PROTECT

Our light-medium roast organic coffee scientifically formulated for liver vitality.

At Purity Coffee we make every decision based on health, and our vision is to improve the world’s health through coffee. We study the latest scientific research to improve continuously how we source, test, roast and deliver our coffees.

We begin with the following fundamental standards as a baseline from which we develop additional standards as the science presents new information:

  • Certified organic and tested free of pesticides and other contaminants
  • Mold-free
  • Mycotoxin-free
  • Rainforest Alliance Certified for environmental and social standards
  • Specialty grade for exceptional taste and highest quality beans
  • Regeneratively and/or biodynamically farmed for sustainability

We continue to look for the best coffees and we’re always researching ways to make our coffee even healthier, and we want consumers to have more choice in coffee to meet their health goals. The deeper we go, the more we understand that coffee is extremely complex, and various beneficial compounds can be created and destroyed at different roast levels.

This year at Purity we wanted to develop a coffee that we believe follows the science on contributing to liver health. It was the obvious place to start because over the last three decades there is mounting evidence for a positive effect of coffee on liver function and health.

Here are the highlights:

  • Studies range from reports on coffee reducing risk of cirrhosis and liver cancer to demonstrating evidence for coffee as a beneficial tonic across the spectrum of liver diseases. In 2013 Saab et. al. published a systematic review that included a table of 12 key studies (over 93,000 subjects) assessing impact of coffee on liver related health outcomes from 1993 to 2010, all of which showed positive health benefits of coffee on the liver.
  • Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. Epidemiological studies strongly suggest that drinking about 3 cups of coffee can reduce the risk or severity of liver damage from various causes (Heath et al. 2017).
  • Elevated liver enzymes often indicate inflammation or damage to liver cells, which then leak higher than normal amounts of certain chemicals into the bloodstream, elevating liver enzymes on blood tests. Coffee consumption is inversely related to serum liver enzyme activity: Results showed that people who said they drank three or more cups of coffee a day had lower levels of these enzymes, compared with people who did not drink any coffee. (Tanaka et al. 1998).
  • In 2010 Lenore Arab reviewed a substantial amount of epidemiological evidence of over 500 papers relating to the consumption of coffee to various human cancers. She condensed the findings of the meta analyses and more recent papers on site-specific human cancers. For hepatocellular and endometrial cancers, there is a strong and consistent protective association (Arab 2010).

Purity Protect is a light-medium roast, very high in CGA, with sweet citrus characteristics.

Purity Protect follows a profile laid out in the scientific literature and hits several points that have been proven to be critical. We searched for a coffee that we believe could reflect the science for liver health.

  1. High chlorogenic acid levels, but balanced by sugars in the coffee, so that the coffee is sweet, flavorful and clean-tasting.
  2. This specific single origin from Colombia is processed via a “honeyed process” allowing the natural coffee fruit sugars to deliver a very drinkable coffee, since the science encourages 3-5 cups of coffee a day.

We hope you enjoy the newest addition to the Purity Coffee lineup.

WHAT THE SCIENCE SAYS: HEALTH BENEFITS OF COFFEE

There are hundreds of compounds working together in a cup of coffee, but these are most often mentioned in scientific studies:

  • Chlorogenic Acids
  • Caffeine
  • Diterpenes (Cafestol and Kahweol)
  • Melanoidins

In order to discuss coffee and the liver, let’s summarize the main diseases of the liver—each of these are studied in conjunction with coffee.

Formulated for:

Liver support
Metabolic vitality
Antioxidant support

Diseases and Coffee's Impact

Fibrosis

There are an overwhelming number of studies that conclude that coffee drinking reduces liver fibrosis (please see bibliography). These studies avoid the mistakes of mid-century research into coffee: They adjust for confounding factors, like cigarette smoking and lifestyle issues.

Liver fibrosis results from chronic damage; eventually the ability of liver to regenerate fails, and hepatocytes are replaced by extracellular matrix (ECM). Fibrosis disorganizes the architecture of the liver anatomically and functionally, which is a characteristic of most types of chronic liver diseases. Under normal conditions of wound healing, tissues are replaced without cellular overgrowth, but injury to the liver from inflammation to physical disturbances or injury can lead to excessive connective tissue formation. Repair happens in a sequence that produces an inflammatory response with numerous actions involving neutrophils, macrophages, lymphocytes and leukocytes, the last one producing cytokines that trigger the proliferation of capillary production, fibroblasts and smooth muscle cells.

If the liver is more severely damaged with longer inflammatory response, the tissue reconstruction (fibrotic process) can include an excessive amount of extracellular matrix (ECM), which ends up as scar tissue and fibrosis. The fibrotic cytokines and hepatic stellate cells (HSCs) are considered the key reason for this fibrous overgrowth, and coffee has been shown to block these effects by acting at various points of the pathological processes mentioned above (Ramos-Tovar & Muriel 2019). The main injuries to the liver that produce hepatic fibrosis include chronic hepatitis C or B infections, alcohol abuse, cholestasis, and nonalcoholic steatohepatitis.

Coffee exerts protective effects against liver fibrosis through antioxidant action and the suppression of fibrogenic cytokines (that trigger ECM growth). Among many antioxidative and hepatoprotective components in coffee, the chlorogenic acids and other polyphenols have been suggested as relevant compounds due to their noteworthy levels in coffee (Ashihara et al. 2019, Farah 2012, Farah et al. 2006). These findings indicated that other components besides caffeine are involved in the hepatoprotective effects of coffee against liver fibrosis (Shin et al. 2010).

Researchers have found that advanced liver fibrosis from chronic liver diseases (CLDs) of various etiologies is associated with low coffee and total caffeine consumption. Demonstrating the clinical significance of coffee consumption, Freedman et al. found that among patients with advanced fibrosis, those who consumed no coffee had a risk of hepatic decompensation or hepatocellular carcinoma (HCC) of 11.1 per 100 patient-years, compared to just 6.3 per 100 patient years in those consuming at least three cups of coffee per day, with no beneficial effect noted with tea or other sources of caffeine (Freedman et al. 2009).

Coffee has been shown to limit the progression of liver fibrosis in established liver disease (Shin et al. 2010, Modi et al. 2010, Shi et al. 2009), and has been associated with reduced hepatic fibrosis in patients with liver diseases like hepatitis C (Molloy et al. 2012). The most impressive evidence came in 2015 with a meta-analysis that included 4 cross-sectional and 2 case-control studies with over 20,000 patients that showed that regular coffee consumption significantly reduces rates and severity of hepatic fibrosis in patients with liver disease (Shen et al. 2015). Caffeine itself was not significantly associated with the results, but regular coffee (naturally caffeinated) intake was significantly associated with reduced hepatic fibrosis. In some cases, depending on the degree, hepatic fibrosis could be reversed, and the liver could return to a normal structure. Coffee caffeine is associated with a significant reduction in risk of fibrosis among patients with nonalcoholic fatty liver disease (Shen et al. 2015).

