Coffee (Coffea arabica)

Coffee Summary

Coffee is by far one of the most popular herbs on the planet. The stimulating, productivity-enhancing effects of the caffeine in coffee is loved by all and its unique flavor has lead to hundreds of different styles, varieties, and combinations of coffee beverages worldwide.

It’s the caffeine in coffee that’s responsible for many of its effects — as well as some of its negative side effects.

The key to using coffee as a health supplement, is to drink plenty of it. Seriously.

The body quickly develops a tolerance to the negative side effects of caffeine through down regulation of the adenosine receptors in the central nervous system. once this happens, the antioxidant, broncho-dilating, hypotensive, and neuroprotective effects of coffee can shine through.

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What Is Coffee Used For?

Coffee contains caffeine, which is a central nervous system stimulant.

Most of its uses stem from this effect — such as helping you stay awake and focused while up late cramming for a test or helping you wake up for that 8 am meeting.

The dried, roasted seeds are also rich in antioxidants — which offer protective effects to the kidneys, blood vessels, lungs, and brain.

Many of the alkaloids and phenolic compounds in coffee need to be proceed by the liver. In doing so, it’s used to stimulate both phase I and phase II liver detox pathways.

Long-term coffee consumption is also used to balance high blood pressure, high cholesterol, and diabetes.

Medicinal Uses of Coffee

• May relieve symptoms of altitude sickness

• Protects the brain from neurodegenerative disorders

• Can be used as a diuretic

• Stimulates liver activity

• Helps regulate blood pressure and blood sugar

• Maintains a feeling of wakefulness

Traditional Uses of Coffee

Coffee use dates back thousands of years in Ethiopia where it originated. It was initially restricted to the Arab world and was primarily grown in Yemen around the 15th century.

Sufi religious practices (related to Islam) promoted the popularity and spread of coffee at this time. This religious group used coffee as a way to encourage wakefulness and trance-like states in their ceremonies, which often lasted all night. [3].

After domestication, it became popular among the Arab world within about a century. By this time, its spread was due less by religious practices, and more by the new social concept of coffeehouses. These became (as they still are) a place for people to meet and socialize over coffee. During this time it was a practice exclusive to men. Women were socially excluded from all of these establishments. By the end of the 17th century, Cairo had become the central coffee market for the far east. [3].

Coffee was introduced to Europe through European travelers passing through Arab cities. This is quite different from many of the other traditional and medicinal plants introduced into Europe, which were mainly introduced through brutal colonial conquest instead. Upon introduction to European culture, it was reserved for therapeutic use, however over time people began to develop a taste for the beverage and coffee consumption took off with the general population and soon became commonplace in the home.

Coffee shops popped up all over Europe, as they adopted the Arab practice for themselves. [3].

Herb Details: Coffee

Herbal Actions:

• Anti-Alzheimer's
• Antioxidant
• Blood Glucose Regulator
• Bronchodilator
• Cardiotonic
• Diuretic
• Eugeroic
• Hepatoprotective
• Hypertensive (without tolerance)
• Hypotensive (with tolerance)
• Nootropic
• Vascular Tonic
• Vasoconsrictor (Without tolerance)
• Vasodilator (with tolerance)
• CNS Stimulant

Dose

• Water Extraction (1:12)
  2-6 cups of brewed coffee a day over a long period of time is best. Sporadic coffee consumption not recommended.
• View Dosage Chart

Part Used

Roasted seed, green seed, berries, leaves

Family Name

Rubiaceae

Distribution

Originated from Ethiopia, but is now cultivated across the tropics and subtropics. Brazil is currently the largest producer of Coffee in the world.

Constituents of Interest

• Caffeine
• 5-, 4-, and 3-O-caffeoyl quinic acid
• Trigonelline
• Caffeol (group)

Common Names

• Coffee
• Café
• Espresso
• Java
• Mocha
• Joe

CYP450

• Unkown

Quality

• Unknown

Pregnancy

• Unknown

Taste

• Unkown

Duration of Use

• Unknown

Botanical Information

Coffea arabica, is an evergreen Shrub, growing to about 5m tall. Leaves are opposite, large, elliptical, glossy, and dark green. The flowers are white, and produce a fragrance reminiscent of jasmine. The fruit is classified as a drupe, that is elliptical, and about 1.5cm long. They start green, and gradually ripen to a bright, or dark red color [2].

