Effects of caffeine on rabbits

“A cup of coffee a day could keep Alzheimer’s at bay,” says the Daily Mail today. It reports that scientists have found that caffeine protects the brain from the harmful effects of high cholesterol, which they say is a risk factor for Alzheimer’s. It explains that previous studies have suggested that cholesterol can cause ‘leaks’ in the ’blood-brain barrier’, which protects the brain from harmful substances in the bloodstream. It concludes that caffeine appears to “maintain levels of proteins key in keeping the barrier strong”.

This study used rabbits fed a cholesterol-enriched diet for 12 weeks as a model for what happens in humans who are developing Alzheimer’s. Some of the rabbits were given 3mg of caffeine a day, which the scientists say is the same as a daily cup of coffee for a person. After three months, “the blood-brain barrier, which protects the central nervous system, was ’significantly’ more intact in the rabbits that received caffeine”. Although, animal models are extremely valuable for studying human diseases, it is not clear how representative this particular animal model is of this very complex human disease.

Alzheimer’s is a disease where protein plaques and tangles develop in and around the nerve cells in the brain. The cause of this debilitating disease remains unknown, but age and hereditary factors are considered the strongest indicators of risk. Certain lifestyle factors have been suggested as potential contributors to the development of the disease. However, the role, if any, of high cholesterol is unclear. This study is not sufficiently robust for us to draw any conclusions about the effects of caffeine on Alzheimer’s disease. At this point, it should not lead anyone to change their consumption of caffeine.

Where did the story come from?

Dr Xuesong Chen and colleagues from the University of North Dakota in the USA carried out the research. The study was funded by the US National Center for Research Resources. It was published in the Journal of Neuroinflammation, a peer-reviewed journal.

What kind of scientific study was this?

This was an experimental study in rabbits. It looked at the effects of caffeine on the membrane that separates the brain from the blood vessels (the blood-brain barrier, or BBB). The BBB helps to protect the brain and regulate its environment.

Rabbits fed cholesterol-enriched diets were used here as models of Alzheimer’s disease. High levels of cholesterol in the blood increase the ’leakiness‘ of the BBB. There is a theory that this may play a role in the disruption of the BBB seen in diseases such as Alzheimer’s. Studies have suggested that caffeine can lead to improvements in animal models of Alzheimer’s disease. The researchers wanted to look at whether such improvements occur because the caffeine protects the BBB against cholesterol-induced damage.

The researchers randomly assigned 24 rabbits to four groups: normal rabbit food (chow), normal chow plus caffeine (3mg daily in drinking water), chow with 2% added cholesterol, or chow with 2% added cholesterol and caffeine. The rabbits ate these foods for 12 weeks after which the researchers looked at the effects on the BBB in three parts of their brains. They assessed BBB leakage by seeing if two proteins that are usually found in the bloodstream but not in brain tissue had leaked into the brain. They also observed whether a dye injected into the bloodstream leaked into the brain. Furthermore, the researchers looked at the levels of two proteins that are involved in keeping the BBB intact and blocking leakage.

For each of these experiments they used two rabbits from each group, and examined six slices from each of the areas of the brain.

What were the results of the study?

The researchers found that the cholesterol-enriched diet increased BBB leakage. In the rabbits that had caffeine added to their cholesterol-enriched diet, this leakage did not occur. They also found that rabbits fed a cholesterol-enriched diet had reduced levels of two proteins involved in keeping the BBB intact and blocking leakage. This reduction was not seen in rabbits that had caffeine added to their cholesterol-enriched diet.

Caffeine did not affect the levels of cholesterol in the blood, either in rabbits fed a normal or a cholesterol-enriched diet.

What interpretations did the researchers draw from these results?

The researchers concluded that daily intake of caffeine over a 12-week period protects the BBB against the effects of a cholesterol-enriched diet. They say that “caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer’s disease”.

What does the NHS Knowledge Service make of this study?

This study is not sufficiently robust for us to draw any conclusions about the effects of caffeine on Alzheimer’s disease.

The main reason for this is that it is not clear how rabbits fed on a high-cholesterol diet for 12 weeks can be representative of high-cholesterol diets in humans, the effects of cholesterol on the human BBB, or how this would relate to Alzheimer’s disease. Even if this animal model does mimic what happens in humans, the researchers would need to show that caffeine prevents or at least slows the formation of plaques in the brain, as well as the cognitive changes associated with the disease. These effects would first need to be tested in other animal models of Alzheimer’s disease before such a treatment could begin to be tested on humans.

The cause of this debilitating disease remains unknown, with age and hereditary factors considered the strongest indicators of risk. Certain lifestyle factors have been suggested as potential contributors to the development of the disease. However, the role, if any, of high cholesterol is unclear. This research should not lead anyone to change their consumption of caffeine.

Sir Muir Gray adds...

I like coffee, but will neither increase nor decrease my intake on the basis of animal studies.