Progression of liver injury from fibrosis to cirrhosis is a slow and terminal process. Fatty liver disease and hepatitis-C have caused an increase in numbers of patients with fibrosis and cirrhosis over the past decade, and a simple, cost-effective mechanism to slow down the process seems to be readily available: Coffee. Even better: Good quality, organic, clean, mycotoxin-free coffee. Aflatoxins in particular are hepatocarcinogenic in humans, especially in conjunction with chronic hepatitis B virus infection (Wild& Gong2010), so consuming coffee that is free of toxins is also critical to a healthy liver.

Metabolic Associated Fatty Liver Disease (MAFLD)

Nonalcoholic fatty liver disease (NAFLD) has been a term used for decades, but in 2019 an international consensus panel presented new terminology to better reflect its causes: Metabolic associated fatty liver disease [MAFLD]. We will use the two interchangeably for this review, because the vast body of literature refers to it as NAFLD.

MAFLD is a condition characterized by a buildup of fat in the liver, and is the most common liver disease globally with estimates at close to a billion people having a degree of the disease. “NAFLD is associated with many metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Its potential to develop into more severe liver conditions, such as nonalcoholic steatohepatitis, advanced fibrosis, cirrhosis and hepatocellular carcinoma, can lead to a state in which liver transplantation is the only treatment option available” (Chalasani 2012).

Because MAFLD is so pervasive, scientists turned their attention to the epidemiological and clinical evidence of the past 20 years that indicated coffee’s potential hepatoprotective effects, including antioxidative, anti-inflammatory, and antifibrotic activity. A 2013 study conducted a systematic review of the epidemiology, magnitude, and mechanisms of possible beneficial effects of coffee consumption in patients with NAFLD using 12 detailed prior studies:

  • Four continuous cycles of the National Health and Nutrition Examination Surveys (NHANES, USA 2001–2008) were used to investigate the effects of dietary behavior in NAFLD patients. Taking into account diet, nutrition, demographics, and other factors, findings showed a strong association between coffee consumption and protection against the development of NAFLD (Birerdinc 2012).
  • In an Italian study, 137 NAFLD cases and 108 controls were enrolled, and coffee intake determined by the absolute number of cups of coffee consumed. When compared with non-coffee drinkers, those who consumed coffee had less severe fatty liver evaluated by ultrasound “bright liver score”. Bright Liver Score (BLS) is the observation of bright liver echo pattern on ultrasound-- it is considered a sign of hepatic steatosis and provides accurate and reliable detection of moderate-severe fatty liver.
  • In a histological examination of liver biopsies using a questionnaire, researchers reported a strong inverse relationship between caffeine consumption and hepatic fibrosis, associating caffeine consumption with both the prevalence and severity of MAFLD (Molloy 2012).

More recently, coffee is associated with a significant reduction in risk of fibrosis among non-alcoholic steatohepatitis (NASH) patients (Kopzhassaruly 2020). NASH is the most severe form of metabolic associated fatty liver disease and is closely related to obesity, pre-diabetes, and diabetes. As with other studies, they showed dose-related results-- that those who drank 2-4 cups per day showed a significant difference to those who drank 1 cup per day.

In 2020, Alessio Calabrò et. al. conducted a literature review on coffee and MAFLD/NAFLD, and they summed up the beneficial effects of coffee consumption reported in dozens of papers, highlighting 7 key studies since 2014. These studies showed that coffee consumption in patients with NAFLD can be protective against liver steatosis, progression of fibrosis and liver damage, primarily through antioxidant activity and coffee caffeine intake, which improves insulin resistance and reduces the production of inflammatory and fibrogenic cytokines. Although the researchers found some controversy due to lack of information on types of coffee, dosages, etc., they concluded that 2-3 cups of coffee a day in patients with MAFLD should be encouraged.

Cirrhosis

Cirrhosis is a late-stage liver disease in which healthy liver tissue is replaced with scar tissue and the liver is permanently damaged. Scar tissue keeps your liver from working properly. Many types of liver diseases and conditions injure healthy liver cells, causing cell death and inflammation (my.clevelandclinic.org). Cirrhosis always develops because of another liver problem or disease: alcohol abuse, nonalcoholic (or metabolic associated) fatty liver disease, hepatitis B, hepatitis C, certain autoimmune diseases, and other causes. Cirrhosis isn't curable, but it's treatable. Doctors have two main goals in treating this disease: Stop the damage to your liver, and prevent complications.

For several decades, researchers have been making connections between liver health and coffee consumption. Data collected from 1978-1985, supported the hypothesis that there were ingredients in coffee that protect the liver against cirrhosis, especially alcoholic cirrhosis. A 10-year study of 128,934 patients hospitalized with cirrhosis carried out by Klatsky et. al. (1992) showed coffee intake was associated with a lower prevalence of cirrhosis. In addition, coffee consumption seemed to help prevent death from cirrhosis.

Ten years later in a study of more than 700 individuals, a relationship was observed between how much coffee was consumed per day and risk of liver cirrhosis. The odds ratio[1] for liver cirrhosis decreased for each cup of coffee:

  • From 1.0 for those who did not drink coffee to 0.47 for those who consumed 1 cup of coffee daily,
  • 0.23 for consumers of 2 cups,
  • 0.21 for 3 cups, and
  • 0.16 for 4 cups

Was it just the caffeine in coffee that caused this? The team studied other beverages that had caffeine, and compared those with the risk of liver cirrhosis, and they found that caffeine alone was not significantly associated with lower cirrhosis risk. These findings support the hypothesis that coffee, but not other beverages containing caffeine, may inhibit the onset of alcoholic and nonalcoholic liver cirrhosis— and there must be something else in the coffee (Corrao 2001).

The following year, a study of 101 cirrhosis patients (with more than 1500 control subjects), risk among coffee drinkers showed a significant reduction in cirrhosis (the odds ratio was 0.54) compared with individuals who never drank coffee. Similar to the previous study, for those drinking more than 3 cups/day there was a significant trend for lower cirrhosis risk with an odds ratio of 0.29. Repeating assumptions from the previous study, the consumption of other caffeine-containing beverages did not reduce the occurrence of cirrhosis. The researchers followed up a few years later and continued to find evidence for a beneficial role of coffee consumption on reduced risk of death from liver cirrhosis. The mortality rate of people who drank 3 or more cups of coffee was lower than those who drank 2 cups of coffee or less (Tverdal 2003).

The correlation was also valid for alcoholic cirrhosis as well as cirrhosis from other causes, which was different than the study from the 1990s. There also seemed to be a threshold in how much coffee was effective: No further decline in mortality when the intake was more than three to four cups of coffee. The meta-analysis done by Kennedy et al. in 2016 concluded that an increase in daily coffee consumption of two cups is associated with a near halving of the risk of cirrhosis.

A number of research studies have examined the role of coffee in preventing liver cirrhosis with consistently positive and sometimes quite dramatic results. A 2002 study also published in the Annals of Epidemiology concluded that there is a 71% lower risk for those drinking more than three cups per day (Gallus 2002). Drinking three or more cups of coffee daily lowers the risk by up to 53% of liver disease progression for patients with chronic hepatitis C. Black tea or green tea, however, had no effect on liver disease (Freedman 2009).