Coffee is a member of the Rubiaceae family of plants. This family contains about 15,500 species, and 611 genera, tho most notable of which include Coffee, and Cinchona.

C. arabica prefers tropical climates, with high amounts of rain, and little or no frost [2].

Habitat, Ecology, Distribution:

Indigenous to mountainous areas of Yemen, and Ethiopia, growing at altitudes of about 1400-1800m.

Cultivation and subsequent naturalization have occurred throughout the world including Indonesia, South America, Central America, The West Indies, and India [2].

The coffee belt, it the aptly named range of latitudes where coffee can be grown to produce high-quality coffees. This belt goes from 25 degrees north to 30 degrees south and covers many parts of central and South America, Africa, the Middle East, Indonesia, Australia, and Asia.

Harvesting, Collection, & Preparation:

Depending on where coffee is grown, the flavor profile will change, altitudes, humidity, soil conditions, and growing techniques will all influence flavor.

Generally, the best species to use for flavor is arabica, which is grown worldwide.

Each region tends to offer its own general characteristic. However, this can also vary quite a bit within the region.

Coffee takes about 3-4 years for the coffee plant to produce berries, after which yearly harvests generally take place. The berries ripen at different times throughout the plant, which makes harvesting a very long and intensive process where harvesters must pick the fruit by hand over a few weeks.

The processing of coffee generally consists of drying and roasting. Which is very similar to the other famous caffeine containing stimulants such as yerba maté, tea, and guarana. This process is suggested to reduce the bitter flavor, add a roasted flavor, prevent further oxidation of the polyphenols through destruction of the enzymes responsible, and free the caffeine and other xanthine alkaloids from the chlorogenic acids. In doing so, the constituents of the seeds change

Coffee in Medical Research

+ Alzheimer's Disease

Caffeine has been relatively well studied in its effects on the prevention of Alzheimer's disease. It has been found through murine animal testing to pass the blood-brain barrier and inhibit γ-secretase initiated cleavage of amyloid precursor protein, which is considered a key process in accumulation of aggregated plaques of Aβ in the brain [5]. Alzheimer's is characterized by a buildup of beta-amyloid deposits which build up over time and lead to the eventual death of the synapse. Several cohort and case studies have suggested a clear relationship between regular coffee consumption and a lower incidence of Alzheimer's [9]. More recent studies have suggested a significantly higher activity in roasted coffee when compared to pure caffeine [10]. This suggests a synergy between other components of coffee in regards to the prevention of cognitive decline and Alzheimer's. This synergy has also been found when investigating neuro-inflammation in mice. It was discovered that caffeine combined with polyphenols had a much stronger effect in reducing and preventing neuro-inflammation than the pure alkaloid [11].

+ Diabetes

Diabetes is the 4th leading cause of death in industrialized countries and affects roughly 177 million people worldwide resulting in about 4 million deaths per year. This number is expected to double by 2025 if current trends continue. [40, 41].

There have been hundreds of studies within the past 20 years on coffee in relation to diabetes, with most of them occurring in the past 10 years. The overwhelming majority of these studies have indicated that regular, moderate consumption of coffee reduces the risk of type 2 diabetes. These effects are noted to be independent of race, gender, and ethnicity, and geographic distribution. In fact, these studies were conducted all over the world with many different ethnic backgrounds and geographical distributions. [42].

More specifically, regular, moderate coffee consumption has been shown to produce a lower prevalence of impaired glucose tolerance, hyperglycemia (fasting and after glucose load), hyperinsulinemia, and insulin sensitivity [43-46]. It has been found to have a positive association with adiponectin as well, which is a hormone that regulates the catabolism of glucose and insulin sensitivity. This hormone is reduced in diabetics and thus is considered a protective agent against diabetes. [47-49]. Other factors that may be at play with the mechanism of action of coffee is through thermogenic effects of caffeine (increase in energy expenditure and metabolism), [50,51], and increases satiety (feeling of being full) [52,53].

