total, with risk of type 2 diabetes and which factors mediate these relations." "...a prospective cohort of 40,011 participants with a mean follow-up of 10 years." The researchers found, "Total daily consumption of at least three cups of coffee and/or tea reduced the risk of type 2 diabetes by approximately 42%. Adjusting for blood pressure, magnesium, potassium and caffeine did not attenuate the associations." And they concluded. "Drinking coffee or tea is associated with a lowered risk of type 2 diabetes, which cannot be explained by magnesium, potassium, caffeine or blood pressure effects. Total consumption of at least three cups of coffee or tea per day may lower the risk of type 2 diabetes."
Coffee, tea, and alcohol intake in relation to risk of type 2 diabetes in African American women (15) Free full text
This study undertaken in the U.S. was reported in 2010. The study included 46,906 Black Women's Health Study participants aged 30-69 y at baseline in 1995. Dietary intake was assessed in 1995 and 2001 by using a validated food-frequency questionnaire. During 12 y of follow-up, there were 3,671 incident cases of type 2 diabetes. "Multivariable RRs (Relative Risks) for intakes of 0-1, 1, 2-3, and ≥4 cups of caffeinated coffee/d relative to no coffee intake were 0.94 (95% CI: 0.86, 1.04), 0.90 (95% CI: 0.81, 1.01), 0.82 (95% CI: 0.72, 0.93), and 0.83 (95% CI: 0.69, 1.01), respectively (P for trend = 0.003). Multivariable RRs for intakes of 1-3, 4-6, 7-13, and ≥14 alcoholic drinks/wk relative to never consumption were 0.90 (95% CI: 0.82, 1.00), 0.68 (95% CI: 0.57, 0.81), 0.78 (95% CI: 0.63, 0.96), and 0.72 (95% CI: 0.53, 0.98), respectively (P for trend < 0.0001). Intakes of decaffeinated coffee and tea were not associated with risk of diabetes." The researchers concluded, "Our results suggest that African American women who drink moderate amounts of caffeinated coffee or alcohol have a reduced risk of type 2 diabetes."
Coffee consumption and risk of type 2 diabetes: a systematic review (16) Free full text
The researchers of this 2005-reported review noted, "Emerging epidemiological evidence suggests that higher coffee consumption may reduce the risk of type 2 diabetes." "We identified 9 cohort studies of coffee consumption and risk of type 2 diabetes, including 193,473 participants and 8,394 incident cases of type 2 diabetes, and calculated summary relative risks (RRs) using a random-effects model. The RR of type 2 diabetes was 0.65 (95% confidence interval [CI], 0.54-0.78) for the highest (>or=6 or >or=7 cups per day) and 0.72 (95% CI, 0.62-0.83) for the second highest (4-6 cups per day) category of coffee consumption compared with the lowest consumption category (0 or >or=2 cups per day). These associations did not differ substantially by sex, obesity, or region (United States and Europe). In the cross-sectional studies conducted in northern Europe, southern Europe, and Japan, higher coffee consumption was consistently associated with a lower prevalence of newly detected hyperglycemia, particularly postprandial hyperglycemia." The researchers concluded, "This systematic review supports the hypothesis that habitual coffee consumption is associated with a substantially lower risk of type 2 diabetes."
Prospective study of coffee and tea consumption in relation to risk of type 2 diabetes mellitus among men and women: the Whitehall II study (17) Free full text
In this 2008 from the U.K., this research team stated, "At least fourteen cohort studies have documented an inverse association between coffee consumption and risk of type 2 diabetes. We examined the prospective association between coffee and tea consumption and the risk of type 2 diabetes mellitus among British men (n 4,055) and women (n 1,768) from the Whitehall II cohort." The researchers described the following as the only significant relationship found: "There was, however, an association between combined intake of tea and coffee (two or more cups per day of both beverage) and diabetes (HR 0.68...) after full adjustment."
Coffee consumption, serum gamma-glutamyltransferase and risk of type II diabetes (18) Free full text
In 2008 this research team in Finland set out "to study the joint association of coffee consumption and serum gamma-glutamyltransferase (GGT) levels on the risk of developing type II diabetes." "A total of 21,826 Finnish men and women who were 35-74 years of age and without any history of diabetes at baseline (years 1982, 1987, 1992 and 1997) were included in the present analyzes. They were prospectively followed up for onset of type II diabetes (n=862 cases), death or until the end of the year 2002. Coffee consumption, serum GGT and other study parameters were determined at baseline using standardized measurements. Analyzes were stratified by the serum GGT level classified into two classes using the 75th sex-specific percentiles as the cut point." The researchers found, "Coffee consumption was significantly and inversely associated with incident diabetes among both men and women. Serum GGT modified the association between coffee consumption and incident diabetes. Subjects in the high category of coffee consumption with the GGT level > or = 75th percentile showed a significant inverse association for women, and for both sexes combined. The association was not significant in subjects with the GGT level < or = 75th percentile. There was a significant interaction effect of GGT and coffee consumption on risk of type II diabetes in data of women (P=0.05) and in both sexes combined (P=0.02)." The researchers concluded, "Habitual coffee consumption is associated with lower incidence of type II diabetes particularly in those with higher baseline serum GGT levels."
Role of coffee in modulation of diabetes risk (19)
This is a 2012-reported review from Italy. "Coffee consumption has been associated with a lower risk of type 2 diabetes. This association does not depend on race, gender, geographic distribution of the study populations, or the type of coffee consumed (i.e., caffeinated or decaffeinated). This review discusses the strength of this relationship, examines the possibility that the pattern of coffee consumption could influence the association, and evaluates the possible relationship between coffee consumption and other risk factors associated with diabetes. Particular attention is paid to the identification, on the basis of the scientific evidence, of the possible mechanisms by which coffee components might affect diabetes development, especially in light of the paradoxical effect of caffeine on glucose metabolism. In addition to the role of coffee in reducing the risk of developing type 2 diabetes, the possible role of coffee in the course of the illness is explored. Finally, the possibility that coffee can also affect the risk of other forms of diabetes (e.g., type 1 diabetes and gestational diabetes) is examined."
