Tea flavonoids: bioavailability in vivo and effects on cell signaling pathways in vitro

The elucidation of the potential health benefits of tea beverage continues to be a focus of research in many laboratories. Beneficial effects of tea have been particularly evident in animal tumorigenesis models, with green and black tea frequently demonstrating similar effectivity. Human data are now emerging to support a beneficial role for tea in cardiovascular disease, but the data with respect to cancer risk at various sites remain inconclusive. The constituent flavonoids of green and black tea beverage are known to be potent antioxidants, and although this may be a major factor in explaining their biological activity, it appears that the gallated flavonoids in particular (e.g., epigallocatechin gallate and the gallated theaflavins) impact on a wide range of molecular targets that influence cell growth and more specifically pathways such as those involving angiogenesis. Data on the pharmacokinetic properties of tea flavonoids, primarily on the catechins and therefore related most closely to green tea, have provided indications of the plasma levels and circulating molecular forms that may be expected in humans following tea consumption. The structural complexity of black tea flavonoids, in particular the thearubigins, has hindered efforts to describe their bioavailability and to perform mechanistic studies. Recent studies on the effects of catechins and theaflavins on growth factor-, nuclear factor-kappaB-, and stress-mediated signal transductions are described in this review, where possible in relation to their bioavailability in vivo. These studies indicate that effects that may be relevant to both cancer and atherosclerosis are often observed at tea flavonoid levels that could realistically be encountered in vivo. However, more studies need to be performed using those molecular forms of tea flavonoids (methylated, sulfated, and glucuronidated conjugates) that are the major circulating species encountered following tea consumption. Such studies, combined with further human epidemiological and interventional data, should ultimately elucidate the full beneficial potential of tea beverage on human health.     

The role of caffeinated beverages in dental fluorosis

Recent studies have demonstrated that the incidence of dental fluorosis has increased during the past decade. Greater availability and use of fluoride-containing gels, mouth rinses, dentifrices, etc., improper prescribing of fluoride supplements and ingestion of fluoride dentifrice by some children are some of the suggested determinants of dental fluorosis. However, based on the increase in consumption of tea, coffee, and other caffeine-containing beverages by the children, and the augmentative effect of caffeine on fluoride bioavailability, we theorize that the rise in incidence of dental fluorosis in North America is mainly due to the replacement of water intake by caffeine-containing beverages among the young population.     

The impact of coffee on health

Objective

Coffee is a beverage used worldwide. It includes a wide array of components that can have potential implication on health. We have reviewed publications on the impact of coffee on a series of health outcomes.

Methods

Articles published between January 1990 and December 2012 were selected after crossing coffee or caffeine with a list of keywords representative of the most relevant health areas potentially affected by coffee intake.

Results

Caffeine, chlorogenic acids and diterpenes are important components of coffee. Tolerance often acts as a modulator of the biological actions of coffee. There is a significant impact of coffee on the cardiovascular system, and on the metabolism of carbohydrates and lipids. Contrary to previous beliefs, the various forms of arterial cardiovascular disease, arrhythmia or heart insufficiency seem unaffected by coffee intake. Coffee is associated with a reduction in the incidence of diabetes and liver disease. Protection seems to exist also for Parkinson's disease among the neurological disorders, while its potential as an osteoporosis risk factor is under debate. Its effect on cancer risk depends on the tissue concerned, although it appears to favor risk reduction. Coffee consumption seems to reduce mortality.

Conclusion

The information gathered in recent years has generated a new concept of coffee, one which does not match the common belief that coffee is mostly harmful. This view is further supported by the discovery of a series of phyto-components with a beneficial profile. Reasonable optimism needs to be tempered, however, by the insufficiency of the clinical data, which in most cases stem from observational studies.     