The alkaloid trigonelline, which can be found in relatively high amounts in green (unroasted) coffee beans, and in smaller amounts in roasted coffee beans, is also found in the herb Trigonella foenum-graecum. This herb is a traditional medicine that has commonly been used to treat diabetes and contains substantial amounts of this trigonelline alkaloid. This same alkaloid, extracted from pumpkin seeds, has been found to produce anti-diabetic actions in mice but has not had any testing done in this regard on humans [5]. It is possible, that this alkaloid is at least partly responsible for the preventative effects on type 2 diabetes, although clearly more research is needed in this area.

+ Hypertension

Short term effects of the caffeine contained within coffee actually cause an increase in blood pressure, however, once tolerance is established, and modulation to the adenosine receptors is established, regular coffee consumption actually offers antihypertensive effects instead. Aside from many of the effects noted in the following section n cardiovascular effects, coffee contains compounds other than caffeine that offer blood pressure control such as flavonoids, melanoidins, magnesium, and potassium [33].

+ Antioxidant

Coffee is an extremely rich source of antioxidants. It contains a good supply of phenolic compounds (200 mg - 550mg/cup). The main phenolic compound in coffee is chlorogenic acid [39], and melanoidins [58, 59]. Caffeine has also shown a mild antioxidant effect [58, 59]. In a few different studies, brewed coffee has shown significant antioxidant capacity, and is noted to be highly bioavailable [60, 61].

+ Cardioprotective

In the past, coffee has been suggested to produce negative effects on the cardiovascular system. However more recent studies (past 5-10 years) it has actually been shown to produce the exact opposite, offering positive effects on the cardiovascular system in various ways. These earlier studies likely derived this suggestion through some of caffeine's short term effects, which includes an increase in blood pressure and increase in anxious feelings and jitteriness, which could easily be perceived as a negative side effect especially with the surge in high blood pressure over the past century. However, these effects are subject to a fast developing tolerance, whereby modulation of the adenosine pathway (from which these original changes occur), causes these effects to be negated.

Once tolerance is developed, the long term benefits of coffee far outweigh the short term adverse side effects.

There is an ever increasing number of recent studies that have demonstrated either a neutral or beneficial effect on cardiovascular health from the long term consumption of coffee [12-29].

Some of the beneficial effects caffeine and its metabolites has on the cardiovascular system is through their actions on adenosine inhibition. Through this action, these alkaloids have been found to improve renal function and enhance the effect of diuretics, both of which directly lowers blood pressure [32].

Chlorogenic acid (another caffeine metabolite) are potent antioxidants as well and improve endothelial and vascular function through increased availability of nitric oxide [33]. These actions have a significant positive effect on the cardiovascular system, and likely play a role in the prevention of developing heart disease over the long term.

Decaffeinated coffee has not been found to deliver the same benefits to the cardiovascular system. However, this may be due to the lack of scientific research in this area, as most of the study on coffee is done on the caffeinated, roasted or raw coffee beans [33].

There has been suggested a U shape association with the safe, and beneficial consumption of coffee. People who drank very little or no coffee (less than 2 cups a day), or excessive amounts of coffee (over 10 cups a day) had a higher incidence of high blood pressure and cardiovascular disease than did medium-high coffee drinkers (3-6 cups a day). Therefore it is suggested that the safe and therapeutic dose with regards to cardiovascular disease is between 3-6 cups of coffee a day, over long periods.

+ Cognitive Effects

Coffee is well known as a cognitive enhancer. However, a recent study conducted on the effects of caffeine on cognitive performance [7] discovered surprisingly that caffeine does not offer any improvements in cognitive performance, but on the other hand harms cognitive performance if chronic consumption is stopped. They noted that the likely perceived benefit on cognitive performance from caffeine, and subsequently coffee, is through reduced sleepiness rather than increased alertness. It was found that people who consume caffeine in medium to high amounts had almost no difference in anxiety, mental alertness, and cognitive performance after consuming caffeine. Non or low caffeine users had an increase in anxiety and wakefulness, however also did not have a significant increase in cognitive performance in this study.

