Gauging genetic riskIf you’re looking for the best diet to prevent Alzheimer’s, you should be aware that a variant in the ApoE gene, called ApoE ε4, increases the risk for developing Alzheimer’s Disease considerably. See also: Can 23andme accurately tell us our ApoE ε4 status? In most cases, those carrying one or two copies of ApoE ε4 will have to be more careful about dietary fat intake, emphasizing bursts of good quality omega-3 fats and excluding high saturated fat foods altogether. This is the case because ApoE ε4 carriers are more likely to absorb cholesterol and to see their LDL-C levels rise when they eat a saturated fat rich diet. In turn, elevated LDL-C and ApoB are associated with significant increase risk for early onset Alzheimer’s (EOAD) and Alzheimer’s in general. Let’s quote a new (2019) JAMA study that looked at what factors drive risk for early onset Alzheimer’s as well as Alzheimer’s later in life:
Elevated LDL-C levels were associated with higher probability of having EOAD
In late-onset AD, elevated circulating cholesterol levels increase AD risk even after adjusting for the apolipoprotein E ε4 (APOE E4) alleleBy contrast, someone with better heart health genes may get away with a diet that is higher in fats because not everyone sees huge upticks in cholesterol when eating saturated fat. The key is to work with a physician to learn whether you see upticks in cholesterol when eating a high fat diet. If you do, change diets. The JAMA research I cite above is a good indication that most ApoE ε4 carriers are not well suited to Paleo and Bulletproof butter coffee style diets because the ApoE ε4 population are the ones who are more likely to see major elevations in cholesterol when eating higher fat diets. This is not to say that elevated cholesterol guarantees you will develop Alzheimer’s, however, we are talking about reducing risk and sky high cholesterol is clearly not helpful.
Test, don’t guessThe message of this post is – test, don’t guess. Know your numbers and how they are impacted by different dietary protocols. If you’re on a high fat, low carb diet to “protect your brain,” but you’re walking around with elevated LDL-C and high blood pressure, you’re likely increasing risk. Conversely, if you’re a heavy bread and refined carbohydrate plant based eater and consistently have high triglycerides and insulin resistance to show for it, you’re not decreasing risk because you are on a vegan diet. The best diet for Alzheimer’s takes into account the metabolic predispositions of each individual and crafts a diet aimed at keeping both blood sugar and cholesterol in a place that makes your doctor happy.
Know your cholesterol levelsVery often, those with the ApoE ε4 genotype have hypercholesterolemia (high cholesterol), which in turn can boost the production and accumulation of the toxic amyloid plaques that lead to dementia. 3 4 5 6 You may have heard about the “new thinking” on saturated fat – namely that fat in the diet doesn’t cause heart disease and that sugar is the root of all evil. Well, there is some truth to that line of thinking. Sugar, and the high triglycerides and diminished liver function that come with sweets, are deadly to the health of your brain. 7
ApoE ε4, saturated fat and inflammationHowever, and especially for those of you with ApoE ε4 variants, a high saturated fat diet can be just as problematic. This is the case because ApoE ε4 carriers are more likely to have an inflammatory reaction to high fat diets. When ApoE ε4 carriers eat foods like fatty beef, eggs and cheese, their bodies make more cholesterol and ApoB count tends to rise. These changes in blood lipids contribute to poor cardiovascular health that over time can contribute to dementia. For example, this study, which appeared in the peer reviewed Journal Nutrients in 2018. Researchers found that carriers of one ApoE ε4 variant had a much greater reduction (when compared with ε2 and ε3 carriers) in LDL-C and total cholesterol when they switched away from saturated fat and instead ate low GI carbohydrates and a lower fat diet.
Plant based diets and Alzheimer’s riskNote: not everyone has this response, but if you are someone who sees elevated LDL-C when you eat a high fat diet, a whole foods plant based diet is probably the right direction for you. If you inherited the ApoE ε4 genotype, you should take special care to follow a heart healthy diet avoiding saturated fats and other foods that promote major upticks in LDL-C, as changes in the LDL:HDL ratio are associated with increased ApoE expression in the brain. 8 In fact, many of the plant based diets in our nutrition plan scoring system, such as Villager, Okinawan, Wayoan, and Vegetarian are often scored that way, in part, because of an ApoE ε4 marker. In practical terms, this means eating Vegan at least 3-4 days a week and completely avoiding butter, ice cream, fatty meats and supplements like MCT oil.
