Keto diet overcomes unfavorable ApoE4 Alzheimer's genetics

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Wiki Rostas

Wiki Fish

... better way to put it - ketogenic diet renders some of the genetical conditions such as ApoE4+  irrelevant or not endangering an individual survival chances! It appears ApoE4+ does represent a handicap ONLY on a high carbohydrate diet! It is probably similar with many other genetic impairments. It seems one needs to have a more than "perfect" genetics to be able to remain healthy until a very old age on a high carbohydrate diet!

"Ketogenic diet rescues cognition in ApoE4+ patient with mild Alzheimer's disease: A case study.", by Morrill SJ, Gibas KJ, Diabetes Metab Syndr., March-April 2019


Quotes:

Abstract
It has been established that there is a correlation between Alzheimer's disease and apolipoprotein E, specifically the ApoE4 genetic variant. However, the correlation between Apoe4, insulin resistance and metabolic syndrome (MetS) pathologies still remains elusive. As apolipoprotein E has many important physiological functions, individuals with the ApoE4 allele variant, also known as the Alzheimer's disease gene, are primarily at a greater risk for physiological consequences, specifically cognitive impairment (Chan et al., 2016). In this case study, a 71-year old female, heterozygous for ApoE4 with a family history of Alzheimer's Disease (AD) and the dual diagnosis of mild AD/metabolic syndrome (MetS) was placed on a 10-week nutrition protocol purposed at raising plasma ketones through carbohyrdrate restricted, high fat ketogenic diet (KD), time- restricted eating and physical/cognitive exercise. Primary biomarkers for MetS were measured pre/mid-/post intervention. The MoCA (Montreal Cognitive Assessment) was administered pre/post intervention by a licensed clinical therapist. The results were statistically significant. The HOMA-IR decreased by 75% from 13.9 to 3.48. Triglycerides decreased by 50% from 170mg/dL to 85mg/dL. VLDL dropped by 50% from 34mg/dL to 17mg/dL, and HgA1c decreased from 5.7% to 4.9%. The baseline MoCA score was 21/30; post treatment score was 28/30. The significant results in both MetS biomarkers and the MoCA score suggest that a ketogenic diet may serve to rescue cognition in patients with mild AD. The results of this case study are particularly compelling for ApoE4 positive (ApoE4+) subjects as ketogenic protocols extend hope and promise for AD prevention.

UPDATE

Within a short time from posting the above, the following comments were posted on Twitter.
(BTW - Thanks Tucker Goodrich and Shaza!)

Indeed, it turns out that it is not the keto diet per-se but rather the improved DHA contents of such a diet that is the critical factor, not just the low carbohydrates aspect of it!    Tsimane (Bolivian natives) diet is high carbohydrate (vegetable & fruit) and low protein (16%), low fat but also most of the protein comes from fish.  The paper on "DHA brain uptake..." of ApoE4 versus non-ApoE4 carriers confirms that the critical factor is abundance of DHA in food for the ApoE4 carriers. In return they have a higher mass of grey matter in the brain than non-ApoE4, which appears to be confirmed by cognition tests [add study refs]. In return for having higher grey matter mass, the uptake of DHA is 20% higher for ApoE4 carriers, making them more vulnerable to DHA starvation.

It seems that this story has evolved in a direction that I did not expect. Perhaps the ApoE4 rather than being a mildly inconvenient adaptation requiring high fat/high fish diet, turns out to be a very beneficial genetic evolutionary trait helping in brain development and achieving higher IQ - which is clearly a survival advantage. Especially for navigation over the high seas or in the Arctic!

Alzheimer and blood glucose

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Sugar’s “tipping point” link to Alzheimer’s disease revealed

For the first time a “tipping point” molecular link between the blood sugar glucose and Alzheimer’s disease has been established by scientists, who have shown that excess glucose damages a vital enzyme involved with inflammation response to the early stages of Alzheimer’s.

Abnormally high blood sugar levels, or hyperglycaemia, is well-known as a characteristic of diabetes and obesity, but its link to Alzheimer’s disease is less familiar.

