The Big Macronutrient Question: Low-Fat, or High-Fat?

[Walker44]

Hey. This is my first time posting. 6'3'', 146lbs, 24-yo e4/e4 male here; when I found out I was e4/e4 a few months ago I immediately began working to adopt the best diet and lifestlye I could. To go on a little tangent before getting to the question in the title of this post - what I've done so far is...

I exercise daily (run for an hour a day; walk avidly), have cut processed carbohydrates from my diet; the carbohydrate-heavy foods that I now eat are veggies, fruits, whole grains, legumes, undercooked/raw sweet potatoes, and whole pseudo-cereals like buckwheat and quinoa; I get my fats primarily from low-saturated fat nuts and seeds and avocados; and I feed via a modified alternate-day-fasting regimen: I eat <10% of my calories on my "fasting" days, and >90% of my calories on "feeding" days. On feeding days, I eat about 5500cal throughout the day, and am finished eating before 8:00pm. On fasting days, I eat one 500cal meal at 8:00pm.

I feel like I've done a lot to improve my health, but one big question is still looming overhead: as an e4 carrier, should I be eating a low-fat diet, or a high-fat diet? I've dug through endless studies via google scholar and can't seem to find any definitive studies on e4 carriers with large sample sizes, so - unless I'm missing something big - it seems like this question is still basically unanswered in the literature.

My question is this: what do you think of high-fat diets versus low-fat diets for e4 carriers? Why? Also, have any of you tried experimenting with high-fat versus low-fat diets? How did they work for you? I'd be especially interested if you measured your cholesterol profile (HDL, LDL, VLDL, triglycerides) and/or insulin sensitivity while undergoing both dietary approaches...

I feel like there is a good argument to be made for either side. On the one hand, high-fat diets have the benefit of providing fewer insulin spikes, which should improve insulin sensitivity. On the other hand... let's recall that the e4 allele became the dominant allele (i.e. was heavily beneficial, and was selected for) in Australopithecus/Homo Erectus, both of which probably consumed something pretty close to a chimpanzee's diet with the addition of perhaps a little more meat. This means that the e4 allele was in it's heyday during a time when our ancestors were probably eating a low-glycemic high-carbohydrate diet, not a high-fat diet. It's this thought that gives me pause about high-fat diets... of course, we want to curb insulin insensitivity, and high-fat diets can help with that... but might the approach that better mimics our ancestral environment be a low-glycemic high carbohydrate diet combined with frequent fasting and heavy exercise to help curb some of the negative effects that carbs have on insulin sensitivity?

[Tincup]

Welcome, Walker44. Glad you found us! Some resources, if you haven't stumbled upon them yet. A primer, written by a GP. How to get the most out of the site, wiki. and the wiki in general. Lastly the search function.

My question is this: what do you think of high-fat diets versus low-fat diets for e4 carriers? Why? Also, have any of you tried experimenting with high-fat versus low-fat diets? How did they work for you? I'd be especially interested if you measured your cholesterol profile (HDL, LDL, VLDL, triglycerides) and/or insulin sensitivity while undergoing both dietary approaches...

I was LF vegan for ~18 years and pretty fit (I'd finish the Pikes Peak Ascent race, for example - 13.2 miles + 7,800' elevation gain topping out at ~14,100'). The standard of care would have thought my lipids were great. TC~150, LDL ~90, however HDL was 40 though Tgs were maybe 60 (I'm making this up, so they won't add, but they are relatively right). Started playing with a glucometer in 2006. Knowing what I know now, I'd say I was insulin resistant. I started trying to eat so I would barely spike my glucose an hour after eating. Didn't really know what I was doing. In 2009, went "traditional" keto. Meat, fat veggies. I've been keto adapted since.

In 2014, I learned my ApoE4 status. Started following Dr. Gundry's program as he treats all his patients as lab rats in a study (last Tuesday had 22 vials of blood drawn for 5 different laboratories for an Aug consult). My LDL is generally higher now, but I'm very comfortable with where they are. I think the lipid hypothesis is BS and insulin is MUCH more important. We've posted all our Gundry labs as well as transcripts of 6 consults linked here. My friend, Dave Feldman, did a nice job in this presentation. There is more as to why this is my opinion, but all I have time for at the moment.

Today my diet is HF keto, but with the fat being mostly monos. My non-veg foods are limited to eggs, white fish & shellfish. In calories, its 75% fat or so. As to glucose/insulin. Normally, I have a glucose/ketone index of say 2.5 (glucose in mg/dL/18/ketones in mmol/L). I can get this under 1 by skipping one meal (I eat daily in a 2 hour window). After a couple of days of fasting, my glucose is in the 50's and ketones between 5 & 8. I looked at the fasting/starvation papers from the 60's from George Cahill & my glucose is lower & ketones higher after a couple of days than their subjects were at 40 days. My fasting insulin is also low. It has been <1 on extended fasts.

[apod]

My question is this: what do you think of high-fat diets versus low-fat diets for e4 carriers? Why? Also, have any of you tried experimenting with high-fat versus low-fat diets? How did they work for you? I'd be especially interested if you measured your cholesterol profile (HDL, LDL, VLDL, triglycerides) and/or insulin sensitivity while undergoing both dietary approaches...

I tend to be of the opinion that lower LDL (particularly lower sdLDL & LDL particles) is going to be more cardioprotective. However, I also believe that higher fat diets (particularly whole foods based Mediterranean style diets) are going to be more neuroprotective. What's sort of tricky, is that higher fat diets tend to raise LDL (but not necessarily sdLDL / LDL-P.) Thinking about where medicine will be in the next 10-20 years, I'm thinking that the plumbing issues around cardiovascular disease will be easier to repair than say, a human brain, but that's a bold bet to make when choosing whether to optimize more for heart health or cognition when facing a choice between the two.

On a low-fat diet, I had LDL of 63 mg/dL, LDL-P of 908, HDL of 58 mg/dL, small LDL <90, and triglycerides at 56 mg/dL. This diet had a ton of fruit, hundreds of grams of carbs/d (upwards of 400g), and was a lot of fun, actually... from a keto perspective, this was like living in the forbidden land of cheat days. My A1C came in at 5.3%. This lowered total cholesterol down to 132 mg/dL.

On a high-fat diet (lots of MCT), I had LDL of 138 mg/dL, LDL-P of 1453, HDL of 92 mg/dL, small LDL <90, and triglycerides at 65 mg/dL. This pushed total cholesterol up to 243 mg/dL.

Somewhere in the middle via a high fat MUFA-rich diet with a few supplements, I had LDL at 79 mg/dL, HDL-C at 77 mg/dL, and total cholesterol at 162 mg/dL (fasting glucose 69 mg/dL, HOMA-IR at 0.2, A1C at 4.9%, and insulin < 2 ulU/mL.) On this diet, my omega-6 tends to run higher than I'd like, which I take CoQ10 to try to hedge against. This tends to be where I hang out most of the time, and "feels" the best for me. (ymmv)

There's definitely a correlation between SFA and LDL / LDL-P for me, and MCT oil doesn't seem to get a free pass. I didn't see too much of a negative impact from sugar / carbs on HDL, TGs, or sdLDL when I ran the experiment, although I was doing quite a bit of exercise, young, and particularly thin at the time, which is somewhat unsustainable into older age as insulin resistance can creep up.

Another interesting macro question is the utility or avoidance of low-fat / high-carb days while on a long-term high-fat / low-carb diet for hormonal health. More often, I've been forgoing the carb refeed and just staying low.

[Stavia]

Hi Walker and welcome.

Remember genetic fitness doesnt mean selection for longevity, just number of surviving offspring who in turn breed successfully. In the wild you'd have fulfilled your genetic destiny already

What diet? My answer is the one you feel best on, with a wide variety of non-processed plants and protein and fat sources, that can be sustained.



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[jgilberAZ]

I'd recommend you do a google search for ldl and all cause mortality.

High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis.

Whites and African-Americans in the lowest quartiles of total cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol (LDL cholesterol) were approximately twice as likely to die as those in the highest quartile (White HR: 2.2, for lowest total cholesterol quartile; HR: 2.3, for lowest non-HDL cholesterol quartile; and HR: 1.8, for lowest LDL cholesterol quartile. African-American HR: 1.9, for lowest total cholesterol, HR: 2.0, for lowest non-HDL cholesterol and HR: 1.9, for lowest LDL cholesterol).

Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non CV causes.

I have no issue with my LDL going up on a keto diet.