Coffee, caffeine, and risk of type 2 diabetes: a prospective cohort study in younger and middle-aged U.S. women (20) Free full text
This is a 2006-published study from the Harvard School of Public Health. The researchers noted, "High habitual coffee consumption has been associated with a lower risk of type 2 diabetes, but data on lower levels of consumption and on different types of coffee are sparse." "This is a prospective cohort study including 88,259 U.S. women of the Nurses' Health Study II aged 26-46 years without history of diabetes at baseline. Consumption of coffee and other caffeine-containing foods and drinks was assessed in 1991, 1995, and 1999. We documented 1,263 incident cases of confirmed type 2 diabetes between 1991 and 2001." "After adjustment for potential confounders, the relative risk of type 2 diabetes was 0.87 (95% CI 0.73-1.03) for one cup per day, 0.58 (0.49-0.68) for two to three cups per day, and 0.53 (0.41-0.68) for four or more cups per day compared with nondrinkers (P for trend <0.0001). Associations were similar for caffeinated (0.87 [0.83-0.91] for a one-cup increment per day) and decaffeinated (0.81 [0.73-0.90]) coffee and for filtered (0.86 [0.82-0.90]) and instant (0.83 [0.74-0.93]) coffee. Tea consumption was not substantially associated with risk of type 2 diabetes (0.88 [0.64-1.23] for four or more versus no cups per day; P for trend = 0.81)." The researchers concluded, "These results suggest that moderate consumption of both caffeinated and decaffeinated coffee may lower risk of type 2 diabetes in younger and middle-aged women. Coffee constituents other than caffeine may affect the development of type 2 diabetes."
Moderate coffee consumption increases plasma glutathione but not homocysteine in healthy subjects (21) Free full text
This 2003 research from Italy was aimed, "To verify the effect of Italian-style coffee consumption on the plasma concentration of glutathione and homocysteine in healthy subjects." "Twenty-two volunteers consumed five cups of coffee per day for 1 week and maintained their usual diet. Five subjects were enrolled as controls. The intervention trial was preceded and followed by seven coffee-free days." The researchers concluded, "A coffee intake regimen, representing the average consumption of coffee drinkers in Italy, increased the plasma concentration of glutathione, but no significant increase in the plasma homocysteine concentration was detected." [Health-e-Iron note: the inverse relationship of GGT to the "master antioxidant" glutathione is demonstrated throughout the literature referenced on this web site]
Coffee intake and glucose homeostasis: is there a role for body iron ? (22) Free full text
This 2010 research was based on a study of 2,682 men from eastern Finland. The investigators "looked at the association of coffee consumption with body iron and glucose homeostasis..." They found, "In an unadjusted linear regression model, IR (insulin resistance) decreased 2.1% per 100-mL increase in coffee intake..." The researchers concluded, "These results suggest that coffee consumption may be associated with both body iron stores and glucose homeostasis as measured by HOMA2 IR and pancreatic Beta-cell function. Furthermore, the results suggest that the association of coffee intake with IR may be partially explained by a decrease in body iron level."
Inhibition of iron absorption by coffee and the reduced risk of type 2 diabetes mellitus (23)
This is an editorial published in 2007. The authors submitteded this to provide their observations on the study described immediately below. "Pereira and colleague1 found an inverse association between coffee consumption and the risk of type 2 diabetes mellitus. Because this relation was stronger for decaffeinated coffee intake, it is likely that constituents other than caffeine are involved in this beneficial association. We suggest that some of the involved mechanisms might be related to inhibition of iron absorption by polyphenol compounds present in coffee, be it regular coffee or decaffeinated coffee. The main phenolic compound in coffee, chlorogenic acid, is a potent inhibitor of nonheme iron absorption. Hurrell et al. report that the polyphenolic content typical in a cup of instant coffee reduces iron absorption from a test meal by 60% to 90%. Among elderly participants in the Framingham Heart Study, each 236 mL/wk (1 cup per week) of coffee consumed was associated with 1% lower serum ferritin concentration." "On the other hand, higher body iron stores are associated with the increased risk of diabetes. Furthermore, induction of near iron deficiency in carbohydrate intolerant subjects has been shown to improve insulin insensitivity. Another intervention study in patients with type 2 diabetes with elevated ferritin levels provided evidence that bloodletting, which resulted in 50% reduction in serum ferritin concentration, improved glycemia and insulin insulin sensitivity." The authors concluded, "Thus, increased intake of polyphenol compounds in coffee may maintain a relatively low iron status and may therefore reduce the risk of diabetes." [Health-e-Iron note: chlorogenic acid, behind caffeine, is the second major component in coffee. We have provided a 2012 lab study near the bottom of this page that describes how "Chlorogenic Acid Stimulates Glucose Transport..: A Contributor to the Beneficial Effects of Coffee on Diabetes."]
Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28,812 postmenopausal women (24) Free full text
In this 2006 study based on data from the Iowa Women's Health Study, the investigators stated, "Our objective was to examine the association between total, caffeinated, and decaffeinated coffee intake..."The study included included "28, 812 postmenopausal women free of diabetes and cardiovascular disease in the general community." "Coffee intake was categorized as 0, less than 1, 1 to 3, 4 to 5, and 6 or more cups per day. During 11 years of follow-up, there were 1,418 incident cases of diabetes." "Compared with women who reported 0 cups of coffee per day, women who consumed 6 or more cups per day had a 22% lower risk ... of diabetes ... The researchers concluded, "Coffee intake, especially decaffeinated, was inversely associated with risk of type 2 diabetes mellitus in this cohort of postmenopausal women."
