It’s one part of your body you really can’t do without. This episode features audio from Advanced Glycation End Products (AGEs) and Cognitive Decline, Brain-Healthy Foods to Fight Aging, and Do Lutein Supplements Help with Brain Function?. Visit the video pages for all sources and doctor’s notes related to this podcast.
Have you ever wondered if there’s a natural way to lower your high blood pressure, guard against Alzheimer's, lose weight, and feel better? Well as it turns out there is. Michael Greger, M.D. FACLM, founder of NutritionFacts.org, and author of the instant New York Times bestseller “How Not to Die” celebrates evidence-based nutrition to add years to our life and life to our years.
Don’t tell me you haven’t put some serious thought on how to avoid developing dementia – a brain disease that has no real cure – as of yet. Here’s our first story.
Although it is known that plant-based foods are important for physical health, less is known about the relationship between plant-based foods and cognitive health. In terms of preventing Alzheimer’s and other forms of actual dementia, there’s data that those who consume meat, including poultry and fish, have two to three times the risk of developing dementia compared with vegetarians. But what about just day-to-day function? Greater adherence to a more plant-based dietary pattern was related to better performance on all cognitive tasks researchers measured.
One possible mechanism that could have been thought to underlie the results is body weight: plant-based diets reduce BMI, and lower BMI has been associated with better cognitive function. But they still found a connection between more plants and better brain function, even after controlling for weight. Another possible mechanism linking diet and cognition is inﬂammation. That’s how saturated fat impairs the memory of lab rats––through brain inflammation. And since fiber can be anti-inflammatory, and meat can be pro-inflammatory, that may help explain some of the eﬀects of plant-based diets on health and cognition.
The saturated fat connection appears to extend to human cognition. A systematic review and meta-analysis covering nine studies found that increased saturated fat intake—which is found mostly in meat, dairy, and junk—was associated with a 40 percent increased risk of cognitive impairment and nearly 90 percent higher risk of Alzheimer’s disease. So wait, does that mean if you put people on a low-carb diet it impairs their brain function? Yes, it does. A high-fat diet not only impairs the heart but also cognitive function.
Men were randomized to just five days of a high-fat, low-carbohydrate diet or a lower-fat diet, and on the low-carb diet, cognitive tests showed they suffered impaired attention, speed, and mood, again—just within days. Conclusion: raising the level of fat in your blood not only decreased energy production in the heart, but reduced cognition––which suggests that a high-fat diet is detrimental to the heart and brain. Now, they were thinking the impaired energy production may have accounted for the brain dysfunction as well, but oral glycotoxins may also link high-fat eating with a loss of cognitive capacity.
Glycotoxins, also known as advanced glycation end products, or AGEs, are a class of oxidant stress-promoting agents, free radical-promoting agents implicated in diabetes and aging––including brain injury due to Alzheimer’s disease and stroke. The development of Alzheimer’s disease in the first place is thought to involve the accumulation of these AGEs, which encourage the formation and deposition of the two hallmarks of Alzheimer’s disease: neuroﬁbrillary tangles and amyloid plaques in the brain, discovered on autopsy. But it’s not just full-blown dementia. Evidence suggests that AGEs contribute to cognitive decline in general.
Dietary advanced glycation end products are associated with decline in memory, and “[s]ince modifying the levels of AGEs in the diet may be relatively easy, these preliminary results suggest a simple strategy to diminish cognitive compromise.” What are the major sources of dietary AGEs to stay away from? Meat cooked using high, dry heat, such as in broiling, grilling, frying, and roasting. From my video The Best Diet for Healthy Aging, there’s a list of all the most AGE-contaminated foods.
AGEs are not only associated with getting Alzheimer’s in the first place, but also the progression of Alzheimer’s disease, as well as lower cognitive performance in general as tracked, interestingly enough, via skin autofluorescence. AGEs have a natural fluorescence that you can pick up using a special detector, enabling a simple non-invasive assessment of advanced glycation end product accumulation in the body.