Liver Cancer

Hepatocellular carcinoma (HCC) is a type of liver cancer that frequently stems from cirrhosis of the liver or hepatitis infection. It is becoming more common in developing countries and is often fatal. For decades scientists have studied the relationship between coffee consumption and preventive effect against liver cancer. In the 1990’s animal experiments showed chlorogenic acids in coffee had inhibitory effects against chemical carcinogenesis in liver tissue (Tanaka 1990).

Researchers found that the subjects with a history of liver disease had a significant inverse relationship between coffee consumption and liver cancer. They concluded that coffee may prevent liver cancer more effectively among subjects with liver disease than among those without liver disease, but at the same time their conclusion stated, “…coffee consumption is significantly associated with a decreased incidence of liver cancer.” (Shimazu 2005).

This followed with several epidemiologic studies:

A large scale study followed 90,000 Japanese subjects over ten years and in the Journal of the National Cancer Institute in 2005 concluded that coffee drinkers have half the risk of developing liver cancer as non-coffee drinkers. This effect was recorded for those who drank just one to two cups daily with increasing effect at three to four cups. Unfortunately, because decaffeinated coffee is rarely consumed in Japan, they could not make a distinction between caffeinated and decaffeinated coffee and could not determine if caffeine were partly responsible for the decreased risk of HCC (Inoue 2005). In a similar study in Italy, where coffee is widely consumed, men and women who drink coffee may be reducing their risk of liver cancer, but tea and decaf did not appear to share regular coffee's protective effects. Abstainers from coffee drinking resulted in a doubled risk for HCC with respect to moderate drinkers (<14 cups/week) (Montella 2007).

In another 2007 meta-analysis of published studies on HCC, quantitative information on coffee consumption from thousands of cases and controlled studies from Europe and Japan (approximately 240,000 thousand people, among them 2,260 diagnosed with HCC) had similar conclusions: They observed a 41% reduction in the risk of HCC among coffee drinkers compared with never-drinkers. Regardless of study design, geography and other bias, men and women who regularly drink coffee have a significantly reduced risk of developing liver cancer and other liver diseases, suggesting a continuum of favorable effect of coffee on liver function (Bravi 2007).

That same year another review of studies that represented hundreds of thousands of cases observed an inverse relation between coffee consumption and risk of liver cancer, and in 6 studies the association was statistically significant. Overall, an increase in consumption of 2 cups of coffee per day was associated with a 43% reduced risk of liver cancer, and the odds drop by 23% with each cup (Larsson 2007).

Additional large studies were done and showed similar results: High coffee consumption was significantly associated with a reduced risk of HCC in subjects, but was reduced in chronic hepatitis B patients by the dominant role of viral replication. They noted that further studies were needed to clarify the protective mechanism of specific ingredients in coffee and the possible interaction between coffee and underlying viral etiologies in the HCC development among chronic liver disease patients (Jang 2014).

The relationship between coffee intake and decreased risk of HCC appears to be consistent for several etiological types of chronic liver disease, including HCC. Lifetime coffee consumption is shown to be an independent protective factor against HCC.

In 2020 Bhurwal et. al. did a meta-analysis to evaluate the association of coffee with HCC or liver cancer development along with the amount of coffee needed to prevent HCC or liver cancer. They reviewed dozens of articles from 1996-2019 that associated coffee with liver cancer, narrowing them down to 20 studies for data. Their systematic review showed that drinking coffee provides benefits with a reduction in the risk of HCC or liver cancer and higher doses of coffee have higher benefits in terms of risk reduction.

Mechanisms of Coffee's Impact on the Liver

Mechanisms of Coffee's Impact on the Liver

Chlorogenic Acids

Chlorogenic acids (CGA) are a rich group of plant polyphenols consumed in the human diet and the components primarily responsible for the functional properties of coffee. CGA are esters formed between quinic acid and some trans-cinnamic acids (caffeic, ferulic, and p-coumaric), and coffee has a high concentration of them, which is why coffee is considered one of the most important contributors to antioxidant intake in many countries, since people drink it often multiple times daily. During the roasting process, some of the original CGAs break down to form CGA lactones (CGL) or quinides up to a point they are degraded by heat (Farah et al. 2005).

Part of the lactone is converted into caffeoylquinic acids after contact with the alkaline pH of human digestive fluids. Therefore, it is likely that a large proportion of lactones consumed in the brew return to their respective chlorogenic acid forms during digestion, indirectly increasing the total chlorogenic acids intake (Farah 2012).

CGA have been shown to have the following impacts/actions: Antioxidant activity, anti-inflammatory, antibacterial, anti-mutagenic, possible anti-opioid activity, hypoglycemic, and others.The polyphenols in black coffee (without milk products) are readily bioavailable, which is not the case with all foods(Duarte & Farah 2011). There is an abundance of literature on coffee CGA and their antioxidant activity, and especially on coffee’s positive impact on liver health.

Pharmacologic properties attributed to caffeoylquinic and dicaffeoylquinic acids include antiviral activity against adenovirus and herpes virus (Chiang et al. 2002), as well as hepatoprotective activity in an experimental model of liver injury (Basnet et al. 1996). CGA has shown anti-hepatitis B virus potency as well (Wang et al. 2009).

Approximately 80%–100% of chlorogenic acids are extracted in coffee brewing yielding approximately 35–100 mg chlorogenic acids per 100-mL cup of arabica coffee in free form and soluble fiber (Díaz-Rubio & Saura-Calixto 2007). Although maintaining coffee brews at a high temperature (like on a hot plate) reduces chlorogenic acids and lactones concentrations, they are still present in relatively high amounts in medium-roasted coffees compared with most food sources (Clifford 2000). Non-coffee drinkers usually take in less than 100 milligrams of chlorogenic acids/day, whereas modest and heavy coffee drinkers ingest 0.1–2 grams (Farah 2012).

Chlorogenic acid lactones were shown to exert blood glucose-normalizing effects in rats, and these effects were later observed for the chlorogenic acids themselves (Farah 2012).

References: Koriem, 2014; Chiang, 2002; Basnet, 1996; Wang, 2009; Díaz-Rubio, 2007; Clifford, 2000; Farah, 2012 & 2013.

Diterpenes: Cafestol & Kahweol  (C&K)

Diterpenes are active compounds found in plants, fungi, bacteria, and animals in both terrestrial and marine environments. Diterpenes have shown medicinal biological activities, and some diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture (de Sousa 2018).

Cafestol and kahweol (C&K) are specific to coffee and contribute to its bitterness. C&K are bioactive compounds and their derivatives, which are mainly salts or esters of saturated fatty acids (predominant) and unsaturated fatty acids, represent approximately 20% of the lipid fraction of coffee, with cafestol accounting for about 0.2%-0.6% of coffee weight (Farah 2012).

