Fidel's tests

[Stavia]

Starting from really metabolically deranged, possibly poorly motivated, people on the SAD, Pam has the opportunity to do great work as a starting point.
I do still feel that currently the evidence is pointing towards the Isaacson, Bredesen, Cunnane etc direction with emphasis on lower carbs for all, for many reasons including IR, mitochondrial dysfunction etc.
I still stand by my review. Her recommendations are not consistent with the body of the evidence and I feel are inadequate in addressing the detailed metabolic issues we have.

[Julie G]

Fidel, sorry to be jumping in so late... Kudos on the excellent LDL-P.

I think Harrison and Stavia’s comments are worth considering. Despite the fact that Pamela McDonald, your resource, and other similar ones- like the Berkley Heart Labs suggest a very fat restricted diet for E4 carriers; the science behind that advice is VERY unsettled. Dr. Dayspring said it best when he warned against relying on the current body of work as it's based on old and poorly constructed studies.

From reading many of those older studies and following E4/diet interactions I’ve observed that E4s typically have an exaggerated response to dietary fat. A low fat approach tends to yield lower TC, LDL-C & LDL-P. The drawbacks are that HDL-C and HDL-P are also lower. Particle sizes tend to be smaller and denser. There are more small LDL-P. Triglycerides glucose, insulin, A1c, LPIR are typically higher. Higher dietary fat tends to yield the opposite results: higher TC, LDL-C & LDL-P (sometimes,) but also higher HDL-C & HDL-P. Particle sizes tend to be type A, big and fluffy. There are less small LDL-P. Triglycerides, glucose, insulin, A1c are typically lower.

EDIT: Caloric restriction can mitigate the negative effects of both approaches; even a mildly HYPOcaloric diet.

E4 carriers must carefully balance BOTH lipid markers and glucose markers. In describing this, Stavia has previously used the visual of a see-saw, with one on each side. As lipid markers improve; glucose markers worsen AND as glucose markers improve; lipid markers worsen This is probably true for all ApoE genotypes, but especially exaggerated in our population. Given the E4 pathology related to both, balance is critical.

I’ve previously mentioned keeping an eye on your Omega-3 levels as we have growing evidence that low levels are related to both heart disease and dementia, especially for E4s. Another marker to work on would be HDL-C/HDL-P. We’ve collected a lot of research suggesting that higher levels are extremely important for our population. High functioning HDL is vital for both reverse cholesterol transport and amyloid clearance- weak spots for us.

I appreciate your sharing. I always say learn the MOST from N=1, diet/lipid and other bio-marker interactions. You’re clearly NOT new to working on optimal health. It’s nice to have your voice in the conversation.

[Fidel]

Thanks for all the input, folks. I guess we do learn the most when we test different approaches on ourselves. After all, the apoE gene is only 1 of so many, and the variations of all of them can make our individual results differ.

I might as well follow through on testing the low fat diet for myself and see what results i get.

Have read that E4 is the ancestral allele, the oldest of the variations. If we did in fact evolve from primates (or maybe even if we were created by a team of highly advanced aliens via some sort of genesis project), it seems consistent that low fat would be healthiest for E4 people since primates eat a very low fat diet in general. The E2 & E3 mutations came later as humans started adapting to eating more fat. Could it be that simple?

[Stavia]

According to Bredesens lecture, genetic "clock" analysis currently shows that E3 appeared 220 000 yrs ago and E2 only 70 000 yrs ago. They are very recent.
Hominins were eating an omnivorous diet much earlier than that.
Australopithecus afarensis for instance lived 2-4 MYA.

[Fidel]

EDIT: Caloric restriction can mitigate the negative effects of both approaches; even a mildly HYPOcaloric diet.

Have instinctively sensed that to be true for a very low body weight person, as all carbs & fat are getting burned up and aren't around to cause trouble.

I imagine the caloric restriction effect you mention also applies to overweight people in the process of losing weight?

[Julie G]

Yes- Sorry, I meant to include that in my initial post. CR certainly mitigates the negative side effects of both approaches.

It's much easier to safely apply in folks trying to lose weight. If they have any degree of insulin resistance, evidence suggests that a lower carb approach can further help restore insulin sensitivity. IMO, CR gets trickier in lean folks. We have to be careful to guard against sarcopenia. This feels important to me and might be worth a new topic...

[Harrison]

Fidel, I noticed the oddly low E4 rate in Italy as well. I found an Alzheimer's disease prevalence study that breaks things down by country:
http://www.ncbi.nlm.nih.gov/pubmed/22179327

The only country with a lower E4 prevalence rate for AD than Italy was China. This is particularly interesting because the link of the Mediterranean diet with low rates of AD might be coincident with lower rates of apoE4 (same goes for "The China Study" like links). This is also surprising to me because of E4 being the ancestral allele, and migration patterns taking a lot of E4's through Italy on their way into Europe even in evolutionary recent times (the past 2000 years).

[Stavia]

I am a bit hazy on this, but doesnt mitochondrial DNA point to migration out of Africa across the RedSea, then spread along the coast right around India first then backwards north and west into Europe? There were geographic barriers to what one would intuitively think would be the diffusion pattern. So Italy would have been populated more recently?

[Harrison]

So Italy would have been populated more recently?

My initial thought is that Italy has presumably seen more recent (Roman Empire era) emigrations from Africa coming directly across the Mediterranean, thereby infusing more E4 alleles into the populace. However, that isn't what they found in the Eichner et al 2002 study (which admittedly only sampled 260 people) or the Ward et al 2012 Alzheimer's disease prevalence which is a meta-analysis that included 18 studies of Italy (among other countries), and is in fact quite the opposite. The country with the most E4 people in both papers was Finland. I found a 2010 paper (Eisenberg et al.) that suggests a benefit of E4 in hotter or colder climates (the apoE latitude hypothesis), but less so in moderate climates, which would explain the data to some extent.

[Fidel]

Wondering if the low prevalence of apoE4 in southern Europe has something to do with the possibility that most E4 people don't do as well as others with higher amounts of monounsaturated fat. This particular study: http://gg.gg/apoE_LDL-size seems to support that, if i'm reading it correctly.

The higher prevalence of E4 in northern Europe might partly be explained by the fact that we tend to be better at making and absorbing vitamin D, which is more of a benefit at that latitude.