Coffee consumption and risk for type 2 diabetes mellitus (25)
In this 2004 study at the Harvard School of Public Health, The investigators noted, "In small, short-term studies, acute administration of caffeine decreases insulin sensitivity and impairs glucose tolerance." In an analysis of data obtained from The Nurses' Health Study and Health Professionals' Follow-up Study, "The authors followed 41,934 men from 1986 to 1998 and 84,276 women from 1980 to 1998. These participants did not have diabetes, cancer, or cardiovascular disease at baseline." "The authors documented 1,333 new cases of type 2 diabetes in men and 4,085 new cases in women. The authors found an inverse association between coffee intake and type 2 diabetes after adjustment for age, body mass index, and other risk factors. The multivariate relative risks for diabetes according to regular coffee consumption categories (0, <1, 1 to 3, 4 to 5, or > or =6 cups per day) in men were 1.00, 0.98, 0.93, 0.71, and 0.46 ..., respectively. The corresponding multivariate relative risks in women were 1.00, 1.16, 0.99, 0.70, and 0.71 ..., respectively. For decaffeinated coffee, the multivariate relative risks comparing persons who drank 4 cups or more per day with nondrinkers were 0.74 ... for men and 0.85 ... for women. Total caffeine intake from coffee and other sources was associated with a statistically significantly lower risk for diabetes in both men and women. [Health-e-Iron note: since this report was written (2004), the protective values of coffee drinking have been shown to be derived from other coffee constituents beyond those that might relate to just caffeine. For instance, several research studies in this section described the inverse association of coffee with GGT, and the positive association of coffee with glutathione synthesis. Although protective elements might be related to caffeine, coffee also reduces the risk of diabetes as a result of reducing iron absorption when it is consumed at mealtime or shortly thereafter. The above studies # 5, #20 and editorial #21 describe the association of lower body iron stores with coffee drinking]
Coffee consumption is inversely associated with type 2 diabetes in Chinese (26) Free full text
In 2011 researchers in China reported that they, "...investigated the relationship between coffee consumption and T2DM (type 2 diabetes) in a population-based cohort of middle-aged Chinese." The researchers determined that, "Habitual coffee drinkers had 38-46% lower risk of T2DM than nondrinkers." "The adjusted mean fasting glucose levels gradually decreased as the frequency of coffee consumption increased (P<0·05)." The researchers concluded, "Coffee intake is inversely associated with T2DM in Chinese. Coffee may be a protective agent for T2DM in Chinese." "In multivariate models participants reporting > or =4 cups of coffee/d had a 30% reduction in risk of diabetes [relative risk (RR): 0.70; 95% CI: 0.53, 0.93] compared with participants who reported nondaily consumption. Participants reporting > or =1 cup of black tea/d had a suggestive 14% reduction in risk of diabetes (RR: 0.86; 95% CI: 0.74, 1.00) compared with participants who reported 0 cups/d, and we observed no association with green tea." The investigators concluded, "Regular consumption of coffee and potentially black tea, but not green tea, is associated with lower risk of type 2 diabetes in Asian men and women in Singapore."
Coffee, tea, and incident type 2 diabetes: the Singapore Chinese Health Study (27) Free full text
This 2008 study was reported in Japan. The investigators noted, "Increasing coffee intake was inversely associated with risk of type 2 diabetes in populations of European descent; however, data from high-risk Asian populations are lacking as are data on tea intake in general." "We investigated the prospective associations between intakes of coffee, black tea, and green tea with the risk of type 2 diabetes in Singaporean Chinese men and women." "We analyzed data from 36,908 female and male participants in the Singapore Chinese Health Study aged 45-74 y in 1993-1998 who had multiple diet and lifestyle measures assessed and then were followed up between 1999 and 2004. We used Cox regression models to investigate the association of baseline coffee and tea intakes with incident type 2 diabetes during follow-up, with adjustment for a number of possible confounding or mediating variables"
Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes (28) Free full text
This 2006 study reported in Finland was "designed to assess the association between coffee consumption and CVD (cardiovascular disease) mortality among patients with type 2 diabetes." "We prospectively followed 3,837 randomly ascertained Finnish patients with type 2 diabetes aged 25 to 74 years. Coffee consumption and other study parameters were determined at baseline." "During the average follow-up of 20.8 years, 1,471 deaths were recorded, of which 909 were coded as CVD, 598 as CHD (coronary heart disease) and 210 as stroke. The respective multivariate-adjusted hazard ratios in participants who drank 0-2, 3-4, 5-6, and > or =7 cups of coffee daily were 1.00, 0.77, 0.68 and 0.70 for total mortality (P<0.001 for trend), 1.00, 0.79, 0.70 and 0.71 for CVD mortality ..., 1.00, 0.78, 0.70 and 0.63 for CHD mortality..., and 1.00, 0.77, 0.64 and 0.90 for stroke mortality...." The researchers concluded, "In this large prospective study we found that in type 2 diabetic patients coffee drinking is associated with reduced total, CVD and CHD mortality."
Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women (29) Free full text
This study 2010 reported study was undertaken in Japan. The investigators "...aimed to investigate the associations between coffee consumption and all-cause and cause-specific mortality in Japan. We included 37,742 participants (18,287 men and 19,455 women) aged 40-64 y without a history of cancer, myocardial infarction, or stroke at baseline in our analysis, based on the Miyagi Cohort Study initiated in 1990." "In women, the multivariate hazard ratios (HR) (95% CI) for all-cause mortality in participants who drank coffee never, occasionally, 1-2 cups... > or =3 cups/d were 1.00, 0.88 ..., 0.82 ..., and 0.75 ..., respectively (P-trend = 0.04)." "Death due to cancer was not associated with coffee consumption in either men or women, except for colorectal cancer in women. Our results suggest that coffee may have favorable effects on morality due to all causes and to CVD, especially CHD, in women."
Pleiotropic preventive effects of dietary polyphenols in cardiovascular diseases (30)
In this 2013-reported review from Japan the authors noted "polyphenols are common constituents of the diet, and research on their health benefits has developed quickly over the past few years. Our purpose is to review recent findings highlighting daily dietary polyphenol intake and the diverse function of polyphenols and their possible relationships to cardiovascular disease (CVD). Several cohort studies have reported an inverse relationship between the daily consumption of polyphenols and CVD risk. Many studies showed that beverages could be a large source of polyphenols. Our previous findings provide that Japanese people intake polyphenols mainly from beverages, especially coffee and green tea (in descending order of polyphenol content). Many kinds of polyphenols act as an antioxidant against low-density lipoprotein oxidation, which is known to promote atherosclerosis. Recent accumulating evidence suggests that dietary polyphenols could exert their cardioprotective actions through their potential to improve metabolic disorder and vascular inflammation. These findings raise the possibility that polyphenols have a wide variety of roles in the intestine, liver and vascular tissue. In addition to identifying mechanisms of polyphenol bioactivity by basic research, much more epidemiological and clinical evidence linking reduced cardiovascular risk with dietary polyphenols intake are needed.
Coffee consumption and risk of stroke in women (31) Free full text
In this 2011 study undertaken in Sweden, the researchers "followed of 34,670 women without a history of cardiovascular disease or cancer at baseline in 1997." "During a mean follow-up of 10.4 years, we ascertained 1,680 stroke events, including 1,310 cerebral infarctions, 154 intracerebral hemorrhages, 79 subarachnoid hemorrhages, and 137 unspecified strokes. After adjustment for other risk factors, coffee consumption was associated with a statistically significant lower risk of total stroke, cerebral infarction, and subarachnoid hemorrhage but not intracerebral hemorrhage. The multivariable relative risks of total stroke across categories of coffee consumption (<1 cup/day, 1 to 2 cups/day, 3 to 4 cups/day, and ≥5 cups/day) were 1.00, ..., 0.75 ..., and 0.77 ..., respectively; P for trend=0.02). The association between coffee consumption and cerebral infarction was not modified by smoking status, body mass index, history of diabetes or hypertension, or alcohol consumption." The researchers concluded, " The researchers concluded, "These findings suggest that low or no coffee consumption is associated with an increased risk of stroke in women."