Diterpenes have been shown to have the following Impacts/actions: Antioxidant, hypoglycemic, hypolipidemic, antimicrobial, antiviral, and cafestol from high habitual coffee consumption is associated with reduced risk of developing type 2 diabetes (Mellbye et al. 2015). Additionally, diterpenes have been associated with anticarcinogenic, hepatoprotective properties in vitro, and as agents for cancer chemopreventive blocking (Cavin et al. 2002).

In human liver epithelial cell lines, C&K treatment resulted in a reduction of aflatoxin B1-DNA binding correlated with the enzyme GST-mu, which is known to detoxify aflatoxin B1. C&K also was found to inhibit one of the human enzymes responsible for aflatoxin B1 activation, which helps explain some of the anticarcinogenic effects of C&K (Cavin et al. 2002).

The brewing method has a direct impact on the dosage of diterpenes per cup: Paper filters trap most of the diterpenes, whereas the metal filters of French press, espresso, Turkish and Scandinavian coffee maximize diterpenes. You can see the oils floating on the surface of your coffee, if you reflect the light off of it the right way. C&K may increase blood cholesterol level, which is something that some people may need to avoid. If this is the case, choosing to brew the coffee with a paper filter using a pourover or drip method will virtually eliminate the diterpenes, while allowing the caffeine and chlorogenic acids to still be bioavailable.

References: Mellbye, 2015; Cavin, 2002; Farah 2012; Guzzo, 2012

Melanoidins

Melanoidins are what make coffee (and other foods) turn brown when roasted, baked or toasted. They are formed during the Maillard reaction, when sugars and amino acids combine at high temperatures and low water activity. They may be considered bioactive compounds (Bekedam et. al. 2008). The extent of roasting-induced antioxidant formation is directly linked to the extent of melanoidin formation, and the longer we roast, the more intermediate and high-molecular-weight melanoidins are produced (Moreira et al. 2019). They are shown to have the following impacts/actions: Antioxidant activity, metal-chelating, antibacterial and prebiotic functionality.

Several studies carried out have shown that melanoidins extracted from coffee possess antioxidant activity. (Tagliazucchi, 2010). They inhibit lipid peroxidation. Increasing evidence shows that oxidized lipids, advanced lipid oxidation end products, and lipid peroxidation play a major role in developing most oxidative stress-related diseases. Lipid peroxidation occurs in all human neurodegenerative diseases, such as Alzheimer’s disease, Parkinson disease and even atherosclerosis (Tagliazucchi, 2010).

Coffee melanoidins do not seem to be absorbed in humans, but they can function as an antioxidant dietary fiber with an overall antioxidant capacity via embedded low molecular compounds. Melanoidins can act like a ‘sponge’ for free radicals in the gut (Garsetti, 2000; Folmer, 2017). This improves the reduced/oxidized glutathione balance in the colon. Glutathione is an antioxidant produced in our cells. Oddly, antioxidative structures formed in coffee melanoidins are similar to vitamin E. These appear to activate their scavenging properties gradually (Bekedam, 2008).

In the same way, coffee melanoidins are able to chelate transition metal ions, that is they are able to bind Zn2+, Cu2+, and Fe2+ (Takenaka, 2005; Morales, 2005). Metal-chelating ability is key to inhibiting lipid peroxidation, among other benefits.

The soluble fiber role of melanoidins enhance the immune-stimulating properties and contribute significantly to reduce the risk of colon cancer. This likely happens by decreasing colon inflammation through improved microbiota balance and by increasing the elimination rate of carcinogens through higher colon motility (urge to use the bathroom) (Vitaglione, 2012; Moreira, 2015; Fogliano, 2011). Melanoidins can also stimulate beneficial microbiota growth in the gut, acting as prebiotics (Sales et al, 2020).

Coffee melanoidins may act to promote the growth of a beneficial colon microbiota, affecting inflammatory pathways in the colon and consequently in the liver (Folmer, 2017). Although melanoidins are modified in the human gut, their capacity to modulate the bacterial colon population is corroborated by model melanoidin solutions (Moreira et al. 2019).

Coffee melanoidins seem to have a protective effect on liver steatosis in obese rats (Vitaglione, 2012), which suggests that the melanoidins in coffee may have an influence on liver fat and functionality. Glutathione may be involved.

References: Bekedamn, E.K., et. al., 2008; Tagliazucchi, 2010; Vitaglione, 2012; Moreira, 2015; Fogliano and Morales, 2011; Takenaka, 2005.

Coffee Caffeine: More Than Just Wakefulness

It is undeniable that many people drink coffee for the effect of caffeine on their wakefulness. However, in the case of liver health, the interaction of coffee’s many beneficial compounds appear to work in tandem with coffee’s caffeine. Scientists have shown caffeine produced in the laboratory does not have the same effect as natural coffee with caffeine. Caffeine metabolites have exhibited an antioxidant activity in vitro (measuring average plasma iron-reducing capacity), demonstrating that whole coffee is more efficient than decaffeinated coffee with respect to its antioxidant capacity (Moura-Nunes et al. 2009).

Caffeine is an alkaloid found in leaves, seeds, and fruits of coffee, tea, cocoa, cola, and guarana plants. Within 10 minutes of drinking coffee, the stomach and first part of the intestine absorb the caffeine, and it reaches maximum concentration in the bloodstream within about an hour. Caffeine has been shown to be anti-inflammatory, and caffeine metabolites have shown antioxidant activity (Farah 2018).

The liver metabolizes the caffeine into paraxanthine, theobromine, and theophylline which contribute to enhancing its effects. Caffeine and theophylline act as an antagonists of adenosine receptors in humans—adenosine interacts with specific cell receptors, most noticeably inhibiting neural activity and causing drowsiness, but it performs numerous other actions in the body (Nehlig et al. 1992). Caffeine’s catabolic products theobromine and xanthine exhibit antioxidant properties (Azam et al. 2003).

Fibrosis, cirrhosis, HCC, MAFLD and alcoholic liver disease all are connected to oxidative stress, which is an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and the antioxidant system that detoxifies these reactive products. The liver metabolizes substances to maintain homeostasis in the organism, but this process produces free radicals, including ROS, which in turn produces more oxidative stress. Antioxidants are molecules that help delay or prevent oxidation, fighting free radicals and keeping us healthy. Caffeine is an effective inhibitor of all three ROS species (Scalbert & Williamson 2000).

In certain parts of the body caffeine modulates intracellular levels of cyclic adenosine monophosphate (cAMP), which regulates immune cell functions, plays an important role in metabolism and promotes the release of insulin from pancreatic beta cells. Upregulation of cAMP inhibits activation of inflammatory effector cells such as T cells. In T cells, cAMP downregulates various cellular functions, including cytokine production and cytotoxicity (Sitkovsky et al. 1988).

The anti-inflammatory properties of caffeine are also due to its function as a phosphodiesterase (PDE) inhibitor (Horrigan et al. 2006). Phosphodiesterase inhibitors encourage blood vessel dilation and smooth muscle relaxation and are used to treat people with pulmonary hypertension or lung issues, sometimes even reversing some of the damage to the heart and lungs.