It appears that if coffee really does improve cognitive performance, it is not due to the caffeine content, and may in fact simply be a perceived cognitive improvement due to a mere reduction in sleepiness instead.

+ Hepatoprotective

One study found that with daily consumption of three or more cups of coffee, patients with HCV-related liver disease is associated with a significant (50%) reduction in oxidative damage indicators (8-OHdG). Oxidative DNA damage is closely correlated with DNA mutation and carcinogenesis. Therefore these results show a positive correlation between coffee consumption and a reduced risk for advanced liver damage [34-36].

In a different randomized study on patients with hepatitis C, found that by drinking 4 cups of coffee a day resulted in reduced collagen synthesis and oxidative DNA damage. This study also noted an increase in both telomere length and level of circulating markers for apoptosis. These are all markers for protective factors in liver disease. [34, 37, 38].

Both of these studies suggest a hepatoprotective effect in the progression of liver disease, especially liver cancer, and hepatitis, but also likely offers protective benefits in such conditions as fatty liver disease, and cirrhosis.

+ Hypertensive

Caffeine, once metabolized into paraxanthine, has been shown to act as an adenosine receptor agonist, which in turn leads to an increase in epinephrine, which is a powerful vasoconstrictor. This will lead to an increase in diastolic blood pressure. This mechanism is subject to tolerance, however, and has been noted that the acute hypertensive effects of caffeine stop occurring through consistent use of the herb. In fact, in one study, researchers noted that 100-200mg caffeine produces symptoms in non-caffeine users, with tolerance noticed in 1-4 days, and generally, moderate doses of caffeine (250-300mg) do not produce clinically significant cardiovascular alterations in people who consumed caffeinated beverages often [2]. This tolerance is suggested to be through changes in the adenosine signaling pathway after repeated exposure to caffeine to combat these effects [7].

+ Weight Loss

Paraxanthine is also held responsible for the lipolytic properties of caffeine. As paraxanthine levels rise in blood plasma, levels of free fatty acids rise with it [8]. Other studies have confirmed coffees ability to stimulate thermogenesis in humans as well [54], and coffee has also been shown to increase satiety [52,53], which in turn promotes smaller and less frequent meals. These effects were noted to be dependant on caffeine but were also significantly increased with the presence of chlorogenic acid [55-57].

+ Athletic Performance

Caffeine appears to be the agent responsible for the athletic performance enhancement effects of coffee, and despite the development of a tolerance for many of the effects of this chemical, it appears to maintain its ability to improve physical performance in both non and low caffeine consumers, as well as medium to high consumers [7].

The sodium ion pumps located throughout the body, are found primarily in nerve and muscle cells and are used to change the concentration gradients on the inside and outside of the cells to produce a charge. Paraxanthine acts as an enzymatic effector of Na+/K+ ATPase, effectively increasing this activity and thus lowering plasma K+, which is associated with skeletal muscle fatigue [8].

Paraxanthine was shown to produce dose-dependent increases in Ca2+ in skeletal muscle. This effect was transient and also associated with theophylline and theobromine. These effects were successfully reduced using a calcium channel blocker (procaine 10mM) [8].

+ CNS Stimulant

Coffee's stimulating effects are mainly due to the xanthine alkaloids present, particularly caffeine. This alkaloid works as an antagonist to the adenosine A1, and A2A receptors, which results in a variety of physiological and behavioral effects. Some of these effects include wakefulness, increased blood pressure, tremors, mildly anxiogenic, and enhances physical performance [7].

These effects are suggested to be subject to a tolerance; however, as with repeated exposure to caffeine, changes to the adenosine signaling pathway develop to oppose its effects. This explains some of the adverse side effects of caffeine withdrawal which includes lowered mental alertness. This is an area highly disputed; however and more research is needed to determine the exact mechanism of action involved with caffeine tolerance [7].

Phytochemistry

Caffeinated coffee is an incredibly complex beverage, containing well over 1000 components. The most important is suggested to be caffeine, diterpene alcohols, and chlorogenic acids. [30, 31].