MCT oil and dementiaNote, that MCT oil has actually shown promise in some studies for treating dementia (once it has already set in), but like fish oil, doesn’t appear to help ApoE ε4 carriers. Researchers suggest that avoiding excess saturated fat and taking in enough healthy Omega 3 fats (so don’t skip the wild salmon) may decrease the risk or postpone the onset of dementia for this group. 9 10 So, the lesson here is if you have high LDL and cholesterol, a diet that emphasizes whole plant based foods with the addition of some wild salmon or good quality cod liver oil is the best diet for Alzheimer’s prevention, especially if you have ApoE ε4. Please do note that a plant based diet does not mean eating refined grains! Flour based foods that spike blood sugar can be just as deadly to brain health as are cheese and red meat for the ApoE ε4 group.
Insulin resistance and dementiaThere is evidence that insulin resistance, characterized by an inability to maintain healthy blood sugar levels can contribute to dementia. 11 Vegetarian populations do develop dementia. 12 Some of us skew towards elevated triglycerides and high blood sugar more so than elevated cholesterol. In our diet matrix, the Forager or Paleo Plus diet types may be more in this range. In these folks, a diet that is lower in carbohydrate, as suggested by books like Dr. Perlmutter’s Grain Brain could be the best diet, however, this is only the case if you can eat this way and keep lipids and blood pressure in range.
Mediterranean diet and Alzheimer’s preventionAnd while ApoE ε4 carriers should avoid the Bulletproof diet, and other diets high in saturated fat, it is important to keep in mind that avoiding saturated fat does not necessarily mean cutting out all fat. Publicly funded research by the NIH has shown that a group following a Mediterranean diet had a slower build up of the amyloid plaques that cause Alzheimer’s than did a group eating a standard Western diet high in refined sugar, red meat, and saturated fat.13 The Mediterranean diet is essentially a plant based diet plus a few servings a week of fish, and occasional goat or sheep cheese and small servings of high quality lean poultry. However, not everyone agrees that ApoE ε4 carriers should eat poultry. Dr. David Gundry, author of The Plant Paradox, recommends that ApoE ε4 carriers remove poultry entirely from their diets.14 This balanced approach to regulating cholesterol levels may explain why the traditional Mediterranean diet is associated with a reduced incidence of Alzheimer’s disease (as well as several other disorders).15 16 For example, in another small study, patients with Alzheimer’s following a Mediterranean diet improved survival almost 5 times compared to those on a normal Western diet. 17 But once again, due to a lack of understanding about the exact causes of Alzheimer’s we can’t home in on exactly why this diet is beneficial. Foods rich in flavonoids and polyphenolic compounds — like fruits, vegetables, red wine, and tea — are also thought to have a protective role due to their antioxidant and anti-inflammatory activity. Vitamins from the B family and vitamin D will exert a benefit, too. 18 However, it is important to note that these recommendations seem to address Alzheimer’s prevention broadly. Dietary interventions can be more difficult for ApoE ε4 carriers. 19
What about ketogenic diets?We’ve established that high saturated fat diets are not a great idea for those with ApoE ε4. But for a more detailed break down, take a look at Aaron’s post specifically on the topic of whether ketogenic diets can prevent Alzheimer’s.
Does Vitamin E slow Alzheimer’s progression?Increased oxidative stress is said to be a risk factor for Alzheimer’s disease, which has led researchers to look at antioxidants, like Vitamin E in the treatment of Alzheimer’s, but not necessarily prevention. After promise in mouse models, some trials have looked at high dose Vitamin E for Alzheimer’s patients, however, the results have been mixed. Having said that, it appears the pro Vitamin E camp may be winning out. The Alzheimer’s Disease Cooperative Study Group (ADCS) supports the use of high dose Vitamin E with Vitamin C for the treatment of the disease. This recommendation is based on this large clinical trial. To quote the study:
Over the mean (SD) follow-up of 2.27 (1.22) years, participants receiving alpha tocopherol had slower decline than those receiving placebo as measured by the ADCS-ADL. The change translates into a delay in clinical progression of 19% per year compared with placebo (approximately 6.2 months over the follow-up period). Caregiver time increased least in the alpha tocopherol group.