Chapter 119
Fatty Brain
When the role of the “Alzheimer gene” protein ApoE4, the main cholesterol carrier in the brain, was discovered in the 1990s, the attention of Alzheimer’s research turned to saturated fatty acids and cholesterol. Frequent consumption of saturated fats (especially from dairy products, meat, and industrial foods) goes hand in hand with poorer memory and accelerated cognitive decline. With increased intake of saturated fatty acids, for example, the Harvard Women’s Health Study found a markedly worse trajectory of cognition and memory. The women who ate the most saturated fatty acids had a 60 to 70 percent higher risk of declining brain performance, whereas the brains of those who ate the least saturated fatty acids functioned as if the women were six years younger.
Meta-analyses of all these studies have shown that higher consumption of saturated fatty acids is associated with a 40 percent increased risk of a decline in brain performance, a 46 percent increased risk of Alzheimer’s, and, in general, a dementia risk that is twice as high. A more recent review concluded that we can regard the link between consumption of saturated fats and Alzheimer’s as “conclusive and detrimental.” Where should we start in order to limit saturated fat consumption? By cutting back where they chiefly appear in the American diet: cheese, cake, ice cream, and chicken, followed by pork, burgers, and beef in every form.
Saturated fats increase dementia risk only indirectly, through factors such as insulin resistance, high blood pressure, inflammation, or blockage of the brain’s blood vessels, but they can also make the brain’s blood vessels leaky. If saturated fats damage the blood-brain barrier, Alzheimer’s risk rises as well.
The permeability of the blood-brain barrier can be measured by injecting a dye into subjects’ blood and then using an MRI scan to see how much of it seeps into the brain. People with Alzheimer’s or vascular dementia tend to have leakier brain blood vessels than age-matched control subjects. Such disease processes can lead to a breakdown of the blood-brain barrier, but the leakiness appears to occur before dementia. With mild symptoms of Alzheimer’s or vascular dementia—namely mild cognitive impairment and cerebral small vessel disease—elevated leak rates could be detected.
Even in healthy people, leakiness of the blood-brain barrier tends to increase with age, especially in brain regions that are particularly susceptible to age-related decline. That means the normal decline in brain performance could be related to impairment of the barrier. What can we do to preserve our blood-brain barrier? Overweight or obesity in midlife correlates with worsened blood-brain barrier function 24 years later. As for diet, saturated fatty acids and cholesterol, or even cholesterol alone, can weaken the blood-brain barrier. In mice, saturated fats increased blood-brain barrier dysfunction 30-fold, dietary cholesterol sevenfold, but both can be blocked by a cholesterol-lowering drug. That kills two birds with one stone, because saturated fats increase production of amyloid precursor protein from the gut, which in mice became beta-amyloid, and more of the protein enters the bloodstream. A single meal high in saturated (dairy) fats can increase the amount of amyloid protein in the blood sevenfold. If a leaky blood-brain barrier is added to that, this could explain why experiments in which animals were fed fat showed increased plaques. Alluding to the emerging science in this area, a recently published introduction in a biology journal bore the title “Beta-amyloid shoots up from below and paralyzes the brain.”
What a single high-fat meal does to our brain
In the chapter on reducing inflammation in How Not to Diet, I list a number of studies on how just a few days of a high-fat, ketogenic diet can dull thinking. Recovering from that takes weeks. Even a single high-fat meal demonstrably impairs a person’s cognitive performance within five hours. The reason could be inflammation of the brain. In laboratory animals, saturated fat breaks through the blood-brain barrier, accumulates in the middle of the brain, and triggers inflammation there. In the original animal experiments, lard was fed, but it appears that butterfat leads to similar results. The scenario can be recreated in a Petri dish. When the saturated fat of the typical American diet (mainly from dairy products and meat) is dripped onto neurons in vitro, it can flip inflammation on like a light switch. Fortunately, it is possible to reverse this process. When the animals went back to their usual low-fat food, the brain inflammation disappeared as well.
Admittedly, extrapolating data from animal experiments is notoriously highly problematic. For one thing, the diets are not comparable. High-fat, lard-based rodent chow, for example, can contain around 60 percent fat, whereas even fatty bacon has only about 40 percent fat. So even if we were to eat nothing but bacon, we still would not have the same fat intake as the rodents. Nevertheless, saturated fats have also been tested in humans.
Scientists quietly increased saturated fat intake in participants in randomized crossover studies and found that this brings about reversible negative changes with respect to inflammation, mood, brain function, and resting metabolic rate and apparently even undermines the motivation to exercise. When fed a lot of saturated fat, subjects were 12 to 15 percent less physically active than when they consumed only little saturated fat. For this experiment, the scientists used palm oil, a saturated plant fat found in various vegan spreads, in dairy-free cheese, and other industrial foods. Anti-inflammatory eating therefore does not consist of more plants in the broadest sense, but of whole, unprocessed plants.
Brain pollution
What besides saturated fat and oxidized cholesterol could still be contained in meat and lead to meat eaters having a risk of developing dementia that is two to three times higher than that of vegetarians? In the chapter on glycation, I discussed the role that advanced glycation end products from baked, fried, and grilled meat play in age-related cognitive decline, brain shrinkage, mild cognitive impairment, and the development and progression of Alzheimer’s. Another factor may be persistent pollutants, for example chlorinated pesticides.
In older people in the United States, DDT and its breakdown product DDE are associated with an increased risk of accelerated cognitive decline, as well as with the development and severity of Alzheimer’s. You can find more detailed information at see.nf/ddtdementia. The toxins still get into our bodies because they are still present in the food. In the United States, samples were taken in supermarkets: fish, meat, eggs, and dairy products showed dioxin and PCB levels five to ten times higher than the plant foods examined.
Endotoxins
Recently, it has been suggested that endotoxins could be the mechanism underlying the association between saturated fatty acids and cognitive impairment. I provide information on the evidence for this at see.nf/endotoxins, but essentially there are two ways to reduce post-meal endotoxin release. One is simply not to eat so many of them in the first place. If you still eat meat, add fiber-rich foods, which blunt the endotoxin spike. The video shows that there are markedly fewer endotoxins in the blood when you eat fiber-rich cereal along with a Sausage & Egg McMuffin. The fiber also reduced the associated oxidative stress, which clearly has “profound effects on postprandial metabolic and inflammatory processes.”