+ Xanthine Alkaloids

The major xanthine alkaloid found in Coffea spp. (seeds) is caffeine, but also contains theobroma, and theophylline in varying amounts depending on the species [2]. One species however Coffea liberica, is different in that its major xanthine alkaloid is theacrine, liberine [2]. The leaves are suggested to include even more caffeine than the seeds and are sometimes consumed as a tea [1].

The most commonly consumed species, however, Coffea arabica, which contains about 0.4-2.5% caffeine in its seeds [2, 62]. Coffea spp. is considered to contain about 3.5% tannin, and 1.25% trigonelline as well (supposedly contained at similar levels as caffeine but unstable and degrades during heating, into pyridines that also provide coffee flavor). While the coffee seeds are being roasted, the caffeine is liberated from the inactive combination with chlorogenic acid. The signature aroma of coffee is due to the caffeol (50% furfurol, traces of valerianic acid, phenol, and pyridine). Herbalist Terry Willard suggests this is what causes unwanted hangover from coffee.

Caffeine is synthesized in plants as a method of chemical defense in the plant and often builds up in the seeds, leaf edges, and sometimes in the stems depending on the species [63]. It can be found in 13 orders of the plant kingdom. Some other well-known plants containing this chemical includes the tea plant (Camellia sinensis), guarana (Paullinia cupana), and yerba maté (Ilex paraguariensis). Caffeine is considered a xanthine alkaloid, which begins as xanthosine, and is converted in the plant to 7-methylxanthine, and subsequently theobromine. This chemical is very similar to caffeine and is contained in high amounts in other stimulating plants such as cacao theobroma. In the coffee plant, this theobromine undergoes another conversion to become caffeine. [2]. The molecule itself is highly soluble in solvents such as chloroform, but only slightly soluble in water and ethanol [2].

+ Chlorogenic Acids

Green coffee seeds are very rich in chlorogenic acids (6-10% dry weight) and contain the largest variety (72), plus 3 separate cinnamic acids [64]. This chemical is found in much higher amounts in green coffee beans than roasted coffee. This chemical supposedly bonds to caffeine making it inactive, and upon heating these chemicals are released, and thus the caffeine becomes active. It is considered a phenol, specifically, an ester formed between caffeic-acid and L-quinic acid. It is also suggested to have mild hypotensive effects. [64].

+ Polyphenols

Green unprocessed coffee beans contain a rich source of polyphenols (especially 5-, 4-, and 3-O-caffeoylquinic acid), as well as the alkaloids trigonelline and caffeine. Upon roasting, chlorogenic acids undergo significant degradation which results in a new set of products including caffeoyl quinides, caffeic acid, and catechol. Trigonelline degradation breaks down into N-methyl-pyridinium and niacin but still remains in fairly high amounts in even highly roasted espresso coffee beans (~5.3mg/g). Trigonelline and N-methylpyridinium are readily absorbed after coffee consumption and reach peak plasma levels after 2.5 and 1 hours respectively. Caffeine is fairly heat stable and remains mostly intact upon heating. [5].

+ Caffeic Acid

Caffeic acid is also found in coffee but only in modest amounts (0.03mg per 100 ml). It can be found in a wide range of other botanicals. Despite the similarity in its name, caffeic acid is unrelated to caffeine. It possesses its own range of medicinal effects including antioxidant, immunomodulatory, anti-inflammatory, anticarcinogenic (controversial).

Caffeol is an umbrella term for the aromatic constituents of coffee, that gives it the signature aroma. Caffeol is made up of many constituents (roughly 850 different volatiles constituents), most of which are formed during the heating (roasting) process. Consists mainly of furfuryl alcohol. It is formed from the degradation of sugars, and pyrolysis of wood fibers.

Coffee contains Oil, wax, caffeine, aromatic oil, tannic acid, caffeotannic acid, gum, sugar, protein. [1].

Synergy

Tynanthus panurensis A 200µg/ml dose of T. panurensis extract was shown to inhibit uo to 40% of uric acid production, possibly prolonging the effects of caffeine and its derivatives. (Source).

