Mediterranean Ketogenic Diet for Alzheimer’s Prevention
New Scientific Paper, April 2021

Don’t Push the Boulder!

I like to analogize Alzheimer’s disease to a boulder on a hill. Once you push the boulder down the hill, it’s almost impossible to stop it. Unfortunately, this is the scenario in which we find ourselves when it comes to Alzheimer’s disease.

Alzheimer’s disease starts in the brain decades before symptoms manifest. Current human clinical trials are only designed to address symptoms or, at best, slow cognitive decline once it has set in. At this point, it may be too late. The boulder is rolling and, try as we might, it’s almost impossible to stop.

But what if we didn’t push the boulder off the hill in the first place? This is the realm of preventative medicine, by which I mean evidence-informed lifestyle and nutrition that may stop disease before it starts in the first place.

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What's the Best Diet to Prevent Alzheimer’s Disease?

The truth of the matter is that we don’t know for sure what diet, if any, will truly help to prevent Alzheimer’s disease. There are epidemiological (association) studies showing that people living in certain areas of the world are at lower risk. But these don’t answer the “best diet” question because there are so many other factors – like activity level, stress level, air quality, sleep quality, social structure, and genetic linkages — that influence risk based on geography.

There are also a few randomized controlled trials, but these are likewise problematic because they use only senior citizens as subjects, most of whom are unhealthy to start, and employ multimodal interventions. In these studies, true prevention isn’t not the goal. Rather, researchers are testing to see what happens over a relatively short period of time when we throw as many obstacles in front of the rolling boulder as we can. Guess what? The boulder keeps rolling.

Given the practical limitations of conducting decades-long human clinical trials that isolate diet as a variable, we cannot rely on clinical trials to discover the best diet for Alzheimer’s prevention. Instead, we need to take a hard look at good basic science studies, including carefully chosen mouse models, to understand the biological and metabolic basis of Alzheimer’s disease. Based on this mechanistic understanding — the “how” of Alzheimer’s disease — we can begin to puzzle together nutritional recommendations for prevention.

What is the Role of ApoE4?

In this particular paper, myself and a team of doctors at one of the world's top Alzheimer's prevention clinics chose to focus on precision nutrition for the prevention of Alzheimer’s disease specifically in those who carry the gene variant ApoE4. ApoE4 is the leading genetic risk factor for Alzheimer’s disease. Having a single copy in your genome increases your risk about 3-fold, while having two copies in your genome increases risk as much as 15-fold!

We chose to focus on ApoE4 for two reasons. First, as alluded to above, the majority of people who develop Alzheimer’s disease carry this genetic variant. Thus, from a population health perspective, it makes sense to focus on this group. Second, insights gained from studying how ApoE4 alters metabolism to increase Alzheimer’s risk could help us better understand the disease in general, thereby paving a path for broader Alzheimer’s prevention.

The ApoE gene codes for a lipoprotein — ApoE protein — similar to those found on your LDL and HDL cholesterol particles. ApoE4 is one form of this lipoprotein with the power to drastically alter brain metabolism. In this paper, we delved in to the most recent and compelling scientific literature on how ApoE4 changes brain metabolism. These new and exciting data revealed…

• (i) ApoE4 can make the blood-brain barrier more vulnerable to damage.
• (ii) ApoE4 can make the brain’s immune cells more active and inflammatory.
• (iii) ApoE4 can impair fat and cholesterol metabolism in the brain.
• (iv) ApoE4 can impair glucose metabolism and contribute to insulin resistance.

Medi-Keto for Alzheimer’s Prevention

Once we felt up to date on all the recent ApoE4 literature (and my desk was thoroughly drowned in well over 178 scientific reports), we went to work identifying strategies that could target the metabolic deficits that contribute to Alzheimer’s disease.

Above: Nick's Desk

Rather the re-write the paper here, I’ll cut to the chase. There was a surprisingly large body of literature suggesting that components of a Mediterranean diet and ketogenic diets target the very pathways and metabolic deficits mentioned above. I’ve made a list of some of these below.