Diabetes patients have an increased risk of developing Alzheimer’s disease compared to healthy individuals. In Alzheimer’s disease abnormal proteins aggregate to form plaques and tangles in the brain which progressively damage the brain and lead to severe cognitive decline.


Dr Rob Williams, Dr Omar Kassaar and Prof Jean van den Elsen

Scientists already knew that glucose and its break-down products can damage proteins in cells via a reaction called glycation but the specific molecular link between glucose and Alzheimer’s was not understood.

But now scientists from the University of Bath Departments of Biology and Biochemistry, Chemistry and Pharmacy and Pharmacology, working with colleagues at the Wolfson Centre for Age Related Diseases, King’s College London, have unraveled that link.

By studying brain samples from people with and without Alzheimer’s using a sensitive technique to detect glycation, the team discovered that in the early stages of Alzheimer’s glycation damages an enzyme called MIF (macrophage migration inhibitory factor) which plays a role in immune response and insulin regulation.

MIF is involved in the response of brain cells called glia to the build-up of abnormal proteins in the brain during Alzheimer’s disease, and the researchers believe that inhibition and reduction of MIF activity caused by glycation could be the ‘tipping point’ in disease progression. It appears that as Alzheimer’s progresses, glycation of these enzymes increases.

Reference:

"Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer’s Disease", by
Omar Kassaar et al.

Its about carbohydrates ...

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The Startling Link Between Sugar and Alzheimer's



Crohn’s disease successfully treated with the paleolithic ketogenic dietCsaba Tóth, Andrea Dabóczi, Mark Howard, Nicholas J. Miller, Zsófia Clemens

Anti diabetic drug works against Alzheimers

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Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer's disease

Report: Scientists Find Alzheimer’s Treatment While Trying To Cure Diabetes

Alzheimer's and lack of arginine

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Arginine is especially abundant in common food such as dairy products, meat, nuts and chickpeas!

(from Dairy Council of California)

Recent study described here:

Alzheimer's breakthrough: Scientists may have found potential cause of the disease in the behaviour of immune cells..

Quote:

They observed that in Alzheimer’s, immune cells that normally protect the brain instead begin to consume a vital nutrient called arginine.

My comment:

Probably because arginine is an essential nutrient for all cells including immune cells. If there is not enough, immune cells will sequester what is available.

Arginine is an amino acid and an essential nutrient for several bodily processes, including cell division, healing and immune responses.

It is found in food, including dairy products, meat, nuts and chickpeas, but the team at Duke said that their study did not suggest eating more arginine would have an impact on Alzheimer’s risk. The blood-brain barrier regulates how much arginine can enter the brain, and the immune response that breaks down arginine would remain the same even if confronted with higher levels of the nutrient.

Really?  Dr. Pickett must be a very wise man knowing that upfront and thus excluding that therapeutic option by his statement, without doing any testing!

“The study suggests that low levels of arginine in the brain could contribute to the death of nerve cells in Alzheimer’s, but there is much more we still need to understand about how and why nerve cells die in the disease,” she added.

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High carb and low caloric intake from fat and proteins may increase the risk of dementia in elderly!

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The title is a short version of the concluding sentence from a new Mayo Clinic study. The study tracked 937 initially healthy people aged 70-89 for 3.7 years. During this period 200 developed mild cognitive impairment (MCI) or dementia.

Those patients who were in the highest quartile (i.e. a group) of carbohydrate consumption (as percentage of total calories), have had approximately twice the risk of MCI or dementia (1.89 times, confidence interval P for trend =0.004(*)). Those who belonged to the highest quartile of fat consumption had about one-half the risk of developing MCI or dementia (0.56, P for trend = 0.03(**)). Those with the highest protein intake had 21% lower risk.

The fact that fat, especially saturated seems to be beneficial in dementia and other neurological degenerative diseases, has been known for some time, see for example the references in my past posts: this or this

This study however, is probably one of the first, if not the first, to concentrate on all three macronutrients' intake rather than some partial aspects of the diet.

