Top Coffee Health Benefits

 

Coffee is a widely consumed beverage.^1-3 It contains over 1,000 compounds, many of which are biologically active. Coffee also contains a complex mixture of polyphenols, making it one of the most popular pharmacologically active beverages.^1,4-11

Scientific interest in uncovering the health benefits contained in a daily cup of coffee has exploded in the last several years.

For example, drinking two extra cups of coffee daily may reduce your risk of developing type II diabetes. That’s the conclusion of a 2014 study of more than a million people, which demonstrated a 12% decrease in diabetes risk for each additional two cups of coffee consumed (the decrease was 11% among decaffeinated coffee drinkers).⁴

That’s only one example of the rapidly expanding literature regarding the benefits of drinking coffee. There now is compelling evidence of coffee’s health benefits regarding cardiovascular disease, metabolic syndrome, neurodegenerative disease, plus liver and kidney cancers.^6,12-19

And a stunning epidemiological study has shown sharp reductions in the risk of overall death among coffee drinkers.⁵

Enjoying a cup of coffee—or more—provides important longevity and protective benefits.^5,14

Coffee Reduces Risk Of Death

In a study funded by the National Institutes of Health and published in the prestigious New England Journal of Medicine, researchers explored the relationship between coffee drinking and the risk of dying. The study included more than 229,000 men and over 173,000 women who ranged in age from 50 to 71 years at the start of the study.⁵ The researchers followed the subjects for up to 13 years—or 5.15 million person-years!—making this one of the most powerful studies of its kind.

The researchers found that the risk of dying was significantly reduced in those who drank coffee (all levels of consumption) compared to those who did not.⁵ Compared to those who drank no coffee, the risk for men of dying from any cause was reduced 6% among those who drank 1 cup/day, 10% for 2-3 cups, 12% for 4-5 cups, and 10% for 6 or more cups/day. For women, the risk reduction was 5, 13, 16, and 15%, respectively.

While these findings are certainly impressive, the researchers also discovered that coffee consumption produced significant reductions in the risk of dying from a number of specific causes, including heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections.⁵

It is evident from this study, and many earlier, smaller studies, that far from being “bad for you,” as was once believed, coffee can be considered an important promoter of long life and good health.

Coffee Provides Cardiovascular Protection

 

The complex mix of anti-inflammatory polyphenols and other bioactive compounds in coffee delivers potent cardioprotective properties. The greatest benefits have been found in filtered coffee consumption.^20-23 Reversing earlier concerns that coffee might increase or aggravate cardiovascular disease risk, large epidemiologic studies reveal important positive effects on the heart, blood vessels, and brain that contribute to a reduction in the risk of heart disease, atherosclerosis, and stroke.^21,24,25

In one large meta-analysis, over 1.2 million participants were evaluated for their cardiovascular disease risk according to their coffee consumption.¹² Compared to subjects who drank no coffee at all, the researchers found a 15% cardiovascular disease risk reduction among those who drank an average of 3.5 cups/day, and 11% for those who had an average of 1.5 cups/day. This was an important study since it showed some level of protection for all amounts of coffee consumption.

One of the most important predictors of cardiovascular disease risk is endothelial dysfunction.²⁶ The endothelium is an ultra-thin layer of cells that lines blood vessels. It sends biochemical signals, including nitric oxide, to smooth muscle cells in the vessel walls, triggering them to relax and dilate, or contract and constrict, thereby regulating blood flow and pressure throughout the body.²⁷ People with atherosclerosis (hardening of the arteries) have perturbed endothelial function, causing vital organs such as the heart or brain to suffer from disrupted blood flow, which in turn can produce a heart attack or stroke.²⁸

The effects of coffee consumption on endothelial function have been controversial, in part because of confusion regarding the role of caffeine. Caffeine has been found to temporarily worsen endothelial function in some studies, but the antioxidant and other benefits of polyphenols in coffee appear to largely negate this effect.^1,15,29 In a group of older adults consuming a typical drink of boiled caffeinated coffee, endothelial function was 49% better in those who reported high consumption compared with those reporting low consumption.¹⁶