The shifting beverage landscape

STOREY, M.L. The shifting beverage landscape. PHYSIOL BEHAV, 2010. — Simultaneous lifestyle changes have occurred in the last few decades, creating an imbalance in energy intake and energy expenditure that has led to overweight and obesity. Trends in the food supply show that total daily calories available per capita increased 28% since 1970. Total energy intake among men and women has also increased dramatically since that time.Some have suggested that intake of beverages has had a disproportional impact on obesity. Data collected by the Beverage Marketing Corporation between 1988-2008 demonstrate that, in reality, fewer calories per ounce are being produced by the beverage industry. Moreover, data from the National Cancer Institute show that soft drink intake represents 5.5% of daily calories. Data from NHANES 1999-2003 vs. 2003-06 may demonstrate a shift in beverage consumption for age/gender groups, ages 6 to > 60 years.The beverages provided in schools have significantly changed since 2006 when the beverage industry implemented School Beverage Guidelines. This voluntary action has removed full-calorie soft drinks from participating schools across the country. This shift to lower-calorie and smaller-portion beverages in school has led to a significant decrease in total beverage calories in schools.These data support the concept that to prevent and treat obesity, public health efforts should focus on energy balance and that a narrow focus on sweetened beverages is unlikely to have any meaningful impact on this complex problem.     

Genotoxicity of instant coffee and of some phenolic compounds present in coffee upon nitrosation

Instant coffee exhibits genotoxic activity upon nitrosation at acidic pH values in the Ames tester strain TA100. Using adsorption chromatography (Amberlit XAD-2) it was observed that the major fraction of molecules responsible for the genotoxic activity upon nitrosation was not retained on this resin, suggesting that the polar molecules present in instant coffee could be responsible for the genotoxicity observed upon nitrosation. Some phenolic molecules present in instant coffee (catechol, caffeic acid, and chlorogenic acid) were also genotoxic upon nitrosation under the same experimental conditions. The concentrations of nitrosatable phenolic compounds in the studied coffee were determined by HPLC and their contributions to the total genotoxicity observed were studied. The results obtained suggest that besides phenolic compounds other molecules were also involved in the genotoxicity of this beverage upon nitrosation. Teratogenesis Carcinog. Mutagen. 20:241-249, 2000.     

Antioxidant capacity of some plant foods and beverages consumed in the Eastern Region of Nigeria

Today plant foods and beverages are receiving more scientific attention because of their potential to curb the effect of free radicals in the human system. The present study reports on the antioxidant potentials of some plants foods and beverages consumed in the Eastern Region of Nigeria. The study made use of the ferric reducing antioxidant power, phenolic and the flavonoid contents assays to assess the quality of the antioxidant potentials of the plant foods and beverages. Of the different classes of foods analyzed the following showed high antioxidant potentials: coffee for beverages, star apple for fruits, thyme for vegetable and spices, and raices for alcoholic beverages. Generally the vegetables and spices registered the highest antioxidant properties. The results obtained in this study could help consumers' choice based on the antioxidant capacity of the samples analyzed.     

Cancer mortality correlation studies. II. Regional associations of mortalities with the consumptions of foods and other commodities

The age-corrected mortalities from cancer at 17 sites were correlated with the consumptions of 12 major food items and the apparent consumptions of alcoholic beverages, cigarettes, beer, coffee, tea and solid fuel, in different countries. Significant direct and inverse correlations with food consumption variables were observed: the results are in essential accord with those of other workers employing different methods of statistical analysis. A modification of the diet in western industrialized nations is proposed as a means of lowering the human cancer risk. For cancers of the mouth and neck, and for liver in males, significant associations with the wine alcohol consumption were observed. Statistical evidence for liver cirrhosis as liver-cancer, and for stomach ulcer as stomach-cancer-predisposing conditions was obtained.     

Effect of temperature and expectations on liking for beverages

Three experiments investigated the influence of expectation on liking ratings of beverages at different temperatures. The first confirmed the general belief that people like certain beverages at certain familiar temperatures and dislike them at others. In the second experiment, subjects tasted and rated how much they liked four beverages (chicken bouillon, red wine, fruit punch and water) at three different temperatures (hot, room temperature, and cold) with their eyes closed (beverages not identified by the experimenter) and with their eyes open (beverages identified by the experimenter). They then rated how much they thought they would like these same beverages plus a number of new beverages at the three temperatures. Subjects rated the tastes of the beverages at unfamiliar temperatures (e.g., cold bouillon) when tasting them better than they thought they would. However, even after a few opportunities to taste a beverage at an unfamiliar temperature, expectations about its taste did not change. Experiment 3 successfully altered liking ratings of beverages by changing expectations concerning the temperature at which an unfamiliar beverage is typically consumed. The results argue for an important role for culture-based expectations in determining preferred temperatures for foods.     

