Drinking several cups of coffee every day may be linked to a lower risk of developing prostate cancer, suggests a pooled data analysis of the available evidence, published in the online journal BMJ Open.
Prostate cancer is the second most common cancer, and the sixth leading cause of cancer death in men. Nearly three out of four cases occur in the developed world, and since the 1970s, new cases of the disease have risen sharply in Asian countries, including Japan, Singapore, and China.
In a bid to advance understanding of the issue, the researchers trawled research databases for relevant cohort studies published up to September 2020.
They pooled the data from 16: 15 reported on the risk of prostate cancer associated with the highest, compared with the lowest, coffee consumption; 13 reported on the risk associated with an additional daily cup.
The highest level of consumption ranged from 2 to 9 or more cups a day; the lowest level ranged from none to fewer than 2 cups a day.
The included studies were carried out in North America (7), Europe (7) and Japan (2). They included more than 1 million men (1,081, 586) of whom 57,732 developed prostate cancer.
Compared with the lowest category of coffee consumption, the highest category was associated with a reduction in prostate cancer risk of 9%. And each additional daily cup was associated with a reduction in risk of 1%.
Further refining the analysis to localised and advanced prostate cancer, showed that compared with the lowest intake, the highest intake was associated with a 7% lower risk of localised prostate cancer, and a 12%-16% lower risk for advanced and fatal prostate cancer, respectively.
The researchers acknowledge that because of the observational design of the included cohort studies, unmeasured or uncontrolled factors in the original studies may have skewed the pooled risk estimate.
The amount of coffee drunk may also have been misclassified as it depended on recall. And the type of coffee and brewing methods varied among the studies. The design and methods of the included studies also varied, so caution in interpreting the findings is warranted, they say.
Nevertheless, there are plausible biological explanations for their findings, they highlight.
Coffee improves glucose metabolism, has anti-inflammatory and antioxidant effects, and affects sex hormone levels, all of which may influence the initiation, development and progression of prostate cancer, they point out.
And they conclude: “This study suggests that increased coffee consumption may be associated with a reduced risk of prostate cancer. Further research is still warranted to explore the underlying mechanisms and active compounds in coffee.
“If the association is further proved to be a causal effect, men might be encouraged to increase their coffee consumption to potentially decrease the risk of prostate cancer.”
Caffeine is the most widely consumed psychoactive or central nervous system (CNS) stimulant in the world . This plant secondary metabolite belongs to the group of xanthine alkaloids and is found in more than 60 different plant species but can also be produced synthetically. Caffeine is consumed in beverages and foods.
It is a well-known component of coffee and green and black tea as well as chocolate and is used as a food additive, for example, in soft drinks or bottled water. The caffeine content ranges from as little as 2 mg caffeine per 100 mL in beverages based on cocoa powder to as much as 200 mg of caffeine per 100 mL of strong espresso coffee [for an overview of caffeine content in common food products, see 2].
In addition, various pharmaceutical products contain caffeine including over-the-counter pain and weight-loss medications and numerous prescription drugs, including Midol® to treat menstrual symptoms, Vanquish® for headache and general pain relief, orphenadrine as a prescription muscle pain medication, and Fiorinal® and Synalgos®-DC as prescription headache medications [3-6].
Caffeine is rapidly and completely absorbed after ingestion. It crosses cell membranes, including the blood-brain barrier, and distributes throughout the body. Although best known as a CNS stimulant, caffeine also acts on myocardial tissue, respiration, smooth muscles, and kidneys (for a thorough review of the pharmacology of caffeine, the reader is referred to Arnaud  and references therein).
More recently, antifibrogenic, anti-inflammatory, and antioxidant activities of caffeine have been reported . Further effects of caffeine have been observed in the microvasculature in the skin, including an enhanced microvascular function in cutaneous arterioles and capillaries  and improved endothelium-dependent microvascular responses in the forearm skin .
Caffeine has been linked to an increased metabolism  and is considered to be an ergogenic aid . Several effects of caffeine are thought to enhance performance, particularly for endurance sports (see Pesta et al.  for an overview of these effects). In 1984, caffeine was banned by the World Anti-Doping Agency (WADA) after reports of its usage as a doping agent [14, 15]. It was removed from the list in 2004, as tests were not able to distinguish between social caffeine use and abuse , but remains on the WADA monitoring list .
The stimulating effects of caffeine after ingestion are primarily mediated via adenosine receptors (ARs). ARs are located in the central and peripheral nervous system as well as in various body organs and compartments, such as the heart and blood vessels. The AR-ligand adenosine regulates the release of neurotransmitters in the brain and modulates myocardial oxygen consumption and blood flow in the heart.
As caffeine acts as an antagonist of AR, it can, for example, indirectly affect the release of neurotransmitters, including dopamine, acetylcholine, serotonin, and gamma-aminobutyric acid (GABA) [17, 18]. Additionally, caffeine inhibits intracellular phosphodiesterase (PDE) enzymes. PDEs regulate cyclic nucleotide signaling and are coupled to diverse physiological functions: Inhibition of PDE increases intracellular concentrations of cyclic adenosine monophosphate (cAMP), which in turn activates several enzymes and transcription factors linked to fat oxidation and lipolysis.
An increase in lipolysis results in a stimulation of cell metabolism due to higher levels of energy [19-21]. Taken together, caffeine can increase metabolic activity and therefore promote cell proliferation via providing higher energy levels to the cells .
Benefits and Safety of Caffeine
Over the last decade, more and more publications have emerged that associate ingestion of coffee with beneficial effects in various diseases, covering dementia, liver diseases, diabetes, several types of cancer, and skin conditions as referred to in this paragraph. While it is not always clear if these effects are specifically due to caffeine or due to other substances or combinations of substances contained in coffee, several studies have found a specific association of positive effects of coffee ingestion with caffeine.
The consumption of coffee has been reported to be linked with a decreased dementia risk. Midlife coffee consumption in general was associated with a decreased late life dementia risk, while caffeine intake in particular was associated with a decelerated cognitive decline .
A reduction in the frequency of liver disease through consumption of coffee/caffeine has also been observed , whereby caffeine consumption from regular coffee above a threshold of approximately 2 coffee cup equivalents per day was accompanied with less severe hepatic fibrosis. Furthermore, coffee intake is associated with a decreased risk of type 2 diabetes (T2DM) .
Although epidemiological studies indicate that even decaffeinated coffee can reduce the T2DM risk , a reduction of T2DM risk in postmenopausal women was linked to caffeine-containing coffee only as caffeinated coffee increased levels of sex hormone-binding globulin, which in turn has a strong inverse association with T2DM risk .
In various cancer entities, positive effects of coffee or caffeine have been described, for instance, in prostate cancer, breast cancer, and skin cancer. In a population cohort study, patients with newly diagnosed prostate cancer had a lower coffee consumption compared to the disease-free population .
Subjects with the highest consumption (>3 cups/day) had a 53% lower prostate cancer risk compared to those with the lowest consumption. Further investigations in prostate cancer cell lines found that caffeine significantly reduced their proliferative and metastatic behavior .
Regarding caffeine and breast cancer, protective effects of caffeine may be mediated through a reduced breast volume. Breast volume is associated with breast cancer risk in lean women, and coffee was associated with a reduction in breast volume in women carrying a specific gene variant, the CYP1A2*1F C-allele .
For basal cell carcinoma, caffeine intake from coffee and other dietary sources was inversely associated with basal cell carcinoma risk, while decaffeinated coffee consumption was not associated with a similar decrease . Oral administration of caffeine affects the skin due to an inverse association between drinking coffee and the risk of incident rosacea. No decreased association was seen with decaffeinated coffee .
In general, oral caffeine consumption is safe for healthy adults at doses typically found in commercially available foods and beverages . However, very high doses of ingested caffeine can produce undesirable effects on mental functions such as fatigue, nervousness, and feelings of anger or depression. The European Food Safety Authority (EFSA) concludes that for healthy adults daily intakes of up to 400 mg per day (about 5.7 mg/kg per day) do not raise safety concerns .
Caffeine is well known for its excellent skin penetration properties: In cosmetic formulations, caffeine is currently in use in concentrations up to 30 mg/mL [30, 31], whereby caffeine penetration through the skin is independent of the skin’s thickness [32, 33].
The combination of ibuprofen together with caffeine (i.e., Thomapyrin® Tension Duo) has been found to provide better pain relief in acute pain and headache than ibuprofen alone . The additive-drug-specific benefits have been demonstrated especially in postoperative pain and migraine headache for a range of different drug combinations.
There is evidence that oral caffeine in combination with ibuprofen can deliver good analgesia at lower doses of ibuprofen. Recently, the effective delivery of caffeine as a hydrophilic model drug out of a topical applied formulation into and through hair follicles was demonstrated [35-37].
Therefore, it was shown that hair follicles and their surrounding regions are a possible treatment route targeted by optimized formulations. In addition to that, the potential of caffeine-catalyzed gels for novel, biocompatible oral drug-delivery systems and biomedical devices has been investigated . In these tailorable systems, caffeine can act as a biocompatible catalyst to create a gel formulation that can be drug-loaded during manufacturing.
These recent investigations strongly emphasize the positive impact the versatile and safe natural active ingredient caffeine can have on human health on a variety of levels. Taken together, there is a growing body of evidence highlighting the positive effects of caffeine in several disease settings, indicating that caffeine is a potent substance associated with multiple beneficial effects. When applied in adequate doses, the ingestion and cosmetic application of caffeine can considered to be safe.
reference link : https://www.karger.com/Article/Fulltext/508228#:~:text=In%20a%20population%20cohort%20study,those%20with%20the%20lowest%20consumption.
More information: Coffee consumption and risk of prostate cancer: a systematic review and meta analysis, BMJ Open (2021). DOI: 10.1136/bmjopen-2020-038902