Even 200 mg of caffeine (equivalent to about 2.5 cups of coffee) improved endothelial function by 160% in patients with known coronary artery disease and by 121% in healthy volunteers, suggesting there may in fact be a beneficial role for caffeine in addition to the polyphenols.⁶ In a separate study, 300 mg of caffeine, given to healthy young men, produced a 25.5% improvement in endothelial function; this effect was traced to an increase in production of the vessel-dilating compound nitric oxide.³⁰

Decaffeinated coffee has also repeatedly been shown to improve endothelial function, reducing the risk of cardiovascular disease. In one study, endothelial function improved 46% one hour after consumption of two cups of decaffeinated Italian espresso coffee, and by 23% one hour after consumption of one cup.³¹

Given that decaffeinated coffee exerts positive effects on endothelial function, it appears that the polyphenol compounds exert substantial benefits. A study of healthy, non-diabetic men showed that ingestion of a single dose of purified caffeine polyphenols improved endothelial function following a glucose challenge (simulating a meal).²³ This is an important finding, given that after-meal increases in blood sugar are strongly associated with poor endothelial function and increased cardiovascular risk.^32-34

Both caffeinated and decaffeinated coffee, even at fairly high levels of consumption, exert favorable effects on endothelial function and on cardiovascular disease risk. Importantly, one study showed no significant negative effects of coffee consumption, either caffeinated or decaf, on certain types of ECG associated with cardiovascular disease.³⁵

What You Need To Know

The Numerous Health Benefits Of Coffee

• Coffee is one of the most widely consumed beverages in the world; it contains more than 1,000 different compounds.
• Once thought likely to be harmful, coffee is now recognized as an excellent source of antioxidant and anti-inflammatory molecules.
• Very large and powerful epidemiological studies show that coffee consumption is associated with longer lifespans and with reduced risks of dying from a host of common, age-related conditions.
• Coffee reduces the risk of cardiovascular disease, metabolic syndrome, diabetes, neurodegenerative diseases, and liver and kidney cancers.
• If you enjoy drinking coffee, go for it — there is ample evidence that coffee is a highly functional beverage that gives one pleasure, robust health, and a long life.

Coffee Protects Against Metabolic Syndrome And Type II Diabetes

The modern lifestyle is contributing to an alarming and constant increase in the prevalence of obesity, type II diabetes, and their deadly long-term consequences.^36-40

In particular, metabolic syndrome—abdominal obesity, hypertension, abnormal blood lipids, and insulin resistance producing borderline/high blood sugar levels—is on the rise, along with increased risks for diabetes, heart disease, cognitive decline, and even cancer.^37,41,42

Fortunately, there’s a growing body of evidence favoring coffee consumption as a means of protection against both metabolic syndrome and diabetes.

In a study from Japan, where rates of metabolic syndrome have been rising sharply over the past decades, all components of metabolic syndrome occurred less frequently among coffee drinkers than among non-drinkers. More components of metabolic syndrome were present in those who drank less coffee.⁴³

Other studies have shown similar effects, with heavy coffee drinkers being more protected from metabolic syndrome components like elevated triglycerides; one study showed that drinking 1.5 to nearly 3 cups/day offered a 49% reduction in the risk of having high blood sugar.¹³

Coffee’s impact on fat accumulation is also favorable. Both light (1-3 cups/day) and moderate (4 or more cups/day) coffee consumption was shown to reduce abdominal fat collections in a group of middle-aged men. Moderate coffee consumption was also associated with higher blood levels of the beneficial hormone adiponectin, which helps regulate metabolic processes, further evidence of reduced deleterious activity of fat tissue.^14,44

Animal studies provide some insights into how coffee exerts its protective effects against metabolic syndrome.

In one study, rats were fed a diet rich in animal fats and sugars, including fructose. They rapidly developed metabolic syndrome, which led to dangerous remodeling of their heart structures and also to non-alcoholic fatty liver disease (NAFLD), both of which occur in humans who consume too much sugar and fat.⁴⁵ But when a supplemental coffee extract was added to the rats’ diet, those unhealthy effects were significantly reduced, and the animals’ glucose tolerance and high blood pressure also resolved.⁴⁵

Similarly, mice fed a high-fat diet gained weight and increased abdominal fat stores, but when fed the same diet and supplemented with coffee (decaf or regular) they had lower body weights and fat stores.⁴⁶ The supplemented animals also had significantly lower levels of liver damage indicators and inflammatory markers, compared with unsupplemented controls.