Mutagenicity screening of foods I. Results with beverages

Following a number of recent reports on the presence of mutagens in certain foods, a general survey of the mutagenic potential of a wide variety of food products has been initiated. Here, results for samples of 28 widely consumed beverages from 13 general categories are reported. Each sample was concentrated and fractionated by polarity and solubility to give up to seven fractions, each of which was assayed for mutagenic potential with Salmonella typhimurium TA98 and TA100 ± fortified liver homogenate. Fractions showing evidence of either mutagenicity or toxicity were retested at the same and lower concentrations. The utility of the fractionation procedure and the sensitivity of the screening strategy were established by assaying six beverages spiked with known mutagens prior to fractionation. Statistical analysis of the data resulted in positive findings for seven beverages, although confirmation of these results through analysis of a second sample was obtained only for red wine, grape juice, and instant coffee. The remaining 21 beverages showed no strong evidence of mutagenic activity. For those foods for which the variation among replicate plates was largest, the false-positive rate for the two-stage screening procedure employed was estimated to be less than 1% while the false-negative rate for a beverage inducing a threefold increase in the background mutation rate was conservatively estimated to be limited to 14%.     

Antioxidants of the beverage tea in promotion of human health

Tea that contains many antioxidants is a pleasant and safe drink that is enjoyed by people across the globe. Tea leaves are manufactured as black, green, or oolong. Black tea represents approximately 78% of total consumed tea in the world, whereas green tea accounts for approximately 20% of tea consumed. The concept of "use of tea for promotion of human health and prevention and cure of diseases" has become a subject of intense research in the last decade. Diseases for which tea drinkers appear to have lower risk are simple infections, like bacterial and viral, to chronic debilitating diseases, including cancer, coronary heart disease, stroke, and osteoporosis. Initial work on green tea suggested that it possesses human health-promoting effects. In recent years, the research efforts have been expanded to black tea as well. Research conducted in recent years reveals that both black and green tea have very similar beneficial attributes in lowering the risk of many human diseases, including several types of cancer and heart diseases. For cancer prevention, evidence is so overwhelming that the Chemoprevention Branch of the National Cancer Institute has initiated a plan for developing tea compounds as cancer-chemopreventive agents in human trials. Thus, modern medical research is confirming the ancient wisdom that therapy of many diseases may reside in an inexpensive beverage in a "teapot."     

Effects of coffee on cardiovascular responses to stress: a 14-week controlled trial.

We studied the cardiovascular responses to orthostatic and mental stress of 43 healthy subjects who daily received six cups of boiled or filtered coffee and of 21 healthy subjects who abstained from caffeine-containing beverages. All 64 subjects first received six cups of filtered coffee/day for 2 weeks. Then blood pressure (BP) and heart rate (HR) were recorded before, during, and after a "stand upright" test and a mental arithmetic test. Subjects were then randomized to either complete abstinence from caffeine-containing beverages (n = 21), or consumption of six cups of filtered coffee (n = 21), or consumption of six cups of boiled coffee/day (n = 22). The stress tests were repeated after subjects had been on these regimens for 8 weeks. Abstinence from coffee did not affect the responses of BP or HR to orthostatic stress, or the response of BP to mental stress. The increase in HR caused by mental stress was five beats/min less (p = 0.02) in the no-coffee group than in the filtered- (95% confidence interval -8.8 to -1.2) or boiled- (95% confidence interval -8.4 to -0.8) coffee group. It is concluded that elimination of caffeine decreases the HR response to mental stress.     

Anti-cariogenic properties of tea (Camellia sinensis)

Various components in green and black tea, the beverages made by infusing appropriately processed dried leaves of Camellia sinensis, notably simple catechins, have properties in vitro that suggest an anti-cariogenic activity. These include: a direct bactericidal effect against Streptococcus mutans and S. sobrinus; prevention of bacterial adherence to teeth; inhibition of glucosyl transferase, thus limiting the biosynthesis of sticky glucan; inhibition of human and bacterial amylases. Studies in animal models show that these in-vitro effects can translate into caries prevention. A limited number of clinical trials in man suggest that regular tea drinking may reduce the incidence and severity of caries. If substantiated, this could offer a very economical public health intervention.     