Author

Justin Cooke, BHSc

The Sunlight Experiment

(Updated November 2018)

Recent Blog Posts:

References:

1. A modern herbal. (n.d.). Coffee. Retrieved from https://www.botanical.com/botanical/mgmh/c/coffee82.html

2. Barceloux, D. G. (2012). Medical Toxicology of Drugs Abuse : Synthesized Chemicals and Psychoactive Plants. Somerset, NJ, USA: John Wiley & Sons. Retrieved from http://www.ebrary.com

3. Jamieson, R. W. (2001). The Essence of Commodification: Caffeine Dependencies in the Early Modern World. Journal of Social History, 35(2), 269-294. doi:10.1353/jsh.2001.0125

4. Kazuhiro Ito, Sam Lim, Gaetano Caramori, Borja Cosio, K. Fan Chung, Ian M. Adcock, and Peter J. Barnes. (2002). A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. PNAS. Vol 99. No. 13. 8921-8926

5. Lang, R., Dieminger, N., Beusch, A., Lee, Y., Dunkel, A., Suess, B., … Hofmann, T. (2013). Bioappearance and pharmacokinetics of bioactives upon coffee consumption. Anal Bioanal Chem, 405(26), 8487-8503. doi:10.1007/s00216-013-7288-0

6. O'Brien, T. G. (2003). CONSERVATION: Caffeine and Conservation. Science, 300(5619), 587-587. doi:10.1126/science.1082328

7. Rogers, P. J., Heatherley, S. V., Mullings, E. L., & Smith, J. E. (2012). Faster but not smarter: effects of caffeine and caffeine withdrawal on alertness and performance.

8. T.J. Hawke, D.G. Allen. M.I. Lindinger. (2000). Paraxanthine, a caffeine metabolite, dose dependently increases [Ca2+]i in skeletal muscle. Journal of Applied Physiology. Vol 89. 2312-2317.

9. Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N (2010) Caffeine intake and dementia: systematic review and meta-analysis. J Alzheimer’s Dis 20:S187–S204

10. Cao C, Wang L, Lin X, Mamcarz M, Zhang C, Bai G, Nong J, Sussman S, Arendash G (2011) Caffeine synergizes with another coffee component to increase plasma GCSF: Linkage to cognitive benefits in Alzheimer’s Mice. J Alzheimer’s Disease 25:323–335

11. Chu YF, Chang WH, Black RM, Liu JR, Sompol P, Chen Y, Wei H, Zhao Q, Cheng IH (2012) Crude caffeine reduces memory impair- ment and amyloid β1-42 levels in an Alzheimer’s mouse model. Food Chem 135:2095–2102

12. Guessous I, Pruijm M, Ponte B, Ackerman D, Ehret G, Ansermot N, Vuistiner P, Staessen J, Gu Y, Paccaud F, Mohaupt M, Vogt B, Pechere-Berstcthi A, Marti PY, Burnier M, Eao CB, Bochud M. Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions. Hypertension 2015;65: 691e696.

13. Rebello SA, van Dam RM. Coffee consumption and cardiovascular health: getting to the heart of the matter. Curr Cardiol Rep 2013;15: 403.

14. O’Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ. Effects of habitual coffee consumption and cardiometabolic disease, cardiovascular health, and all-cause mortality. J Am Coll Cardiol 2013;62:1043e1051.

15. Steffen M, Kuhle C, Hensrud D, Erwin PJ, Murad MH. The effect of coffee consumption on blood pressure and the development of hyper- tension: a systematic review and meta-analysis. J Hypertens 2012;30: 2245e2254.

16. Zhang Z, Hu G, Caballero B, Appel L, Chen L. Habitual coffee con- sumption and risk of hypertension: a systematic review and meta- analysis of prospective observational studies. Am J Clin Nutr 2011;93:1212e1219.

17. Griggey PP, Wendell CR, Zonderman AB, Waldstein S. Greater coffee intake in men is associated with steeper age-related increases in blood pressure. Am J Hypertens 2011;24:310e315.

18. Mesas AE, Leon-Munoz LM, Rodriguez-Artelejo F, Lopez-Garcia E. The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis. Am J Clin Nutr 2011;94:1113e1126.

19. Liu J, Sui X, Lavie CJ, Hebert JR, Earnest CP, Zhang J, Blair SN. Association of coffee consumption with all-cause and cardiovascular disease mortality. Mayo Clin Proc 2013;88:1066e1074.

20. Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specific mortality. N Engl J Med 2012;366:1891e1904.

21. De Koning Gans JM, Uiterwaal CS, van der Schouw YT, Boer JM, Grobbee DE, Vershuren M, Beulens JW. Tea and coffee consumption and cardiovascular morbidity and mortality. Arterioscler Thromb Vasc Biol 2010;30:1665e16

22. Ding M, Bhupathiraju SN, Satija A, van Dam RM, Hu FB. Long-term coffee consumption and risk of cardiovascular diseases. A systematic review and dose-response meta-analysis of prospective cohort studies. Circulation 2014;129:643e659.

23. Suriyama K, Kuriyama S, Akhter M, Kakizaki M, Nakaya N, Ohmori- Matsuda K, Shimazu T, Nagai M, Sugawara Y, Hozawa A, Fukao A, Tsuji I. Coffee consumption and mortality due to all causes, cardio- vascular disease, and cancer in Japanese women. J Nutr 2010;140: 1007e1013.

24. Lopez-Garcia E, Rodriguez-Artalejo F, Li TY, Mukamal KJ, Hu FB. van dam RM. Coffee consumption and mortality in women with car- diovascular disease. Am J Clin Nutr 2011;94:218e224.

25. Floegel A, Pischon T, Bergmann MM, Teucher B, Kaaks R, Boeing H. Coffee consumption and risk of chronic disease in the European Pro- spective Investigation into Cancer and Nutrition (EPIC)—Germany study. Am J Clin Nutr 2012;95:901e908.

26. Kokubo Y, Iso H, Saito I, Yamagishi K, Yatsuya H, Ishihara J, Inoue M, Tsugane S. The impact of green tea and coffee consumption on the reduced risk of stroke incidence in Japanese population. The Japan Public Health Center-Based Study Cohort. Stroke 2013;44:1369e1374.

27. Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose- response meta-analysis. Am J Epidemiol 2011;174:993e1001

28. Mostofsky E, Rice MS, Levitan EB, Mittleman MA. Habitual coffee consumption and risk of heart failure. A dose-response meta-analysis. Circ Heart Fail 2012;5:401e405.

29. Wang Y, Tuomilehto J, Jousilahti P, Antikainen R, Mahonen M, Mannisto S, Katzmarzyk P, Hu G. Coffee consumption and the risk of heart failure in Finnish men and women. Heart 2011;97: 44e48.

30. O’Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ. Effects of habitual coffee consumption and cardiometabolic disease, cardiovascular health, and all-cause mortality. J Am Coll Cardiol 2013;62:1043e105

31. Zhao Y, Wang J, Ballevre O, Luo H, Zhang W. Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens Res 2012;35: 370e374.

32. Cano-Marquina A, Tarin JJ, Cano A. The impact of coffee on health. Maturitas 2013;75:7e21.

33. Chrysant, S. G. (2015). Coffee Consumption and Cardiovascular Health. The American Journal of Cardiology, 116(5), 818-821. doi:10.1016/j.amjcard.2015.05.057

34. Cardin, R., Piciocchi, M., & Farinati, F. (2014). Letter: coffee and chronic liver damage.Alimentary Pharmacology & Therapeutics, 39(6), 643-643. doi:10.1111/apt.12637

35. Kuchino Y, Mori F, Kasai H, et al. Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature 1987; 327: 77–9.

36. Farinati F, Cardin R, Piciocchi M. Coffee, chronic diseases and cancer. Eur J Clin Nutr 2013; 67: 898

37. Lade A, Noon LA, Friedman SL. Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer. Curr Opin Oncol 2014; 26: 100–7.

38. Bambha K, Wilson LA, Unalp A, et al. Coffee consumption in NAFLD patients with lower insulin resistance is associated with lower risk of severe fibrosis. Liver Int 2013;. doi:10.1111/liv.12379

39. Bravo L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev. 1998;56:317–333

40. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332:73–78.

41. Woodward M, Zhang X, Barzi F, et al. The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region. Diabetes Care. 2003;26:360–366.

42. Natella, F., & Scaccini, C. (2012). Role of coffee in modulation of diabetes risk. Nutrition Reviews, 70(4), 207-217. doi:10.1111/j.1753-4887.2012.00470.x

43. van Dam RM, Dekker JM, Nijpels G, et al. Coffee consumption and incidence of impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes: the Hoorn Study. Diabetologia. 2004;47:2152–2159.

44. Agardh EE, Carlsson S, Ahlbom A, et al. Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women. J Intern Med. 2004;255:645–652.

45. Bidel S, Hu G, Qiao Q, et al. Coffee consumption and risk of total and cardiovas- cular mortality among patients with type 2 diabetes. Diabetologia. 2006;49:2618–2626.

46. Yamaji T, Mizoue T, Tabata S, et al. Coffee consumption and glucose tolerance status in middle-aged Japanese men. Diabetologia. 2004;47:2145–2151.

47. Williams CJ, Fargnoli JL, Hwang JJ, et al. Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study. Diabetes Care. 2008;31:504–507.

48. Imatoh T, Tanihara S, Miyazaki M, et al. Coffee consumption but not green tea consumption is associated with adiponectin levels in Japanese males. Eur J Nutr. 2010;50:279–284.

49. Ziemke F, Mantzoros CS. Adiponectin in insulin resistance: lessons from trans- lational research. Am J Clin Nutr. 2010;91:S258–S261.

50. Costill DL, Dalsky GP, Fink WJ. Effects of caffeine ingestion on metabolism and exercise performance. Med Sci Sports. 1978;10:155–158.

51. Ryu S, Choi SK, Joung SS, et al. Caffeine as a lipolytic food component increases endurance performance in rats and athletes. J Nutr Sci Vitaminol (Tokyo). 2001;47:139–146.

52. Kovacs EM, Lejeune MP, Nijs I, et al. Effects of green tea on weight maintenance after body-weight loss. Br J Nutr. 2004;91:431–437.

53. Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res. 2005;13:1195–1204.

54. Tagliabue A, Terracina D, Cena H, et al. Coffee induced thermogenesis and skin temperature. Int J Obes Relat Metab Disord. 1994;18:537–541

55. Dellalibera O, Lemaire B, Lafay S. Svetol®, green coffee extract, induces weight loss and increases the lean to fat mass ratio in volunteers with overweight problem [in French with English abstract]. Phytothérapie. 2006;4:194–197.

56. Onakpoya I, Terry R, Ernst E. The use of green coffee extract as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials. Gastroenterol Res Pract. 2011;doi:.10.1155/2011/382852.

57. Thom E. The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in over- weight and obese people. J Int Med Res. 2007;35:900–908.

58. Shi X, Dalal NS, Jain AC. Antioxidant behaviour of caffeine: efficient scavenging of hydroxyl radicals. Food Chem Toxicol. 1991;29:1–6.

59. Lee C. Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation. Clin Chim Acta. 2000;295:141–154.

60. Halvorsen BL, Carlsen MH, Phillips KM, et al. Content of redox-active com- pounds (i.e., antioxidants) in foods consumed in the United States. Am J Clin Nutr. 2006;84:95–135.

61. Pellegrini N, Serafini M, Colombi B, et al. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr. 2003;133:2812–2819.

62. Taylor, L. (2005). The healing power of rainforest herbs: A guide to understanding and using herbal medicinals. Garden City Park, NY: Square One Publishers.

63. Schimpl, F. C., Da Silva, J. F., Gonçalves, J. F., & Mazzafera, P. (2013). Guarana: Revisiting a highly caffeinated plant from the Amazon. Journal of Ethnopharmacology, 150(1), 14-31. doi:10.1016/j.jep.2013.08.023

64. Hoboken, GB: Wiley-Blackwell. (2011). Teas, Cocoa and Coffee : Plant Secondary Metabolites and Health (1). 2011. ProQuest ebrary. Web. 15 May 2016.