Coffee’s Beneficial Compound

Coffee has numerous beneficial properties that appear to be independent of its caffeine content. While coffee is known to contain more than a thousand bioactive compounds, scientists have learned that one such compound, chlorogenic acid, is responsible for the lion’s share of coffee’s healthful activities.

Chlorogenic acid is a polyphenol, making it a member of one of the largest classes of plant molecules that promotes human health. Chlorogenic acid also has powerful anti-oxidant and anti-inflammatory effects.^75-80

It is also recognized as one of the important cardioprotective components of coffee, capable of improving heart muscle cell health, potentially reducing the risks of congestive heart failure after a heart attack.⁷⁷ It inhibits the clumping of platelets that contributes to blood vessel blockage to produce heart attacks and strokes.⁸¹

Chlorogenic acid also has a potent impact on how our bodies effectively handle sugars and fats.⁸² Studies show that this polyphenol provides important anti-obesity and glucose-lowering effects,⁸² and treatment of diabetic animals with chlorogenic acid was able to partially prevent the biochemical and cognitive changes associated with diabetes, improving memory and decreasing anxiety.⁸³ In studies of animals with long-term consequences of diabetes, such as painful diabetic neuropathy and poor wound healing, chlorogenic acid not only lowered blood sugar, but directly reduced pain and enhanced healing rates.^84,85

The beneficial effects of coffee drinking on neurodegenerative diseases such as Parkinson’s and Alzheimer’s is largely attributable to chlorogenic acid, according to recent studies.^76,86,87 Chlorogenic acid reduces oxidative stress-induced brain cell death, and also preserves the activity of vital neurotransmitters (nerve cell signaling molecules) that are lost in Alzheimer’s patients.^79,88,89

Finally, chlorogenic acid, by modulating genetic expression, promotes immune system activation that favors detection and destruction of cancer cells by patrolling immune cells, helping to abort an incipient cancer before it can take root and grow.⁸⁰

There’s no longer any doubt about coffee’s health-giving properties. Modern coffee processing techniques that enhance the chlorogenic acid content may serve to make your daily “cuppa” contribute strongly to your health and life span.

Even in animals with both metabolic syndrome and diabetes, coffee has proved to be therapeutic. A study of rats that had both disorders showed coffee consumption reduced serum glucose, total cholesterol, and triglycerides, thus lowering risk factors for developing cardiovascular disease and other complications of metabolic syndrome.⁴⁷

The benefits of coffee on metabolic syndrome were summarized in a comprehensive review in late 2013. Of the studies examined, all of the animal and most of the human research demonstrated protective effects of coffee on metabolic syndrome and on development of non-alcoholic fatty liver disease (the few human studies that showed no effect were conducted among young populations, who have a relatively low incidence of metabolic syndrome at baseline).⁴⁸

A main risk posed by metabolic syndrome is the development of full-blown type II diabetes, the result of sustained exposure to fat-related inflammatory cytokines and poor insulin sensitivity.⁴⁹ As with metabolic syndrome itself, coffee is highly protective against type II diabetes.

A large multi-ethnic study of more than 75,000 men and women showed that drinking 3 or more cups/day of regular coffee reduced risk of developing type II diabetes 35% in women, and 14% in men; this study did not find significant risk reduction with decaffeinated coffee.⁵⁰

That difference between caffeinated and decaf coffees, however, seemed to disappear in research that examined even larger populations. Two important 2014 meta-analyses, each including more than a million participants, provide definitive evidence that both kinds of coffee offers protective effects against type II diabetes. The first demonstrated that compared with little or no consumption, the risk for developing diabetes was reduced by 8, 15, 21, 25, 29, and 33% for consumption of 1 to 6 cups/day (respectively), with protection seen for both caffeinated and decaffeinated brews.⁵¹

The second meta-analysis showed similar results. Compared with the lowest level of coffee intake, those drinking the largest amounts of regular coffee had a 29% lower risk, while those drinking the largest amount of decaf had a 21% lower risk.⁴ This study also demonstrated that each additional two cups of regular coffee reduced diabetes risk by 12% (11% in decaf drinkers).⁴