Coffee consumption and risk of stroke in women (32) Free full text
This 2009 study was reported by the Harvard School of Public Health. This study was very similar to the above-reported study from Sweden. A notable difference is that the rate of coffee consumption is significantly higher in Sweden that in the U.S. The researchers "analyzed data from a prospective cohort of 83,076 women in the Nurses' Health Study without history of stroke, coronary heart disease, diabetes, or cancer at baseline. Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years, with follow-up through 2004. We documented 2,280 strokes, of which 426 were hemorrhagic, 1,224 were ischemic, and 630 were undetermined." The researchers reported a 20% reduction in stroke risk for women who drank more than 4 cups of coffee a day. "The association was stronger among never and past smokers (RR for >or=4 cups a day versus <1 cup a month, 0.57; ..." The researchers concluded, "Long-term coffee consumption was not associated with an increased risk of stroke in women. In contrast, our data suggest that coffee consumption may modestly reduce risk of stroke."
Coffee and tea consumption and risk of stroke subtypes in male smokers (33) Free full text
This was a study reported in 2008 from Sweden. The researchers conducted, "a cohort study of 26,556 male Finnish smokers aged 50 to 69 years without a history of stroke at baseline. Coffee and tea consumption was assessed at baseline using a validated food-frequency questionnaire. During a mean follow-up of 13.6 years, from 1985 through December 2004, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were ascertained from national registries. "After adjustment for age and cardiovascular risk factors, both consumption of coffee and tea was statistically significantly inversely associated with the risk of cerebral infarction but not intracerebral or subarachnoid hemorrhage." "The multivariate relative risk of cerebral infarction for men in the highest category of coffee consumption (>/=8 cups/d) was 0.77 ... compared with those in the lowest category (<2 cups/d). The corresponding relative risk comparing men in the highest category of tea consumption (>/=2 cups/d) with those in the lowest category (nondrinkers) was 0.79 ..."The researchers concluded, "These results suggest that high consumption of coffee and tea may reduce the risk of cerebral infarction among men, independent of known cardiovascular risk factors."
Coffee, caffeine, and risk of hospitalization for arrhythmias (34) Free full text
This 2011 research was aimed to determine the "...relations of coffee drinking to risk of cardiac arrhythmia in 130,054 persons with previous data about coffee habits." "Controlled for number of cups of coffee per day, total caffeine intake was inversely related to risk (HR highest quartile vs lowest = 0.6; p = 0.03). The researchers concluded, "The inverse relations of coffee and caffeine intake to hospitalization for arrhythmias make it unlikely that moderate caffeine intake increases arrhythmia risk."
Coffee, nutritional status, and renal artery resistive index (35)
This 2010 study was reported by Italian researchers. "The aim of this study is to investigate whether coffee habits, and/or quantity of coffee consumption, have any relationship with renal resistive index (RRI), a hallmark of arterial stiffness (AS). The relationship of AS with nutritional status assessed by body composition and serum albumin, insulin resistance (assessed by HOMA), and renal function assessed by glomerular filtration rate (GFR) is concurrently investigated. Methods: This study was done with 221 consecutive patients, without diabetes, cancer, liver, renal, and heart disease, referred for clinical noninvasive assessment and nutritional counseling: 124 essential hypertensive and 97 nonhypertensive patients were eligible. Personalized Mediterranean diet, physical activity increase, and smoking withdrawal counseling were provided." After analyzing the variables, the researchers concluded, "Coffee use is inversely associated with RRI. Habitual coffee users have risk protection to higher RRI; lower serum albumin, insulin resistance, and renal insufficiency are associated with greater RRI."
Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer (36) Free full text
The investigators noted in this 2006 study out of Finland noted that, "Only three Japanese prospective studies have suggested an inverse association between coffee drinking and liver cancer risk. No prospective studies on the association between serum gamma-glutamyltransferase (GGT) and liver cancer risk have been reported." "We aimed to determine the single and joint associations of coffee consumption and serum GGT with the risk of primary liver cancer. Study cohorts included 60,323 Finnish participants who were 25-74 years of age and free of any cancer at baseline. During a median follow-up period of 19.3 years (interquartile range: 9.3-29.2 years), 128 participants were diagnosed with an incident liver cancer." "The multivariable-adjusted (age, sex, alcohol consumption, education, smoking, diabetes and chronic liver disease at baseline and during follow-up, and body mass index) hazards ratios of liver cancer in participants who drank 0-1, 2-3, 4-5, 6-7, and > or =8 cups of coffee daily were 1.00, 0.66, 0.44, 0.38, and 0.32 (P for trend = 0.003), respectively." "The multivariable-adjusted and coffee-adjusted hazard ratio of liver cancer for the highest versus the lowest quartile of serum GGT was 3.13 (95% confidence interval = 1.22-8.07)." "A combination of very low coffee consumption and high level of serum GGT was associated with nearly nine-fold increased risk. CONCLUSION: Coffee drinking has an inverse and graded association with the risk of liver cancer. High serum GGT is associated with an increased risk of liver cancer."
Coffee consumption and risk of cancers: a meta-analysis of cohort studies (37)
In 2011 this Chinese research team noted, "Coffee consumption has been shown to be associated with cancer of various sites in epidemiological studies. However, there is no comprehensive overview of the substantial body of epidemiologic evidence." They reviewed 59 studies, consisting of 40 independent cohorts, met the (meta-analysis) inclusion criteria. Compared with individuals who did not or seldom drink coffee per day, the pooled RR (relative risk) of cancer was 0.87 ... for regular coffee drinkers, 0.89 ... for low to moderate coffee drinkers, and 0.82... for high drinkers. Overall, an increase in consumption of 1 cup of coffee per day was associated with a 3% reduced risk of cancers... In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers."
Coffee consumption and risk of endometrial cancer: Findings from a large up-to-date meta-analysis (38)
In this 2011 study from the Harvard School of Public Health, the investigators "conducted a meta-analysis of observational studies published up to October 2011" "A total of 16 studies (10 case-control and six cohort studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta-analysis. The pooled RR (relative risk) of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71.... By study design, the pooled RRs were 0.69 (95% CI: 0.55-0.87) for case-control studies and 0.70 (95% CI: 0.61-0.80) for cohort studies." "By geographic region, the inverse association was stronger for three Japanese studies (pooled RR = 0.40; ... than five studies from USA/Canada (pooled RR = 0.69;...) or eight studies from Europe (pooled RR = 0.79;...). The researchers concluded, "...our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case-control studies."
