Is there research showing benefit of low fat diet for apoe4 phenotype?

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BJ56
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Is there research showing benefit of low fat diet for apoe4 phenotype?

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Hello, Does anyone on this forum know of published research that suggests that a low fat diet (all fat, not just saturated) is helpful for mitigating cardio vascular disease for those with apoE4 phenotypes?

A low fat (<25% of calories from fat) has been the recommendation of a cardiologist for a patient with one ApoE4 allele. I've sought out research that corroborates this and explains the mechanisms but haven't come across any studies indicating a benefit to reducing all fat intake. The only paper I found on this topic is 18 years old and seems to indicate no correlation between reduced CVD risk and a low fat diet: https://www.ahajournals.org/doi/full/10 ... V.15.1.105 -- "There was no significant change in plasma apoB level within any of the apoE phenotype groups on the low-fat diet"
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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BJ56 wrote: Mon Sep 18, 2023 11:30 am Hello, Does anyone on this forum know of published research that suggests that a low fat diet (all fat, not just saturated) is helpful for mitigating cardio vascular disease for those with apoE4 phenotypes?
Hi BJ56 and welcome to the Forum! You bring up a great question on the nuanced topic of diet. As you have probably gathered from your search, the research and recommendations are somewhat mixed as no one diet is likely to work for everyone, especially someone who may have cardiac risk factors. Research shows benefit for low saturated fats in diets, but you may find that many people here follow either a Mediterranean style diet or a version of a ketogenic diet with healthy fats like nuts, avocados and lean meats. This link to the Wiki on Fats contains additional information on dietary fat (with published research studies) that you may find interesting.
If you haven't already checked out the Primer, you may also find it helpful. It includes information about the biochemistry of the ApoE4 gene and offers a variety of research-based prevention strategies, in addition to diet, that may be helpful for someone with one copy of Apoe4.

I hope this is helpful and gives you a starting point as you continue your research. Please let us know if you have any questions or need further support as you navigate the site!

With love, in health,
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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BJ56 wrote: Mon Sep 18, 2023 11:30 am Hello, Does anyone on this forum know of published research that suggests that a low fat diet (all fat, not just saturated) is helpful for mitigating cardio vascular disease for those with apoE4 phenotypes?

A low fat (<25% of calories from fat) has been the recommendation of a cardiologist for a patient with one ApoE4 allele. ...
I am unaware of any credible paper supporting a low-fat diet as beneficial to preventing cardiovascular disease in ApoE4s. Fat is important for everyone’s overall health, but of course, they need to be the good fats (preferably heavy on monounsaturated while minimizing saturated/trans and eliminating the inflammatory so called “vegetable” oils aka industrial seed oils). The good fat intake also needs to be in balance with other nutrients. If a person goes low fat, they tend to reciprocate with carbohydrate intake, which can lead to insulin resistance, the bane of ApoE4s. Remember what our Primer stresses: "GLYCAEMIC CONTROL TRUMPS LIPIDS, EVERY TIME"

Have you heard of Dave Feldman? He’s a fellow ApoE4. His interest lies with cholesterol levels in lean mass hyperabsorbers (ApoE4s usually are hyperabsorbers, therefore we have high LDL levels). Dave is founder of the Cholesterol Code website. For years he offered a bounty for every study (non-drug/non-gene) showing that high LDL equates to a high chance of cardiovascular disease when triglycerides are low and HDL is high. To my knowledge he never paid his bounty.

Dr Goodenowe, PhD biochemist, said in his second ApoE4.info podcast interview https://www.apoe4.info/ep003-dayan-goodenowe/ with regard to the high LDL levels that ApoE4s typically have, “That is not bad, that is completely irrelevant to your health.”

Dr Hussain Yassine, head of the Yassine lab https://yassinelab.com/ studies the APOE4 allele specifically. His dietary recommendations includes a diet high in vegetables with healthy fats and low in simple sugars.

Although not ApoE4 specific, Dr Mark Hyman, has said, “Eating a fat-free diet is not good for your health. We need fats to survive. Every cell is made of fat; our nerve coverings are made of fat; our brain is mostly fat; our hormones are made of fat, our cells and metabolism run better on fat.”

Offering the advice to lower all fat to reduce the chance of cardiovascular disease is basing the advice on antiquated thinking. Even the American Heart Association from this link The Skinny on Fats says,
What you eat can affect your LDL (bad) cholesterol. Knowing which fats raise LDL cholesterol and which ones don’t can help you lower your risk of heart disease and stroke.
Your body naturally produces all the LDL cholesterol you need. Eating foods containing saturated and trans fats causes your body to produce even more LDL — raising the level of “bad” cholesterol in your blood.
It’s worth understanding the different kinds of fats: Saturated, trans and unsaturated.
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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BJ56 wrote: Mon Sep 18, 2023 11:30 am Hello, Does anyone on this forum know of published research that suggests that a low fat diet (all fat, not just saturated) is helpful for mitigating cardio vascular disease for those with apoE4 phenotypes?

A low fat (<25% of calories from fat) has been the recommendation of a cardiologist for a patient with one ApoE4 allele. I've sought out research that corroborates this and explains the mechanisms but haven't come across any studies indicating a benefit to reducing all fat intake. The only paper I found on this topic is 18 years old and seems to indicate no correlation between reduced CVD risk and a low fat diet: https://www.ahajournals.org/doi/full/10 ... V.15.1.105 -- "There was no significant change in plasma apoB level within any of the apoE phenotype groups on the low-fat diet"

Low fat WFPB is a promising area of research. I recommend that you read the work of Dean Ornish (a fellow e4), clinical professor of medicine at UCSD, who is currently pursuing a study on AD and lifestyle using a low fat diet together with Rudy Tanzi at Harvard. Here's a short interview with him from last year. Ornish will be speaking about his newest Alzheimers findings at the Lifestyle Medicine conference this fall, so I expect we'll hear more soon. In the mean time, If I come across a study or two, I'll post the links here.

This is my approach (whole foods plant based low fat low sugar) and several others' approach here too. The general idea is that what's good for the heart is good for the brain is good for your glycemic control is good for longevity is good for ... you get the point. My lipid and glucose numbers are in the optimal range and I feel great. My apob went from 90 on a WFPB diet to 72 on a low fat WFPB diet in three months. My current apob range is now 65 (spring 2023) to 74 (summer 2023 (vacation eating)). It would be impossible to eat no fat. No one eats no fat. Vegetables and supplements have fat after all. I still eat nuts and chia or flaxseeds every day and sometimes fish. If I were extremely strict about my diet, i.e. no restaurant meals ever, no chocolate ever, etc, I believe my apob could be 60 as an apoe4 hyperabsorber woman, age 54, moderate exercise. But I do eat out occasionally and I do eat chocolate in small amounts.
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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Adding Peter Attia's podcast where he notes that lowering lipids prevents neurodegeneration (minute 1:55:30)
https://peterattiamd.com/ama46/
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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Thank you for the responses and resources. My take aways: 1) healthy diets seems to converge on Mediterranean or predominantly plant-based diet with some variations; 2) the wiki on fats was helpful to differentiate between the fats considered most beneficial although I didn't find studies in it about limited fat diets and their impact; 3) @Plumster offered some evidence that low fat (and otherwise healthy) diet could help reduce LDL cholesterol, 4) I looked into Feldman and other contrarian points of view of LDL and they ask good questions about LDL's role but I don't feel ready to discount it as a marker for cardio vascular risk.
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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BJ56 wrote: Sat Sep 23, 2023 10:03 am 3) @Plumster offered some evidence that low fat (and otherwise healthy) diet could help reduce LDL cholesterol,
My personal experience is that my LDL is lower on low fat diets. I did that consistently for ~15 years, stopping around 15 years ago. My last test, in 2007 was Total 149 mg/dL, LDL 92 mg/dL, HDL, 48 mg/dL and Trigs 43 mg/dL. My highest LDL (if memory serves) was at the end of a seven day water fast @ 175 mg/dL. Trigs also at least doubled in this circumstance, from ~50 or 60 to 125. In fact values will be materially higher if I fast longer before a regular lab test. Meaning if I go from 15 hours to 19 hours before the fast (I typically finish eating by 5 PM and the phlebotomist office doesn't open till 9 AM & sometimes they are delayed by a couple hours). In chatting with my doc, the higher values when fasting make sense as I'm using a lot of fat for fuel, from my own storage.
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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My highest LDL (if memory serves) was at the end of a seven day water fast @ 175 mg/dL.
Very interesting. So when someone is in ketosis it looks like LDL spikes and, based on that, it makes sense that lowering fat intake would result in lower LDL numbers. In your experience, do LDL levels to fat metabolism describe a linear relationship or is there a threshold amount of fat intake (or fat use) before LDL levels rise meaningfully?
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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BJ56 wrote: Mon Sep 25, 2023 12:05 pm Very interesting. So when someone is in ketosis it looks like LDL spikes and, based on that, it makes sense that lowering fat intake would result in lower LDL numbers. In your experience, do LDL levels to fat metabolism describe a linear relationship or is there a threshold amount of fat intake (or fat use) before LDL levels rise meaningfully?
I haven't done that study. One question is how long before you test do you need to keep the fat (and type of fat) intake constant. My intuition is not very long, but I don't know. Not looking at that question, I've done studies where I weigh with a gram scale and record all food. While I certainly can do it, I'm not fond of doing it, so generally don't (two weeks was the longest time I could force myself to do it at one time). It is kind of like the fasting mimicking diet protocol. If I'm going to fast, I just water fast rather than construct and consume an FMD. It is much less brain damage.

