One of the reasons I do keto is to try to avoid dementia/Alzheimers.
Well, I did my genetic test at 23andMe and found out I have APOE-4, known as an Alzheimers gene. (I only have one, the other is APOE-3, considered neutral.)
This research is showing that keto doesn’t do much for us APOE-4s. On the other hand, Doc Nally says he recommend keto anyway to his APOE-4 patients.
Does anyone know of other info on keto for APOE-4s?
Well, the study you referenced said, “ketosis does appear to be highly beneficial for ApoE4 carriers, even if prior studies indicate it’s even more helpful for those without this risk factor,” so I would find that alone to be kind of reassuring.
I’m waiting on my own test results right now. Because of family history, I suspect that I carry ApoE4, so I feel for you.
Thank you so much for pointing that out!
I was only focusing on this part:
In the earlier study, medium chain triglycerides improved cognitive function only in participants without the ApoE4 allele, a genetic risk factor for AD. Similarly, in the later study, cognitive improvements were stronger and persisted longer–out to 90 days–in those without the ApoE4 allele. A new PLOS One study confirmed different responses to diet depending on genetics in mice, reporting that a high-fat diet lowered brain levels of ApoE only in mice without the ApoE4 gene.
When I got my results, I wasn’t really worried about Alheimer’s risk because I’m keto, but then when I read these studies — with some suggesting we APOE-4s avoid all saturated animal fat — I got worried.
The section you refer to definitely helps ease my mind – haha, no pun intended. Good luck with your results!
For anyone else interested/concerned about this, Amy Berger seems to be the go-to person these days. She notes that “50% of people with AD are not E4 carriers.” But she also says exogenous ketones, which have shown to be very helpful to many Alzheimer’s patients, aren’t as effective on E-4s, and in some cases don’t work at all.
Sigh. 
What’s interesting is that E-4 is considered the oldest of the three APOE genotypes. It’s called the “hunter-gatherer” genotype, which is “poorly suited for the modern diet’s evolutionarily discordant amount of refined carbohydrates.”
There are some otherwise pro-low carb doctors (Dr. Steven Gundry) out there who advise E-4s to cut out animal fats, but I wonder if the opposite is true. Maybe we E-4s need MORE fat, since our brains are resistant to the effects of ketones?
Review Article
Insulin resistance and reduced brain glucose metabolism in the aetiology of Alzheimer’s disease
Amy L. Berger
http://insulinresistance.org/index.php/jir/article/view/15/32
Gundry has an in-depth video about lowering small dense LDL, and is very much against cheese, butter and other animal fats for E-4s. Bye-bye bacon nectar… (At least he encourages eating tons of olive oil and fish oil!)
If I’m missing something, please help – I’m trying to get up to speed on this.
Check out this website https://www.apoe4.info/wp/ They are all with at least 1 apoe4, they follow Dr. Dale Bredesen Protocol, https://www.apoe4.info/wiki/Bredesen_Protocol
Dr. Gundry’s program, and other ketonians like Dave Feldman.
I just read Dr. Gundy’s Plant Paradox and he claims that Red meat has this sugar molecule neu5gc which increases IGF1 with increases inflammation. But the only science out there is on mice and wasn’t done in the way that would happen in humans. What was tricky for me is that Dr. Gundry never mention that fish and cheese also has it. You should read his book its really good, he has modified keto program, where you eat fish instead of meat. I just don’t understand if this sugar molecule neu5gc is in meat protein or in fat too?
I also ordered "The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline Hardcover – August 22, 2017, by Dale Bredesen.
https://www.amazon.com/gp/product/0735216207/ref=oh_aui_detailpage_o02_s00?ie=UTF8&psc=1
You can watch Dale Bredesens you tube videos, his protocol reversed mild to moderate Alzheimers D.
https://www.youtube.com/watch?v=QqQ_X3mD16U
Pritty much all of them encouraging Keto and IF and fasting. Bredesens protocol has all the steps with blood work to look for with supplements to take. The only argument is to eat animal protein or not…
I hope that helps.
Wow, thank you so very much — Dale Bredesen’s work is fascinating and I’d never heard of it. Will be devouring his book.
Is 23 and Me the best route to go for getting an APOE- test? I’ve seen some posts saying they didn’t get full info etc. Is there anything else to know about how I should order this? I don’t even know which questions to ask so any insight for getting the test and getting as much info as possible is appreciated. Thank you.
It’s true 23 and Me doesn’t explain a whole lot of details, but their tests actually do include a lot more data than they tell you about — and you can import that data into other sites. If you spend $5 to import your 23 and Me info into a web site called Promethease, you can see your full gene profile (or at least a whole lot more – literally hundreds of genotypes). Promethease appears to be a not for profit operation as far as I can tell.