Coffee drinking and risk of endometrial cancer--a population-based cohort study (39) Free full text
The researchers in this 2009 study reported from Sweden, "...used data from the Swedish Mammography Cohort, a population-based prospective cohort study of 60,634 women. During 17.6 years of follow-up, 677 participants were diagnosed with incident endometrial cancer (adenocarcinoma). We examined the association between self-reported coffee consumption (at baseline 1987-90 and in 1997) and endometrial cancer risk... Each additional cup (200 g) of coffee per day was associated with a rate ratio (RR) of 0.90 ... In women drinking 4 or more cups of coffee a day, the RR for the risk reduction of endometrial cancer was 0.75 ...when compared with those who drank 1 cup or less. The association seemed largely confined to overweight and obese women, who showed a respective risk reduction of 12% ... and 20% ... for every cup of coffee, but was not observed among normal-weight women." The researchers concluded, "These data indicate that coffee consumption may be associated with decreased risk of endometrial cancer, especially among women with excessive body weight. If confirmed by other prospective studies, these results are of major public health significance."
Coffee consumption modifies risk of estrogen-receptor negative breast cancer (40) free full text
In this 2011 study from Sweden, the researchers noted, "Breast cancer is a complex disease and may be sub-divided into hormone-responsive (estrogen receptor (ER) positive) and non-hormone-responsive subtypes (ER-negative). Some evidence suggests that heterogeneity exists in the associations between coffee consumption and breast cancer risk, according to different estrogen receptor subtypes. We assessed the association between coffee consumption and postmenopausal breast cancer risk in a large population-based study (2,818 cases and 3,111 controls), overall, and stratified by ER tumour subtypes." "In the stratified case-control analyses, a significant reduction in the risk of ER-negative breast cancer was observed in heavy coffee drinkers (OR> 5 cups/day compared to OR≤ 1 cup/day ...in a multivariate-adjusted model. The breast cancer risk reduction associated with higher coffee consumption was significantly higher for ER-negative compared to ER-positive tumours ..." The researchers concluded, "A high daily intake of coffee was found to be associated with a statistically significant decrease in ER-negative breast cancer among postmenopausal women."
Coffee consumption and risk of breast cancer: a metaanalysis (41)
This is a 2009 meta-analysis reported by Chinese investigators. "Nine cohort and 9 case-control studies met the inclusion criteria." "...borderline significant associations were observed among cohort and case-control studies and studies conducted in Europe and the United States. However, no significant association was noted among studies conducted in Asia. The investigators concluded, "Our findings suggest a possible influence of high coffee consumption or an increased coffee consumption on (reducing) the risk of breast cancer."
Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status (42)
This study was undertaken in Sweden and the results were published in 2013. The study was undertaken to ascertain "Whether coffee modulates response to endocrine therapy in breast cancer patients is currently unknown. The CYP1A2 and CYP2C8 enzymes contribute to tamoxifen and caffeine metabolism. The purpose was to investigate the impact of coffee consumption on tumor characteristics and risk for early events in relation to breast cancer treatment and CYP1A2 and CYP2C8 genotypes. The results of questionnaires distributed preoperatively to 634 women were analyzed." "The proportion of estrogen receptor negative (ER-) tumors increased with increasing coffee consumption (p (trend) = 0.042). Moderate to high consumption was associated with lower frequency of discordant receptor status (ER + PgR-) OR 0.38 (0.23-0.63) compared to low consumption. Median follow-up time was 4.92 (IQR 3.01-6.42) years. Tamoxifen-treated patients with ER+ tumors (n = 310) who consumed two or more cups/day had significantly decreased risk for early events compared to patients with low consumption, adjusted HR 0.40 (0.19-0.83). Low consumption combined with at least one CYP1A2*1F C-allele (n = 35) or CYP2C8*3 (n = 13) was associated with a high risk for early events in tamoxifen-treated patients compared to other tamoxifen-treated patients, adjusted HRs 3.49 (1.54-7.91) and 6.15 (2.46-15.36), respectively." The researchers concluded, "Moderate to high coffee consumption was associated with significantly decreased risk for early events in tamoxifen-treated patients and modified hormone receptor status. If confirmed, new recommendations regarding coffee consumption during tamoxifen treatment may be warranted."
A meta-analysis of coffee consumption and pancreatic cancer (43) Free full text
In this 2012 Italian meta-analysis the investigators "conducted a systematic bibliography search updated March 2011 to identify observational studies providing quantitative estimates for pancreatic cancer risk in relation to coffee consumption." The investigators' findings indicated, "This meta-analysis provides quantitative evidence that coffee consumption is not appreciably related to pancreatic cancer risk, even at high intakes." [Health-e-Iron note: the following study report concludes that coffee consumption does reduce the risk of pancreatic cancer]
Coffee drinking and pancreatic cancer risk: a meta-analysis of cohort studies (44) Free full text
This is a 2011 meta-analysis of coffee consumption and pancreatic caner risk reported by Chinese researchers. This analysis reported results significantly differently than those reported directly above. "Fourteen studies met the inclusion criteria, which included 671,080 individuals (1,496 cancer events) with an average follow-up of 14.9 years. Compared with individuals who did not drink or seldom drank coffee per day, the pooled RR of pancreatic cancer was 0.82 ... for regular coffee drinkers, 0.86 ... for low to moderate coffee drinkers, and 0.68 ... for high drinkers. In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of pancreatic cancer in men, while this association was not seen in women. These associations were also similar in studies from North America, Europe, and the Asia-Pacific region." The researchers concluded, "Findings from this meta-analysis suggest that there is an inverse relationship between coffee drinking and risk of pancreatic cancer."
Coffee and cancers of the upper digestive and respiratory tracts: meta-analyses of observational studies (45) Free full text
This 2011 Italian meta-analysis reviewed "Data of epidemiological studies on the relation between coffee drinking and upper aerodigestive tract cancer risk are scattered and inconclusive. We therefore conducted systematic meta-analyses of observational studies published before October 2009. Materials and methods: We combined relative risks (RR) with 95% confidence intervals (CI) for cancers of the oral cavity/pharynx (OP) and larynx, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), comparing the highest versus the lowest categories of coffee consumption, using random-effects models. "For OP cancer, the pooled RR was 0.64 ... for highest versus lowest coffee drinking, based on a total of 2,633 cases from one cohort and eight case-control studies..." The investigators did not find similar relationships with the other cancers studies. Their conclusion was, "Coffee drinking is inversely related to OP cancer risk, while there is no relation with laryngeal cancer, ESCC and EAC."