The other part of this is that saturated fat is generally the driver. I've gotten close to the low fat numbers if I really drop the sat fat. At one point I was consuming a lot of oil from algae (no longer made) rather than from EVOO, so my sat fat was really low. This was in August of 2017. All of these are mg/dL TC 163, TG 58, HDL 57, LDL 102, sdLDL 20, APO B 84, APO A-1 150, APO B/APO A-1 ratio 0.56, LP (a) 26 (goal < 30). I was also doing cycles of water fasting 5 out of every 14 days, but drew blood at the end of an eating cycle (I was weight stable when looking at day 1 of a cycle to day 1 of the next - hence eating more calories on eating days than I would if I hadn't been fasting). Again, no data, but my intuition is that it was the low sat fat, not the fasting that made the difference. Also likely that 9 days is long enough to hold the intake constant because these data don't look like those at the end of a fast.
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Re: Is there research showing benefit of low fat diet for apoe4 phenotype?

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BJ56 wrote: Mon Sep 18, 2023 11:30 am Hello, Does anyone on this forum know of published research that suggests that a low fat diet (all fat, not just saturated) is helpful for mitigating cardio vascular disease for those with apoE4 phenotypes?

A low fat (<25% of calories from fat) has been the recommendation of a cardiologist for a patient with one ApoE4 allele. I've sought out research that corroborates this and explains the mechanisms but haven't come across any studies indicating a benefit to reducing all fat intake. The only paper I found on this topic is 18 years old and seems to indicate no correlation between reduced CVD risk and a low fat diet: https://www.ahajournals.org/doi/full/10 ... V.15.1.105 -- "There was no significant change in plasma apoB level within any of the apoE phenotype groups on the low-fat diet"

While a low fat diet is only implied here, I thought I'd mention neurologist Dr. Kellyann Niotis who states (here) that elevated serum cholesterol is an independent risk factor for AD. She points to the following three studies:

Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease (2022)
https://pubmed.ncbi.nlm.nih.gov/12160362/

Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases (2022)
https://pubmed.ncbi.nlm.nih.gov/35831869/

Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease (1998)
https://pubmed.ncbi.nlm.nih.gov/9549720/
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