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Don’t Try to Move the Boulder!

Alzheimer’s disease reminds me of a boulder on a hill. It’s quite impossible to halt the boulder once you’ve pushed it down the hill. Unfortunately, we find ourselves in this situation when it comes to Alzheimer’s illness.

Decades before symptoms appear, Alzheimer’s disease begins in the brain. Human clinical trials are now only meant to treat symptoms or, at best, halt cognitive decline once it has begun. It may be too late at this time. The boulder is rolling, and no matter how hard we try, we can’t seem to stop it.

But what if we hadn’t pushed the boulder down the hill to begin with?
This is the field of preventive medicine, which refers to evidence-based lifestyle and nutrition changes that can help prevent disease from occurring in the first place.

What is the Best Diet for Alzheimer’s Disease Prevention?

The truth is that we don’t know which diet, if any, is most effective in preventing Alzheimer’s disease. People residing in specific parts of the world are at a decreased risk, according to epidemiological (association) studies. However, because there are so many other factors that influence risk dependent on geography, such as exercise level, stress level, air quality, sleep quality, social structure, and genetic links, these don’t address the “optimal diet” question.

There are a few randomised controlled studies, but these are problematic as well because they exclusively involve older citizens as subjects, the majority of whom are already sick, and they use multimodal therapies.
True prevention isn’t the focus in these trials. Rather, researchers are experimenting to discover what happens when we throw as many barriers in front of a rolling boulder as we can in a short amount of time. What’s more, guess what? The boulder continues to roll.

Given the practical difficulties of performing decades-long human clinical trials that isolate nutrition as a variable, we cannot rely on clinical trials to determine the ideal diet for Alzheimer’s prevention. To understand the molecular and metabolic foundation of Alzheimer’s disease, we need to look at strong fundamental science studies, including well chosen mice models. We may begin to piece together nutritional suggestions for prevention based on this mechanical understanding — the “how” of Alzheimer’s disease.

What is ApoE4’s Function?

In this research, I and a team of doctors from one of the world’s leading Alzheimer’s preventive clinics focused on precision nutrition for the prevention of Alzheimer’s disease in people who have the ApoE4 gene variation. ApoE4 is the most common genetic risk factor for Alzheimer’s. A single copy of the gene in your genome increases your risk by around 3-fold, whereas two copies increases your risk by up to 15-fold!

We chose ApoE4 as our target for two reasons. First, as previously stated, this genetic mutation is seen in the majority of persons who get Alzheimer’s disease. As a result, focusing on this group makes sense from the standpoint of population health. Second, understanding how ApoE4 modifies metabolism to increase Alzheimer’s risk could lead to a deeper understanding of the illness in general, paving the way for more comprehensive Alzheimer’s prevention.

The ApoE gene produces a lipoprotein called ApoE protein, which is identical to the LDL and HDL cholesterol particles. One kind of this lipoprotein, ApoE4, has the ability to substantially change brain metabolism. We looked at the most recent and persuasive scientific data on how ApoE4 affects brain metabolism in this paper. These brand-new and intriguing findings revealed…

  1. ApoE4 has the potential to impact the blood-brain barrier.
  2. ApoE4 can increase the activity and inflammation of immune cells in the brain.
  3. ApoE4 in the brain can affect fat and cholesterol metabolism.
  4. ApoE4 can cause insulin resistance by impairing glucose metabolism.

Alzheimer’s Disease Prevention with Medi-Keto

We proceeded to work exploring techniques that could target the metabolic deficiencies that contribute to Alzheimer’s disease once we were up to date on all of the new ApoE4 material (and my desk was completely inundated in over 178 scientific studies).

Rather than rewriting the paper, I’ll get right to the point. There was a surprising amount of evidence indicating components of the Mediterranean and ketogenic diets target the pathways and metabolic abnormalities identified earlier. I’ve compiled a list of some of them here.

Low-Carb Ketogenic Diets Provide Health Benefits

  • Insulin resistance can be avoided or improved.
  • Prevent impairment of Aꞵ degradation by insulin
  • Prevent GSK3ꞵ mediated hyperphosphorylation of tau
  • Increase the flow of blood to the brain
  • Reduce the production of AGEs and ApoE4 glycation
  • Improve lipophagy and avoid lipotoxicity
  • To avoid a metabolic crisis, supplement with acetyl-CoA
  • To boost memory genes, increase histone acetylation
  • Reduce the toxicity of Aꞵ
  • Inhibit the development of NLRP3
  • CypA-NFkB-MMP9 inhibition
  • Stabilize the brain’s network

Components of a Mediterranean Diet

  • The phenolic chemicals oleocanthal and hydroxytyrosol found in extra virgin olive oil have anti-amyloid and anti-tau characteristics, raise LRP1 levels to aid in amyloid efflux and lipoprotein-mediated miRNA transport, and inhibit the CypA-NFkB-MMP9 pathway to preserve the blood-brain barrier.
  • Compounds found in cruciferous vegetables, capers, and red onions can reduce NFkB-MMP9 expression to protect against neuroinflammation and tauopathy, inhibit NLRP3 production to quiet microglia, and reduce NFkB-MMP9 expression to protect against neuroinflammation and tauopathy.
  • In animal models, omega-3s from fatty fish inhibit the CypA-NFkB-MMP9 pathway and NLRP3 production, ameliorate amyloid and tau pathologies, and provide a crucial brain building block to disadvantaged ApoE4 brains that burn through omega-3s like kindling.
  • ApoE4 carriers almost certainly require more omega-3s than non-carriers.

This list is merely indicative, and I encourage you to try reading the original work.

But the point is this: new research, much of which came out after Martina and I began working on the New Mediterranean Diet Cookbook two years ago, appears to back up our hypothesis: Medi-Keto is a fantastic place to start on your path to better health, including brain health.

It’s More Than a Coincidence, Isn’t It?

If I were you, I’d be “curious” about the fact that a peer-reviewed scientific paper supporting the Mediterranean-ketogenic diet is being published around the same time that the New Mediterranean Diet Cookbook is being released. Is this a marketing ploy? Is it possible that it’s just a coincidence?

It’s neither, in fact. It’s not a sales pitch, because I can assure you that the magazine has no financial motive to publish an article in support of the book. Conflicts of interest, which I openly admit in the study, serve to disincentivize them.

However, it’s not entirely coincidental. The New Mediterranean Diet Cookbook is unique in that it use a scientific method to create dishes that are both delicious and nutritious. It’s not a diet; rather, it’s a way for combining scientific data into food formulations.

When this Nutrients research went through scientific peer review, the New Mediterranean Diet “method” was put to the test. It’s not a fluke; it’s part of the scientific method.

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