 What's the best way to stay healthy in the face of so much conflicting nutrition information? Well, ideally you would go to the source, the gold standard, the peer-reviewed medical literature, and read through the stacks of the latest medical journals. But who's got time for that? I do! Welcome to the Nutrition Facts podcast. I'm your host, Dr. Michael Greger. Don't tell me you haven't put some serious thought onto how to avoid dementia, a brain disease that has no real cure as of yet. Here's our first story. Although it's known that plant-based foods are important for physical health, less is known about the relationship between plant-based foods and cognitive health. Now, 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 like 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. I mean, 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 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 meat, dairy, and junk, was associated with a 40% increased risk of cognitive impairment and nearly 90% 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. Neurofibrillary tangles and amyloid plaques in the brain discovered on autopsy. But it's not just full-blown dementia. Evidence suggests AGEs contribute to cognitive decline in general. Dietary advanced glycation end products are associated with a decline in memory. And since 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. For my video, The Best Diet for Healthy Aging, here is the 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 the AGE skin autofluorescence you get, which then correlates with cognitive impairment. In fact, one of these days, these fluorescent scanners may be included in routine medical checkups. Since meat is the main high AGE food, it should be no surprise that AGE's skin autofluorescence measurements are significantly lower in those eating more plant-based. So the data suggests reduction of food-derived AGEs is feasible and may provide an effective treatment strategies for our epidemics of Alzheimer's and metabolic disease. In our next story, we look at the best source of lutein, the primary carnoid 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's 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 over 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 carnoid 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. 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? I mean, 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 and out-pouching 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 the diffusion tensor imaging, which provides unique insights into brain network connectivity, allowing you to follow the nerve tracks 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 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. Well, let's not wait that long, though. We know macular pigment densities related to cognitive function in older people. What about during middle age? One apparent consequence of aging appears to be the 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 the 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 our central nervous system, is ultimately constructed and maintained by diet, and 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 a cup of kale has 50 times more than an egg, a spinach salad, or a 50-egg omelet. In the earlier, the better. Pregnant and breastfeeding women should definitely be checking off my daily dozen green 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 zeaxanthine 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 green's 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 surprisingly that macular pigment, the concentration of lutein in the center of your 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 green's nutrient called zeaxanthine and visual and cognitive health throughout the lifespan is compelling, but that was based on observational studies, where you observe that higher lutein levels in 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 zeaxanthine be supplemented as part of a lifestyle intervention to both improve brain function and reduce the probability of slipping into dementia? The reason everyone's 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 zeaxanthine 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 10-ounce package of frozen spinach can significantly boost macular pigment in most people. And it's not just good for treating diseased eyes or 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, giving the equivalent about a half cup of days of cooked kale, or a full cup of cooked spinach, and got significant improvements in cognitive function compared to those randomized to the placebo. Maven working young adults, too, average age 21. Daily supplementation with the same amount of lutein as the xanthine 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, you know, 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. We would love it if you could share with us your stories about reinventing your health through evidence-based nutrition. Go to nutritionfacts.org slash testimonials. We may be able to share it on our social media to help inspire others. To see any graphs, charts, graphics, images, or studies mentioned here, please go to the Nutrition Facts podcast landing page. There you'll find all the detailed information you need plus links to all the sources we cite for each of these topics. 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