Quote:

A dietary pattern with relatively high caloric intake from carbohydrates and low caloric intake from fat and proteins may increase the risk of MCI or dementia in elderly persons.

Although the full text is pay-walled, a short writeup is posted on the Mayo Clinic website.

Interestingly, a comparison between the highest quartile of total carbohydrates with the highest sugar (see the quote below), shows that the sugar impact was negative but not to the same extent as the total carbohydrate. This may be indicating that some other form of cabohydrate than the sugar alone, may be the most detrimental to the neurological health. Perhaps the total starch [ *** WHEAT?! ***] or just the total glycemic load?

Those who reported the highest carbohydrate intake at the beginning of the study were 1.9 times likelier to develop mild cognitive impairment than those with the lowest intake of carbohydrates. Participants with the highest sugar intake were 1.5 times likelier to experience mild cognitive impairment than those with the lowest levels.

But those whose diets were highest in fat - compared to the lowest - were 42 percent less likely to face cognitive impairment, and those who had the highest intake of protein had a reduced risk of 21 percent.

When total fat and protein intake were taken into account, people with the highest carbohydrate intake were 3.6 times likelier to develop mild cognitive impairment.

"A high carbohydrate intake could be bad for you because carbohydrates impact your glucose and insulin metabolism," Dr. Roberts says. "Sugar fuels the brain - so moderate intake is good. However, high levels of sugar may actually prevent the brain from using the sugar - similar to what we see with type 2 diabetes."

Wiki 

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Notes:
(*) It means that the probability of the result being by chance is 1/250.
(**) Probability of the result being by chance is 1/33.
(***) Added 13/01/2013, inspired by this .

(I am grateful and indebted to the best source of alerts about new interesting nutrition studies - vegan discussion groups!  Oh my oh my...  Thank you drmcdougall.com )
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Coconut fat - ketone precursor curing neural diseases

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Cocos nucifera  (wiki)

Watch this CBN video

This is based on the same story I posted here, see also these posts. It goes beyond that story. In the second half they claim that the healing effect of coconut fat is due to its role as the ketone bodies precursor, in the liver. Ketone bodies being the alternative (to glucose) fuel for the neurons. They list the following neurological disease that can or might be treated by boosting ketone production:

• Alzheimers
• ALS
• Epilepsy
• Dementia
• Schizophrenia
• Autism

Ketone bodies appear to have a strong anti-viral effect, helping protect or fight against viral diesases.  (Is that why I never got a flu since 1999?)
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Alzheimer's: The detrimental role of a high carbohydrate diet

Interesting paper just published:
"Nutrition and Alzheimer's disease: The detrimental role of a high carbohydrate diet", S.Seneff, G.Wainwright, L.Mascitelli, European Journal of Internal Medicine 22 (2011) 134–140.

Quote:

"A ketogenic diet has been found to be therapeutic in AD patients [72,73]. It involves an extremely high fat diet, with up to 88% of calories derived from fats. This benefit may be likely due in part to the bioavailability of a plentiful supply of fats to repair damaged membranes. However, this diet leads to the generation of a significant concentration of ketone bodies in the blood serum, which can be used as an alternative fuel to glucose ..."

A very good and brief summary by Ted Hutchison is here (TUESDAY, 11 OCTOBER 2011).
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Vegans, dietary fat and Alzheimer's

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I like browsing through some vegan discussion groups looking at the papers, publications and studies they use to support their belief system. McDougall's forum is particularly useful because of their tenacity in trying to use science to justify themselves. Experience taught me that such studies are always ambivalent and very often prove a completely opposite views to those of the vegan believers who posted them.

The following study from 2003, did not disappoint me:

Dietary fats and the risk of incident Alzheimer disease.

The abstract looked very foreboding, for example, quote:

Persons in the upper fifth of saturated-fat intake had 2.2 times the risk of incident Alzheimer disease compared with persons in the lowest fifth

Not all is lost fortunately, because of the widely known practice in the medical "science" to print only the politically correct (i.e. false) information in the abstracts while hiding the true albeit inconvenient facts in the full text.