Animal studies show that coffee (decaf and regular) contributes to decreased insulin resistance (the precursor to type II diabetes) and reduces blood sugar levels by modulating several proteins involved in insulin signaling and down-regulating genes involved in inflammation.⁵² Subsequent research suggests these effects may in turn lead to increased energy utilization and energy expenditure, both important factors in reducing total body fat stores and reducing the risk for diabetes and metabolic syndrome.⁵³

Coffee Protects Brain Cells

 

Both caffeine and coffee show powerful effects in protecting brain cells from age-related degeneration. Epidemiologic studies show that people with higher intakes of coffee and caffeine are less likely to develop Alzheimer’s or Parkinson’s diseases, two of the most feared cognitive disorders of aging.^54-59

People with mild cognitive impairment (MCI, the precursor to Alzheimer’s) who have higher blood caffeine levels are significantly less likely to progress to full-blown dementia, and rates of cognitive decline are slower in people with higher caffeine intake.^60,61 Coffee drinkers who consume 3 cups/day are 28% less likely to develop Parkinson’s disease.⁶²

In animal studies, it has been shown that caffeine and caffeinated coffee can prevent Alzheimer’s-like cognitive impairment from developing as mice age, and reverse the cognitive impairment and accumulation of the abnormal Alzheimer’s brain protein called Amyloid Beta in aged mice.⁶³ Caffeine also prevented the brain changes associated with Parkinson’s disease in an animal model, through reduction in inflammatory cytokines and preservation of brain cells in important memory regions.^55,64

But that’s not the only beneficial component of caffeinated coffee. Studies have shown that caffeinated coffee elevates plasma levels of a growth factor (GCSF—or granulocyte-colony stimulating factor) that is associated with improved memory. GCSF is also thought to promote formation of new brain cells and the synapses that connect them.⁶⁴ And a specific non-caffeine coffee component called EHT ( eicosanoyl-5-hydroxytryptamide) has direct anti-inflammatory and antioxidant effects that preserve the specific neurons that die off in Parkinson’s disease.⁵⁸

Caffeine is also associated with a decreased risk of depression, as shown by studies documenting up to a 43% risk reduction in people with the highest versus the lowest caffeine consumption.^65,66 Consumption of coffee itself provides a 39 to 77% reduction in risk of depression.^66,67

Coffee Prevents Liver And Kidney Cancers

The rich brew of bioactive compounds in coffee is now credited with preventing certain cancers, particularly those of the liver and kidneys.¹⁸

Hepatocellular carcinoma is the most common primary malignant cancer of the liver; it is strongly associated with hepatitis B and C viral infections, and coffee drinking appears to confer a protective effect.⁶⁸

Compared with people drinking 0-1 cups of coffee/day, those drinking 2-3, 4-5, 6-7, and 8 or more cups/day have reductions in liver cancer risk of 34, 56, 62, and 68%, respectively.¹⁷ This level of protection is provided by coffee, regardless of whether a person has been infected with either or both hepatitis B and C viruses, both of which are strongly associated with liver cancer.⁶⁹ Overall, studies show a remarkably consistent average risk reduction of about 50% in coffee drinkers versus non-drinkers, regardless of study design or location.⁷⁰

Proposed mechanisms for protection against liver cancer include induction of toxin-destroying and anti-oxidant enzymes, and reducing enzymes that activate carcinogens.¹⁸

Coffee consumption appears to reduce kidney cancer risk as well, with laboratory evidence demonstrating that coffee helps destroy renal cancer cells.^18,19 Compelling evidence also shows general improvements in kidney function among coffee drinkers.

Several studies have now shown that coffee significantly increases kidney function as measured by glomerular filtration rate (GFR), the amount of toxin-containing fluid that is filtered through the kidney each minute (higher numbers are better).^71,72 The effect was demonstrated to be even greater in middle-aged and elderly coffee-consuming female diabetics.⁷³ Also, cardiovascular risk increases among kidney dialysis patients and coffee drinking is associated with signifcant improvements in their lipid profiles.⁷⁴

Summary

Coffee, one of the world’s most popular beverages, is a complicated mix of more than a thousand compounds. In addition to caffeine, which itself appears to have beneficial effects, coffee also contains polyphenols and other compounds capable of modifying gene expression, protecting tissues from oxidant and inflammatory damage, and other favorable effects.