The beneficial effects of coffee and caffeine extract against liver fibrosis have been demonstrated by several studies using standard rodent models. In almost every study, coffee blocked toxin-induced liver fibrosis and cirrhosis. In one key study using rats, the scientists induced liver disease in the animals and then tested regular coffee, decaffeinated coffee and a water-caffeine solution. The regular coffee produced the most impactful positive results, showing that it was not just the caffeine that benefits the liver. “A reduction in hepatic TGF-β1 expression in the group receiving decaffeinated coffee indicates that caffeine may not be the solely hepatoprotective compound in coffee beverages” (Furtado 2012).

Numerous studies indicate that damage of the genetic material plays a crucial role in a variety of human diseases, in particular in the etiology of cancer. Chronical consumption (8 weeks) of a pure arabica dark-roast coffee blend significantly reduced spontaneous DNA strand breaks in blood cells of healthy volunteers, pointing to a DNA protective effect (Pahlke et al 2019) and (Schipp et al. 2018).

Caffeine and Telomeres: Telomeres play a vital role in preserving the information in our genome. Telomeres are DNA–protein structures found at both ends of each chromosome that protect the genome from degradation, unnecessary recombination, repair, and interchromosomal fusion. Caffeine promotes the expression of telomerase reverse transcriptase (TERT), extending the telomere length and preventing cellular deterioration and loss of division/growth capacity (Tao et al. 2021).

Caffeine has also been shown to improve microscopic structural changes of the thymus, spleen and liver due to aging, which helps to clarify different ways coffee benefits health in regard to longevity (Tao et al. 2021).

Caffeine and Adenosine: Research suggests that the protective effect of caffeine may be due to its blocking of adenosine, which is a potent internal regulator of inflammation and tissue repair (Chakraborti et al. 2003). There are four subtypes of extracellular adenosine: A1, A2A, A2B, and A3 (Fredholm et al. 2001). Activation of adenosine A2A receptors promotes tissue repair, wound healing, and matrix production (Montesinos et al. 1997 & 2002), it reduces inflammation and prevents acute inflammatory injury in the liver [Ohta & Sitkovsky 2001]. In other cell types, adenosine A2A receptors stimulate collagen production via mitogen-activated protein (Revan et al. 1996).

At high doses, caffeine inhibits cAMP, yet a low dose of caffeine regulates cAMP levels through antagonism of the A2A receptor. In short, the lower doses of caffeine were proinflammatory, which would be difficult to deduce from the observational and epidemiological studies (Ohta & Sitkovsky 2001). This is one reason that scientists believe it is the caffeine in conjunction with other compounds in coffee (chlorogenic acid, caffeic acid, ferulic acid, etc.), diterpenes (cafestol, kahweol), and trigonelline, which may exert liver protective effects (Farah et. al. 2019).

References: Setkovsky, 1988; Horrigan, 2006; Furtado, 2012; Pahlke, 2019; Schipp, 2018; Tao, 2021; Chakraborti, 2003; Fredholm, 2001; Montesinos, 1997 & 2002; Ohta, 2001 & 2007; Revan, 1996; Farah et. al., 2019; Carrillo, 2000; Hsu, 2009; Jnkiewicz, 2007.

Purity Coffee® PROTECT Certificates of Analysis

Click the links below to view the lab results for PROTECT. Results are based upon 15g of roasted & ground coffee, which is equal to the recommended amount used for brewing one 8 oz cup of coffee.

