Does ketosis cause AD?

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
J11
Contributor
Contributor
Posts: 3351
Joined: Sat May 17, 2014 4:04 pm

Does ketosis cause AD?

Post by J11 »

Under the category of medicine does not start from first principles one might file this next item.

Apparently it was only discovered yesterday that aerobic glycolysis (AG) drops to near zero in the brain's of those over 60.
During brain development there is intense AG. Amyloid formation initiates in those areas with this intense AG in youth, though
low AG in those as they mature.

This has me wondering whether all of the efforts to move into ketosis might be exactly the wrong direction to head in to prevent AD. Perhaps encouraging a more youthful dependence on AG would be brain healthy. Unfortunately, as cancer is a high user of AG, it is possible that such a shift might increase the risk of cancer while decreasing the risk of AD.

So many questions ... so few answers.

"The authors suggest that loss of glycolysis could serve as a biomarker for brain aging."
" “My suspicion is that people with a less youthful metabolic brain profile might be more vulnerable to the neurodegeneration seen in Alzheimer’s disease, and might develop it faster,” "


http://www.alzforum.org/news/research-n ... ysis-brain
User avatar
Stavia
Contributor
Contributor
Posts: 5255
Joined: Tue Apr 29, 2014 6:47 pm
Location: Middle Earth

Re: Does ketosis cause AD?

Post by Stavia »

J11, please refer to my real-time summary of our group's attendance at LowCarb San Diego for some leaders in the field's opinion and research, you could start with Georgia Ede's work. There is a huge amount of research in this field - we have discussed it a lot on the boards.

Sent from my SM-G930F using Tapatalk
J11
Contributor
Contributor
Posts: 3351
Joined: Sat May 17, 2014 4:04 pm

Re: Does ketosis cause AD?

Post by J11 »

Stavia, thank you for the suggestion to review the literature.
That is a good idea.

Yet, the research that I have noted above, seems very different from what I am aware of.
Ketones might be a beneficial way to patch up energy problems in a AD brain, though from what
I understand now the evidence is pointing to the idea that those with high AG brains into mature age
are AD resistant. I am not sure whether I have ever encountered this idea before.

Is this new to anyone else on the forum?
User avatar
Stavia
Contributor
Contributor
Posts: 5255
Joined: Tue Apr 29, 2014 6:47 pm
Location: Middle Earth

Re: Does ketosis cause AD?

Post by Stavia »

J11, this paper does not suggest in any way that ketosis causes AD.
Here is the author's opinion
That led Goyal to think that the reason the human brain loses aerobic glycolysis across adulthood is because it finally grows up. “It might be that regions with high aerobic glycolysis in young adults are still developing. When they reach maturity, they don’t need aerobic glycolysis anymore, and that’s why we see this flattening,” Goyal said.
Sent from my SM-G930F using Tapatalk
J11
Contributor
Contributor
Posts: 3351
Joined: Sat May 17, 2014 4:04 pm

Re: Does ketosis cause AD?

Post by J11 »

Yes, I might need to do a retraction of the title in the fine print later in the thread just as the tabloids do.

However, the title might not be entirely off the mark.
It might not be so much that ketosis causes AD as the loss of AG is related to the development of AD.

The figure on the alzforum site shows the brain of a 60 year old and there is ZERO AG.
The more youthful brain to the left in the same figure shows intense AG activity.
It would be extremely interesting to investigate the consequences on brain function and development
in those who might have a mutation that allows for a prolonged "young" brain profile throughout life
(bright AG brain readings).


The aging brain shifts almost entirely to non-aerobic glycolysis metabolism (OXPHOS?).
Ketosis can also induce non-aerobic glycolysis metabolism (OXPHOS?).

This research has raised a large number of questions.
For example, what might be the longer term consequences on brain development if one were to reduce
the intense AG seen in younger adults and replace it with more OXPHOS as seen in older adults?

“My suspicion is that people with a less youthful metabolic brain profile (i.e. less AG) might be more vulnerable to the neurodegeneration seen in Alzheimer’s disease, and might develop it faster,”

"... he thinks of glycolysis as a marker of the brain’s youthfulness. In older people, he sees a lot of variability in the pattern of glycolysis. “In some people in their 70s, the pattern of aerobic glycolysis looks more or less like it does in the young adult, whereas in another older person it looks completely different,” he said. Are those differences important? “My suspicion is that people with a less youthful metabolic brain profile might be more vulnerable to the neurodegeneration seen in Alzheimer’s disease, and might develop it faster,” he said. "

"In the meantime, they are measuring glycolysis in people with amyloid pathology, both presymptomatic and mildly symptomatic. ... showing that, in cognitively normal people with amyloid, aerobic glycolysis and tau went in opposite directions. In other words, people with higher glycolysis had less tau pathology."


