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Is Coffee Good or Bad for You?

Is Coffee Good or Bad for You?
Date Published: 08/03/2022
Date Modified: 09/07/2022

Coffee contains hundreds of biologically active compounds that influence long-term health. Coffee consumption is associated with lower all-cause and cardiovascular (CV) mortality as well as protection from diabetes, cardiovascular disease, neurodegenerative diseases, liver diseases, cancer, and asthma. Additionally, coffee may improve fertility [1,2]. Three or four cups of coffee per day appears to be safe and is associated with coffee’s most beneficial effects. Most coffee studies are based on observational data, and there have been few randomized, controlled trials.


What are the biologically active compounds in coffee?

The bioactive compounds in coffee include polyphenols, especially chlorogenic acids in green beans and caffeic acid in roasted coffee beans, along with alkaloids (caffeine and trigonelline, and diterpenes (cafestol and kahweol) [3]. Many of these compounds have overlapping effects.

Green coffee beans contain a group of polyphenols called chlorogenic acids. Green coffee extract is sold in supplement form to provide a concentrated dose of chlorogenic acids. These compounds have been shown to reduce blood pressure, reduce blood glucose, elevate mood, and destroy certain infectious bacterial species. Chlorogenic acid can lower both systolic (~2.5 mmHg) and diastolic (~1.5mmHg) blood pressure.

This reduction in blood pressure is not a result of changes in nitric acid production or endothelial function [4]. Instead, chlorogenic acids inhibit an enzyme called alpha-glucosidase, which is produced by cells of the small intestine to break down complex carbohydrates and disaccharides like amylopectin (potato starch) and sucrose. This reduces the uptake of glucose during digestion [5-8]. A small pilot study of elderly individuals found that decaffeinated coffee with high chlorogenic acid content improved mood [9]. Other studies have yielded mixed results.

Chlorogenic acids in coffee have also been shown to possess antibacterial properties. Chlorogenic acids inhibit sortase A, an enzyme, in staphylococcus aureus. Sortase A is also an enzyme, and it links proteins in the bacterial cell wall. Therefore, inhibiting sortase A causes the bacterial wall to break down, which is lethal to bacteria subject to this effect [10]. This phenomenon may be a double-edged sword. Some healthy gut microbiota, including enterococci, are also subject to membrane destruction resulting from the inhibition of sortase A [11].

Caffeic acid, which is highly concentrated in roast coffee beans, has antioxidant, anti-inflammatory, anti-cancer, and anti-viral properties. It may also prevent toxicity related to chemotherapy and radiation, reduce the likelihood of developing diabetes, reduce exercise-related fatigue, and help stave off neurodegenerative disease.

Caffeic acid’s anticancer properties stem from its antioxidant and pro-oxidant capacities. These properties are a function of its chemical structure, which has free OH groups attached to phenol rings.

Caffeic acid

The effects of CAPE

If caffeic acid is esterified, it becomes caffeic acid phenethyl ester (CAPE), which has several effects on the body, including inhibition of DNA methylation. DNA methylation is associated with cancer, atherosclerosis, imprinting disorders, and cardiovascular diseases [12].

Additionally, CAPE can also destroy cancer cells. CAPE enters cancer cells where DNA is more likely to be uncoiled and interacts with copper to form hydroxyl radicals. Hydroxyl radicals react readily with DNA to cause DNA strand breaks. This inhibits cancer cell division and can cause apoptosis [13].

In vitro studies show that caffeic acid inhibits influenza, herpes simplex, polio virus, and HIV [14]. Caffeic acid exerts its antiviral effects through multiple mechanisms. When viruses attempt to inject viral DNA into cells, CAPE can break the DNA strands before they are integrated into chromosomal DNA. CAPE has also been shown to inhibit the action of viral integrases, which are enzymes that splice viral DNA into our chromosomes. If this step is nullified, it is difficult for the virus to truly hijack the DNA replication machinery of the cell.

The viral Tax protein, which plays a pivotal role in the development of adult T-cell leukemia (ATL), is directly inhibited by CAPE. CAPE also inhibits NFκB, undermining the work of Tax. The ability of Tax to activate the NF-κB pathway plays an essential role in HTLV-1-induced cellular transformation [15].

Caffeic acid is believed to prevent UV-B radiation damage in the leaves of plant species as well as X-ray radiation damage in animals during preclinical testing. The precise mechanism through which this occurs is not well understood [13]. X-ray-induced heart damage in rats was prevented by early treatment involving CAPE [16]. Caffeic acid was also shown to prevent hematopoietic stem cell damage in the bone marrow of mice subjected to total body irradiation [17].

