Chapter 118
The Role of Inflammation
The single most important gene by far for a long life
Complex gene-mapping techniques such as genome-wide association studies, in which the DNA of centenarians is compared with that of people under 100, can identify genes associated with longevity. In the video see.nf/gwas, I describe how this works and what researchers have found. A review of all these studies on life expectancy found only one gene that multiple independent meta-analyses had identified: ApoE, the “Alzheimer’s gene.” ApoE not only determines dementia risk, but is also the most important gene for a long and healthy life (even if that may not mean much).
How can this gene influence our health and longevity so strongly? It codes for the main cholesterol carrier in the brain and plays an important role in packaging and transporting (“bad”) LDL cholesterol throughout the body. The good news is that diet can beat genetics. In the video, I explain the so-called Nigerian paradox: The population with the highest rate of the “Alzheimer’s gene,” thanks to a diet low in animal fats and their extremely low cholesterol levels, also has one of the lowest Alzheimer’s rates. Evolutionarily, humans should have an LDL cholesterol level of about 25 milligrams per deciliter. In the Western world, the average is about 120. Perhaps it is no wonder that in richer countries the number one killer is heart disease and dementia, according to the WHO, is number two.
The Role of Inflammation
More than a dozen theories have been published about the cause of Alzheimer’s, one of them the “inflammation hypothesis.” I discuss the arguments for and against it in see.nf/braininflammation. I conclude that inflammation is most likely to play a role when it occurs in younger years.
Alzheimer’s manifests in older people, but like heart disease and most cancers it can develop over decades. Alzheimer’s is usually diagnosed in people over 70, but we know that the deterioration of their brains began much earlier. In many thousands of autopsies, pathologists have discovered the first, still unnoticed stages of the disease—apparently very fine deposits in the brain, so-called tangles—that occur in half of 50-year-olds and even in 10 percent of people between 20 and 30. The good news: The onset of the disease is preventable.
The Role of Oxidation
Is our brain simply rusting? In see.nf/brainoxidation, I contrast the failed trials of antioxidant supplements with long-term population studies that associate the intake of brain-targeting antioxidants with a lower rate of dementia. For example, in the largest and longest-running cohort study on this question, those who, on average, consumed daily the amount of anthocyanins contained in a tablespoon of blueberries had a 76 percent lower risk of dementia than those who consumed only the anthocyanins from less than a teaspoon of blueberries. (Unfortunately, the participants’ main source of anthocyanins was not blueberries, but rather blueberry muffins.)
It has been demonstrated in vitro that polyphenols such as anthocyanins are not only antioxidants but also protect nerve cells, because they inhibit the formation of Alzheimer’s-triggering plaques and tangles in the brain. Theoretically, they could also “pull out” the accumulated metals from the brain regions that play a role in the development of Alzheimer’s and other neurodegenerative diseases.
And Aluminum?
The “aluminum hypothesis” for the cause of Alzheimer’s dates back to 1965, when aluminum was accidentally injected into the brains of rabbits, leading to cognitive deficits and, in association with that, findings that initially looked like Alzheimer’s tangles. In the 1970s, it was then first reported that a higher aluminum content was found in Alzheimer’s brains at autopsy than in the brains of the control group. In the period that followed, there was a cluster of fatal dementia cases that were linked to aluminum-containing dialysis fluids. These three observations led scientists to assume that aluminum, the third most common element in the Earth’s crust (after oxygen and silicon), played a role in the development of Alzheimer’s and other neurodegenerative diseases.
This hypothesis met with fierce criticism in the scientific community. As only later came to light, the loudest critics were secretly paid by the aluminum industry. In hindsight, that probably wouldn’t have been necessary anyway, because as I report in see.nf/aluminium, a flood of evidence ultimately arose against the relevance of aluminum. What convinced me was a meta-analysis that could find no association between Alzheimer’s and the regular use of antacids—the main source of aluminum exposure.
The fact that aluminum does not cause Alzheimer’s does not mean that its intake is harmless, as I explain in see.nf/aluminiumpots. Anyone who cooks or stores acidic foods such as yogurt and tomatoes in aluminum pots damages their DNA significantly more. This has prompted some authorities to issue consumer guidance not to use aluminum containers for acidic or salted foods.
In see.nf/antiperspirants, I point out that European safety authorities and the FDA explicitly advise against applying aluminum-containing sweat blockers, antiperspirants, to damaged or injured skin. This includes use after shaving. Absorption of the “metalloestrogen” aluminum would be one explanation for why, in women who use antiperspirants and shave their underarms more than three times per week, breast cancer can occur 20 years earlier.
To avoid excessive aluminum intake from food, one can, for example, bake with aluminum-free baking powder and avoid processed cheese. Aluminum salts cause the cheese to have the “desired slicing property,” but that means that, under some circumstances, a single grilled cheese sandwich contains more than 200 percent more aluminum than the World Health Organization has provisionally set as the upper limit for daily intake.
Iron in the Fire
If aluminum does not cause Alzheimer’s, why does the metal-binding drug deferoxamine help? A remarkable study published more than 30 years ago on the metal-chelating (binding) agent deferoxamine is among the few clinical trials ever to show a change in the course of Alzheimer’s. I go into the details in see.nf/deferoxamine, but in short, the scientists attributed the halving of cognitive decline in the deferoxamine group to the drug’s ability to bind aluminum. However, deferoxamine was developed as an iron chelator. Deferoxamine binds six times more iron than aluminum, and iron is 1000 times more common in the brain. So was the reason for the impressive effect possibly that the brain was freed of excess iron?
I address the relevant evidence in the video, but I can say that iron does indeed accumulate in the same places as Alzheimer’s plaques. But only in people with amyloid deposits does it seem to accelerate plaque formation, so excess iron likely drives the disease rather than triggering it. As I explore in see.nf/copper, copper also seems to affect the pathology of the brain, but only in people who consume too many saturated fatty acids. The Chicago Health and Aging Project found that the older people in Chicago who consumed the most copper—mostly from multivitamin and mineral supplements—had a higher risk of cognitive decline only when the high copper intake went along with a diet high in saturated fatty acids. This group declined in performance as though they had aged 19 years over the six years of the study. The researchers suspected that the saturated fatty acids trigger the buildup of amyloid plaques, and copper then promotes the progression of the disease. Many polyphenols naturally bind metals. The practical takeaway from this is: Eat lots of fruits and vegetables and avoid copper-containing dietary supplements as well as excessive intake of iron and saturated fatty acids.