The more meat you eat, the more of the AGE skin autofluorescence you get, which then correlates with cognitive impairment. In fact, one of these days, these fluorescence scanners may be included in routine medical check-ups. Since meat is the main high-AGE food, it should be no surprise that AGE skin autoﬂuorescence measurements are significantly lower in those eating more plant-based. So, the data suggest reduction of food-derived AGEs is feasible and may provide an effective treatment strategy for our epidemics of Alzheimer’s and metabolic disease.
In our next story, we look at the best source of lutein, the primary carotenoid antioxidant in the brain.
There’s an “extensive scientific literature [describing] the positive impact of dietary [plant compounds] on overall health and longevity.” “However, it is [only] now becoming clear that the consumption of diets rich in [plant foods] can influence neuro-inflammation [brain inflammation] leading to the expression of cytoprotective [cell protective] and restorative proteins.” Just “[o]ver the last decade, remarkable progress has been made to realize that oxidative…stress…and chronic, low-grade inflammation are major risk factors underlying brain aging.” So, no wonder antioxidant and anti-inflammatory foods may help.
“The brain is especially vulnerable to free radical attack [oxidative stress] due to its high fat content and [its cauldron of] high metabolic activity.” You don’t want your brains to go rancid. So, you’d think one of the major fat-soluble dietary antioxidants like beta-carotene would step in, but the major carotenoid concentrated in the brain is actually lutein; the brain just preferentially sucks it up.
For example, if you look at the “oldest old,” like in the Georgia centenarian study. Recognizing that oxidation “is involved in age-related cognitive decline,” they figured dietary antioxidants “may play a role” in its prevention or delay; so, they looked at eight different ones: vitamin A, vitamin E, on down the list, and “only…lutein was significantly related to better cognition.” Now, in this study, they looked at brain tissue on autopsy, but by then, it’s a little too late. So, how could you study the effects of diet on the brain while you’re still alive? If only there was a way we could physically look into the living brain with our own two eyes. There is! With our own two eyes.
The retina, the back of our eyeball, is actually “an extension of” our central nervous system—an outpouching of the brain during development, and right in the middle there’s a spot. This is what the doctor sees when they look into your eye with that bright light. That spot, called the macula, is our HD camera, where you get the highest resolution vision, and it’s packed with lutein.
And indeed, levels in the retina correspond to levels in the rest of your brain; so, your eyes can be a window into your brain. So, now, we can finally do studies on live people, to see if diet can affect lutein levels in the eyes, which reflects lutein levels in the brain, and see if that correlates with improvements in cognitive function. And indeed, significant correlations exist between the amount of macular pigment—these plant pigments like lutein in your eye—and cognitive test scores. You can demonstrate this on functional MRI scans, suggesting lutein and a related plant pigment called zeaxanthin, “promote cognitive functioning in old age by enhancing neural efficiency”—the efficiency by which our nerves communicate. Like, check out this cool study on white matter integrity using something called diffusion tensor imaging, which “provide[s] unique insights into brain network connectivity,” allowing you to follow the nerve tracts throughout the brain. And researchers were able to show enhanced circuit integrity based on how much lutein and zeaxanthin they could see in people’s eyes—”further evidence of a meaningful relationship between diet and neural integrity” of our brains, particularly in regions vulnerable to age-related decline.
So, do Alzheimer’s patients have less of this macular pigment? Significantly less lutein in their eyes, significantly less lutein in their blood, and a higher occurrence of macular degeneration, where this pigment layer gets destroyed. The thickness of this plant pigment layer in your eyes can be measured, and may be a potential marker for the beginnings of Alzheimer’s. Let’s not wait that long, though. We know macular pigment density is related to cognitive function in older people; what about during middle age?
“One apparent consequence of aging appears to be loss of some aspects of cognitive control,” which starts out early, in ‘mid-adulthood,’ but not in everybody—suggesting maybe something like diet could be driving some of these differences. Here’s a measure of cognitive control, showing younger, on average, do better than older adults. But, older adults who have high macular pigment, lots of lutein in the back of their eyes, do significantly better. These results suggest that the “protective role of carotenoids like lutein within the [brain] may be evident during early and middle adulthood, decades prior to the onset of” more apparent cognitive decline later in life.
You can take 20-year-olds and show superior auditory function in those with more macular pigment in their eyes. Look: “The auditory system, [our hearing,] like the rest of the central nervous system, is ultimately constructed and maintained by diet, and it is therefore, not surprisingly, sensitive to dietary intake throughout life”—all the way back to childhood.
