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Could drinking espresso coffee reduce the risk of Alzheimer‘s disease?

15th August 2023

With a recent study suggesting that components within espresso coffee extract nullified the adverse effects of the Alzheimer‘s-associated tau protein, is drinking coffee a potential lifestyle preventative measure for reducing the risk of such neurodegenerative conditions? Hospital Healthcare Europe‘s clinical writer and resident pharmacist Rod Tucker takes a look at the evidence.

There’s no doubt that coffee is a widely consumed beverage and coffee culture has taken the world by storm from the espresso bars of Italy to the commercial giants on seemingly every street corner. Deemed to be one of the most widely traded commodities in the world, around two billion cups of coffee are consumed worldwide each day, according to the British Coffee Association.

Coffee is prepared and drunk in a number of different ways from dehydrated instant varieties revived by adding boiling water, to the perfect European espresso in which high pressure hot water is passed through 5-7g of finely-ground powder to produce an energising 30 ml serving.

For many years, a large proportion of healthcare professionals advised against drinking coffee, particularly for those with anxiety, arrhythmias, palpitations or tachycardia. This was based on the premise that the stimulant effects of caffeine – of which there’s just over 60mg in a single espresso shot – would most likely exacerbate cardiac arrhythmias. However, there is a lack of evidence to support this view. In fact, it seems that the opposite may be true.

For instance, a meta-analysis of seven observational studies including 115,993 individuals concluded that caffeine exposure is not associated with increased risk of atrial fibrillation, and that it may even be protective.

More recently, a 2022 analysis of data from the UK Biobanks, suggested that two to three daily cups of coffee was associated with a lower incidence of cardiac arrhythmias. But coffee is purported to have a plethora of health benefits, which were extolled in a 2017 umbrella review, which concluded that there were large risk reductions for a range of health outcomes when consuming three to four cups of coffee per day.

The risk of Alzheimer‘s disease

One of the intriguing findings identified in the umbrella review was habitual coffee drinking being linked to a 27% lower risk of developing Alzheimer‘s disease. Some of the earliest evidence identifying a possible protective effect against Alzheimer‘s disease, came from a study in 2002.

Using a case-control study, researchers observed a significant and inverse association between caffeine exposure and Alzheimer‘s disease (odds ratio, OR = 0.40, 95% CI 0.25 – 0.67). Moreover, other work appeared to confirm this benefit, with a further study reporting that drinking three to five cups of coffee a day during midlife was associated with a 65% lower risk of developing dementia or Alzheimer‘s disease during later life.

But this observational study evidence can only be used to demonstrate correlation and not causation. That is to say, just because the two factors of coffee and Alzheimer‘s disease are correlated does not mean that one either causes or protects against the other. However, evidence of a plausible biological mechanism, which accounts for this correlation, helps to support the observed relationship.

For instance, it has been found that caffeine prevents the β-amyloid-induced neurotoxicity in cultured cerebellar neurons of rats via blockade of adenosine A2A. In fact, the authors concluded that their study constituted the first in vitro evidence to suggest that blockade of adenosine A2A receptors, may be the molecular target for the observed beneficial effects of consuming caffeine in relation to the development of Alzheimer’s disease.

Despite this biological plausibility, not all observational studies demonstrate a positive relationship between caffeine intake and cognitive disorders. In a 2015 meta-analysis of 19 studies, the authors found that in all 19 studies caffeine intake was not significantly associated with the risk of cognitive disorders including dementia, Alzheimer’s disease, cognitive impairment and cognitive decline (OR = 0.82, 95% CI 0.67 – 1.01).

But if coffee does offer protection against Alzheimer‘s disease, could this arise from components other than caffeine?

Espresso coffee and tau aggregation

With a good deal of research focusing on the possible protective role of coffee, it has also been recognised that coffee is actually a mixture of a number of bioactive compounds. These include polyphenols, especially chlorogenic acids and caffeic acid in roasted coffee beans; alkaloids, such as caffeine and trigonelline; and the diterpenes cafestol and kahweol. So, is it possible that some of these bioactive agents are responsible for the purported protective effect against Alzheimer’s disease?

A recent study set out to address this issue. The researchers used nuclear magnetic resonance to characterise the molecular composition of an espresso coffee extract. Since aggregation of the protein tau is implicated in the pathophysiology of Alzheimer’s disease, the researchers focused on any components that affected this process. In particular, they considered whether any components in the espresso extract could prevent tau aggregation, condensation – which is a purported mechanism initiating aggregation – and the seeding activity of the tau protein whereby further aggregation occurs once tau fibrils have been formed.

The research uncovered several important actions of the espresso coffee extract in relation to tau. First, the extract had an inhibitory effect on tau fibril formation, preventing aggregation and the ability to induce intracellular tau fibrillisation. Second, the extract interfered with early events (condensation), which led to the accumulation of tau. Finally, the tau fibrils that were formed in the presence of the espresso extract not only had a reduced ability to aggregate, but the resulting species displayed either reduced or no cellular toxicity and were unable to ‘seed‘ further aggregation.

Taken together, the findings suggested that the espresso extract was neuro-protective against tau-induced toxicity in cultured cells. In fact, the authors even suggested that ‘based on the bioavailability of coffee components in the brain, and on the results of our study, we expect that moderate coffee consumption may provide a sufficient amount of bioactive molecules to act separately or synergistically as modulators of tau protein aggregation and toxicity‘.

Is it time to start drinking espresso coffee?

The evidence to date indicates that coffee intake may be a protective factor against Alzheimer‘s disease. Moreover, there is data showing neuro-protective effects for many of the bioactive components within coffee. While much of the evidence is derived from observations studies, one Mendelian randomisation study that avoids the influence of confounders, has shown that genetically predicted higher plasma caffeine levels were associated with a non-significant lower risk of Alzheimer’s disease.

With the totality of the evidence appearing to suggest a possible benefit from drinking coffee in relation to the development of Alzheimer‘s disease, the espresso research was cell-based and therefore preliminary in nature.

Nevertheless, whether drinking espresso coffee over a lifetime might reduce the risk of developing Alzheimer‘s disease remains an intriguing thought and certainly provides basis for future studies.

Oesophageal cancer risk related to higher genetically predicted coffee consumption

1st September 2022

Oesophageal cancer risk is associated with genetically predicted coffee consumption even after adjustment for factors such as body mass index (BMI), smoking initiation and alcohol intake according to the findings of a Mendelian randomisation study by UK and Swedish researchers.

Coffee drinking has been found to have a wide range of health benefits including a reduced risk of cardiovascular disease and cancer.

Coffee contains a wide range of compounds, some of which including kahweol that has been reported to exert anti-cancer properties. Moreover, coffee has been associated with a significant decrease in the risk of colorectal cancer and colon cancer with a higher intake of the beverage also linked to a lower risk of prostate cancer.

Nevertheless, much of the data has been derived from epidemiological studies which can be subject to confounding and reverse causality, i.e., where the direction of causality between to factors is the opposite of what might be expected.

A Mendelian randomisation (MR) study is designed to avoid the problems due to confounding and reverse causality and assesses whether the genetically-predicted levels of a risk factor, for instance, coffee consumption, and a disease outcome, such as oesophageal cancer are associated.

Since genetic variants are present at birth, MR studies reduce the potential for reverse causality and confounding and are therefore more likely to generate a causal interpretation.

In the present study, researchers investigated the association of genetically-predicted coffee consumption and the risk of 22 different cancers which, for example, included those affecting the ovary, thyroid and bladder.

There were a total of 15 single nucleotide polymorphisms (SNPs) identified to be associated with coffee consumption although only 12 of these were used in the analysis. Most of the SNPs were in gene regions (one for example was near a locus linked to the smell/test perception of coffee) that were likely to affect coffee drinking behaviour or behaviour indirectly by altering the metabolism of caffeine.

The researchers tested the association using data from the UK Biobank and also tested these for replication in the FinnGen consortium. The results were then adjusted for differences in genetically-predicted body mass index, smoking and alcohol consumption.

The effect sizes of the associations between genetically-predicted coffee consumption and cancer risk were scaled to a 50% increase in coffee consumption.

Oesophageal cancer risk and coffee consumption

Using a sample of 367,561 European participants, 59,647 had one of the 22 site-specific cancers. However, genetically-predicted coffee consumption was not associated with the risk of any cancer in the main analysis (odds ratio, OR = 1.05, 95% CI 0.98 – 1.14, p = 0.183) even after adjustment for BMI, smoking and alcohol intake.

But when the team looked at digestive system cancers overall, there was an increased risk (OR = 1.28, 95% CI 1.09 – 1.51, P = 0.003) and which remained significant after adjustment for BMI, smoking initiation and alcohol consumption.