Making the connection between diet and nutrition and cardiovascular and Alzheimer's diseases

Houston, we have a problem, and it involves the Apo E gene as it relates to heart disease, Alzheimer’s disease, and the environment that goes with an individual’s particular set of Apo E genes. This means the Apo E gene requires a gene-supportive environment in the form of the food chemistry of every meal, every day. Does the dietary environment of the individual matter to support cardiovascular health and neurovascular health? The answer seems to be a solid yes.And we also now know that the technological remedies of allopathic medicine don’t always get the job done. Integrative medicine brings a new paradigm of thinking that looks at all options for disease management and prevention. The new integrative medicine provider embraces all the clinical tools we have at our disposal to give a greater advantage to the patient.In addition, it’s important to utilize the cultural/traditional whole food diets we now realize are optimal for human health. We need to closely reexamine and place greater emphasis on the powerful role of the person’s environment by utilizing not just external food sources, but also examining their established internal feeding system based on their unique body composition. A person’s current body composition is likely very poor if the wrong nutritional input for their individual genetic expression has been chosen.Returning to the question I wondered about almost 30 years ago—as I walked slowly back across the famous square at St Bartholomew’s, stopping once again to check the ice in the fountain—I pondered the question even further: do people’s diets cause these horrible diseases? I am now asking the question again, and with some true clarity can say nutrition and diet are strongly connected. Are they the only cause? No, we don’t have the full picture yet, but I think we can say that diet is a powerful contributing factor.Once the medical field has a clearer understanding and acceptance of diet as a powerful tool, not just for prevention but also as a powerful treatment option, we will begin to change disease patterns by leaps and bounds. The climate is now ready for a strong, simple answer. As with most epidemics, the best outcomes are from the simplest, most fundamental remedies—practical processes clinicians on the front lines can use, such as good nutrition.

Conclusions

I know I am not alone in this search for answers. Many of you are asking the same questions as I am. The goal is to work with what we know and provide what is safe for the individual. The individual has to eat. Guiding people to make better choices around diet and nutrition is the key to helping. Exploring why people consume the foods they consume can be helpful. For example, people like hot beverages in the morning, yet is it the coffee they like or is it the hot fluid, the pretty warm cup, and the time they give themselves to drink a warm, nurturing beverage? Changing from coffee to green tea is not too much of a shift, yet the health benefits can be enormous.Keeping an open mind to new science and treatment options regarding genes and diet, simple steps can be incorporated into current medical practices that can help in a big way. One interesting way to understand how powerful this is: try it for yourself. There is no substitute for personal experience.     

Anthocyanins and Human Health: An In Vitro Investigative Approach

Anthocyanin pigments and associated flavonoids havedemonstrated ability to protect against a myriad of humandiseases, yet they have been notoriously difficult to study withregard to human health. Anthocyanins frequently interact withother phytochemicals to potentiate biological effects,thus contributions from individual components are difficult todecipher. The complex, multicomponent structure of compounds ina bioactive mixture and the degradation of flavonoids duringharsh extraction procedures obscure the precise assignment ofbioactivity to individual pigments. Extensive metabolic breakdownafter ingestion complicates tracking of anthocyanins to assessabsorption, bioavailability, and accumulation in various organs.Anthocyanin pigments and other flavonoids that are uniformly,predictably produced in rigorously controlled plant cell culturesystems can be a great advantage for health and nutritionresearch because they are quickly, easily isolated, lackinterferences found in whole fruits, can be elicited to provokerapid and prolific accumulation, and are amenable to biolabelingso that metabolic fate can be investigated after ingestion.     