So for example, 23 and Me told me I had only one APOE-4 gene but didn’t tell me what the other APOE was. Promethease showed it was APOE-3. Why 23 and Me doesn’t say that I don’t know, but at least Promethease is only five bucks, so it’s worth running your 23 and Me data there.
I feel pretty satisfied with the results. I honestly don’t know if any competitors are better.
If all that makes sense…
@gatita. Yes, that’s great info. Details I wouldn’t have known to ask about. Thanks for your time!
I just got my 23AndMe results and ran them through Promethease. I went to Promethease originally because while 23 said I didn’t have the ApoE4 gene, they didn’t say what I had. Promethease says I’m ApoE3 in both places, which is considered “neutral risk”. E4 E4 is considered risk for stroke, Alzheimer’s, etc. E3 E3 is neutral and E2 E2 is considered good (they don’t use the term “protective”).
Are there other things to look for?
I think we need a post for Genetic markers from Promethease that would be of interest to us. I don’t know what exactly to look for. My wife got both of us tested and ran us through Promethease but it was really just more entertainment for me at the time. I want to run it again with some things to look for now that I know better.
I am too paranoid to get myself tested but am wondering if I can convince my parents to get tested since they have nothing to lose. That way if neither has APO 4 that will work and if they do, then I can always get tested later. Anything else I should be looking at?
Is this a plan or a waste of money?
I didn’t watch the video yet, but I’m looking at one line that is shown. “The high sat fat diet increased LDL size in Apo E4/3 subjects the most.” Remember, increasing LDL size is good! That is exactly what happened to me when I started eating more fat (saturated and other healthy fats) and less carbs. My particle sizes got larger which reduced my risk.
It’s really up to you. Important also to remember that having APOE-4 doesn’t guarantee you’ll get Alzheimer’s and not having it doesn’t guarantee you won’t.
Did the small particle size go down? I was wondering because i was reading that your LDL would go up and that small particle would increase as well. Even if there were now more larger ones.
Apoe4 and keto
@gatita - your original post was in August, but seems to me that almost everything is pointing to keto being good for almost everybody in this respect, ApoE4 gene or not. Ketosis - implying blood sugar readings that are lower than they’d be if not in ketosis - seems to me to be very desirable, given the connections between persistently high blood sugar levels and neurodegenerative disease that I’m seeing more and more about these days.
Specific to Alzheimer’s disease - ketones easily cross the blood-brain barrier, and if they are being used to fuel the brain, then the brain isn’t dependent on glucose. The brain needs fuel to make adenosine triphosphate (ATP). ATP is a huge deal - for all our cells it’s what keeps things going. Amazingly, every day we use and recycle our body weight in ATP.
One of the most, if not the most, prominent markers of Alzheimer’s disease is reduced glucose metabolism in the brain. Endothelial cells in the brain are responsible for getting glucose across the blood-brain barrier, and they contain a special protein transporter (‘GLUT1’ or ‘Glucose transporter 1’) for this purpose.
If there is a problem with the endothelial cells and/or a deficiency in GLUT1, things are really changed for the crossing of the blood-brain barrier by glucose and the function of the neurons that are so dependent on the ATP they get from their fuel - the neurons starve, to some extent.
If ketones are the fuel, the disruption in energy supply from the lack of glucose crossing the blood-brain barrier may be solved, as simple as that.
For Alzheimer’s disease, the way we break down Apolipoprotein E and how well we clean up the breakdown products is very important. Protein buildups cause some neurodegenerative diseases, becoming toxic if not gotten rid of. “Tau tangles” and “amyloid plaques” are a couple of types of these. One study (I’ll put a link at the end of this post) indicates that people with the ApoE4 gene may have more buildup of the protein breakdown products.
ApoE4 or not, autophagy would seem to be very important here, as an aid to getting rid of the “bad stuff.” I think that ketogenic eating and fasting provides an excellent foundation, here.
The number of small particles went down, yes. Basically all the particles got larger, so there were less small ones.
I am wondering if the studies he bases his recommendations on included people who were on a VLC/keto diet? Perhaps sat fat is dangerous in the presence of high carb, but not low carb. I’m not sure those studies have been done? My (ApoE4) lipids improved a lot on a hflc diet, full of sat fat.
If you’re referring to Amy Berger’s paper, it’s an article that references lots of studies — but in the main one referring to lack of response by ApoE4-postive people, everyone was following a ketogenic diet.
For now, I’m still eating saturated fat until I hear otherwise. But I wish there was more research on this topic.