People with higher glycolysis had less tau pathology.
This certainly makes one wonder whether higher glycolysis --> less tau pathology --> less amyloid pathology --> less AD
lol
Contributor
Contributor
Posts: 194
Joined: Wed Oct 30, 2013 6:25 am

Re: Does ketosis cause AD?

Post by lol »

Interesting, J11. Do I have this right? The brain relies on glucose, doesn't have reserves, and needs a steady supply. Those fasting or eating a low carb diet use up their glycogen and use the keytone bodies for fuel (from fat). It is my understanding that fatty-acid eating is associated with the development of ALZ, especially for APOE4 people, because we have trouble transporting cholesterol in the blood. The increased eating of fat leads to increases in circulating cholesterol levels that may predispose individuals with APOE4 to atherosclerosis, which is also an ALZ risk factor. Many members here get into ketosis without eating high fat. I get that. But what about not getting enough glucose to the brain?

Seems that if you do not have a problem with hyperglycemia or diseases related to high sugar, a diet of nutritious carbs would be beneficial in supplying the brain with necessary glucose.
User avatar
TheresaB
Mod
Mod
Posts: 1607
Joined: Wed Feb 03, 2016 9:46 am
Location: Front Range, CO

Re: Does ketosis cause AD?

Post by TheresaB »

lol wrote:o I have this right? The brain relies on glucose, doesn't have reserves, and needs a steady supply. Those fasting or eating a low carb diet use up their glycogen and use the keytone bodies for fuel (from fat). It is my understanding that fatty-acid eating is associated with the development of ALZ, especially for APOE4 people, because we have trouble transporting cholesterol in the blood. The increased eating of fat leads to increases in circulating cholesterol levels that may predispose individuals with APOE4 to atherosclerosis, which is also an ALZ risk factor.
That is not what the current literature is saying. The brain runs on glucose as it's first "choice" of fuel source, with ketones it's primary alternate source. Impaired glucose metabolism is the issue leading to cognitive decline, especially when the brain can't access ketones as an alternative source.

This reduced glucose metabolism is likely:
(1) contributing to AD development (hypothesized, not yet scientifically proven), and
(2) a consequence of AD (known fact).

In other words, there’s a vicious cycle: the slowed brain glucose uptake (hypometabolism) leads to chronic brain energy deprivation, that in turn deteriorates the neuronal function, which further diminishes the demand for glucose thereby furthering cognitive decline. This hypometabolism may begin 30 or more years before the onset of AD especially in individuals with ApoE4 genotype or maternal family history of AD.

From this paper, "Insulin resistance and reduced brain glucose metabolism in the aetiology of Alzheimer’s disease" published December 2016,http://insulinresistance.org/index.php/ ... le/view/15
“There is a significant link between Alzheimer’s disease and impaired fuel metabolism in the brain, with disturbed cerebral glucose metabolism being an invariant pathophysiological feature of AD.23 The defining metabolic signature of AD is a decrease in the cerebral metabolic rate of glucose (CMRglu). This may be the primary underlying cause of neuronal degeneration and death: at its heart, AD is an energy crisis in the brain. It is the death of neurons via starvation, as they have lost the capacity to effectively harvest energy from glucose.”
-Theresa
ApoE 4/4
lol
Contributor
Contributor
Posts: 194
Joined: Wed Oct 30, 2013 6:25 am

Re: Does ketosis cause AD?

Post by lol »

Thank you, Theresa. So according to some current literature, the problem is not getting enough glucose, but is not being able to use the glucose. But still seems important to feed the brain the glucose.
User avatar
TheresaB
Mod
Mod
Posts: 1607
Joined: Wed Feb 03, 2016 9:46 am
Location: Front Range, CO

Re: Does ketosis cause AD?

Post by TheresaB »

lol wrote:seems important to feed the brain the glucose.
Can I correct you slightly? I'd say it's important to keep the brain healthy so that it can use glucose. Just feeding glucose will do no good if the brain is swimming in glucose but can't use it.
-Theresa
ApoE 4/4
User avatar
Stavia
Contributor
Contributor
Posts: 5255
Joined: Tue Apr 29, 2014 6:47 pm
Location: Middle Earth

Re: RE: Re: Does ketosis cause AD?

Post by Stavia »

lol wrote:Thank you, Theresa. So according to some current literature, the problem is not getting enough glucose, but is not being able to use the glucose. But still seems important to feed the brain the glucose.
lol there will always be enough glucose available in the insulin sensitive person for the parts of the brain that are glucose dependent whether they are in ketosis or not. In ketosis, the liver will supply enough glucose via gluconeogenesis. However in the presence of insulin resistance the glucose cannot be used effectively, regardless of level. It can go as high as it likes but the GLUT 4 receptors un the hypothalamus will be resistant.

Its not as simple as upping glucose in the blood improves uptake in the brain




Sent from my SM-G930F using Tapatalk
Post Reply