Wednesday, June 22, 2011

Ancestral Allele ApoE4: Super Brain Power, Fertility, Lipophilic Immunity




Ancestral Nutrition: The Imperfect Diet Cleaves Adaptive Genetic Polymorphisms

Hat tip to B. Pottenger for the latest science daily (HERE) on the importance of ancestral, customized nutrition for our health. Chilton et al found desaturase/FADS variants in African Americans which take medium chain n-6 PUFAs (polyunsaturated fatty acids) and convert them into long chain n-6 PUFAs, like arachidonic acid which may increase systemic inflammation. They purport this may explain the inordinate increase in Western diseases observed in African Americans who display a certain FADS genotype variant for fatty acid disposal when they eat the high n-6 PUFA Western diet, including prostate cancer, diabetes, diabetic complication, heart attacks, obesity and dementia/Alzheimers. [I edited the last post -- continental Africans also have a high rate of apoE4 in addition to current hunter-gatherer groups in Africa.]








ApoE4, The Ancestral Allele = Carnivorous and Fatty Acid-Adaptive Allele

It is clear that our ancient hominid predecessors had something special that allowed them to leave Africa ~2 mya and navigate the terrain and uncertain food, energy and climate allotments. Like others I subscribe to the marine hypothesis (Cunnane SC) that certain brain nutrients are essential for IQ and brain function. Both Cunnane and Jonathon CK Wells writes about the 'fattiness' of the human brain and how this factored into our brain evolution and global domination of every potential ecological niche... not withstanding the moon and interplanetary travel as well. Wells' book 'The Evolutionary Biology of Human Body Fatness: Thrift and Control' details the fats that built our history and brains.

A couple evolutionary biologists also assert that the APOE4 allele is our 'meat-adaptive' gene. Well. This makes sense to a finite degree however no research that I could find illustrates apoE increasing proteins into the brain or digestion... On the other hand, the research is highly demonstrative of apoE4 increasing FATTY ACIDS into our brains, mitochondrial metabolism and enhancement of neural efficiency.

My view:
apoE4 -- Infiniti of cars (same Nissan engine), running on super premium fuel (ancestral allele)
apoE3 -- Nissan Maxima (wild type allele), runs both regular and premium fuels
apoE2 -- Nissan Sentra, on regular unleaded (agarian allele??)
apoE combos -- Prius hybrids (phenotype varying by degrees)

One change of the protein structure of apoE at the 61 spot from T to R/arginine may have set the stage for evolution of other nervous system and housekeeping genes that not only grew a superior engine in the brain but also the chassis/architecture of our hard drives. The ancestral apoE4 allels may be one among several genetic variations that sets us vastly apart from our not so distant primate past.







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.

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 Fertility = (Pre-Industrial) ApoE4 Populate the World

The literature abounds with cases of higher infertility in apoE4 women. FYI All literature needs to be viewed from an evolutionary perspective and in this context the great majority of these studies for me only demonstrate that the Western diet/lifestyle are particularly adverse to the hunter-gatherer types who carry the E4 allele. If a person carries the E4, then consuming an anti-HG diet (e.g. refined, non-ancestral), then the preponderance of small dense, oxidizable LDL and a hyperactive immune system which searches and scars, yes of course, will result in higher rates of infertility, fibroids, ovarian cysts, PCOS and less pregnancies, as countless PubMed articles report.

One study looked at HG super fertility... In African-Ecuadorians and a HG group, Capaya Indians, indeed the # of gestations and pregnancies were astoundingly higher in E4 carrier women. See citation below Corbo et al. They hypothesize that higher rates of sex hormone steroidogenesis can potentially occur with the E4 genotype.