Citations and Studies Which Support Our Views

  1. Alferink LJM, Fittipaldi J, Kiefte-de Jong JC, Taimr P, Hansen BE, Metselaar HJ, Schoufour JD, Ikram MA, Janssen HLA, Franco OH, Darwish Murad S (2017). Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: the Rotterdam study. Journal of Hepatology;67:339–348.
  2. Arab, L (2010). Epidemiologic evidence on coffee and cancer. Nutr Cancer; 62(3):271-83
  3. Ashihara H, Fujimura T, Crozier A. 2019. Chapter 4: Coffee Plant Biochemistry in Coffee: Production, Quality and Chemistry, Farah A-Editor. The Royal Society of Chemistry.
  4. Azam S, Hadi N, Khan NU, Hadi SM (2003). Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. Med Sci Monit. Sep;9(9):BR325-30.
  5. Basnet P, Matsushige K, Hase K, Kadota S, Namba T (1996). Four di-0-caffeoyl quinic acid derivatives from propolis. Potent Hepatoprotective activity in experimental liver injury models. Biol Pharm Bull. 19, 1479–1484.
  6. Bhaktha G, Shantaram M, Nayak S (2016). Beneficial effects of coffee and maintenance of uric acid levels. Intl Jnl Pharm & Pharm Sci 8(4):393 to 395
  7. Bhurwal a, Rattan P, Yoshitake S, Pioppo L, Reja D, Dellatore P, Rustgi V (2020). Inverse Association of Coffee with Liver Cancer Development: An Updated Systematic Review and Meta-Analysis. Journal of Gastrointestinal & Liver Diseases . Sep2020, Vol. 29 Issue 3, p421-428. 8p.
  8. Bilzer M, Roggel F, Gerbes A (2006). Role of Kupffer cells in host defense and liver disease. Liver Int., 26, 1175–1186.
  9. Birerdinc A, Stepanova M, Pawloski L, Younossi ZM (2012). Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther.; 35: 76–82.
  10. Bravi F, Bosetti C, Tavani A, Bagnardi V, Gallus S, et al. (2007): Coffee drinking and hepatocellular carcinoma risk: a meta-analysis. Hepatology 46, 430– 435.
  11. Cadden IS, Partovi N, Yoshida EM (2007). Review article: possible beneficial effects of coffee on liver disease and function. Aliment Pharmacol Ther;26:1-8.
  12. Calabrò A, Procopio AC, Gualtieri P, Primerano F, Larussa T, Luzza F, Di Renzo L, De Lorenzo A, Gualtieri P, Abenavoli L (2020). Beneficial effects of coffee in non-alcoholic fatty liver disease: a narrative review. Hepatoma Res 2020;6:69.
  13. Carmona-Cuenca I., Roncero C., Sancho P., Caja L., Fausto N., Fernandez M. Fabregat I. Upregulation of the NADPH oxidase NOX4 by TGF-beta in hepatocytes is required for its pro-apoptotic activity. J. Hepatol. 2008, 49, 965–976.
  14. Carrillo JA, Benitez J (2000). Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin. Pharmacokin, 39, 127–153.
  15. Cavin C, Holzhaeuser D, Scharf G, Constable A, Huber WW, Schilter B (2002). Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem. Toxicol. 2002, 40, 1155–1163.
  16. Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T (2003). Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem;253:269–85.
  17. Chiang LC, Chiang W, Chang MY, Ng LT, Lin CC (2002). Antiviral activity of Plantago major extracts and related compounds in vitro, Antiviral Res. 55, 53–62.
  18. Choi HK, Curhan G (2010) Coffee consumption and risk of incident gout in women: the Nurses’ Health Study. Am J Clin Nutr92(4), 922–7.38
  19. Choi HK, Willett W, Curhan G (2007) Coffee consumption and risk of incident gout in men: a prospective study. Arthritis Rheum56(6), 2049–55
  20. Chopra S (2001). Dr. Sanjiv Chopra’s Liver Book: A Comprehensive Guide to Diagnosis, Treatment and Recovery. Pocket Books, a division of Simon & Schuster, Inc.
  21. Clifford MN (2000). Chlorogenic acids and other cinnamates—nature, occurrence, dietary burden, absorption and metabolism, J. Sci. Food Agric. 80, 1033–1043.
  22. Corrao G, Zambon A, Bagnardi V, D’Amicis A, Klatsky A (2001), Collaborative SIDECIR group. Coffee, caffeine, and the risk of liver cirrhosis. Ann. Epidemiol., 11, 458–465.
  23. Day Y J, Marshall MA, Huang L, McDuffie MJ, Okusa MD, Linden J (2004). Protection from ischemic liver injury by activation of A2A adenosine receptors during reperfusion: inhibition of chemokine induction. Am. J. Physiol. Gastrointest. Liver Physiol., 286, 285–293.
  24. De Minicis S, Brenner D (2008). Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex. J. Gastroenterol. Hepatol., 23, S98–S103.
  25. De Roos B, Sawyer JK, Katan M B, Rudel LL (1999) Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects. Proc. Nutr. Soc., 58, 551–557.
  26. de Sousa IP, Sousa Teixeira MV, Jacometti Cardoso Furtado NA (2018). An Overview of Biotransformation and Toxicity of Diterpenes. Molecules. Jun 8;23(6):1387.
  27. Desmet VJ (2009). The amazing universe of hepatic microstructure. Hepatology 2009, 50, 333–344.
  28. Devasagayam TP, Kamat JP, Mohan H (1996). Caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive O2 species. Biochim. Biophys. Acta, 1282, 63–70.
  29. Díaz-Rubio ME, Saura-Calixto F (2007). Dietary fiber in brewed coffee. J. Agric. Food Chem. 55, 1999–2003.
  30. Faist V, and Erbersdobler HF (2001). Metabolic transit and in vivo effects of melanoidins.
  31. Farah A (2012). Coffee: Emerging Health Effects and Disease Prevention. IFT Press, Ch. 2 Coffee Constituents, 22-58.
  32. Farah A (2018) Nutritional and health effects of coffee. Lashermes P. (ed.), Achieving sustainable cultivation of coffee, Burleigh Dodds Science Publishing, Cambridge, UK., 1-31.
  33. Farah A editor (2019). Volume 1 - Coffee: Production, Quality and Chemistry. Royal Society of Chemistry.
  34. Farah A editor (2019). Volume 2 - Coffee: Consumption and Health Implications. Royal Society of Chemistry.
  35. Farah A, de Paulis T, Moreira DP, Trugo C, Martin P (2006). Chlorogenic Acids and Lactones in Regular and Water-Decaffeinated Arabica Coffees. Agricultural and Food Chemistry, 54, 374-381.
  36. Farah A, de Paulis T, Trugo C, Martin P (2005). Effect of Roasting on the Formation of Chlorogenic Acid Lactones in Coffee. Agricultural and Food Chemistry, 53, 1505-1513.
  37. Forrester LM, Nealt GE, Judah DJ, Glancey MJ, Wolf RC (1990). Evidence for involvement of multiple forms of cytochrome P-450 in aflatoxin B1 metabolism in human liver. Proc. Nat. Acad. Sci. U. S. A., 87, 8306–8310.
  38. Fredholm BB, Chern Y, Franco R, Sitkovsky M (2007). Aspects of the general biology of adenosine A2A signaling. Prog. Neurobiol., 83, 263–276.
  39. Freedman ND, Everhart JE, Lindsay KL, Ghany MG, Curto TM, Shiffman ML, et al. (2009). Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology; 50:1360-1369.
  40. Friedman S (2003). Liver fibrosis—from bench to bedside. J. Hepatol., 38, S38–S53.
  41. Furtado KS, Prado MG, Aguiar E, Silva MA, Dias MC, et al. (2012) Coffee and caffeine protect against liver injury induced by thioacetamide in male Wistar rats. Basic Clin Pharmacol Toxicol;111:339-47.
  42. Gelatti U, Covolo L, Franceschini M et al. (2005) Coffee consumption reduces the risk of hepatocellular carcinoma independently of its aetiology: a case-control study. Journal of Hepatol.; 42: 528–34.
  43. George SE, Ramalakshmi K, Mohan R, Lingamallu JA (2008) perception on health benefits of coffee. Crit. Rev. Food Sci. Nutr., 48, 464–486.