Researchers have found that caffeic acid exhibits significant potential as an antidiabetic agent by reduction of hepatic glucose output and an improvement in adipocyte glucose uptake, insulin secretion, and antioxidant capacity [18].

Caffeic acid has been shown to decrease exercise-induced fatigue in animal studies. Treated animals have demonstrated higher exercise tolerance, reduced blood lactate, and reduced markers of liver oxidation [19]. Furthermore, CAPE appears to protect against hyperthermal stress induced by endurance exercise [20].

Studies suggest that CAPE may be useful in treating neurodegenerative diseases. CAPE treatment decreased beta amyloid-induced neuronal apoptosis and neuroinflammation, improved learning and memory, and protected mice against decrements in spatial cognition [21]. In another study using human neuroblastoma cells, fruit flies, and mice, CAPE was shown to improve disease symptoms and activate physiological functions. CAPE-treated mice showed increased levels of the neurotrophin BDNF, the neural progenitor marker Nestin, and the differentiation marker NeuN, both in the cerebral cortex and hippocampus. Collectively, these findings suggest that caffeic acid could slow the progression of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, among others [22-24].

Caffeine appears to reduce cardiovascular disease (CVD) risk through multiple mechanisms. It appears to favorably regulate the expression of LDLR and PCSK9. The expression of these genes exerts a great deal of control over LDL levels, which are thought to be important indicators of CVD risk.

This common compound was also shown to reduce circulating levels of PCSK9 and increase LDLR expression. The mechanism behind these changes was a caffeine-induced increase in liver endoplasmic reticulum (ER) Ca+2 levels. Increased ER Ca+2 levels, in turn, block SREBP2, which is responsible for the regulation of PCSK9. Inhibition of PCSK9 leads to an increase in the low-density lipoprotein receptor (LDLR), which is essentially a docking point where “bad” cholesterol can be taken out of circulation [25].

Caffeine is the most consumed psychoactive substance on earth. It promotes wakefulness by blocking adenosine receptors in the brain. It is absorbed and metabolized in the liver by cytochrome P450 enzymes. Paraxanthine is the major metabolite of caffeine in plasma, while methylated xanthines and methyluric acids are the main metabolites found in urine.

The documented health benefits of caffeine include improvements in mood and behavior and exercise performance, antioxidant and anti-inflammatory properties, antimicrobial defenses, and slowed progression in neurodegenerative and liver disease. However, too much caffeine can induce cardiac arrhythmias and disturbances in normal sleep patterns while interfering with calcium balance and glucose metabolism. Insulin resistance effects and carcinogenicity have also been documented. Some studies indicate potentially adverse effects associated with fertility and early development [26].

Trigonelline, like caffeine, is an alkaloid. It reduces blood sugar and serum lipid levels, has antitumor and antiviral properties, and is neuroprotective [27-29]. It also appears to reduce platelet aggregation. The multiple mechanisms behind trigonelline’s function are not well understood, but it is known that trigonelline affects beta cell regeneration, insulin secretion, reactive oxygen species [30], axonal extension, and neuron excitability [31].

Cafestol and kahweol are natural diterpenes extracted from coffee beans. These compounds increase fat circulation in the bloodstream, downregulate inflammation mediators, increase glutathione (GSH), prevent tumor blood vessel formation, induce apoptosis in tumor cells, protect the liver, and have anti-diabetic properties. Additionally, these compounds can play important roles in bone remodeling and loss. 

Coffee and obesity

Several bioactive compounds in coffee, including chlorogenic acid, caffeine, trigonelline, and magnesium, have demonstrated an anti-obesity benefit [32]. A meta-analysis of coffee drinkers found conflicting results, but it indicated that men may gain a modest weight loss benefit from coffee consumption [33].

Side effects of coffee

Coffee’s high caffeine content carries with it some risks, including anxiety, insomnia, headaches, tremulousness, and palpitations. Coffee may also increase risk of fracture in women, and when consumed in pregnancy, coffee increases the risk of low birth weight and preterm labor [34].


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About the author
Stephen Rose

Stephen Rose

Chris is one of the writers at His interest in regenerative medicine and aging emerged as his personal training client base grew older and their training priorities shifted. He started his masters work in Bioengineering at Harvard University in 2013 and is currently completing his PhD at SUNY Polytechnic University in Albany, NY. His dissertation is focused on the role of the senescent cell burden in the development of fibrotic disease. His many interests include working out, molecular gastronomy, architectural design, and herbology.