Ancestral ApoE4: Super Brain Power, Super Lipophilic Immunity

About This Blog

While my expertise is in the pharmaceutical world, I explore the various scientific, nutritional, and pharmacological ins and outs of optimal health. My training includes 4 years in plant biology, bachelor in nutritional science and food science, doctorate in pharmacy, and Crossfit Nutrition Certified by Robb Wolf (and Nicki Violetti). Like Orwell discovered, writing can fuse together favorite purposes. In this case, it melds medicine, music and MAXIMUM VITALITY.

As you can see from Mahley and Rall's 2000 publication, LDL sharply corresponds to apoE status. E4, the highest; E2, the lowest LDL. Do most cardiologists know this as they prescribe cookie-cutter NCEP/ATPIII-aligned statins? Please.

The density of the LDL determines its function. Small dense is damaging. For E4, dietary carbohydrates and dietary deficiencies of saturated fat dramatically shape and create small, dense, harmful LDL particles. The only rare cases of coronary calcification improvement on EBCT at a coronary heart website were the uncommon participant on a lower carb, HIGH SATURATED FAT intake. E4 appear exquisitely more sensitive to diet, exercise, fats/carbs and environmental toxicants.

Mondadori et al used new technology fMRIs to brain scan young chess-playing individuals and compared their the apoE status. The apoE4 showed increased memory, retrieval, neuropsychology and apparently neural efficiency. E4 indeed appear to run their brains on better fuel, e.g. fatty acids, the currency of nervous system cells.

Why is this not observed in E4 carriers in older age in the industrial populations? In the prior post, researchers discussed how the cysteine amino acid is lacking in E4, at the 112 site. E2 has 2 cysteine's per allele; E3, 1 cysteine; E4, N-O-N-E. This protein conformation apparently stupendously reduces the capacity for apoE to shuttle trace metals out of nervous system tissues. Many enzymes regulate and control metals in the brain however having the E4 allele is like a neuronal death sentence in a world that is contaminated by metals, not excluding one's own oral cavity. Sources of neolethal metal: dental amalgams (50% are mercury which gas off), stents, ortho/dental implants, well water, water purification at municipal plants (alum/Al), lead from leaded fuel/diesel, copper piping, fish intake (the EPA advises pregnant women limit fish, shouldn't we non-pregnant as well?), vaccines (Hep B, flu, whooping cough, Td, etc) and broken Hg thermometers.

Super Brain Power + Super Brain Fuel

Though in the medical literature is rife with negative associations between apoE4 and a variety of conditions, my observations are that in those who exhibit high LDLs appear to display the most supreme levels of super-healing and extraordinary intelligence. See Hyperlipid (Peter D. for studies where high LDL associated with positive improvements and longevity, HERE J-LITT. Please also review the neurobio series on Alzheimer's by the wonderful Emily D. at Ev Psych and how low cholesterol is associated with lower cognition HERE.

As you can see from Mahley and Rall's 2000 publication, LDL sharply corresponds to apoE status. E4, the highest; E2, the lowest LDL. Do most cardiologists know this as they prescribe cookie-cutter NCEP/ATPIII-aligned statins? Please.

Super Immunity

In a seminal article in PNAS, Caleb Finch's 'Evolution of the human lifespan and diseases of aging: Roles of infection, inflammation, and nutrition' talks about how humans evade infections and the role of apoE4. As a carnivorous creature, hominids had access to ingestion of better protein, trace minerals and fats. The apoE system shuttles cholesterol and the contents of LDL and HDL particles into nervous system tissues (iodine, zinc, tocopherols, ubiquinone, vit K2, etc).

By absorbing fats from the intestines quickly, this sequesters fat from parasites, bacteria and other pathogens. It is believed this might be one mechanism of super immunity which is observed in E4 carriers.

Peter M said...

Interesting. I've always thought that the Apoe4 allele has to be adaptive in any number of yet unexplored ways. If it is so hideously inferior a gene it seems pretty unlikely it could have hung in as long as it has.

So, any chance you might ring in on what a speculative anti-Alzheimer strategy might look like for those of us who are Apoe4 positive or suspect as much? Particularly when there is a family history of non-vascular (or at least primarily non-vascular) dementia.

I imagine one would want to mimic the old ancestral diet, which means a classic low-carb, higher saturated fat diet, replete with colorful vegetables etc. But should one go the oral chelation route, and if so, for how long? Would lower dose lithium have a place? 8 hr feeding window to encourage autophagy?

If you might indulge the question, what beyond diet are your top 3 or 4 considerations/ strategies for Apoe4 people who have a commitment to delaying or preventing Alzheimer onset?

For those of us crossing 60 it's one big a*s question.

Many thanks for the always intriguing, entertaining blog.

Dr. B G said...

Mr. Peter M,

Thank you for your thoughts, questions and comments! Your 2nd comment is where this thread is indeed heading.

E2 is not only an adaptation IMHO to the grain-based diet, but also to the infectious diseases that arose from a grain-based and livestock culture.
--?plaque from fleas -- some theories are the Great Plaque wiped out a lot of E4
--bacteria, viruses, prion
--fungus (grain storage)

The eco-immunological, darwinian medicine approach is the best way to view the changes, I believe.

Paleo is probably not enough for the E4 carriers. The gut-brain axis and any potential heavy metal toxicity would need to be assessed and addressed for a non-demented long life for any E alleles but particularly E4 or anyone with reduced toxin/metal clearance abilities.

The diet has to be somewhat customized but I honestly like DeVany's the most
--foundation: water (clean, filtered, no metals Cl- Fl- or other reactive halides)
--herbs: detoxify, remove xenobiotics and xenometals
--vegs + meat (I like fatty meat but whatever works)
--starches (as tolerated -- white rice, potatoes, yams, etc)
--fruit: preferable what one can tolerate or what the ancestors consumed

Exercise, daily movement, some lifting, daily sun, daily fresh air, daily hugs and kisses are all essential as well!

The carbs v. protein v. fat is really dependent on what is going on metabolically -- for insulin and leptin resistance, it is helpful to up the carbs or cycle up a ton more frequently. Going ketotic when one is adrenally fatigued (which most of modern America and even teenagers are) is IMHO the best way to kill the adrenals.

What are your thoughts? What has worked so far?

Yes -- I think chelation in some form (herbs--cilantro, parsley, etc, fiber, exercise, infrared sauna, EDTA, td-DMPS, alpha lipoic acid, OPCs, melatonin, etc) is called for if the soft tissues and glands are deeply harboring neolethal metals.


Dr. B G said...

I gravely left out fermented foods (probiotics) which is the topic of the upcoming AHS!

I don't fully understand the role yet but probiotics in our foods help our body to amp up the immunity and elimination of toxins. The biofilms can harbor many metals but if disrupted and a healthy gut can grow, then the detox/elimination pathways can do what they are supposed to do. Many microbes hijack Fe (iron) for their own use. I suspect they do the same with other transitional metals too. An optimal gut biome is challenging however if the metals stall in the soft tissues.

Peter M said...

Excuse that double post. Got interrupted and didn't realize the first one took.

So, many thanks for your wide-ranging response. Certainly a great deal to reflect upon there.

My first premise in approaching the whole Apoe4/Alzheimer connection is nature simply could not have designed an organism ultimately programed for dementia or sub optimal cognition. It just flies in the face of the entire evolutionary model. Which begs the question: how do we Apoe4s (and many 3s I'll bet) optimize diet, exercise and environmental factors in our favor. Obviously it's a speculative, nuanced game. Stephanie Seneff has weighed in interestingly on the issue and you are taking a still more sweeping crack at the possibilities. Your thinking and insights are original and definitely intriguing.

I will of course be following any future posts on the topic with complete interest. You know, don't be fatalistic, be pro-active!

(And FWIW: 35 years of a whole foods diet (progressing from the now ancient Pritikin to the Med diet to the high sat fat, low-carb diet gives me a zero calcium score on the EBT scan. That with a bad family history. So I'm a serious believer on intervention.)

Again, a big appreciation for your thoughts. Very cool.

Dr. B G said...

Mr. Peter M,

*aaahhhhHH* You are E4... and so clever and bright :) See you confirm my suspicions. Lower carb, whole foods and saturated fat have served you well!!

I totally agree, the beautiful design of humans is sublime... we can't underestimate the ultimate majesty.

Thanks for clue-ing me into S. Seneff! She is totaly right on about cholesterol, the role of saturated fats etc. I do think b-amyloid a role she missed is that it 'envelops' metals. I don't know if the purpose is to neutralize, eliminate or some other function. She is also probably right about the bacteria... leaky gut causes leaky brains.

She is interesting. I actually entirely disagree with a couple of her points. A mod-high carb MCT diet failed to show improvement in Alz E4 so far, as she stated. Only the non-E4 improved cognitively. If that study or the new drug study was 'truly' ketogenic and low carb it is possible the results would've been different but we don't know. On the net, I have read of numerous improvements on ketosis in Alz pts but I don't know which were E4.

Statins -- I'm not sure from the limited reading so far if statins harm E4 because of all the allele carriers, E4 have the highest endogenous production of cholesterol as well as the maximal GI cholesterol absorption and optimized functioning of FABP (fatty acid binding protein) to absorb dietary fats incl the supernutritious vits ADEK2, quinones, Q10 etc... E4 on a mod fat diet (or even low) may be the only ones 'buffered' against statin neuro damage... ok sorry to be heretical.

I saw one study or two that showed no harm in E4, but I'd have to look again. Seneff failed to show any study results I think... it's a good theory but I don't see evidence yet. E4 dock and shuttle into neurons VLDL particles whereas E2 and E3 doc the HDL particles which are dense and not as chock full of CEs/TGs as VLDL which are contrastingly VERY LIGHT, buoyant, BIGGGG (esp if lower carb/high saturated fat in the diet w/some exercise and some good sex hormones).

Well. You've done your research -- good job!

Keep the questions and thoughts coming!!! -- I have a big 'to do list' this wk but I'll get back to this... (*ggggggrrrr* I have a session at traffic school for a SPEEDING TICkET and other stuff)


Anonymous said...

Dr. B G,

Thanks so much for your interesting/insightful research and commentary. I've been loving reading all the ApoE4 findings, mainly because I found out I'm the dreaded 4/4. Though I'm trying not to dread it, given that research says Apoe4 genes may only be about 30% of the Alzheimer's equation. Plus, half of people with AD don't have an E4 gene at all.

I'm looking forward to reading more of your posts -- thanks again for the work you do; it's been helpful for me as I research what I should do given my genotype. (I'm somewhat confused as to how much fat to eat -- whether high or low. For now I'm going with a fair amount, but not too much because I can't digest too much at once. I stick to animal fats [incl. organ meats], coconut oil, some macadamia nuts, etc.)

Sorry to be long-winded -- thanks again. Any any general thoughts/recs for 4/4s will be appreciated -- it obviously could be considered extremely worrisome, but I try to remind myself it's only a risk factor, and a very gray area right now -- research is still in the early stages. (And I'm young-ish, so hoping research sheds more light on this in coming years.)

Thanks again,

Dr. B G said...


Do not be distressed -- there is so much one could do b/c only the integrative medical approach can protect health the best. I used to think paleo was enough but for a surprisingly great number, it's not. TO handle the greatest risk factor for E4 which has shown promise is addressing either/both iron overload and metal overload. Will talk later...