A major study demonstrated that coffee drinkers are at significantly lower risk of dying from all causes, as well as from many of the specific conditions that are the leading cause of death among Americans, from cardiovascular disease to diabetes. Additional studies have shown benefits from coffee consumption on metabolic syndrome, neurodegenerative diseases, and cancers of the kidney and liver.

So, find a brand of coffee that you enjoy, preferably one with known quantities of antioxidant molecules, and drink up—you’ll be doing yourself and your health a pleasurable favor.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-800-226-2370 

References

1. Buscemi S, Verga S, Batsis JA, et al. Acute effects of coffee on endothelial function in healthy subjects. Euro J Clin Nutr. 2010 May;64(5):483-9.
2. O’Keefe JH, Bhatti SK, Patil HR, et al. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. J Am Coll Cardiol. 2013 Sep 17;62(12):1043-51.
3. 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. 2011 Jun;50(4):279-84.
4. Jiang X, Zhang D, Jiang W. Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Europ J Nutr. 2014 Feb;53(1):25-38.
5. Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specificmortality. NEJM. 2012 May 17;366(20): 1891-904.
6. Shechter M, Shalmon G, Scheinowitz M, et al. Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease. Amer J Cardiolog. 2011 May 1;107(9):1255-61.
7. O’Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. J Am Coll Cardiol. 2013 Sep 17;62(12):1043-51.
8. Lee KW, Im JY, Woo JM, et al. Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson’s disease. Neurotherapeutics. 2013 Jan;10(1):143-53.
9. Huber WW, Parzefall W. Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk. Methods Enzymol. 2005;401:307-41.
10. Cavin C, Holzhaeuser D, Scharf G, et al.Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem Toxicol. 2002 Aug;40(8):1155-63.
11. Murase T, Misawa K, Minegishi Y, et al. Coffee polyphenols suppress diet-induced body fat accumulation by downregulating SREBP-1c and related molecules in C57BL/6J mice. Am J Physiol Endocrinol Metab . 2011 Jan;300(1):E122-33.
12. Ding M, Bhupathiraju SN, Satija A, van Dam RM, Hu FB. Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies. Circulation. Feb 11 2014;129(6):643-59.
13. Takami H, Nakamoto M, Uemura H, et al. Inverse correlation between coffee consumption and prevalence of metabolic syndrome: baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan. Japan Epidemiological Association. 2013;23(1):12-20.
14. Mure K, Maeda S, Mukoubayashi C, et al. Habitual coffee consumption inversely associated with metabolic syndrome-related biomarkers involving adiponectin. Nutr. 2013; Jul-Aug 29(7-8):982-7.
15. Buscemi S, Batsis JA, Arcoleo G, Verga S. Coffee and endothelial function: a battle between caffeine and antioxidants? Eur J Clin Nutr. 2010 Oct;64(10):1242-3.
16. Siasos G, Oikonomou E, Chrysohoou C, et al. Consumption of a boiled Greek type of coffee is associated with improved endothelial function: the Ikaria study. Vascu Med. 2013 Apr;18(2):55-62.
17. Hu G, Tuomilehto J, Pukkala E, et al. Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer. Hepatology. 2008 Jul;48(1):129-36.
18. Nkondjock A. Coffee consumption and the risk of cancer: an overview. Cancer Lett. 2009 May 18;277(2):121-5.
19. Choi MJ, Park EJ, Oh JH, et al. Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation. Chem Biol Interact. 2011 Apr 25;190(2-3):102-8.
20. Di Castelnuovo A, di Giuseppe R, Iacoviello L, de Gaetano G. Consumption of cocoa, tea and coffee and risk of cardiovascular disease. Euro J Intern Med. 2012 Jan;23(1):15-25.