Tea, coffee and oral cancer risk (46) Free full text
This 2011 study from the U.K. was a "pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. "Caffeinated coffee intake was inversely associated with the risk of cancer of the oral cavity and pharynx: the ORs (odds ratios) were 0.96 (95% CI, 0.94-0.98) for an increment of one cup per day and 0.61 ... in drinkers of >4 cups per day versus non-drinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46...for oral cavity; OR, 0.58; ... for oropharynx/hypopharynx; and OR, 0.61;... for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; ...in drinkers of >4 cups per day versus non-drinkers)." The researchers concluded, "This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx."
Caffeinated and decaffeinated coffee and tea intakes and risk of colorectal cancer in a large prospective study (47)
This 2012 reported study was part of the NIH-AARP Diet and Health Study. The study included "489,706 men and women who completed a baseline (1995-1996) self-administered questionnaire of demographics, diet, and lifestyle. Over a median of 10.5 y of follow-up, we identified 2,863 proximal colon, 1,993 distal colon, and 1,874 rectal cancers." "Approximately 16% of participants drank ≥4 cups coffee/d. Compared with nondrinkers, drinkers of 4-5 cups coffee/d (HR: 0.85; 95% CI: 0.75, 0.96) and ≥6 cups coffee/d (HR: 0.74; 95% CI: 0.61, 0.89; P-trend < 0.001) had a lower risk of colon cancer, particularly of proximal tumors (HR for ≥6 cups/d: 0.62; 95% CI: 0.49, 0.81; P-trend < 0.0001). Results were similar to those overall for drinkers of predominantly caffeinated coffee. Although individual HRs were not significant, there was a significant P-trend for both colon and rectal cancers for people who drank predominantly decaffeinated coffee. No associations were observed for tea." The researchers concluded, "In this large US cohort, coffee was inversely associated with colon cancer, particularly proximal tumors."
Coffee, colon function and colorectal cancer (48)
The abstract of this 2012 review follows: "For several years the physiological effects of coffee have been focused on its caffeine content, disregarding the hundreds of bioactive coffee components, such as polyphenols, melanoidins, carbohydrates, diterpenes, etc. These compounds may exert their protection against colorectal cancer (CRC), the third most common cancer worldwide. However, the amount and type of compounds ingested with the beverage may be highly different depending on the variety of coffee used, the roasting degree, the type of brewing method as well as the serving size. In this frame, this paper reviews the mechanisms by which coffee may influence the risk of CRC development focusing on espresso and filtered coffee, as well as on the components that totally or partially reach the colon i.e. polyphenols and dietary fiber, including melanoidins. In particular the effects of coffee on some colon conditions whose deregulation may lead to cancer, namely microbiota composition and lumen reducing environment, were considered. Taken together the discussed studies indicated that, due to their in vivo metabolism and composition, both coffee chlorogenic acids and dietary fiber, including melanoidins, may reduce CRC risk, increasing colon motility and antioxidant status. Further studies should finally assess whether the coffee benefits for colon are driven through a prebiotic effect."
Increased Caffeine Consumption Is Associated with Reduced Hepatic Fibrosis (49) Free full text
In this 2011 study reported by the National Institutes of Diabetes and Digestive and Kidney Diseases, investigators stated, "Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically." "One hundred seventy-seven patients (99 male, 104 white, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions." "Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75(th) percentile for the cohort (308 mg = approximately 2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33; ... and the protective association persisted after controlling for age, sex, race, liver disease, body mass index, and alcohol intake in all patients (OR, 0.25;..., as well as the subset with HCV infection (OR, 0.19; ... Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis."
Tea and coffee consumption and MRSA nasal carriage (50) Free full test
In this 2011 epidemiological study undertaken in the U.S. the researchers noted that "Hot tea and coffee have been found to have antimicrobial properties." "We performed a secondary analysis of data from the 2003-2004 National Health and Nutrition Examination Survey to investigate the relationship between the consumption of coffee, hot tea, cold tea, and soft drinks, and MRSA nasal carriage among the noninstitutionalized population of the United States." "In an adjusted logistic regression analysis controlling for age, race, sex, poverty-income ratio, current health status, hospitalization in the past 12 months, and use of antibiotics in the past month, individuals who reported consuming hot tea were one-half as likely to have MRSA nasal carriage relative to individuals who drank no hot tea (odds ratio = 0.47; 95% confidence interval, 0.31-0.71). Similarly, individuals who reported consuming coffee had about a one-half reduction in the risk of MRSA nasal carriage relative to individuals who drank no coffee (odds ratio = 0.47; 95% confidence interval, 0.24-0.93)."
Does coffee protect against hepatocellular carcinoma? (51) Free full text
In this 2002 study from Italy the researchers "analysed the relation between coffee consumption and hepatocellular carcinoma in two case-control studies conducted between 1984 and 1998 in Italy and Greece, including 834 cases and 1912 controls." The researchers concluded, "Compared to non coffee drinkers, the multivariate odds ratio was 0.7 (i.e. a 30% reduction in risk) for drinkers of three or more cups per day."
Inhibition of iron absorption by polyphenols as an anti-cancer mechanism (52) Free full text
The attached paper was written in 2010. Health-e-Iron recommends reading this short paper because it ties in the cancer reductions findings reported by Zacharski, et al. near the top of the Iron Reduction Therapy page with the alternated mechanism of reducing iron absorption by dietary means to potentially lead to a similar anti-cancer results. Among other things, the authors report, "Haem and non-haem iron enter intestinal mucosal cells by two independent pathways, haem iron being more efficiently absorbed (25–30%) from the diet than non-haem iron (5–15%). Although non-haem iron is not absorbed as well as haem iron, it is an important source because haem iron comprises only about 15% of total iron in the typical western diet." The authors concluded, "It is therefore plausible that increased intake of polyphenol compounds may, among other beneficial effects, maintain a relatively low iron status and, as a result, reduce the risk of cancer. It is important in future studies of polyphenols action to include assessments of the effects of the intervention on iron status.