  44. Gressner O (2009). Less Smad2 is good for you! A scientific update on coffee’s liver benefits. Hepatology, 50, 970–978.
  45. Gressner OA, Lahme B, Siluschek M, Weiskirchen R, Gressner AM (2008). Activation of TGF-beta within cultured hepatocytes and in liver injury leads to intracrine signaling with expression of connective tissue growth factor. J. Cell. Mol. Med., 12, 2717–2730.
  46. Gross G, Jaccaud E, Huggett AC (1997). Analysis of the content of the diterpenes cafestol and kahweol in coffee brews. Food Chem. Toxicol., 35, 547–554.
  47. Gudowska M, Gruszewska E, Panasiuk A, Cylwik B, Świderska M, Flisiak R, Szmitkowski M, Chrostek L (2016). "Selected Noninvasive Markers in Diagnosing Liver Diseases". Laboratory Medicine. 47 (1): 67–72.
  48. Guzzo LS, Perez AC, Romero TR, Azevedo AO, & Duarte ID (2012). Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides. Clinical and Experimental Pharmacology and Physiology, 39(5), 412–416.
  49. Hayes JD, Ellis EM, Neal GE, Harrison J, Manson MM (1999). Cellular response to cancer hemopreventive agents: contribution of the antioxidant responsive element to the adaptive response to oxidative and chemical stress. Biochem. Soc. Symp., 64, 141–168.
  50. He P, Noda Y, Sugiyama K (2001). Suppression of lipopolysaccharide-induced liver injury by various types of tea and coffee in D-galactosamine-sensitized rats. Biosci. Biotech. Biochem., 65, 670–673.
  51. Heath RD, Brahmbhatt M, Tahan AC, Ibdah JA, Tahan V (2017). Coffee: The magical bean for liver diseases. World Journal of Hepatology. May 28; 9(15): 689-696.
  52. Helal MG, Ayoub SE, Elkashefand WF, Ibrahim TM (2018). Caffeine affects HFD-induced hepatic steatosis by multifactorial intervention. Hum Exp Toxicol;37:983-90.
  53. Homan D, Mobarhan S (2006). Coffee: good, Bad, or just fun? A critical review of coffee’s effects on liver enzymes. Nutr. Rev. 2006, 64, 43–46.
  54. Honjo S, Kono S, Coleman MP, Koichi S, Sakurai Y, Todoroki I, Umeda T, Wakabayashi K, Imanishii K, Nishikawa H, Ogawa S, Katsurada M, Nakagawa K, Yoshizawa N (2001) Coffee consumption and serum aminotransferases in middle-aged Japanese men. J. Clin. Epidemiol. 54, 823–829.
  55. Horrigan LA, Kelly JP, Connor TJ (2006). Immunomodulatory effects of caffeine: friend or foe? Pharmacol. Ther., 111, 877–892.
  56. Hsu HR, Mei YY, Wu CY, Chiu PH, Chen HH (2009). Behavioural and toxic interaction profile of ketamine in combination with caffeine. Basic Clin. Pharmacol. Toxicol., 104, 379–383.
  57. Huber WW, Rossmanith W, Grusch M, Haslinger E, Prustomerskya S, Peter-V¨or¨osmarty B, Parzefall W, Scharf G, Schulte-Hermann R (2008). Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver. Food Chem. Toxicol., 46, 1230–1238.
  58. Huber WW, Scharf G, Rossmanith W, Prustomersky S, Grasl-Kraupp B, Peter B, Turesky RJ, Schulte-Hermann R (2002). The coffee components kahweol and cafestol induce -glutamylcysteinesynthetase, the rate limiting enzyme of chemoprotective glutathione synthesis, in several organs of the rat. Arch. Toxicol., 75, 685–694.
  59. Inoue M, Yoshimi I, Sobue T, Tsugane S (2005). Influence of Coffee Drinking on Subsequent Risk of Hepatocellular Carcinoma: A Prospective Study in Japan. J Natl Cancer Inst;97:293-300.
  60. Jang ES, Jeong SH, Lee SH et al. (2013). The effect of coffee consumption on the development of hepatocellular carcinoma in hepatitis B virus endemic area. Liver Int.; 33: 1092–9.
  61. Jankiewicz K, Chroscinska-Krawczyk M, Błaszczyk B, Czuczwar SJ (2007) Caffeine and antiepileptic drugs: experimental and clinical data Przegl Lek, 64, 965–967.
  62. Kenichi Y, Kwang-Geun L, Hirotomo O, Takayuki S (2002). Antioxidant activity of heterocyclic compounds found in coffee volatiles produced by Maillard reaction. J. Agric. Food Chem., 50, 5480– 5484.
  63. Kennedy OJ, Roderick P, Buchanan R, Fallowfield JA, Hayes PC, Parkes J (2016). Systematic review with meta-analysis: coffee consumption and the risk of cirrhosis. Aliment Pharmacol Ther;359:562-74.
  64. Kim JY, Jung Kyung S, Jeong HG (2004). Suppressive effects of the kahweol and cafestol on cyclooxygenase-2 expression in macrophages. FEBS Lett., 569, 321–326.
  65. Kim JY, Kim DH, Jeong HG (2006). Inhibitory effect of the coffee diterpene kahweol on carrageenan induced inflammation in rats. Biofactors., 26, 17–28.
  66. Klatsky A L, Armstrong M A (1992). Alcohol, Smoking, coffee, and cirrhosis. Am. J. Epidemiol., 136, 1248–1257.
  67. Klatsky AL, Morton C, Udaltsova N, Friedman GD (2006). Coffee, cirrhosis and transaminase enzymes. Arch. Intern. Med., 166, 1190–1195.
  68. Komes D, Belščak-Cvitanović A (2014). Effects of Preparation Techniques on the Antioxidant Capacity of Coffee Brews. Processing and Impact on Antioxidants in Beverages, 87–97.
  69. Kopzhassaruly D, Darzhigenov B (2020). PE-317 : Association of Coffee and Caffeine Consumption with Fatty Liver Disease, Non-Alcoholic Steatohepatitis, and Degree of Hepatic Fibrosis. Korean Liver Association. Publication: Spring/Autumn Conference (KASL), Volume 1, 308.
  70. Koriem KMM, Soliman RE (2014). Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine. J. Toxicol. 583494.
  71. Kreisel W, Schaffner D, Lazaro A, Trebicka J, Merfort I, Schmitt-Graeff A, Deibert P (2020). Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension. International Journal of Molecular Sciences, 21, 6223.
  72. Kurozawa Y, Ogimoto I, Shibata A et al. (2005) Coffee and risk of death from hepatocellular carcinoma in a large cohort study in Japan. Br. J. Cancer; 93: 607–10.
  73. Lam LK, Sparnins VL, Wattenberg LW (1982). Isolation and identification of kahweol and cafestol palmitate as active constituents of green coffee beans that enhance glutathione S-transferase activity in the mouse. Cancer Res., 42, 1193–1198.
  74. Larsson SC, Wolk A (2007). Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology, 132: 1740–45.
  75. Lawrence T, Willoughby DA, Gilroy DW (2002). Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat. Rev. Immunol., 2, 787–795.
  76. Mahmoud AM, Hussein OE, Hozayen WG et al. (2020)Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats. Environ Sci Pollut Res 27, 7910–7921.
  77. Masterton GS, Hayes PC (2010). Coffee and the liver: a potential treatment for liver disease? Eur J Gastroenterol Hepatol;22:1277-1283.
  78. medicalnewstoday.com/articles/320089#Coffee-and-the-liver accessed March 2021.
  79. Mellbye FB, Jeppesen PB, Hermansen K, Gregersen S (2015). Cafestol, a bioactive substance in coffee, stimulates insulin secretion and increases glucose uptake in muscle cells: studies in vitro. J. Nat. Prod. 78, 2447e2451.
  80. Michels KB, Willett WC, Fuchs CS, Giovannucci E (2005). Coffee, Tea, and Caffeine Consumption and Incidence of Colon and Rectal Cancer. J Natl Cancer Inst;97:282-92. Gallus S, Tavani A, Negri E, La Vecchia C (2002). Does coffee protect against liver cirrhosis? Ann. Epidemiol., 12, 202–205.
  81. Modi AA, Feld JJ, Park Y, Kleiner DE, Everhart JE, Liang TJ, et al. (2010). Increased caffeine consumption is associated with reduced hepatic fibrosis. Hepatology; 51:201–209.