21. Rebello SA, van Dam RM. Coffee consumption and cardiovascular health: getting to the heart of the matter. Curr Cardiol Reports. 2013 Oct;15(10):403.
22. Tangney CC, Rasmussen HE. Polyphenols, inflammation, and cardiovascular disease. Curr Atherosclerosis Rep. 2013 May;15(5):324.
23. Ochiai R, Sugiura Y, Shioya Y, Otsuka K, Katsuragi Y, Hashiguchi T. Coffee polyphenols improve peripheral endothelial function after glucose loading in healthy male adults. Nutrition Research. 2014 Feb;34(2):155-9.
24. Kishimoto Y, Tani M, Kondo K. Pleiotropic preventive effects of dietary polyphenols in cardiovascular diseases. Eur J Clin Nutr. 2013 May;67(5):532-5.
25. Kim B, Nam Y, Kim J, Choi H, Won C.Coffee Consumption and Stroke Risk: A Meta-analysis of Epidemiologic Studies. Korean J Fam Med. 2012 Nov;33(6):356-65.
26. Lind L, Berglund L, Larsson A, Sundstrom J. Endothelial function in resistance and conduit arteries and 5-year risk of cardiovascular disease. Circulation. 2011 Apr 12;123(14):1545-51.
27. Cines DB, Pollak ES, Buck CA, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998 May 15;91(10):3527-61.
28. Crowther MA. Pathogenesis of atherosclerosis. Hematology Am Soc Hematol Educ Program. 2005:436-41.
29. Papamichael CM, Aznaouridis KA, Karatzis EN, et al. Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci. 2005 Jul;109(1):55-60.
30. Umemura T, Ueda K, Nishioka K, et al. Effects of acute administration of caffeine on vascular function. American J Cardiol. 2006 Dec 1;98(11):1538-41.
31. Buscemi S, Verga S, Batsis JA, et al. Dose-dependent effects of decaffeinated coffee on endothelial function in healthy subjects. Eur J Clin Nutr. 2009 Oct;63(10):1200-5.
32. Lacroix S, Rosiers CD, Tardif JC, Nigam A. The role of oxidative stress in postprandial endothelial dysfunction. Nutrition Res Rev. Dec 2012;25(2):288-301.
33. Torimoto K, Okada Y, Mori H, Tanaka Y. Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus. Cardiovasc Diabetol. 2013;12:1.
34. Mah E, Bruno RS. Postprandial hyperglycemia on vascular endothelial function: mechanisms and consequences. Nutri Res. Oct 2012;32(10):727-40.
35. Buscemi S, Mattina A, Tranchina MR, Verga S. Acute effects of coffee on QT interval in healthy subjects. Nutr J. 2011;10:15.
36. Wierzejska R, Jarosz M. Coffee drinking and risk of type 2 diabetes mellitus. Optimistic scientific data. Przegl Epidemiol. 2012;66(3):509512.
37. Matsuura H, Mure K, Nishio N, Kitano N, Nagai N, Takeshita T. Relationship between coffee consumption and prevalence of metabolic syndrome among Japanese civil servants. J Epidemiol/JEA. 2012;22(2):160-6.
38. Crawford MA. Diet and cancer and heart disease. Nutr Health. 2014 Mar 11.
39. Orozco-Solis R, Sassone-Corsi P.Epigenetic control and the circadian clock: Linking metabolism to neuronal responses. Neuroscience. 2014 Apr 4;264C:76-87.
40. Grantham JP, Staub K, Rühli FJ, Henneberg M. Modern diet and metabolic variance­—a recipe for disaster? Nutr J. 2014 Feb 6;13:15
41. Watts AS, Loskutova N, Burns JM, Johnson DK.Metabolic syndrome and cognitive decline in early Alzheimer’s disease and healthy older adults. J Alzheimers Dis. 2013;35(2):253-65.
42. Hsu IR, Kim SP, Kabir M, Bergman RN. Metabolic syndrome, hyperinsulinemia, and cancer. Am J Clin Nutr. 2007 Sep;86(3):s867-71.
43. Hino A, Adachi H, Enomoto M, et al. Habitual coffee but not green tea consumption is inversely associated with metabolic syndrome: an epidemiological study in a general Japanese population. Diabetes Res Clin Prac. Jun 2007;76(3):383-9.
44. Kamon J, Yamauchi T, Terauchi Y, Kubota N, Kadowaki T.The mechanisms by which PPARgamma and adiponectin regulate glucose and lipid metabolism. Nihon Yakurigaku Zasshi. 2003 Oct;122(4):294-300.