Ethical issues raised by incorporation of genetics into the National Birth Defects Prevention Study

Investigators involved in public health research must conduct high-quality studies that advance scientific knowledge for the collective benefit of the public's health, while at the same time ensuring that the individual rights of human subjects are protected. Successful completion of the Human Genome Project provides greater opportunity to incorporate the study of genetic factors into public health research. Integration of DNA specimen collection into epidemiological studies of complex disorders, such as birth defects, is necessary to identify genetic risk factors that affect susceptibility to potentially modifiable environmental risk factors, but collection of DNA samples often heightens concerns about ethical issues. Some of these issues include ensuring informed consent in an ongoing study as new genetic risk factors and novel genetic technologies for study continue to be identified, achieving a balance between improving participation using incentives and avoiding coercion, ensuring confidentiality of individual genetic data, and considering when and how to report research results to study participants. We present a discussion of ethical issues addressed by investigators of the National Birth Defects Prevention Study, a multisite, population-based, case-control study of risk factors for birth defects, which has incorporated the study of genetic risk factors. Study participants include infants and young children whose parents consent on their behalf, increasing the complexity of the ethical issues. Discussion of these issues and the methods employed to ensure protection of human subjects might be helpful to other investigators working to integrate genetics into large epidemiological studies.     

Fever from caffeine

Since childhood, a 53-year-old women had developed chills, high-grade fever, myalgia, and cephalea after the ingestion of coffee, tea, cola beverages, and some oral "antiflu" compounds. Skin prick tests performed with all the implicated substances were negative. Single-blind oral challenges with both caffeine and theophylline were positive, reproducing exactly the same clinical symptoms and fever. Oral challenge with pentoxifylline was negative. We report a case of caffeine-induced fever in which we have demonstrated cross-reactivity with theophylline, but not with pentoxifylline.     

Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota

Tea is rich in polyphenols and other phenolics that have been widely reported to have beneficial health effects. However, dietary polyphenols are not completely absorbed from the gastrointestinal tract and are metabolized by the gut microflora so that they and their metabolites may accumulate to exert physiological effects. In this study, we investigated the influence of the phenolic components of a tea extract and their aromatic metabolites upon bacterial growth. Fecal homogenates containing bacteria significantly catalyzed tea phenolics, including epicatechin, catechin, 3-O-methyl gallic acid, gallic acid and caffeic acid to generate aromatic metabolites dependent on bacterial species. Different strains of intestinal bacteria had varying degrees of growth sensitivity to tea phenolics and metabolites. Growth of certain pathogenic bacteria such as Clostridium perfringens, Clostridium difficile and Bacteroides spp. was significantly repressed by tea phenolics and their derivatives, while commensal anaerobes like Clostridium spp., Bifidobacterium spp. and probiotics such as Lactobacillus sp. were less severely affected. This indicates that tea phenolics exert significant effects on the intestinal environment by modulation of the intestinal bacterial population, probably by acting as metabolic prebiotics. Our observations provide further evidence for the importance of colonic bacteria in the metabolism, absorption and potential activity of phenolics in human health and disease. The bioactivity of different phenolics may play an important role in the maintenance of gastrointestinal health.     

The First Case of Erythritol-Induced Anaphylaxis in Korea

Erythritol is a natural sugar alcohol found in some fruits and fermented foods, which is used as a dietary sweetener because it has few calories. Here, we describe a 36-year-old woman who experienced anaphylaxis upon ingestion of an erythritol-containing drink. She presented to the emergency department with dyspnea and angioedema after drinking a peach-containing diet beverage. Her blood pressure dropped to 70/40 mmHg and the symptoms improved after administration of an antihistamine, glucocorticoid, and epinephrine. After 10 days, she drank another peach-containing diet beverage and experienced urticaria. No serum-specific immunoglobulin E findings were observed, including against peach components. A skin prick test (SPT) was performed using a peach, the two ingested diet beverages, and another peach-containing beverage. The SPT results for the peach and the peach-containing product were negative, but the wheal sizes for the two diet beverages were > 3 mm. The diet beverages contained erythritol as a food additive. The SPT result was positive for erythritol. The patient was diagnosed with anaphylaxis to erythritol and was instructed to avoid foods containing erythritol. She was prescribed a self-injectable epinephrine pen. To our knowledge, this is the first case of erythritol-induced anaphylaxis in Korea. Physicians should be aware of the possibility of allergic reactions to food additives, and additives should be evaluated to prevent the recurrence of symptoms.     

The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway

Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated by alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD in 50 individuals from eight families. The mutations cause changes (Ala to Val) in the N-terminal region of two MR-1 isoforms. The MR-1L isoform is specifically expressed in brain and is localized to the cell membrane while the MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress. Our results suggest a mechanism whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD. Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias.