EXPERT REACTION: Caffeine may help cells' 'batteries' boost heart health in mice

People who habitually drink coffee are less likely to develop heart disease and type 2 diabetes. However, we don’t know whether or not this association is causal, or whether such people are also likely to engage in other behaviours that might be driving this association (eg. diet and exercise).

This current study describes a series of laboratory experiments that indicate that caffeine may improve heart function, and repair after heart attack, via actions on the mitochondria, and in particular, the protein mitochondrial p27.

These mechanisms support a causal role for caffeine and coffee for improving heart health. But a randomized trial is required to provide more definitive proof that drinking coffee improves heart health in humans. In the meantime, the available evidence suggests that drinking a couple of coffees a day is unlikely to be causing you harm, and may actually be good for your heart.

The article presents plausible evidence that reasonable blood levels of caffeine, that might be achieved in humans by drinking large amounts of coffee for a few days, might have a positive impact on the risk of suffering bad cardiac events like heart attack. This work seems to have been done expertly by a group of German scientists, but does not address whether this can be confirmed in the clinic. They largely used mice to study this, over a period of 10 days, in short-term studies.

These studies have obvious limitations in terms of how the findings translate into elderly humans drinking coffee over a prolonged period of time. Mice hearts behave very differently to human hearts, especially with respect to capacity to withstand heart attack and cardiac repair or regeneration after heart attack - that happens to some extent, especially in young mice. The team did however study in some depth the effect of ageing the mice, and what happens if they are diabetic and obese- as are many patients who suffer heart disease. Indeed, the acute effects of caffeine were more remarkable in the older or diabetic mice. They also explored precisely how these effects of caffeine are produced biochemically- and found a really new way that this much-explored but natural drug works. And the pharmacological mechanism makes sense in terms of “protecting" the heart -as far as it goes.
 
However, caffeine in high doses (or lots of espressos) has some downsides too - especially on the heart and brain. It is a stimulant - and probably the wrong kind of stimulant (even dangerous) for someone who might suffer a heart attack, or has just had one. The potentially beneficial effects of caffeine on the arteries of the heart are interesting – but not really proven to help much in the long term. It is also important to emphasise that drinking lots of coffee can in no way replace the proven benefits of reducing blood cholesterol (whether by drugs or attention to diet and lifestyle), and keeping blood pressure normal (again drugs or lifestyle).

Also unknown, and not studied in these reports, are how long the demonstrated effects of caffeine last – the mice were given the equivalent of coffee for only 10 days. Over many years, especially in the elderly, benefits of many such drugs can wane – and may present other downsides in the longer term. So all in all, this report is interesting, but much more needs to be done to determine whether  coffee might be of any consequence in elderly, obese or diabetic patients in the longer term. And there is no suggestion here that drinking coffee could offer as much protection or prevention of heart attack and stroke, as does reducing high cholesterol and managing high blood pressure. These remain the main line of defence against devastating heart attacks, strokes and heart failure.

Over the last two years there have been two umbrella reviews of coffee consumption, both of which indicated that coffee can be part of a healthful diet and may be associated with some benefits.

In one review of 112 meta-analyses of observational studies, coffee was associated with a probable decreased risk of breast, colorectal, colon, endometrial, and prostate cancers; cardiovascular disease and mortality; Parkinson's disease; and type-2 diabetes (8 of 59 outcomes examined). This benefit could be due to caffeine or coffee polyphenols or both combined.

In 20 selected meta-analyses of observational studies, caffeine was associated with a probable decreased risk of Parkinson's disease and type-2 diabetes and an increased risk of pregnancy loss (3 of 14 outcomes examined). The second study involved 201 meta-analyses of observational research with 67 unique health outcomes. The largest relative risk reduction was seen at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83), cardiovascular mortality (0.81 ), and cardiovascular disease (0.85)  High versus low consumption was associated with an 18% lower risk of incident cancer (0.82). Results for cardiovascular mortality and total mortality were similar for decaffeinated coffee.

Comments in relation to these papers called for randomised controlled trials in humans of coffee and caffeine. For diabetes specifically, decaffeinated coffee was just as protective as caffeinated suggesting the benefit may come from the polyphenols and not caffeine. In addition, in humans and animals acute caffeine ingestion increases insulin resistance and exacerbates postprandial glycemia whereas chronic caffeine ingestion reverses aging associated insulin resistance in rats via increasing the glucose transporter glut 4. 

How does this paper on p27 in mitochondria in mice help?  It suggests that caffeine may be responsible for some benefit in terms of cardiovascular risk by improving mitochondrial function via stimulation of p27, suggesting chronic coffee consumption may provide benefit through both polyphenols and caffeine. In type 2 diabetes it is argued that impaired mitochondrial function is part of the causative pathway (or just secondary to diabetes) but it is a controversial area. Caffeine should improve mitochondrial function in muscle and improve insulin sensitivity in humans if they behave the same as mice. In humans, data on p27 is sparse - a polymorphism in the gene may be related to stent blockage while mutations are associated with endocrine tumours but nothing has been observed in relation to type 2 diabetes. Overall it would appear that it is not necessary to drink decaffeinated coffee."