My own family may also be a prime example. On low carb, mod-high sat fat, my LDLs are greater than 130s which is 'high' for the medical establishment, EVEN THOUGH THE HDL-CHOLESTEROL ECLIPSES THE S.A.D. HDL for women at 105 mg/dl. Both my father and stepmother's side each have 12 children (with 1-2 nonsurviving siblings). How is this humanly possible, as a mom, I used to WONDER OUT LOUD IN HORROR. I think Catholic families might relate... I could have a litter kids if I didn't have a brakestop. My parents and step mother are from an ancient nomadic group (Hakka, part of Han) and in all likelihood harbor the E4 allele somewhere, as my LDLs my appear to indicate. Each of my siblings and I (4 total) have had an autoimmune disorder and are somewhat sensitive to modern pollution and toxicants (gluten, dairy/casein, medications, and sulfa-, nickel-, metal-allergies).




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. Finch and Stanford (QJB, 2004) report 'In chronic infections by hepatitis C virus (HCV), apoE4 carriers had milder liver disease (Wozniak et al. 2002). The protection against HCV by apoE4 is consistent with the role of lipoproteins in transmission of HCV and other viruses (Wozniak et al. 2002), and fulfills hypotheses that apoE4 is a resistance factor for lipophilic parasites (Martin 1999) and that apoE4 confers advantages in early life (Charlesworth 1996). ApoE may also influence infections by other viruses and by prions, but the evidence is less clear (Table 3, Note 1d and Appendix).'




Human Migration: Evolution of Machinery to Convert Saturated Fat into Omega-3 PUFAs

How did humans go so far north, such high altitudes where seemingly harsh climate and terrains existed? Many SNP variants have apparently evolved which helped our ancestors thrive and live very full lives in certain microecological niches on earth. One thing that has baffled me to know end is the apparent n-3 pufa sources in northern Europe, Africa or northern China as hominids moved there 200,000 years ago. The FADS gene clusters of polymorphisms definitely explains a lot as to how the delta 5 and 6 desaturases control elongation of fatty acids to the ever important essential brain nutrient n-3 pufa.

Terrestrial Brain nutrient allocation and Adaptation from Sahara marine-sources (hypothesis):
EPA DHA n-3 pufa: ???! from where, ?megafauna and small animal predation
ALA n-3 pufa: wild greens
Iodine: ApoE4, possible iodine-oral cavity cellular conservative adaptations, polymorphs of MT1,2,3
Zinc: ApoE4
Magnesium: ApoE4
Taurine: Raw megafauna hunt successes, small animals, fish/seafood from local rivers/tributaries
UVB induced vitamin D: grubs, lighter eyes, lighter skin, melanin reduction, megafauna livers
Red wine: j/k


In a prospective human intervention trial, Dabadie et al gave myristic acid, a 14 carbon SATURATED FATTY ACID, to humans and showed an increase and significant enrichment of DHA, omega-3 pufa, in tissues. The authors later performed another study, increasing the myristic and giving ALA and found a J- or U-shaped curve where less DHA changes were seen at higher saturated fat intakes.

I think this is the first and only study that I could find where saturated fat can be under the influences of our desaturases to produce and synthesize a necessary and essential brain long-chain omega-3. Lard is 1% myristic, the head oil of sperm whale 15% and dairy fat 10%.






Citations

1. The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans. Mathias RA, Sergeant S, Ruczinski I, Torgerson DG, Hugenschmidt CE, Kubala M, Vaidya D, Suktitipat B, Ziegler JT, Ivester P, Case D, Yanek LR, Freedman BI, Rudock ME, Barnes KC, Langefeld CD, Becker LC, Bowden DW, Becker DM, Chilton FH.
BMC Genet. 2011 May 20;12:50.

2. Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk.
Simopoulos AP.
Exp Biol Med (Maywood). 2010 Jul;235(7):785-95.

3. A 'desaturase hypothesis' for atherosclerosis: Janus-faced enzymes in omega-6 and omega-3 polyunsaturated fatty acid metabolism.
Martinelli N, Consoli L, Olivieri O.
J Nutrigenet Nutrigenomics. 2009;2(3):129-39.

4. Apolipoprotein E polymorphism and fertility: a study in pre-industrial populations.
Corbo RM, Ulizzi L, Scacchi R, Martínez-Labarga C, De Stefano GF. Free PDF.
Mol Hum Reprod. 2004 Aug;10(8):617-20.

5. n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood. Free PDF. [This will be discussed later (someday). N-3 is a surrogate for mercury toxicity via fish/seafood consumption esp in apoE4 who hoard/harbor trace metals.]
Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, Fox HC.
Am J Clin Nutr. 2008 Feb;87(2):449-54.

6. Moderate intake of myristic acid [MEDIUM CHAIN SATURATED FAT] in sn-2 position has beneficial lipidic effects and enhances DHA [OMEGA-3 PUFA] of cholesteryl esters in an interventional study [HUMAN].
Dabadie H, Peuchant E, Bernard M, LeRuyet P, Mendy F.
J Nutr Biochem. 2005 Jun;16(6):375-82.

7. Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention. Free PDF.
Ma QL, Teter B, Ubeda OJ, Morihara T, Dhoot D, Nyby MD, Tuck ML, Frautschy SA, Cole GM.
J Neurosci. 2007 Dec 26;27(52):14299-307.

8. Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers. Free PDF.
Mondadori CR, de Quervain DJ, Buchmann A, Mustovic H, Wollmer MA, Schmidt CF, Boesiger P, Hock C, Nitsch RM, Papassotiropoulos A, Henke K.
Cereb Cortex. 2007 Aug;17(8):1934-47.

9. Superior performance [CHESS PLAYING/STRATEGIZING] and neural efficiency: the impact of intelligence and expertise.
Grabner RH, Neubauer AC, Stern E.
Brain Res Bull. 2006 Apr 28;69(4):422-39.

10. Evolution in health and medicine Sackler colloquium: Evolution of the human lifespan and diseases of aging: roles of infection, inflammation, and nutrition. Free PDF.
Finch CE.
Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1:1718-24.

11. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Free PDF.
Dorus S, Vallender EJ, Evans PD, Anderson JR, Gilbert SL, Mahowald M, Wyckoff GJ, Malcom CM, Lahn BT.
Cell. 2004 Dec 29;119(7):1027-40.

12. Apolipoprotein E: far more than a lipid transport protein. Free PDF.
Mahley RW, Rall SC Jr.
Annu Rev Genomics Hum Genet. 2000;1:507-37.

13. Meat-adaptive [URRG fat adaptive] genes and the evolution of slower aging in humans. Free PDF.
Finch CE, Stanford CB.
Q Rev Biol. 2004 Mar;79(1):3-50. Review.

21 comments:

Peter M said...

Interesting. It certainly seems that the ApoE3 and ApoE2 allele variants are relatively recent adaptations to a heavily grain-based diet.

The ponderous question for those of us who are ApoE4 positive is: will a low-carb, high saturated fat diet really provide any measure of Alzheimer's protection as we age.

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.
--parasites
--?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.

-G

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)

-G

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,
Mary

john said...

You and I think a lot a like. Love the post. come take a look at my blog some time. Dr. Jack Kruse.

Dr. B G said...

Dr, Kruse,

I've already looked at the blog which is INCREDIBLE-- I think Dexter introduced me but I've been following your deep insights for a while on PH. I'd concur -- we're alike *haa!*

David and I weighed in on adrenals for Jessica. You were once a dentist, no? What are your thoughts regarding the effects on metals?
http://drbganimalpharm.blogspot.com/2010/04/brain-and-adrenal-health.html

The Quilt discusses endocrine disruption but I perhaps missed the metals? Would be delighted to know your thoughts.







Mary,

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...

G

Steve Cooksey said...

Fascinating post Dr. BG.

Family history tells me my great grandmother was Native American.

Your posts/site have meant much to me. I have not stated this in awhile... THANKS for all you do.

Steve

Patri Friedman said...

Another e4/e4 here, with great personal interest in the topic! Was already eating primal/paleo 2.0 w/ intermittent fasting, curious to learn more about testing to confirm metal accumulation & then how best to reverse it.

Dr. B G said...

Patri,

A hair test or urine provokation test are all useful. The hair test however will be ineffectual to really tell much until the metals start to be stripped out of internal soft tissues and glands...

I use the cardio am/pm from extremehealthusa.com - -there is also an affordable $89 hair test they sell. Doctor's Data also does comprehensive hair test which i would strong recommend. My sister and her children have done this and mine is pending.

So... identify and then get them the f*ck out... (safely) *ha*

Replenishment of the stripped good minerals is also very important. We take extra minerals (like iodine and Thorne's trace minerals) or a liquid one is good too.




Steve,

I LOVE YOU TOO SHRINKING BIG GUY *big hug and kisses!!*

I cannot tell you how many people I appear to know who are part Native American Indian. Seriously dude. This is not a joke... Actually one of my best friends from when we used to live in Philipsburg PA was half Native American Indian and we fell out of touch after college unfortunately. You are now the 2nd blogger that I know that's part Native Am indian...

From my observations, those of Native Am Indians background appear to have THE WORST neolethal damage however upon healing (no grains, more vegs, more movement), they seem to be SUPER AMAZING healers. THE BEST recover I have had the opportunity to observe were in those with Native Am genetics (on mod-high sat fat)... reversal of neuropathy, brain damage, memory losses, numbness/tingling in peripheral tissues, diabetic damage, nephropathy and psoriasis/autoimmune reversal...

G

Dr. B G said...

Below is Dr. James Robert MD, cardiologist reviewing the RCTs and trials relating to chelation outcomes (and a couple of fraudulent studies trying to slime chelation).

The review of the products currently available to us is excellent. To me it is appalling that our industrial nation created the current toxic waste in our bodies via contamination of air, water, soil, mercury amalgams, food/drinks (like mercury in high fructose corn syrup -- worse than Roman leaded crystal goblets) yet reversing the damage is NOT covered by dental or medical/Medicare insurance.

http://www.heartfixer.com/CHC%20-%20Treatments%20-%20Chelation%20Therapy.htm

Patri Friedman said...

Thanks Dr. B G!

I've started a blog for the primal perspective on ApoE4, I will be linking to this article and some of your source when I get a chance. Look forward to whatever else you find: http://primale4.wordpress.com/

Jack said...

Wow. I hadn't seen this bfore. Dr B.G., what do you make of my situation? Since switching from SAD to LC Paleo (~50g) then to Mod Carb Paleo (~150g), I have seen my HDL drop, LDL drop, VLDL skyrocket, Trigs Skyrocket, with sdLDL dominance.

I hate all of this, and I'm trying very hard to correct it. Many people are trying to assess what might be going on with me since it's so puzzling.

I checked into how much an ApoE testing would be for me to see if I have the gene. LapCorp quoted me at $390. Does that sound right or is that a ripoff?

Here is my thread on PaleoHacks.

http://paleohacks.com/questions/64890/hack-jack-kronks-latest-lab-results-sept-2011

Thanks,
Jack Kronk

Dr. B G said...

Jack --
I was reading your comments on the other threads. The fact that your father had significant blockages suggests a high likelihood of silent inflammation and possibly SCD, sudden coronary death which kills ~1 million Americans yearly if not more (that is a statistic from a few years ago). I'm so sorry to hear about father's death at 53. You have made AMAZING, shwingtastic health improvements!! Wt loss!! Muscular gains -- come on you are totally HAWWWT. You must know that you will NOT have the same path... If you continued on the SAD high carb/high GI path, no doubt that is a fate that would'v ebeen heard to evade. The AHA is malpracticing with prescribing the step 1 or 2 AHA heart diet which has been shown to exponentially increase sdLDL, inflammation and lower HDL worse than any other diet.

Good for you for doing the VAP with such a family history. I like your comments and optimistic attitude at PH and have already provided ideas for you -- I'm 'grace' in case you didn't realize!! You and your sister have something going on. I would entirely concur with both Melissa's and Kruse's astute assessments. There is something going on and likely it is gut-related. Fix priority #6 and all the above will reverse. Fix #1 priority the adrenals and it will dramatically speed the improvements of all the below.

Check out:
--heavy metal damage -- read modernpaleo.com or vitalobjectives.com latest post (it's the same from Christian Wernstedt) metals can cause everything #1-6
--rule out hemochromatosis -- see your doc again. You might consider the value of bleeding out *scratch* donating blood unless you have a blood borne condition (Lyme, hiv, hep B/C, etc). Dr.Eades has discussed this for paleo/ancestral folks at his blog and latest book. Low grade inflammation from iron overload is frequent in the population and underdiagnosed (and frequent among those with ancestral genes like Vikings and apoE4)... I have some cool articles if you want...
--low level sepsis via leaky gut/SIBO/intestinal permeability

Masterjohn said in his talk which was new thing I learned that the HDL has a function to scavenger endotoxins which include microbial toxins/LPS. HDL is for me the marker and essential indicator of immune function and longevity (like Kruse). Unless it is artificially elevated (like some genetic cases or by pharmaceutical, it is usually a good reliable distinction when taken in context with the whole picture. The HDL on the 'nonfasting' in July was surprisingly low for a guy doing all the right things. With high carb/high GI potatoes (GMO potatoes most likely), it of course, naturally is still low but should improve dramatically with the correct, stepwise interventions. Honestely the value of rechecking is low because when health is transitioning, the lipoproteins are all f*cked... just FYI. Not reliable.

The apoE4 is interesting. It can add value but if you are going to pinch pennies then I'd go for doing a stool analysis preferably metametrix which employs DNA sequencing. Yeasts and some bacteria do not come out on 'conventional'cultured assays. The value of identifying these other species is that it gives important context to the SIBO overgrowth extent. For instance for a lot of peeps, the candida/yeasts don't culture because they produce something that prevents culturing. If this is missed, then a big picutre for the pathogenic basis of the dysbiosis is being missed (like metals, like anti-yeast strategies, etc).

(sorry for my rant) How much do you spend on maintaining your automobiles? Insurance, gas? oil changes? 10,000 mile major tuneups??? Why not spend what you need to spend to assess the neolethal damages instead of waiting another 10, 20yrs for accumulated damage??

Good luck and would love to hear your progress later.

Thanks,
G (aka grace aka dr.bg)

Olga said...

Hi Dr. BG:

Did you see this study:

http://www.ncbi.nlm.nih.gov/pubmed/21673053

Dean said...

Great posts on ApoE4 here and at PH! Makes much more sense than conventional recommendations!

I'm curious:

My TC went up to 400 ( http://i.imgur.com/wj2oq.jpg ) after going VLC/high sat fat, and I *did* have mild IBD, SIBO and probably big problems with LPS, my health has been transitioning, and the lower the carbs the better I felt. I'm now eating almost zero carb to keep things in check (still got mild problems sometimes). I also got rid of the IBD.

How safe is it to assume I have ApoE4 with these labs?

Can it ever be problematic to eat coconut oil and butter instead of tallow and lard, which have more monounsaturated fat?

Dr. B G said...

Dean,

Thank you for the kind words! I'm glad you're a fan of PH too!!

You know the presence of the thyroid antibodies is indicative of autoimmunity which matches with your GI description of SIBO and gut dysbiosis. I'm glad you are feeling better. With hypothyroidism/hypoadrenalism, the LDL will naturally rise due to the metabolic changes. The LDL labs DOUBLED with your diet transition (VLC, high fat). It could be an indicator of apoE4 allele(s) but also could indicate being a carrier for FHC, familial hypercholesterolemia. Read Jonathon Carey's story at TripleYourHDL.com (his heterozygous for FHC).

Your story is complicated by the endocrine disruption at the thyroid and adrenal levels... If you check rT3 and do a salivary cortisol 4x (zrt labs -- you can self order) later on, more would be clarified. During healing stages the labs like the LDL are funky and not reliable. I would not worry to an extreme amount at this time if you are still fixing the gut... and reversing the thyroid attack and autoimmunity.

The problem I have with VLC (very low carb, ketosis) you do run the risk of going into frank and 100% adrenal failure and insufficiency. That's wonky and not fun. The salivary cortisol can be helpful. Then the problem with adding carbs is that you'll trigger SIBO and fermentation in the small intestines. I had this problem and there really is no way around it except with supplemental digestive enzymes and Betaine HCl at every meal. Stomach acidity goes way down with hypothyroidism/hypoadrenalism...

I have found it to be a struggle to walk the fine line between healing the gut and the adrenals at the same time.

The carbs most easily digested for me are small amounts of honey, organic palm or coconut or succanat sugar and vegetables. Some people use Ribose. Paul Jamiment seems to enjoy rice bran syrup. Using liberal (if you tolerate) probiotics helps the gut microbiota to transition to carb food sources... (and controls of the overgrowth). Prescript Assist has one study with nearly 100% efficacy in IBS patients; it is a soil based organism product and widely used by integrative practitioners like David Rostellan ND and others. I'll probably give that a try when I return to the US.

B. laterosporus (FloraBalance at iherb.com) has great activity against the common pathogens in SIBO/dysbiosis, eg yeasts, candida, etc.

The last post, Dean, you might find the resources for adrenals and thyroid helpful! Good luck and I'd love to hear your continued progress in the future!!

BTW You may also want to have the ferritin, Hgb, Hct, MCV, iron panel and a liver panel evaluated. A triple digit ferritin sometimes indicates iron overload, again another characteristic in those with more 'HG' type ancestral backgrounds from northern Europe and China. In low thyroid, ferritin tends to go DOWN, therefore to see the lab mildly elevated indicates something amiss. It could be from a reaction to inflammation and/or iron overload.

G

Dean said...

Many thanks, G!

I need to clear up that with "low antibodies" I meant they were in the

low normal range. The thyroid checkup was completely normal. Sorry for the mixup.

The latest blood test also tested for antibodies against transglutaminase, ANA

and AMA, of which there were none. (Little wonder I was living gluten free

already). I don't really think I have thyroid autoimmunity... the TSH went up

after I supplemented 1mg iodide, which was probably too much of an increase. I

backed down to 250mcg. My temperature is fine, as long as I eat enough.

My experience with probiotics (VSL3, l. acidophilus) and reintroduced plant foods is bad. Proctitis only stopped completely after I stopped eating spinach. With the Lutz diet there is gradual improvement in colitis patients over up to 8 years. Voegtlin has a more limited/carnivorous approach and he talks about major gut flora changes in about three months. It makes sense that "zero carb" would be the most effective, my experience confirms it. I've used betaine and digestive enzymes all summer and am now doing fine without.

I already got those labs, and they seem normal!
Hgb 14,8 g/dl (14-18)
Hct 44% (38-52)
MCV 97 (82-103)
too much typing... liver and iron values were also in the normal range! No signs of inflammation even while my colon *was* inflammed. Cholesterol and then TSH were the only abnormalities of what was tested.

I will try well cooked vegetables again at some point... once the presumable LPS problems like fuzzy thinking, muscle twitching and proteinuria have been absent for longer. I'll let you know how it goes in a couple of months.

Concerning FHC: It would surprise me simply because very high LDL on VLC paleo has

been reported more often than I would expect, assuming a 1:500 incidence of FH.

ApoE4 could be a more common cause...
Yes, I'm not too worried about it since I'd sooner have high LDL as long as I feel better.
It still leaves the question: would these cases benefit by eating less butter/CO and more monounsaturated fats?
It will be interesting to see what happens when Jonathan Carey adds CO and ghee.

Anonymous said...

Really appreciate this blog post. I read it every few months, stil trying to fully understand it.

When I got my E3/E4 results on 23andMe 2 years back, this post really helped blunt the stress of dealing with this issue.

It also helped me have a starting point for understanding why my body seems to respond to food (I feel so much better in ketosis) and toxins (heavy metals) so differently from the family and friends around me.