Health Benefits of Low-Carb Ketogenic Diets

• Prevent or improve insulin resistance
• Avoid impairment of Aꞵ degradation by insulin
• Avoid GSK3ꞵ mediated hyperphosphorylation of tau
• Improve cerebral blood flow
• Reduce AGE formation and ApoE4 glycation
  
• Enhance lipophagy and protect from lipotoxicity
• Provide acetyl-CoA to circumvent ‘metabolic crisis’
• Increase histone acetylation to promote memory genes
• Reduce Aꞵ toxicity
• Inhibit NLRP3 formation
• Inhibit CypA-NFkB-MMP9
• Improve brain network stability

Mediterranean Dietary Components

• Extra virgin olive oil’s phenolic compounds, oleocanthal and hydroxytyrosol, possess anti-amyloid and anti-tau properties, increase levels of LRP1 to help with amyloid efflux and lipoprotein-mediated miRNA delivery, and inhibit the CypA-NFkB-MMP9 pathway to protect the blood-brain barrier.
• Compounds in cruciferous vegetables, and capers and red onions, can decrease NFkB-MMP9 expression to likewise protein the blood-brain barrier, inhibit NLRP3 formation to quiet microglia and protect against neuroinflammation and tauopathy.
• The omega-3s found in fatty fish also inhibit CypA-NFkB-MMP9 pathway and NLRP3 formation, improve amyloid and tau pathologies of in animal models, and supply an essential brain building block to disadvantaged ApoE4 brains that burn through omega-3s like kindling. In fact, it’s almost certain
• ApoE4 carriers need more omega-3s than non-carriers.

This list is only meant to be illustrative, and I invite you to attempt to read the actual manuscript for more details.

But the point is this: New science, much of which was published after Martina and I started working on the New Mediterranean Diet Cookbook two years ago, appears to confirm our hypothesis: Medi-Keto is a great starting point on your journey to find optimal health, including brain health.

The New Mediterranean Keto Diet method was put to the test in the scientific peer-review process and passed. The New Medi Keto is good for the brain!

More Than a Coincidence?

If I were you, I’d immediately by “curious” about the fact that a scientific journal is publishing a peer-reviewed scientific paper promoting Mediterranean-ketogenic diet around the same time that we are launching the New Mediterranean Diet Cookbook. Is this a sales tactic? Or could it be a coincidence?

Actually, it’s neither. It’s not a sales tactic because I can promise you the journal has no incentive to publish an article supporting this book. If anything, they’re disincentivized by conflicts of interest, which I fully acknowledge in the paper. I also have nothing to gain financially from this project as 100% of any royalties I obtain from our book will go to education or research.

But it’s also not entirely a coincidence. The New Mediterranean Diet Cookbook is special because it uses a scientific approach to generate recipes optimized for taste and nutrition. It’s not a diet, it’s a method in which we puzzled together used scientific data into recipe formulas. This is similar to what you do in writing a scientific paper, just without the yummy bit at the end.

The New Mediterranean Diet “method” was just put to the test when this Nutrients paper underwent scientific peer review. It’s not a coincidence, it’s the scientific process.

Where to Learn More

If you want to learn more about this particular topic there are at least three options. First, you can read the paper itself, which comes complete with a video abstract and table of dietary and supplement options. I also gave a two-hour continuing medical education-accredited lecture on this topic to the Society of Metabolic Health Practitioners, which you can access if you are a member or become a member.

And for those without quite as much scientific background, I will be giving a simpler version of the lecture at the Low Carb International Allstars 2021 conference in mid-June, and tickets are available now. (Below is a sneak preview of a slide with a shout out to the great Dave Feldman, for those of you are Cholesterol Code fans!)

Finally, if you believe in the work we are doing, we’d greatly appreciate if you’d buy our book, share our content with your friends and family who could benefit, and possibly find the time to write an Amazon review. Those really make a difference. It would mean a lot.

With gratitude and to your health! - Nick

The #1 Keto Diet App Intelligent Fasting Easily record or schedule fasting periods with our intelligent fasting tool. Auto Fill Automatically complete your day with meals and snacks that perfectly match your macro targets. Unlimited Meal Plans Create bespoke meal plans tailored to your preferences while hitting your macros. Trialed and Tested Recipes Enjoy delicious, foolproof recipes developed exclusively for KetoDetApp. AI Assistant Get instant answers to all your questions about the keto diet, the app, and more. Net vs Total Carbs Switch seamlessly between tracking net and total carbs at any time. Barcode Scanning Quickly scan product barcodes to track your food intake with ease. High Protein Keto Tailor your protein intake to support your fitness goals, from shedding stubborn pounds to building strong, lean muscle. iPhone & iPad Get Started for Free