A major theory of Alzheimer’s is that it develops through an accumulation of inflammation in the parts of brain cells that do not contain DNA. The inflammation theory of Alzheimer’s was proposed by Alois Alzheimer, the discoverer of the disease, nearly a century ago. He noticed that people who had head injuries or brain infections tended to get the disease. Arthritis sufferers who take copious quantities of anti-inflammatory medications tend not to get AD.
The inflammation theory explains the progress of AD as a series of reactions in neurofibrillary tangles in brain tissue. Injured brain cells send a call to the immune system for a “clean-up crew.” These dead or dying brain cells attract macrophages, the white blood cells activated by bacterial infection or inflammation.
Macrophages break down the dead tissue, but the blood-brain barrier (the structure that makes blood “seep” in and out of the brain) does not allow the macrophages to leave. Eventually so many macrophages break down so many cells that the electrical connections of the brain become clogged with debris.
The inflammation theory matches what scientists know about changes in connections in the brain. At its peak performance state, usually around the age of 30, the human brain may have up to 10,000 connections per each of its approximately 100 billion nerve cells, yielding as many as 1,000 trillion cell-to-cell connections, that is, a quadrillion nerve pathways. In Alzheimer’s disease up to 90 percent of these connections are lost. By the end of life, an Alzheimer's patient may have virtually nothing remaining of the CA1 region of the hippocampus, the region of the brain in which memories are formed. If something could allow the brain to repair itself, give the demands on circulation a “rest” so that macrophages and inflammatory chemicals in the brain could clear out of circulation, however, AD might be preventable.
The something that may allow the brain to repair itself is caloric deprivation. Scientists long ago noticed that AD is a little more than half as frequent in Asia as it is in North America, Europe, Australia, New Zealand. They also noticed that people in Asia tend to consume a little more than half as many calories as people in North America, Europe, Australia, and New Zealand.
Calorie comparisons are a clumsy way of comparing food intake, since people who eat more tend to have not only greater fat mass, but also greater muscle mass. Heavier people also tend to use their muscles less efficiently. For these reasons, the real significance in the differences in caloric intake requires more careful inspection.
The weight of the scientific evidence is that AD is the result of cumulative oxidative stress on the tissues of the brain. Oxidative stress occurs during oxidation, the burning of glucose in cells for fuel. Damage caused by oxidative stress, whatever the cause, is most easily repaired when less oxidation is going on. That is, oxidative damage to the tissues of the brain is lowest when food intake is lowest.
Researchers have investigated whether the brain benefits more from reducing calorie intake all the time, that is, the nearly impossible task of trying to force a large appetite to be satisfied with a little food on a lifelong basis, or by periodic, short-term fasting. The short-term fasts scientists studied are very short term, only 12 to 18 hours, little more than skipping lunch or dinner. The purpose of these mini-fasts is to give the brain a few hours to rebuild its connections, not to “detoxify” the body as a whole. Here is what research has found:
Sticking to a low-calorie diet over a period of months or years always lowers body weight. Fasting for twelve to eighteen hours at a time may or may not lower body weight, but usually does not, since people eat more the next meal. (Remember, the objective studied here is preventing AD, not losing weight.)
Long-term calorie restriction reduces body fat. Intermittent fasting also reduces body fat.
Long-term calorie restriction lowers body temperature (slowing down the process of oxidation). Intermittent fasting also lowers body temperature.
Long-term calorie restriction lowers blood pressure and slows the heart rate. Intermittent also fasting lowers blood pressure and slows the heart rate.
Long-term calorie restriction lowers blood insulin levels. Intermittent fasting also lowers blood insulin levels.
Long-term calorie restriction increases HDL (the “good” cholesterol). Intermittent fasting also increases HDL.
Long-term calorie restriction decreases homocysteine. Intermittent fasting also decreases homocysteine.
In laboratory experiments with animals, long-term calorie restriction produces a 50 percent increase in the brain protective chemical beta-hydroxybutyrate. Intermittent fasting produces a 100 percent increase in beta-hydroxybutyrate.
In laboratory experiments with animals, long-term calorie restriction produces a modest decrease in the vulnerability of the brain to experimentally induced oxidative damage. Intermittent fasting produces a large decrease in the vulnerability of the brain to experimentally induced oxidative damage.
Lowering blood sugar levels, by long-term changes in diet, fasting, or medication, reduces the sensitivity of brain tissue to excitotoxins. It changes the electrical charge of cell membranes of brain tissue so that tissue-corrosive calcium ions stay outside the brain cell.
Jose A. Luchsinger, M.D., of Columbia University, New York, NY, and his colleagues studied the association between caloric intake and AD in 980 elderly individuals without AD at the start of their study. The researchers followed these patients for an average of four years and recorded how many calories they ate. They also tested for the presence of the apolipoprotein E (APOE) epsilon 4 allele, a gene that has been associated with AD.
During the study, 242 patients developed AD, and 28 percent tested positive for the APOE epsilon 4 gene. The average daily caloric intake of the women studied (67 percent of the study population) was 1,267 kcals. Men consumed an average of 1,316 kcals per day. Average daily fat consumption in both groups was 38 grams.
The researchers divided the study group into four groups depending on how many calories the patients consumed every day. The group that consumed the most calories had a 50 percent greater chance of developing AD. Among the 263 patients who tested positive for the APOE epsilon 4 gene, those who consumed the most calories had a 2.3 times greater chance of developing AD compared to those who ate the fewest calories.
Anyone who has ever tried to stick to a low-calorie diet knows that consumption inevitably creeps back up. Fortunately for the prevention of AD, an occasional one-meal fast is more effective than sticking to a low-calorie diet. Experiments have found that skipping a meal is superior to fasting even if the lost calories are made up at the next meal. The bottom line of this research is that skipping one meal every day or every other day, or at least replacing one meal every other day with a low-calorie snack, should slow or prevent the onset of AD.