HCC, diet, and metabolic factors: Diet and HCC (53) Free full text
This editorial review was published in 2011. The authors summarized the dietary factors that are associated with hepatocellular carcinoma (HCC). They note that, "Coffee consumption has been studied extensively and appears to have a favorable effect on the prevention of liver diseases, including HCC. One hypothesis suggests that coffee intake lowers serum levels of gamma-glutamyltransferase (GGT), which is associated with a lower incidence of HCC." The authors note several studies that point to the relationship of high dietary iron intake with HCC and high intake of foods including yogurt, milk, white meat and eggs with its prevention.
Associations of tea and coffee consumption with prostate cancer risk (54)
This 2013-published study was reported based on research undertaken in the U.S. The researchers noted that, "Tea and coffee contain bioactive compounds and both beverages have recently been associated with a reduced risk of prostate cancer (PCa)." "We studied associations of tea and coffee consumption with PCa risk in a population-based case-control study from King County, Washington, USA. Prostate cancer cases were diagnosed in 2002-2005 and matched to controls by 5-year age groups. Logistic regression was used to generate odds ratios (ORs) and 95 % confidence intervals (CIs)." "Among controls, 19 and 58 % consumed at least one cup per day of tea and coffee, respectively. The analysis of tea included 892 cases and 863 controls, and tea consumption was associated with a reduced overall PCa risk with an adjusted OR of 0.63 (95 % CI: 0.45, 0.90; P for trend = 0.02) for men in the highest compared to lowest category of tea intake (≥2 cups/day vs. ≤1 cup/week). Risk estimates did not vary substantially by Gleason grade or disease stage. Coffee consumption was not associated with risk of overall PCa or PCa in subgroups defined by tumor grade or stage."
Association of coffee drinking with total and cause-specific mortality (55) Free full text
The investigators in this 2012 reported study undertaken in the U.S. "examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health-AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded." "During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline." The researchers concluded, "In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality."
Coffee, but not caffeine, has positive effects on cognition and psychomotor behavior in aging (56)
This is another 2013-reported study similar to the one discussed directly above. This was an animal study reported by the United States Department of Agriculture-ARS, Human Nutrition Research Center on Aging at Tufts University. The researchers interpreted the result of their study as follows: "...the effects of caffeine alone did not account for the performance improvements, showing that the neuroprotective benefits of coffee are not due to caffeine alone, but rather to other bioactive compounds in coffee. Therefore, coffee, in achievable amounts, may reduce both motor and cognitive deficits in aging."
Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains (57)
This 2011-reported study investigated "the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains." "The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive function." [Health-e-Iron note: the results and conclusions reached in this study and the study immediately below, both reported in Brazil, present plausible explanations of the important antioxidant protection afforded by constituent ingredients of the coffee bean]
Increase of the activity of phase II antioxidant enzymes in rats after a single dose of coffee (58)
This was a 2011-reported study from Brarzil. "This study evaluated the acute effect of the administration of coffee brew in the activity of phase II antioxidant enzymes in the hepatic tissue of rats. A single dose of this beverage increased the activity of the enzymes SOD, CAT, and GPx; the maximum increase occurred 1 h after administration (19.1, 22.1, and 25.1%, respectively). These changes were statistically significant (p < 0.05), the response was shown to be dose-dependent (p < 0.05), and the return to basal levels took >4 h from the intervention, suggesting a long-term effect. The total antioxidant capacity of the hepatic tissue also exhibited a peak 1 h after the intervention (6.5%), but the increase was not statistically significant and the response was not dose-dependent due to the low exposure to coffee." The researchers concluded, "These results indicate that coffee increases the activities of antioxidant enzymes, improving protection against oxidative stress."
Effects of Green Tea Supplementation on Elements, Total Antioxidants, Lipids, and Glucose Values in the Serum of Obese Patients (59) Free full text
This 2012 reported study from Poland first noted that, "There have been some studies on the influence of green tea on the mineral status of obese subjects, but they have not yielded conclusive results." "The aim of the present study is to examine the effects of green tea extract on the mineral, body mass, lipid profile, glucose, and antioxidant status of obese patients." "Forty-six obese patients were randomly assigned to receive either 379 mg of green tea extract, or a placebo, daily for 3 months. At baseline, and after 3 months of treatment, the anthropometric parameters, blood pressure, and total antioxidant status were assessed, as were the levels of plasma lipids, glucose, calcium, magnesium, iron, zinc, and copper. We found that 3 months of green tea extract supplementation resulted in decreases in body mass index, waist circumference, and levels of total cholesterol, low-density cholesterol, and triglyceride. Increases in total antioxidant level and in zinc concentration in serum were also observed. Glucose and iron levels were lower in the green tea extract group than in the control, although HDL-cholesterol and magnesium were higher in the green tea extract group than in the placebo group." The researchers concluded, "The present findings demonstrate that green tea influences the body's mineral status. Moreover, the results of this study confirm the beneficial effects of green tea extract supplementation on body mass index, lipid profile, and total antioxidant status in patients with obesity." [Health-e-Iron note: in the full text article, the researchers noted that green tea reduced iron status among the participants. Apparently only serum iron was tested and not other serum measures such as ferritin. Serum iron is not a valid measure of iron stores and without such a measurement it would have been difficult to assess the adequacy of iron stores.]
Epidemiologic Evidence of a Relationship between Tea, Coffee, or Caffeine Consumption and Cognitive Decline (60)
This was a 2013-reported review from UCLA Medical School. "A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men."
Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes (61) Free full text
This is a 2012 lab animal study that was reported in Singapore. Chlorogenic acid is the second most common constituent on coffee, behind only caffeine. The investigators describe their findings as demonstrating for the fist time that chlorogenic acid stimulates glucose transfer and "it appears that CGA (Chlorogenic acid) may contribute to the beneficial effects of coffee on Type 2 diabetes mellitus. [Health-e-Iron note: Chlorogenic acid is described in paper # 23 above as "a potent inhibitor of nonheme iron absorption." Therefore, this single food constituent might have two independent protective functions that can each assist in the preventive diabetes incidence and its progression. An an article on the natural antioxidant and iron chelation properties of chlorogenic acid follows:]
Iron Chelation by Chlorogenic Acid as a Natural Antioxidant (62) Free full text
This was a 1998 lab study reported in Japan. "Chlorogenic acid, a dietary antioxidant, effectively inhibited the iron-induced lipid peroxidation of bovine liver microsomes in a concentration-dependent manner. In the Fenton-type reaction, chlorogenic acid inhibited the production of the hydroxyl radical by iron-EDTA or iron-ADP, while iron plus chlorogenic acid did not generate the hydroxyl radical. The formation of an iron complex with chlorogenic acid was demonstrated by UV/vis absorbance spectroscopic, ESR and 1H-NMR studies. The ferric complex with chlorogenic acid was in the ferric high-spin state near rhombicity, and had no radical scavenging activity." The authors concluded, "the results indicate that chlorogenic acid prevented the formation of the hydroxyl radical by forming a chelate with iron whose complex cannot catalyze the Fenton-type reaction."