  82. Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DM, Harrison SA (2012). Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology; Feb; 55(2):429-36.
  83. Montesinos CM, Desai A, Chen JF, Yee H, Schwarzschild MA, Fink SJ, Cronstein BN (2002). Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A2A receptors. Am. Soc. Invest. Path., 160, 2009–2018.
  84. Montesinos CM, Desai A, Delano D, Chen JF, Fink JS, Jacobson MA, Cronstein BN (2003). Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis and Rheum., 48, 240–247.
  85. Moreno M G, Chavez E, Aldaba-Murato L, Segovia J, Vergara P, Tsutsumi V, Shibayama M, Rivera-Espinoza Y, Muriel P (2011). Coffee prevents CCl4-induced liver cirrhosis in the rat. Hepatol Int., Jan 25.
  86. Muriel P, Arauz J (2012). Coffee and Liver Health, in Coffee: Emerging Health Effects and Disease Prevention. Ch. 7.
  87. Murillo MM, Carmona-Cuenca I, Del Castillo G, Ortiz C, Roncero C, Sanchez A, Fernandez M, Fabregat I (2007). Activation of NADPH oxidase by transforming growth factor-beta in hepatocytes mediates up-regulation of epidermal growth factor receptor ligands through a nuclear factor-kappa-B dependent mechanism. Biochem. J., 405, 251–259.
  88. Nehlig A, Daval JL, Debry G (1992). Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Research Reviews, 17(2), 139–170.
  89. Nemeth ZH, Leibovich JS, Deitch EA, Sperlagh B, Virag L, Sylvester VE, Szabo C, Hasko G (2003). Adenosine stimulates CREB activation in macrophages via a p38 MAPK-mediated mechanism. Biochem. Biophys. Res. Comm., 312, 883–888.
  90. Ohta A., Sitkovsky M (2001). Role of G-protein-coupled adenosine receptors in down regulation of inflammation and protection from tissue damage. Nature, 414, 916–920.
  91. Pérez-Burillo S, Rajakaruna S, Pastoriza S, Paliy O, & Angel Rufian-Henares J. (2020). Bioactivity of food melanoidins is mediated by gut microbiota. Food Chemistry, 316 (126309).
  92. Poisson L, Blank I, Dunkel A, & Hofmann T. (2017). The chemistry of roasting – Decoding flavor formation. In B. Folmer (Ed.), The craft and science of coffee (pp. 273–309). Cambridge, MA: Academic Press.
  93. Revan S, Montesinos CM, Naime D, Landau S, Cronstein BN (1996). Adenosine A2 receptor occupancy regulates stimulated neutrophil function via activation of a serine/threonine protein phosphatase. J. Biol. Chem., 271, 17114–17118.
  94. Ruhl C, Everhart J (2005). Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology, 128, 24–32.
  95. Saab S, Mallam D, Cox G A, & Tong M J (2013). Impact of coffee on liver diseases: a systematic review. Liver International, 34(4), 495–504.
  96. Sanchez GI, Jimenez EF, Saura CF (2005). In vitro antioxidant activity of coffees brewed using different procedures (Italian, espresso and filter). Food Chem. 2005, 90, 133–139.
  97. Scalbert A, Williamson G (2000). Dietary intake and bioavailability of polyphenols. J. Nutr., 130, 2073S–2085S.
  98. Scharf G, Prustomersky S, Huber WW (2001). Elevation of glutathione levels by coffee components and its potential mechanisms. Adv Exp Med Biol., 500, 535–539.
  99. Schilter B, Perrin I, Cavin C, Huggett AC (1996). Placental glutathione S-transferase (GST-P) induction as a potential mechanism for the anticarcinogenic effect of the coffee-specific components cafestol and kahweol. Carcinogenesis 1996, 17, 2377–2384.
  100. Sedlak TW, Saleh M, Higginson DS, Paul BD, Juluri KR, Snyder SH (2009). "Bilirubin and glutathione have complementary antioxidant and cytoprotective roles". Proceedings of the National Academy of Sciences of the United States of America. 106 (13): 5171–6.
  101. Shen H, Rodriguez A, Shiani A, Lipka S, Shahzad G, Kumar A, Mustacchia P (2015). Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis. Therapeutic Advances in Gastroenterology; July. DOI: 10.1177/1756283X15593700.
  102. Shi H, Dong L, Zhang Y, Yanhua B, Zhao J, Zhang L (2009). Protective effect of a coffee preparation (Nescafe pure R ) against carbon tetrachloride-induced liver fibrosis in rats. Clin. Nutr. 2009, 29, 399–405.
  103. Shimazu T, Tsubono, La Vecchia C (2005). Coffee, liver enzymes, cirrhosis and liver cancer. J. Hepatology 2005, 42, 444–446.
  104. Shin JW, Wang J H, Kang J K, Son C G (2010) Experimental evidence for the protective effects of coffee against liver fibrosis in SD rats. J. Sci. Food Agric., 90, 450–455.
  105. Sitkovsky MV, Lukashev D, Apasov S, Kojima H, Koshiba M, Caldwell C, Ohta A, Thiel M (2004). Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Ann. Rev. Immunol., 22, 657–682.
  106. Sugiyama H, Chen P, Hunter MG, Sitkovsky MV (1997). Perturbation of the expression of the catalytic subunit C alpha of cyclic AMP-dependent protein kinase inhibits TCR-triggered secretion of IL-2 by T helper hybridoma cells. J. Immunol. 1997, 158, 171–179.
  107. Tacke F, Luedde T, Trautwein C (2009). Inflammatory pathways in liver homeostasis and liver injury. Clin. Rev. Allergy Immunol., 36, 4–12.
  108. Tanaka K, Tokunaga S, Kono S, Tokudome S, Akamatsu T, Moriyamad T, Zakoujid H (1998). Coffee consumption and decreased serum gamma-glutamyltransferase and aminotransferase activities among male alcohol drinkers. Int. J. Epidemiol., 27, 438–443.
  109. Tao l, Wei Z, Zhang Y, Zhang M, Zhang Y, Niu X, Zhao Q, Liu Z, Li Y, Diao A (2021) Caffeine promotes the expression of telomerase reverse transcriptase to regulate cellular senescence and aging. Food & Function; Feb.
  110. Torres DM, Harrison SA (2013). Is it time to write a prescription for coffee? Coffee and liver disease. Gastroenterology;144:670-672.
  111. Tverdal A, Skurtveit S (2003). Coffee intake and mortality from liver cirrhosis. Annals of Epidemiology, 13, 419–423.
  112. Venugopal R, Jaiswal, AK (1996). Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H: quinone oxidoreductase1 gene. Proc. Nat. Acad. Sci. USA, 93, 14960–14965.
  113. Victor-Vega C, Desai A, Montesinos MC, Cronstein BN (2002). Adenosine A2A receptor agonists promote more rapid wound healing than recombinant human platelet-derived growth factor (becaplermin gel). Inflammation., 26, 19–24.
  114. Vitaglione P, Morisco F, Mazzone G, Amoruso DC, Ribecco MT, Romano A, Fogliano V, Caporaso N, and D’Argenio G. (2010). Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology, 52, 1652–1661.
  115. Vitaglione P, Morisco F, Mazzone G, Amoruso DC, Ribecco MT, Romano A, Fogliano V, Caporaso N, D’Argenio G (2010). Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology, 52, 1652–1661.
  116. Wang GF, Shi LP, Ren YD, Liu QF, et. al. (2009). Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo and in vitro. Antivir. Res. 83, 186e190
  117. Wild C, Gong YY (2010). Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis. Jan; 31(1): 71-82.
  118. Yanagimoto K, Ochi H, Lee KG, Shibamoto T (2004). Antioxidative activities of fractions obtained from brewed coffee. J Agric Food Chem. Feb 11;52(3):592-6.
  119. Zeisberg M, Yang C, Martino M, Dunca M, Rieder F, Tanjore H, Kalluri R (2007). Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J. Biol. Chem., 282, 23337–23347.