Is Diet-Induced Alzheimer’s Disease Type 3 Diabetes? | Hacker News Reader

Is Diet-Induced Alzheimer’s Disease Type 3 Diabetes?

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57 pointsfasteo27 comments

It's really important to not forget the genetic factors at play in Alzheimer's. Between 65-80% of all Alzheimer's patients have at least one genetic version of the ApoE4 allele, a genotype found in around 25% of the population [1]. ApoE is made in astrocytes and is involved in cholesterol transport to neurons and in repairing damage done to neurons that occurs with normal aging. That isn't to say there isn't a dietary link or that critical lifestyle factors don't interact with these genetics, however! Insulin resistance leads to inflammation (which has been shown to accelerate brain aging) and may be one way in which type 2 diabetes is linked with Alzheimer's. I think calling Alzheimer's disease "type 3 diabetes" may be a somewhat dramatic oversimplification and a bit misleading, though, since the mechanism would be a bit more general (in this case).

[1]: http://www.ncbi.nlm.nih.gov/pubmed/21787325

Is diet-induced (or even diet-associated) Alzheimer's Disease a proven phenomenon in the first place? The article seems to be pretty speculative on the whole thing, and I'm under the impression that the research on lifestyle risk factors is quite inconclusive (e.g. risk factors show up in ecological studies but produce no significant difference in controlled intervention trials).

>I'm under the impression that the research on lifestyle risk factors is quite inconclusive

Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/

Conclusions: "Altogether, the results from these studies provide strong evidence in support of the hypothesis that AD represents a form of diabetes mellitus that selectively afflicts the brain."

This seems to be a much better source than the article, but I don't think it's actually claiming to show any clear connection to diet. A high-fat diet is mentioned in the description of a mouse model of type 2 diabetes (which the authors then seem to say didn't actually serve as a good Alzheimer's model), but I don't see the authors actually making a direct case for dietary influence.

The article, by contrast, has a headline worded as though diet-induced Alzheimer's disease is an established phenomenon and the type 3 diabetes hypothesis is a proposed explanation of that phenomenon.

There is evidence of the neuroprotective effects of a ketogenic diet (low carb, moderate protein, very high fat) [1][2]. The original formulation of the ketogenic diet was for epilepsy, after all [3].

The dogma for decades has been that the brain needs glucose to function. A highly simplified and inaccurate explanation of Alzheimer's is that the brain has diminished capacity to use glucose.

Luckily, the body has an alternate fuel source: ketones. The problem is most people never enter ketosis, where the body is depleted of glycogen and resorts to converting fat to ketone bodies.

[1]: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/

[2]: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826507/

[3]: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133288/

Blindly encouraging a ketogenic diet can actually be damaging. While the average person slightly benefits from a high-fat, low-carb diet, a small group of people (who have the APOE4 allele) are unable to properly digest fat and thus are greatly harmed by it.

Similarly, light alcohol consumption seems to slightly benefit the majority of people. But, for those with APOE4, it causes significant harm. So, tonic for one group is toxic to another.

It is far better if Alzheimer's treatment is prescribed on a case-by-case basis, based on genetic, environmental, and familial factors. This maximizes the outcomes for all, and not just the average.

Do you have sources for those?

I've never heard that.

So you think apoe4's should eat a high carb diet?

Not necessarily high in sugar, since the insulin causes just as much damage as high fat. But a lower-fat diet would be beneficial

You seem to have those the exact wrong way around, or? I have never heard any evidence that people with APOE mutations are "greatly harmed" by eating a ketogenic diet. Link? Ditto for alcohol.

My original post is correct. APOE 4/4 is sensitive to dietary fat; high fat diets cause large LDL [0]. Further, fat causes atherosclerosis in APOE 4/4 individuals more quickly than others [1].

It would make sense that APOE 4/4 would have this effect, because it is the "defective" form of APOE. Individuals with APOE 4/4 do not clear oxidized fats from the brain as quickly as APOE 2 or 3 individuals.

[0] http://jn.nutrition.org/content/134/10/2517.full [1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674716/

Update to previous post:

A study on diet and APOE genotype showed that fat content affects APOE 4 and APOE 2 or 3 people differently.

"No diet can be recommended unequivocally without knowing more about those being targeted. Even though a MUFA-rich diet increases LDL size compared with a CHO-rich diet, this effect is dependent on apoE genotypes. Thus, the replacement of a CHO diet by a MUFA diet increases LDL-size in apoE 3/3, whereas it decreases it in apoE 4/3 subjects"

http://jn.nutrition.org/content/134/10/2517.full.pdf+html

Isn't this a little like saying that blindly encouraging the consumption of healthful tree nuts is damaging to people who are allergic to tree nuts?

True, that is, but not at all interesting?

The effects of tree nut allergies are acute and visible, but the effects of APOE genotype are chronic and insidious. Further, genetic testing is readily available and cheap ($99), so that the cost of determining whether someone should have a low-fat or high-fat diet is far outweighed by the benefits of:

a) lowered risk of alzheimer's b) lowered risk of calcified deposits c) lowered risk of stroke

Of course, a ketogenic diet is quite the shock to the system for the average sugar burner. If you're otherwise healthy, it's usually not a big deal. But if you're using insulin for T2D, blood thinners, etc. and it could be pretty dangerous.

People who are on medications should definitely find a good doctor who knows the full ramifications of a ketogenic diet, and how to taper off medications that treat symptoms reversed by a ketogenic diet.

I'd be very interested to see specific references for this. I'll have a look for myself later, but if you have some to hand, that would be much appreciated.

Actually, the problem is that keto diets are usually high in saturated fat. That increases the risk of heart disease.

Are we really still stuck on the saturated fat being 'evil' thing ? Even the mainstream guidelines are backing down on this now.

Which mainstream guidelines are you referring to?

This is called the lipid hypothesis, you could say it has 'shaky' relationship with the truth. A shining example of the quote, "science advances one funeral at a time".

"Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats." [1]

This myth has caused untold millions to die from western diseases, billions of wasted dollars on health care, and yet it still lives on. The future won't shine a good light on this era of nutrition.

[1]: http://annals.org/article.aspx?articleid=1846638

Do you have the PDF?

https://publichealthmatters.blog.gov.uk/2015/10/09/do-you-kn...

No, mainstream advice is still to control the amount of saturated fat you eat. This advice has remained the same for a while now. It hasn't changed. Shitty newspaper reporting makes people think it's changed.

I'm willing to consider that Alzheimer's Disease may be affected by diet, but this article seems awfully slim on real data and in one instance seems to diverge from actual experimental results.

They claim that Type-2 diabetes and AD are "exacerbated by high fat diets", but the link with regards to the diabetes study specifies diet-induced obesity, not "high fat" diet. Dietary fat has much less effect on blood glucose levels than carbohydrates, so insulin's role is markedly decreased.

A steak causes the release of as much insulin as pure sugar.

Also, http://nutritionfacts.org/video/lipotoxicity-how-saturated-f...

Anyone have a mirror? Link seems down.

[Linked Page seems to be down]

I once read tha claim that wheat causes Alzheimer's.

The idea that Alzheimer is Type 3 diabetes it not new. I also remember a paper which claimed that nasal applied insulin improves Alzheimer symptoms.

Assuming that Alzheimer could be a type of diabetes and taken into account a connection between Diabetes I and Celiac disease, the idea that Wheat consumption could trigger Alzheimer is not absurd.

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