This higher risk was largely driven by oesophageal cancer (OR = 2.79, 95% CI 1.73 – 4.50) in the Biobank and remained after adjustment for the effect of BMI, smoking and alcohol intake. In the FinnGen consortium, genetically predicted coffee consumption was associated with a non-significant increase in oesophageal cancer (OR = 2.01, 95% CI 0.57 – 7.05, p = 0.27) and which was attenuated after adjustment for BMI.

Coffee consumption was also associated with an increased risk of multiple myeloma in the Biobank data (OR = 2.25) even after adjustment and a reduced risk of ovarian cancer.

Interestingly, when the researchers looked at coffee consumption and individual’s preferences for drinking, they found that a preference for drinking warm (OR = 2.74) and hot (OR = 5.45) coffee was also significantly associated with a higher risk of oesophageal cancer but, surprisingly, not for very hot.

In a further subgroup analysis based on self-reported coffee intake, the risk of oesophageal cancer was similar among those drinking 1 – 3 cups/day compared with those who did not drink coffee and which the authors suggested might be due to consumption of tea.

The authors concluded that their study found evidence that coffee consumption was causally associated with a risk of oesophageal cancer and that there was some evidence that this was related to a temperature effect.

Carter P et al. Coffee consumption and cancer risk: a Mendelian randomisation study Clin. Nutr 2022

Study suggests increased coffee consumption lowers rate of kidney function decline in diabetics

11th May 2022

A higher level of coffee consumption in type 2 diabetics significantly reduces the rate of decline in estimated glomerular filtration rate

A greater coffee consumption in those with type 2 diabetes is significantly associated with a reduction in the rate of decline in the estimated glomerular filtration rate (eGFR).

This was the key finding from a prospective study by researchers from the Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Chronic kidney disease (CKD) is a non-communicable disease and which usually develops as a consequence of diabetes and hypertension. Disease severity in CKD can be assessed by a low serum creatinine-based eGFR, which indicates excretory kidney function and by a raised urinary albumin.

Lifestyle management is deemed to be a fundamental aspect of diabetes care and this encompasses self-management education and support, medical nutrition therapy, physical activity, smoking cessation counselling and psychosocial care. Nutritional therapy, however, does not just include what foods to eat but also what should be drunk.

One commonly consumed beverage is coffee and a higher coffee consumption, as well as green tea, has been found to be associated with a reduction in all-cause mortality, particularly in patients with type 2 diabetes. Furthermore, some data suggests that a higher coffee consumption is associated with lower risk for incident CKD.

Nevertheless, this finding is not consistent, with other work undertaken in men, find that there was no significant association between coffee consumption and CKD.

What remains unclear though, is if a higher level of coffee consumption in patients with type 2 diabetes would reduce the decline in kidney function.

For the present study, the Japanese team carried out a prospective study of adult diabetic patients attending diabetic clinics throughout the country. They carried out a dietary survey which asked about coffee consumption but also had access to clinical measurements such as blood pressure and eGFR taken at the clinics.

Coffee consumption was recorded as none, less than 1 cup/day, one cup/day or two or more cups/day. The primary outcome was set as a decline in eGFR to <60 mL/min/ 1.73 m2, based on two consecutive measures of eGFR during the follow-up period.

Coffee consumption and decline in eGFR rate

In total, 3,805 patients with type 2 diabetes and a mean age of 64.2 years (44.4% female) and eGFR ≥60ml/min/1.73 m2 were followed-up for a median of 5.3 years.

During the period of follow-up, 840 participants experienced a decline in eGFR of < 60 mL/min/1.73 m2. Using multivariate analysis, the researched found that compared to those who drank no coffee, the adjusted hazard ratio (aHR) for a decline in eGFR associated with drinking less than one cup/day was 0.77 (95% CI 0.63 – 0.97) and this increased slightly to 0.75 (95% CI 0.62 – 0.91) for those drinking two or more cups/day.

The mean eGFR change per year was -2.16ml/min/1.73 m2 with no coffee consumption, and -1.78ml/min/1.73 m2 with two or more cups per day (p for trend 0.03).

There was also no significant effect on coffee drinking and the decline in eGFR based on age, gender, body mass index, smoking status, those who exercised regularly or blood pressure.

The authors concluded that coffee consumption is significantly associated with a lower risk of a decline in eGFR, which suggested a progressive impairment in renal function, in patients with type 2 diabetes.

Komorita Y et al. Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry J Diabetes Investig 2022