Update On The Mind

The statin dilemma

In the recent Alzheimer's article, I cited Dr Bredesen's The End of Alzheimer's and Dr Saladino's Carnivore Code as interesting references for those who are interested in Alzheimer's. I was given new insights this week I wanted to share with you.

Dr Peter Attia has a super web site at peterattiamd.com with a lot of interesting articles and podcasts. He charges for subscriptions, a fee I decided is worth my money. I’m looking forward to reviewing more of his materials. But much of his material is freely available, including a set of three articles on cholesterol he wrote on cholesterol as it affects cognition and brain health. His determination is it does not.

I’ve been struggling with the apparent conflict between Dr Bredesen who recommends cholesterol greater than 150, and Dr Esselstyn (How To Prevent and Reverse Heart Disease) who recommends cholesterol less than 150. And Dr Saladino demonstrates that cholesterol and other blood fats are healthy unless we have insulin dysfunction, which he recommends treating with low carb diet. So what should I do? I took a simple approach and tried to split the difference. It worked for a while, but my cholesterol has been increasing on my low carb diet.

My cardiologists tolerated my wishes, but maintained a conventional approach, recommending prioritizing my heart. They wanted statins. I’m determined to avoid my parents’ fate, and maintained a priority on brain health. They didn’t offer reconciliation until this week.

My cholesterol has risen a lot in the year I’ve been on a keto diet as encouraged by both Bredesen and Saladino. My HDL has risen a lot, a very good thing according to Saladino, and triglycerides plummeted, another good outcome, as predicted by Saladino. But a couple of markers of vascular inflammation were increasing with the LDL. That’s an indicator of plaques building up in the arteries. Saladino didn’t mention that. My cardiologists continued to recommend reducing LDL with a PCSK9 inhibitor, an injection that specifically targets LDL, the transporter of all the cholesterol to the cells.

Cholesterol is synthesized in every cell in the body, including the brain, which holds 20% of the cholesterol in the body. It is produced in the liver and distributed to the cells by LDL in the blood. Brain cells use cholesterol like all other cells as a structural component of cell walls. But the brain also uses cholesterol for the myelin sheath enclosing all the neurons, facilitating the electrical communication essential for cognition. The brain is valuable enough that it is guarded by a blood-brain barrier that prevents most molecules from moving from the bloodstream to the brain. The important revelation from Dr Attia is that the brain produces all the cholesterol it needs and is unaffected by blood cholesterol. It may be that statins used to reduce blood cholesterol can get through the blood-brain barrier and reduce cholesterol production in the brain.

Brain cholesterol can’t be directly measured, though a spinal tap can be accomplished, with considerable discomfort, expense, and risk. But it turns out a molecule in the blood, desmosterol, correlates very closely to brain cholesterol levels. It seems to be a good indicator of whether statins or other medicines are affecting essential brain cholesterol levels.

Conventional treatment for high cholesterol is often done with statin drugs. They work pretty well by interrupting the enzymes that prevent clearing out excess LDL. There are two types - lipophilic versions like simvastatin (Zocor) and atorvastatin (Lipitor), and hydrophilic versions like rosuvastatin (Crestor) and prevastatin (Pravachol). These inhibit cholesterol production, which raises the risk of brain deficiency. FDA has issued a warning of cognitive effects with statins.

But like many biological questions, it’s not that simple.

The lipophilic statins appear to penetrate the brain, so should be considered very cautiously, especially in those of us with the ApoE4 gene. However, the hydrophilic versions are believed not to have access to brain chemistry, so they should be safer. This hasn’t been confirmed yet, according to Dr Attia.

Another option is a newer medicine called PCSK9 inhibitors. It targets LDL directly. I have used a PCSK9 inhibitor product called Repatha which comes with a computerized injector that we apply at home. I stick it to my leg, press a button, and it hums for a few minutes. I used it together with Crestor. The combo worked to reduce my LDL dramatically, and my cholesterol, while raising HDL and desmosterol a little. I stopped both after a few months due to worries about cognitive effects of the cholesterol reduction, as encouraged by Bredesen and Saladino, though I didn’t notice any effects in that short time.

I agreed with my cardiologist this week to try the Repatha again for a few months, without the Crestor this time, and get lab tests again to see how it performs. My target isn’t really the cholesterol or the LDL — I like Saladino's analysis of that — but the inflammatory indicators (Lp(a), LpPLA, and NT-proBNP). If the next blood tests don’t indicate improved inflammation markers, I’ll consider adding Crestor as a theoretically safer statin. But I hope to avoid that risk.

Dr Bredesen is right to discourage statins — especially the lipophilic versions — to reduce cholesterol in people susceptible to Alzheimer's — especially for the 80% of people who have insulin dysfunction, as described by Dr Saladino.

And Dr Esselstyn is correct that our hearts want low cholesterol, especially if we have the insulin dysfunction described by Dr Saladino.

They both glossed over the distinctions of the type of statin used, and the importance of controlling insulin metabolism, though Dr Bredesen includes it in his protocol.

It shows we always need to dig beneath the surface of conventional advice.

My highest priority remains brain health, so I’ll be especially attentive to my cognition during this experiment. If the inflammation remains I’ll consider adding Crestor. One step at a time.

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The thing that really sold me on the Attia subscription was his interest in longevity, a big interest of mine. I’ve studied it for a while but hadn’t run across his name. They’re making amazing progress in keeping us all healthy longer. We all need to work on preventing early checkout so we can be around to enjoy the benefits of much longer lives.