45. Panchal SK, Poudyal H, Waanders J, Brown L. Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. J Nutr. 2012 Apr;142(4):690-7.
46. Fukushima Y, Kasuga M, Nakao K, Shimomura I, Matsuzawa Y. Effects of coffee on inflammatory cytokine gene expression in mice fed high-fat diets. J Agricult Food Chem. 2009 Dec 9;57(23):11100-5.
47. Abrahao SA, Pereira RG, de Sousa RV, Lima AR, Crema GP, Barros BS. Influence of coffee brew in metabolic syndrome and type 2 diabetes. Plant Foods Hum Nutr. 2013 Jun;68(2):184-9.
48. Yesil A, Yilmaz Y. Review article: coffee consumption, the metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Ther. Nov 2013;38(9):1038-44.
49. Grundy SM. Pre-diabetes, metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol. 2012 Feb 14;59(7):635-43
50. Doo T, Morimoto Y, Steinbrecher A, Kolonel LN, Maskarinec G. Coffee intake and risk of type 2 diabetes: the Multiethnic Cohort. Public Health Nutr . Feb 27 2013:1-9.
51. Ding M, Bhupathiraju SN, Chen M, van Dam RM, Hu FB. Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Diabetes Care. Feb 2014 Feb;37(2):569-86.
52. Jia H, Aw W, Egashira K, et al. Coffee intake mitigated inflammation and obesity-induced insulin resistance in skeletal muscle of high-fat diet-induced obese mice. Genes Nutr. 2014 May;9(3):389.
53. Takahashi S, Saito K, Jia H, Kato H. An integrated multi-omics study revealed metabolic alterations underlying the effects of coffee consumption. PloS one. 2014;9(3):e91134.
54. Cao C, Wang L, Lin X, et al. Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice. JAD. 2011;25(2):323-35.
55. Chen JF, Xu K, Petzer JP, et al. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson’s disease. J Soc Neuro. 2001 May 15;21(10):Rc143.
56. Hermansen K, Krogholm KS, Bech BH, et al. Coffee can protect against disease. Ugeskrift Laeger. 2012 Sep 24;174(39):2293-7.
57. Hu N, Yu JT, Tan L, Wang YL, Sun L, Tan L. Nutrition and the risk of Alzheimer’s disease. BioMed Res Int. 2013;2013:524820.
58. Lee KW, Im JY, Woo JM, et al. Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson’s disease. Neurotherapeutics. Jan 2013;10(1):143-153.
59. Palacios N, Gao X, McCullough ML, et al. Caffeine and risk of Parkinson’s disease in a large cohort of men and women. Mov Disord. Sep 1 2012;27(10):1276-82.
60. Cao C, Loewenstein DA, Lin X, et al. High Blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimer’s Dis. 2012;30(3):559-72.
61. Vercambre MN, Berr C, Ritchie K, Kang JH. Caffeine and cognitive decline in elderly women at high vascular risk. J Alzheimer’s Dis. 2013;35(2):413-21.
62. Qi H, Li S. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease. Geriatr Gerontol Int. 2013 Jul 23 .
63. Arendash GW, Cao C. Caffeine and coffee as therapeutics against Alzheimer’s disease. JAD. 2010;20 Suppl 1:S117-26.
64. Cao C, Wang L, Lin X, et al. Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice. J Alz Dis. 2011;25:323-335.
65. Lucas M, Mirzaei F, Pan A, et al. Coffee, caffeine, and risk of depression among women. Arch Intern Med. 2011 Sep 26;171(17):1571-8.
66. Pham NM, Nanri A, Kurotani K, et al. Green tea and coffee consumption is inversely associated with depressive symptoms in a Japanese working population. Public Health Nutr. 2014 Mar;17(3):625-33.
67. Ruusunen A, Lehto SM, Tolmunen T, Mursu J, Kaplan GA, Voutilainen S. Coffee, tea and caffeine intake and the risk of severe depression in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Public Health Nutr. 2010 Aug;13(8):1215-20.
68. Montella M, Crispo A, Giudice A. HCC, diet and metabolic factors: Diet and HCC. Hepat Mon. 2011 Mar;11(3):159-62.
69. Inoue M, Kurahashi N, Iwasaki M, et al. Effect of coffee and green tea consumption on the risk of liver cancer: cohort analysis by hepatitis virus infection status. Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1746-53.