A role for ferritin in the antioxidant system in coffee cell cultures (63) Free full text
[Health-e-Iron note: we included this laboratory study on the role of iron toxicity in coffee plants to demonstrate how plants synthesize ferritin to sequester potentially toxic iron accumulation during cell growth. The process described as the plant's system to protect itself from excessive oxygen stress is virtually identical to the process described for animals, including of course, humans. Several investigators report findings that suggest the protective antioxidants obtained from consuming coffee and other plant constituents are obtained directly from the plant's own protective biochemical stores.]
This 2011-reported study was conducted in Brazil. The investigators noted that, "Iron(Fe) is an essential nutrient for plants, but it can generate oxidative stress at high concentrations. In this study, Coffea arabica L. cell suspension cultures were exposed to excess Fe (60 and 240μM) to investigate changes in the gene expression of ferritin and antioxidant enzymes. Iron content accumulated during cell growth, and Western blot analysis showed an increase of ferritin in cells treated with Fe." "The increase in ferritin gene expression was accompanied by an increase in the activity of antioxidant enzymes. Superoxide dismutase, guaiacol peroxidase, catalase, and glutathione reductase activities increased in cells grown in the presence of excess Fe, especially at 60μM, while the activity of glutathione S-transferase decreased. These data suggest that Fe induces oxidative stress in coffee cell suspension cultures and that ferritin participates in the antioxidant system to protect cells against oxidative damage." The researchers concluded, "Thus, cellular Fe concentrations must be finely regulated to avoid cellular damage most likely caused by increased oxidative stress induced by Fe. ..."
Consumption of green tea favorably affects oxidative stress markers in weight-trained men (64) Free full text
This Brazilian study was reported in 2008. "This study investigated the effects of the consumption of green tea (GT) for 7 d on biomarkers of oxidative stress in young men undergoing resistance exercise." "In the control group, exercise did not affect the values of LH, thiobarbituric acid–reactive substances, and FRAP, although it did reduce the levels of GSH (P < 0.05)." "Green tea reduced the postexercise concentration of LH and increased the values of total polyphenols, GSH, and FRAP." The researchers concluded, "Consumption of GT, a beverage rich in polyphenols, may offer protection against the oxidative damage caused by exercise, and dietary guidance for sports participants should be emphasized."
Effect of green tea on iron status and oxidative stress in iron-loaded rats (65)
This is a 2008 green tea study from Thailand. "Plasma non-transferrin bound iron (NTBI) is potentially toxic and contributes to the generation of reactive oxygen species (ROS), consequently leading to tissue damage and organ dysfunction. Iron chelators and antioxidants are used for treatment of thalassemia patients. Green tea (GT) contains catechins derivatives that have many biological activities. The purpose of this study was to investigate the iron-chelating and free-radical scavenging capacities of green tea extract in vivo. Blood was collected monthly for measurement of iron overload and oxidative stress indicators. Levels of PI, TIBC, NTBI and MDA, and erythrocyte ROS increased in the iron-loaded rats. Intervention with GT extract markedly decreased the PI and TIBC concentrations. It also lowered the transferrin saturation and effectively inhibited formation of NTBI. It also decreased the levels of erythrocyte ROS in week 4, 12 and 16. Therefore, green tea extract can decrease iron in plasma as well as eliminate lipid peroxidation in plasma, and destroy formation of erythrocyte ROS in the rats challenged with iron. The bifunctional effects could be beneficial in alleviating the iron and oxidative stress toxicity. In prospective, these GTE activities should be further examined in thalassemic animals or humans."
Coffee Improves Insulin-Stimulated Akt Phosphorylation in Liver and Skeletal Muscle in Diabetic KK-Ay Mice (66) Free full text
The investigators of this 2013-reported mouse-model study noted, "coffee has an anti-diabetic effect, specifically the amelioration of both hyperglycemia and insulin resistance, in KK-Ay mice, a type 2 diabetes animal model." The investigators investigated "coffee's effect on insulin signaling in liver, skeletal muscle, and adipose tissue (epididymal fat)..." "Coffee ingestion ameliorated the development of hyperglycemia but did not affect insulin signaling in liver or skeletal muscle under such conditions." "In Expt. 2, ..."The levels of tyrosine phosphorylation of insulin receptor in response to insulin injection in insulin-sensitive tissues were not different between mice that drank water and those that drank coffee." Coffee ingestion significantly increased the insulin-induced serine phosphorylation of Akt in liver and skeletal muscle, but not in epididymal fat, of KK-Ay mice. The investigators concluded, "Our results also indicated that coffee ingestion may contribute to the improvement of insulin resistance and hyperglycemia in KK-Ay mice via the activation of Akt in insulin signaling in liver and skeletal muscle."
Dose- and Gender-dependent Interactions between Coffee Consumption and Serum GGT Activity in Alcohol Consumers (67)
This is a 2013-reported study from Finland. "Coffee consumption has been recently linked with decreased blood gamma-glutamyltransferase (GGT) activities and protection from alcoholic liver disease. To explore the relationship and dose response, we assessed the impacts of coffee and alcohol intake on serum GGT activity in apparently healthy men and women with varying levels of coffee and alcohol consumption. Data on coffee, alcohol consumption and serum GGT activities were collected from 18,899 individuals (8807 men and 10,092 women), mean age 48 years, range 25-74 years, who participated in a large national cross-sectional health survey. Body mass index, smoking index and age were used as covariates in all analyses. Among the study population, 89.8% reported varying levels of coffee consumption; 6.9% were abstainers from alcohol, 86.1% moderate drinkers, 3.7% heavy drinkers and 3.3% former drinkers. In men, the elevation of GGT induced by heavy drinking (>280 g/week) was found to be significantly reduced by coffee consumption exceeding 4 cups per day. A similar trend was also observed among women, which however, did not reach statistical significance. The research team concluded, "Coffee modulates the effect of ethanol on serum GGT activities in a dose- and gender-dependent manner. These observations should be implicated in studies on the possible hepatoprotective effects of coffee in alcohol consumers."
Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study (68) Free full text
This was a 2012-reported study undertaken in Korea. "The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs (liver function tests) in Korean health-check examinees." "We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits." "Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking." The researchers concluded, "Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted."