Russ, it's a mutual admiration
I have to admit your news hurts me. Both, because I care about you & because I wanted to believe you were impervious. I certainly don't have answers. I'm searching for the best diet for E4 carriers along with everyone else here
to avoid both AD and CVD.
For me (and most of us,) it comes down to personal experience; how our bodies/bio-markers react to a given diet. And, regarding genetics, much more than our APOE status is clearly at play. I'm also eating a high fat diet, but lower carbs than you & I have NOT experienced a dramatic LDL-P rise My two tests have put me at 1118 and 1089. I agree with you that Spunky is right about E4's reacting to higher dietary fat with LDL increases. The science is pretty decisive there (with G/"Bri" being our exception), but that doesn't necessarily translate to higher LDL-P.
I've conducted multiple n=1 experiments, followed others, and have read much research and I've concluded that the ratio of fats to carbs matters...(maybe a lot) AND the type of fat matters as well. I'll throw a few ideas out there that you can explore or toss as you see fit
-A while back I theorized that it might
be important when practicing HFLC to shoot for at least mild keto-adaptation, so that the fats are being used as fuel. Otherwise, with E4's poor ability to clear, they remain in circulation too long and are more likely to become oxidized- that's where real trouble occurs Maybe your ratio of fats to carbs was a part of the problem? The fats too low/carbs too high?
-I think you are on to something with the CR...and I would add daily exercise. IMO, eating higher fat without both is NOT a good idea. Both create more ketone bodies (burning & clearing fat) and increase BDNF production. I agree with your theory that E4s "hyperabsorb" more fat to possibly protect us in times of famine. By staying mildly keto-adapted through CR & exercise, we regularly CREATE that famine. By living a sedentary Westernized lifestyle without ever experiencing hunger; we work against our ancestral genotype.
-E4 carriers exhibit glucose uptake problems decades before symptoms show, in a dose dependent fashion- (4/4s are more severely affected.) Ketone bodies can replace some of that cerebral glucose deficiency avoiding the neuronal death that occurs with lack of fuel. For me, an other justification for HFLC.
-I suspect that type
of fat we eat matters. Evidence is mounting, both with research and with my own n=1 experiment, that MUFAs might yield the best results for both brain & heart health- even more so for E4s. I still eat more SFA than Spunky would approve of, but I carefully and purposefully choose the MOST healthful options: pastured eggs (for the phosphatidylcholine) and grass-fed, live cultured kefir/yogurt for the healthful gut bacteria. Like Skibike, I was able to drop both my LDL and LDL-P by 40 and 28 points respectively by switching to more MUFAs.
You know I'm not a scientist, just a 4/4, trying to extend my useful life. Please feel free to knock my theories around
I'm truly wide open to learning & figuring out the best path forward, fully knowing that it may not be the same for all of us. Huge thanks to you, Russ, for sharing your results. They reiterate to me the importance of testing often when experimenting with diet. One quick question: Did you do a CIMT before jumping straight to the CAC?
Skibike, I've followed your struggle with agony, my friend. Kudos on improving your numbers with more MUFA. I really think you're onto something there. I'm not that surprised by your rapid improvement. Research demonstrates that E4s (of all APOE genotypes) respond the MOST quickly to dietary changes. Time will tell if this is a significant and lasting effect- fingers crossed. Thanks also to James for making me aware that plant fats vs. animal fats may be an important distinction for us.