E4 carriers protected against parasitic infections?

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Julie G
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E4 carriers protected against parasitic infections?

Post by Julie G »

Here’s an interesting new paper adding to the evidence that the E4 genotype is a mismatch with modern society. and that our pro-inflammatory allele may even be protective. E4 carriers, living primitively, with a high white blood cell count demonstrated maintenance of cognition or even a slight improvement. Fascinating.

Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden.
https://www.ncbi.nlm.nih.gov/pubmed/28031319
apolipoprotein E4 (E4) allele is present worldwide, despite its associations with higher risk of cardiovascular morbidity, accelerated cognitive decline during aging, and Alzheimer 'S: disease (AD). The E4 allele is especially prevalent in some tropical regions with a high parasite burden. Equatorial populations also face a potential dual burden of high E4 prevalence combined with parasitic infections that can also reduce cognitive performance. We examined the interactions of E4, parasite burden, and cognitive performance in a traditional, nonindustrialized population of Amazonian forager-horticulturalists (N = 372) to test whether E4 protects against cognitive decline in environments with a heavy pathogen burden. Contrary to observations in industrial populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas non-E4 carriers with a high parasite burden showed reduced cognitive performance. Being an E4 carrier is the strongest risk factor to date of AD and cognitive decline in industrial populations, it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions. The current mismatch between postindustrial hygienic lifestyles and active parasite-rich environs may be critical for understanding genetic risk for cognitive aging.
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Re: E4 carriers protected against parasitic infections?

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Juliegee,

Excellent article. Thanks.
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Julie G
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Re: E4 carriers protected against parasitic infections?

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This evidence dovetails nicely with Dr. Bredesen's observations. As you'll recall from this paper, he's recently discover that mycotoxins/biotoxins appear to be driving a subset of AD cases. Initially, E4 carriers appeared to be protected from this sub-type. A description of his subtypes can be found in this paper. But, as he examines the CIRS biomarkers from more and more patients, he's making two interesting observations:

1.) CIRS (discussed in this thread) appears to be driving many more AD cases than he first suspected. Folks who initially present as Type 1, 1.5, and 2 are later turning out to have the disease process driven by some chronic inflammation process; mycotoxins, biotoxins, reactivated viruses, etc. He's finding that type 3s are much more prevalent than he originally suspected.

2.) E4 carriers are NOT exempt from this sub-type as he originally hypothesized. We just handle the inflammation better, i.e. we don't experience severe cognitive impairment (at least initially) like the other APOE genotypes when exposed to chronic inflammation. The many members of our community who've checked their CIRS biomarkers have played a part in this new finding. Indeed, I'm a great case study... sigh.

I initially presented as a classic 1.5 subtype when I first became aware of my cognition slipping as I entered menopause. I applied many of the strategies outlined in Dr. Bredesen's seminal paper and lo and hold, I improved dramatically, but my cognition and overall health ultimately plateaued. The tip-off in my case was my worsening IgG levels and chronic infections. Dr. Bredesen pushed me to get my CIRS biomarkers checked and they were extremely out-of-whack. My FMP has found that a parasitic infection, a Lyme co-infection called Babesia duncani, along with a few other longstanding GI issues appear to be driving the inflammation. I'm making rather heroic efforts to combat this, including IVIG therapy, but may be treading water. Time will tell.

This recent paper demonstrates that our ancestral "pro-inflammatory" allele may have been designed to better handle infections, BUT says nothing about how this impacts our longevity. We have no idea where in the disease process, these E4 carriers were. My white count was also very high for years, until it dropped below the reference range and my IgG dropped along with it. Perhaps we can "healthfully" sustain a highly inflamed state for a lengthy period, but certainly not indefinitely. Fascinating to put the pieces together. I still suspect that identifying and treating the drivers of CIRS will be very important for the long term survival of our population. You'll recall that E4 is inversely associated with longevity. It may take heroic efforts to keep us afloat ;).
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Re: E4 carriers protected against parasitic infections?

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Hmm, calling our efforts the Hero's Journey has a nice ring to it. :D
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Re: E4 carriers protected against parasitic infections?

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I haven't read the whole paper, but I'm guessing maybe the E4 advantage wrt parasites turns into over-inflammatory disadvantage in a world that's too hygienic. Maybe E4 works synergistically with the biome and microorganism-laden environment in the immune department. I've been working on restoring some skin biome while keeping a focus on resistant starches etc for the gut biome. For both skin and gut I often have the issue of probiotics, the very thing that's supposed to help support the immune system, usually causing an excess histamine/inflammation reaction. My immune system is already tipped and I need to get it back. I've been tempted to buy organic potting soil and put small amounts between my toes, in my armpits etc and may just try a minuscule test to see if it would work, but I've already found that I react to soil-based oral probiotics. According to the Mother Dirt website our biomes grow most at night. If so, applying soil before sleeping might be an interesting if eccentric practice.

Dave Asprey offers a probiotic spray to apply to the home itself which he claims will also help combat mold, but he provides no clinical studies to support his claims. Applying probiotics to one's environment is an interesting concept, but it seems to me good, organic soil applied sparingly around one's body is more economical and may provide an even richer background biome. Biggest caveat may be molds in the soil. Not sure if they're avoidable.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: E4 carriers protected against parasitic infections?

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Hmm, calling our efforts the Hero's Journey has a nice ring to it. :D
LOL, Susan- a new tag line? ApoE4.Info: A Hero's Journey?

Circ, I enjoyed your musing on this. The hygiene hypothesis may very well be at play here. E4 carriers appear to be well equipped to deal with nasties. Lack of exposure could be a bad thing for us. Lots of evidence suggests that our innate immune systems are ramped up for a fight and may not do well under more hygienic conditions. You've gotten very creative in your approach to dealing with this! FWIW, I've also had histamine reactions to several probiotics, but had luck with this soil-based probiotic.

The more I learn about optimizing health, the more convinced I am that our gut microbiome may be regulating everything. Through several IFM lectures, I recently learned that probiotics are no more helpful in healing the gut than tylenol is for treating a headache. Both treat symptoms. Probiotics, sadly, have no long term effect on our guts. They temporarily populate it with beneficial bacteria, but that exogenous bacteria disappears within a relatively short period (a day?) after ingestion. That being said, I have noticeably positive health effects from my probiotics (especially VSL #3) and have no intention of giving them up anytime soon. Under optimal conditions (vaginal birth, no antibiotics, controlled stress, adequate sleep, etc.) a consistent diet rich in colorful, varied, vegetables and tons of fermented food should do the trick, but many of us may need more help -probiotics- while working towards gut microbiome optimization.

I like that you're working on your skin biome. Please share more. Dr. Bredesen thinks we should all be working on our nasal biomes. By virtue of proximity, the nasal cavity has the closest access to our brains. Nasal probiotics are just coming on the scene. Has anybody tried them?
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Re: E4 carriers protected against parasitic infections?

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Haha, "creative". Like that diplomatic streak!

True, we need to keep taking gut probiotics if they help :( . I've been hoping a focus on resistant starches might be the way to build a stable population that eventually may reduce the need for the supplements? I wonder if they don't establish colonies only in people who don't eat enough of what the microorganisms want to eat to get established?

Unfortunately I reacted to the soil based probiotics as well as VSL3. I know Susan likes VSL3 too. I've tried it three times and had to stop allowing denial to creep in. I also react to house plants because the soil seems to emit molds or whatever into the air in my home. I'm beginning to think the only thing my body might accept is living in Africa somewhere primal! I think it isn't just the gut biome regulating so much, but also the environmental biome. I suspect the environmental biome contributes to regulating the body biomes and in turn they interact with our genomes and everything else to influence pathways. We are SO out of context!

Researchers have found that different areas of skin harbor different colonies (as do different areas of the gut), so I realize my measly attempts at reconstructing things are pretty much just that, but hey, it's something.

I got on the skin bandwagon because I developed recurring eczema over the last 1-2 years.

So far I have been using:

Mother Dirt shampoo (nice that just one wash works) this probiotic soap
Mother Dirt AO+ Mist Dermatic

The Mother Dirt one only has one strain and is expensive but studied. I use it more sparingly to make it last.

I can't be sure the soap is biome friendly, just hoping. From what I gather as long as the skin care ingredients are natural (ie no harsh chemicals, detergents ...) it's the preservatives and citrus ingredients that kill the skin biome, but there may be other specifics. Mother Dirt products are the only ones tested as far as I know. Their cleanser dries out my skin while the soap above works well for cleaning and shaving (I'm not ready to give up shaving so my biome has a more suitable home!). The moisturizer was fine but *very* expensive and didn't last long at all. Not a solution on my budget which I'm already stretching. So I'm in the air about a safe lotion. The maker of the soap I use has a lotion but I reacted to it.

Haven't had an eczema episode since ditching usual store bought products and using these, but I do still have high histamine in the capillaries below my skin that may have more of an internal cause.

I've also started using Dr. Bronner's castile soap for household cleaning (hands, counters, cosmetic brushes ...), but I don't want it in the shower because I'm slippery shower phobic :lol: I add antibiotic oils to the counter and brush cleaners but not sure that's wise if I'm worried about my environment being too hygienic ~ duh. Going to work with it in my dishwasher and laundry. It's supposed to be a cost saver as well as gentler on the environment. Help offset the skin products in the long run.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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SusanJ
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Re: E4 carriers protected against parasitic infections?

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Circ, good to hear from you my friend!

Haven't thought much about the skin angle. Interesting stuff.

I don't take VSL#3 any more. I tried another multi-strain concoction and flared my RA (think it was the Plantarum which boosts the immune system Th1 response). So I switched a while back to a formula with just 4 bifidobacterium. (Seeking Health ProBiota Bifido)

And I've had an amazing turn-around of no histamine reactions to food. None. Zip. Nada. Something in the VSL slowly caused me to have more and more reactions. No VSL, no reactions.

I've been researching the different strains to better understand what was happening. (Maybe someday I'll get it organized enough to do another wiki post.)

I am also experimenting with galacto-oligosaccharides as a prebiotic (less likely to cause problems than FOS or resistant starch). Supposed to help both the bifidos and lactobacs grow. Using Seeking Health's ProBiota Immune. Like you, I'd like to feed my microbiome the right stuff and ditch the probiotics eventually.

A couple references for you:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593662/
http://onlinelibrary.wiley.com/doi/10.1 ... 911.x/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607002/
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Re: E4 carriers protected against parasitic infections?

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Hi Susan, thanks, and thanks for the followup on your experience with VSL3. I've also used a combo bifidobacterium product before, but I didn't notice any difference one way or the other. I'm glad you're food reactions have improved! What freedom that must be!

I hadn't begun to consider different effects of different types of prebiotics. I've mainly aimed for eating, daily, a variety of foods believed to be high in them and haven't noticed adverse gut side effects. Maybe I should try to see if they have histaminic effects?

Thanks for the links. BTW your second link appears to be broken.

I like Dr. Davis' perspective on this (just found) where this caution may prove helpful to some:
If you are interested in GOS and obtaining the beneficial effects of prebiotic fibers, note that these are strategies that should only be pursued if you are wheat/grain-free, have been taking a high-potency probiotic (e.g., 50 billion CFUs per day), and do not have dysbiosis. (Prebiotic fibers will make dysbiosis worse, signaled by abdominal pain, excessive bloating and gas, and diarrhea, since they feed undesirable microbial species as well as desirable.)
I'd like to know which microorganisms produce the most butyrate (or other ketones). I've been contemplating a ketogenic diet that is higher carbs, but where if the added carbs are prebiotics that produce the highest amounts of butyrate they would offset the higher carb content of the diet from the ketone perspective, while if the additional carbs don't produce much or any butyrate (or other ketones?), then one would fall out of ketosis. I have often thought our simple fat/protein/carb breakdowns were too oversimplified and that fiber should be added as a fourth macro, and that also split between types of prebiotics as the science gets more established.

To tie this back to the OP, I wonder how carb vs fat burning interacts with apoe4 and protection vs parasites. If there's a difference, does it depend what kind of prebiotics are in the carb burning diet? These prebiotics may be the pivot point for metabolic and immune health more so than a more generalized ratio of fat/protein/carbs.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: E4 carriers protected against parasitic infections?

Post by SusanJ »

Interesting thought, circ. We know our ancestors ate a much higher fiber diet. Plenty of prebiotics there. And they certainly didn't guzzle olive oil by the liter.
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