Fueling the Alzheimer’s brain with fat

LONDON – A 3-month diet comprised of 70% fat improved cognition in Alzheimer’s disease patients better than any anti-amyloid drug that has ever been tested.

In a small pilot study, Alzheimer’s patients who followed the University of Kansas’s ketogenic diet program improved an average of 4 points on one of the most important cognitive assessments in dementia care, the Alzheimer’s Disease Assessment Scale–cognitive domain (ADAS-cog). Not only was this gain statistically significant, but it reached a level that clinical trialists believe to be clinically meaningful, and it was similar to the gains that won Food and Drug Administration approval for donepezil in 1996, according to Russell Swerdlow, MD, director of the University of Kansas Alzheimer’s Disease Center in Fairway.

To put the results in perspective, donepezil was approved on a 4-point spread between the active and placebo arm over 3 months, said Dr. Swerdlow, who is also the Gene and Marge Sweeney Professor of Neurology at the university. Part of this difference was driven by a 2-point decline in the placebo group. Relative to its baseline, the treatment group improved, on average, by about 2 points.

But in the Ketogenic Diet Retention and Feasibility Trail (KDRAFT), also 3 months long, patients’ ADAS-cog scores didn’t decline at all. Everyone who stayed with the diet and kept on their baseline medications improved, although to varying degrees.

KDRAFT was very small, with just 10 patients completing the intervention, and lacked a comparator group, so the results should be interpreted extremely cautiously, Dr. Swerdlow said in an interview. “We have to very careful about overinterpreting these findings. It’s a pilot study, and a small group, so we don’t know how genuine the finding is. But if it is true, it’s a big deal.”

Diet and dementia

Emerging evidence suggests that modifying diet can help prevent Alzheimer’s and may even help AD patients think and function better. But this research has largely focused on the heart-healthy diets already proven successful in preventing and treating hypertension, diabetes, and cardiovascular disease. Most notably, the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet cut the risk of AD by up to 53% (Alzheimers Dement. 2015 Sep;11[9]:1007-14) and also slowed aging-related cognitive decline (Alzheimers Dement. 2015 Sep; 11[9]:1015-22).

MIND is a combination of the low-salt, plant-focused DASH diet, and the heart-healthy Mediterranean diet. It is a moderate-fat plan, with a ratio of 33% fat, 38% carbohydrates, and 26% protein. Ideally, only 3% of the fat should be saturated, so MIND draws on olive oil, nuts, and other foods with monounsaturated fats, largely eschewing animal fats. It’s generally considered fairly easy to follow, since it allows a wide variety of whole grains, beans, nuts, fruits, vegetables, salads, fish, and poultry. Butter, red meat, fried foods, full-fat dairy, and fast foods are strict no-nos.

A ketogenic diet, however, turns MIND on its head. With a 70% fat, 20% protein, 10% carbohydrate ratio, a typical ketogenic diet nearly eliminates most fruits, and virtually all starchy vegetables, beans, and grains. It does, however, incorporate a large amount of fat from many sources, including olive oil, butter, cream, eggs, nuts, all kinds of meat, and fish. For a ketogenic diet, Dr. Swerdlow said, the ratio of fat to protein and carbs is more critical than the source of the fat.

MIND was designed to prevent the cardiovascular and endocrine disorders than predispose to dementia over the long term. But a ketogenic diet for patients with Alzheimer’s acutely manipulates the brain’s energy metabolism system, forcing it to use ketone bodies instead of glucose for fuel.

In normal energy metabolism, carbohydrates provide a ready supply of glucose, the brain’s primary fuel. When carbs are limited or absent, serum insulin decreases and glucagon increases. This promotes lipolysis. Ketones (primarily beta-hydroxybutyrate and acetoacetate) are formed in the liver from the newly released fatty acids, and released into the circulation, including into the brain during times of decreased glucose availability – a state characteristic of Alzheimer’s disease.