70. Sang LX, Chang B, Li XH, Jiang M. Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis. BMC gastroenterol. 2013;13:34.
71. Nakajima K, Hirose K, Ebata M, Morita K, Munakata H. Association between habitual coffee consumption and normal or increased estimated glomerular filtration rate in apparently healthy adults. Br J Nutr. 2010 Jan;103(2):149-52.
72. Saito M, Nemoto T, Tobimatsu S, Ebata M, Le Y, Nakajima K. Coffee consumption and cystatin-C-based estimated glomerular filtration rates in healthy young adults: results of a clinical trial. J Nutr Metab. 2011;2011:146865.
73. Kim BH, Park YS, Noh HM, Sung JS, Lee JK. Association between Coffee Consumption and Renal Impairment in Korean Women with and without Diabetes: Analysis of the Fourth Korea National Health and Nutrition Examination Survey in 2008. Korean J Fam Med. 2013 Jul;34(4):265-71.
74. Grzegorzewska AE, Mlot-Michalska M, Wobszal P. Does ingestion of regular coffee influence serum lipid profile in dialysis patients? Adv Perit Dial. 2009;25:181-6.
75. Hwang SJ, Kim YW, Park Y, Lee HJ, Kim KW. Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm Res. 2014 Jan;63(1):81-90.
76. Lang R, Dieminger N, Beusch A, et al. Bioappearance and pharmacokinetics of bioactives upon coffee consumption. Anal Bioanal Chem. 2013 Oct;405(26):8487-503.
77. Li Y, Shen D, Tang X, et al. Chlorogenic acid prevents isoproterenol-induced hypertrophy in neonatal rat myocytes. Toxicol Lett. 2014 Feb 28;226(3):257-63.
78. Ruifeng G, Yunhe F, Zhengkai W, et al. Chlorogenic acid attenuates lipopolysaccharide-induced mice mastitis by suppressing TLR4-mediated NF-kappaB signaling pathway. Eur J Pharmacol. 2014 Jan 20;729c:54-58.
79. Shen W, Qi R, Zhang J, et al. Chlorogenic acid inhibits LPS-induced microglial activation and improves survival of dopaminergic neurons. Brain Res Bull. 2012 Aug 1;88(5):487-94.
80. Kang TY, Yang HR, Zhang J, et al. The studies of chlorogenic Acid antitumor mechanism by gene chip detection: the immune pathway gene expression. J Anal Methods Chem. 2013;2013:617243.
81. Amin RP, Kunaparaju N, Kumar S, Taldone T, Barletta MA, Zito SW. Structure elucidation and inhibitory effects on human platelet aggregation of chlorogenic acid from Wrightia tinctoria. J Complement Integr Med. 2013;10.
82. Meng S, Cao J, Feng Q, Peng J, Hu Y. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review. Evid Based Complement Alternat Med. 2013;2013:801457.
83. Stefanello N, Schmatz R, Pereira LB, et al. Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats. Mol Cell Biochem. 2014 Mar;388(1-2):277-86.
84. Bagdas D, Ozboluk HY, Cinkilic N, Gurun MS. Antinociceptive Effect of Chlorogenic Acid in Rats with Painful Diabetic Neuropathy. J Med Food. 2014 Mar 10.
85. Bagdas D, Cam Etoz B, Inan Ozturkoglu S, et al. Effects of systemic chlorogenic Acid on random-pattern dorsal skin flap survival in diabetic rats. Biol Pharm Bull. 2014 Mar 1;37(3):361-70.
86. Farah A, Monteiro M, Donangelo CM, Lafay S.Chlorogenic acids from green coffee extract are highly bioavailable in humans. J Nutr . 2008 Dec;138(12):2309-15.
87. Monteiro M, Farah A, Perrone D, et al.Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans. J Nutr. 2007 Oct;137(10):2196-201.
88. Cho ES, Jang YJ, Hwang MK, Kang NJ, Lee KW, Lee HJ. Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals. Mutat Res. 2009 Feb 10;661(1-2):18-24.
89. Oboh G, Agunloye OM, Akinyemi AJ, Ademiluyi AO, Adefegha SA. Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer’s disease and some pro-oxidant induced oxidative stress in rats’ brain-in vitro. Neurochem Res. 2013 Feb;38(2):413-9.