Higher macular pigment is associated with higher academic achievement among schoolchildren. You can look into a kid’s eyes and get some sense of how well they may do in subjects like math and writing. “This finding is important because macular [lutein] is modifiable and can be manipulated by dietary intake.” Okay, okay, so, where is lutein found? The avocado and egg industries like to boast about how much of these macular pigments they have in their products, but the real superstars are dark green leafy vegetables. A half-cup of kale has 50 times more than an egg, a spinach salad, or a 50-egg omelet.
And the earlier the better. Pregnant and breastfeeding women should definitely be checking off my Daily Dozen greens servings. But it’s also apparently never too late. While some age-related cognitive decline is to be expected, these effects may be less pronounced among those eating more green and leafy.
Finally, today – avocados, greens, and lutein and zeaxanthin supplements are put to the test for improving cognitive function.
Dark green leafy vegetables are packed with a brain antioxidant called lutein. And so, increasing our greens intake could be an “important public health strategy for reducing the risk of visual or cognitive impairment.” Lutein is the dominant dietary pigment in the retina of the eye as well as the brain; and so, “not surprising that macular pigment,” the concentration of lutein in the center of the eye called the macula, “was found to be significantly correlated with levels in” the brain, which may explain the link between how much of these greens nutrients you can see in the back of the eye and cognitive function. The neuroprotection is assumed to be because lutein is such a powerful antioxidant, but it also has anti-inflammatory properties.
“This relationship between lutein and [another greens nutrient called] zeaxanthin and visual and cognitive health throughout the lifespan is compelling.” But that was based on observational studies, where you observe that higher lutein levels and brain function seem to go together, but you don’t know if it’s cause and effect until…you put it to the test. “Could [lutein] and [zeaxanthin] be supplemented as part of a lifestyle intervention to both improve [brain] function and reduce the [probability of slipping into dementia]?” The reason everyone is so excited about the possibility is because of the hopeful data from eye health studies that have convinced many ophthalmologists to start recommending people start increasing their lutein and zeaxanthin intake to prevent and treat macular degeneration, a leading cause of age-related vision loss. You don’t have to take pills, though. Adding as little as 60 grams of spinach a day for a month—that’s like one-fifth of a ten-ounce package of frozen spinach—can significantly boost macular pigment in most people.
And it’s not just good for treating diseased eyes. A randomized, placebo-controlled study found that these greens goodies can improve visual processing speed in young healthy people—that’s like when you’re trying to hit a fastball and your body has to start reacting before you even consciously register it, with real-world benefits outside the major leagues, improving, for example, visual driving performance. Okay, but what about cognition?
A randomized, double-blind, placebo-controlled trial of adults, average age 73, given the equivalent of about a half-cup a day’s worth of cooked kale, or a full cup of cooked spinach, and got significant improvements in cognitive function compared to those randomized to the placebo.
It may even work in young adults too: average age 21. Daily supplementation with that same amount of lutein and zeaxanthin not only increased their macular pigment, but resulted in significant improvements in brain function—spatial memory, reasoning ability, and complex attention.
Have they ever tried putting whole foods to the test? Hard to get Americans to eat greens every day, but not so hard to get them to eat guacamole. “This study tested the effects of the intake of avocado on cognition. …[a] six-month, randomized, controlled trial.” What was the control? One avocado a day, or a potato, or a cup of chickpeas, and…those in the avocado group had a significant improvement in cognitive function. But, to the Avocado Board’s chagrin…so did the tater and chickpea group. That’s the problem with having healthy placebos; maybe they should have used iceberg lettuce or something.
What about the impact on cognition of those who really need it: Alzheimer’s disease patients? Their vision got better; that’s good, but no significant changes in cognitive function. Now, it’s possible that eating whole foods, like dark green leafies, might have worked better than just the pigments in pill form.
Yes, “oxidation and inflammation appear to be key” to both Alzheimer’s and macular degeneration, but “neither [disease] seems particularly amenable to late-stage treatments.” That’s why prevention is the key. Reducing oxidation and inflammation in the earliest stages may be “our most promising approach.”