The Effects of AGE Glycotoxins on Our Muscles, Minds, and Mortality

What evidence do we have that cutting down on dietary AGEs will benefit us? Population studies have found that those with elevated AGEs in their blood are at greater risk for cataracts and macular degeneration, and hypertension, and heart disease, stroke, anemia, kidney disease, and osteoporosis, but most of the studies have focused on the effects of AGEs on our muscles, minds, and mortality.

Age-related muscle wasting can be AGE-related muscle wasting, caused by the inflammatory impairment of muscle structure and function. The accumulation of AGEs in the elderly has been linked to decreased muscle mass, strength, and power, and increased physical frailty and difficulty performing regular activities of daily living. Having higher blood levels of AGEs has also been correlated with living a shorter life.

In a study of a thousand elderly men and women, those in the top third of blood AGE levels had as much as an 84 percent increased risk of death over the subsequent six years they were followed compared to those in the bottom third of AGE levels. A meta-analysis of all such studies linked higher AGE blood levels with greater mortality, but some studies have failed to find such a connection. This may be due to the day-to-day variability of blood levels and the fact that most of the studies only took a single measurement. A more robust measure would be to assess the accumulation of AGEs over time.

Skin collagen, upon which AGEs form, can have a half-life of more than a decade. So, a tissue sample could offer a reflection of long-term AGE buildup over the years. Thankfully, a noninvasive approach to skin biopsies has been developed based on the curious fact that many AGEs are fluorescent. Using the right wavelength of light and a special detector, researchers can measure human skin autofluorescence, which has been validated to correlate to AGE levels in the skin and the consumption of high-AGE foods in the diet. Over time, we become more and more fluorescent as AGEs build up in our skin.

Skin autofluorescence is not a perfect marker, since many AGEs aren’t fluorescent at all, but can give a more accurate picture than blood levels which only offer a snapshot in time. For example, one research team unexpectedly found that lacto-ovo vegetarians had higher AGE blood levels, but subsequent studies found that skin and retinal autofluorescence was significantly lower among those eating vegetarian, as one would expect.

Skin autofluorescence is associated with lower muscle mass in middle-age and with frailty status in the elderly. Based on a systematic review and meta-analysis of seven studies, elevated skin autofluorescence could also be a predictor of all-cause mortality, indicating a 91 percent higher risk of premature death.

It’s also associated with lower cognitive function in both old and middle age, as well as brain atrophy.

As we age, our brain literally shrinks. In our seventies and eighties, we lose an average of about five cubic centimeters of total volume of brain tissue annually, but some lose more than others. Brain atrophy may be reduced in very healthy individuals, and a few people don’t lose any brain at all. Skin autofluorescence and AGE blood levels have been linked with this kind of cerebral brain loss, just as AGEs in the blood, in the urine, and diet have all been associated with cognitive decline. “Since modifying the levels of AGEs in the diet may be relatively easy, these preliminary results suggest a simple strategy to diminish cognitive compromise in the elderly.”

People with Alzheimer’s disease have higher levels of AGEs in their cerebrospinal fluid and, on autopsy, a 3-fold increase in AGE content in their brains. Not only are AGEs implicated in the development of Alzheimer’s disease in the first place but accelerated progression of the condition for those already suffering. In the influential paper, “Oral Glycotoxins are a Modifiable Cause of Dementia…” the reduction of food-derived AGEs is suggested as a feasible, effective strategy to combat the dementia epidemic.

AGEs may help explain why those who eat the most meat were found to have up to nearly triple the risk of getting dementia compared to long-time vegetarians, but other factors may be contributing. For example, high intake of saturated fat, found mostly in meat, dairy, and junk, is associated with a 40 percent increased risk of cognitive impairment and nearly 90 percent higher risk of Alzheimer’s disease. Even just a few days on a high-fat, low-carb diet has been shown to cause cognitive dysfunction. But, that’s the problem with all these studies. Maybe the correlation between AGEs and chronic disease is just a correlation between high AGE foods like processed meat and chronic disease. The only way to prove cause-and-effect is to put it to the test, which I’ll cover, next.