The facts are that the saturated fat data and most of the other results are generally not statistically significant!

The facts are that even when one takes the trend line across saturated fat quintiles and makes it appear statistically more significant than an individual datum (the so-called "p value for the trend") - the resulting p is still much greater than 0.05 and thus is still not statistically significant! Best illustration is the following (upper) portion of the Table 3:

The facts are that if you take the most basic age-adjusted only data (look at the first row called "Age-adjusted+"), there is no clear trend at all since the middle and the second highest saturated fat columns (quintiles) have exactly the same Alzheimer's risk as the lowest reference quintile of saturated fat!  The second and the third row (headed by "Multivariable" and "Multivariable... other fats") above are the more processed data, that seem to exhibit a weak rising trend, albeit also not statistically significant!  One shall always keep in mind that multivariable-corrected trends are dependent upon some specific model-dependent assumptions that may or may not be correct.

It gets more intereseting as one reads down the table. If one takes the above discussed saturated results on faith, beliving that the weak statistics may be reflecting some real underlying trend rather than being some artefacts of the data gathering and processing methodology (as I suspect is the case), then one should also take a notice and state that the rest of the data "proves" (also not statistically significanly) that the total fat consumption, dietary cholesterol intake, animal fat consumption and vegetable fat consumption all seem either not to correlate or to correlate NEGATIVELY (protectively) with the Alzheimer's risk! See the lower portion of the Table 3:

For example, the total fat consumption seems to be protective against Alzheimer's! The second lowest and the middle quintile in consumption of animal produce (indicated by dietary cholesterol!) also have higher Alzheimer's risk than the two highest quintiles! Animal fat consumption seems to show no correlation to Alzheimer - the trend curve is pretty flat except the third row ("Multivariable adjusted for vegetable fats and trans-fats") which shows a weak NEGATIVE (i.e. protective) trend!

Last but not least the bottom group Vegetable fats shows the strongest correlation in the whole study. That correlation is strongly NEGATIVE (protective), that is the more vegatable fat the less Alzheimer's cases! In fact that result, after "Multivariable adjusted for vegetable fats and trans-fats" - is the only one, alongside the omega-6 fat result ( which is basically its subset) that does exhibit a statistically significant trend!

Unfortunately for those who believe in the low fat dogma, this is not a good news! Especially when compared with other sources, see for example this and that.
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Alzheimer's, B12 and homocysteine - vegans beware!

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 Sunny Side Up (Wikipedia)

This is based on the newly published Scandinavian study:
Homocysteine and holotranscobalamin and the risk of Alzheimer disease

Quote:

Results: The odds ratios (ORs) (95% confidence interval [CI]) for AD were 1.16 (1.04–1.31) per increase of 1 µmol/L of tHcy at baseline and 0.980 (0.965–0.995) for each increase of 1 pmol/L baseline holoTC.

Notice how did the authors skillfully manage to conceal the impact (really huge!) - by not putting the risk ratio over the full range in the abstract. Instead they mitigated their grant-loosing risk by showing only an incremental change per 1umol/L or per 1pmol/L of the intependent varaibles. (Note: tHcy=homocysteine, holoTC=B12, AD=Alzheimer's Disease).

The impact seems to be huge indeed, based on some quick-and-dirty calculations of the typical tHcy and B12 variability among some populations. Taking two other studies (see [1] and [2] below) giving the average difference between vegetarians and non-vegetarians for tHcy and B12 ( 2.6 to 12.3 umol/L and -94 to -195 pmol/L respectively),   applying the above incremental ratios of (1.16 and 0.980 respectively) one obtains the estimated ralative risk ratio for AD for vegetarians versus non-vegetarians of: 1.5 to 6.2 based on the homocysteine, and 6.7 to 51 based on the B12 data.

(Disclaimer: risk ratio estimates that are based on statistical data do not prove nor disprove causuation.)

My conclusion: the study indicates that the B12 defficiency as well as (independently) high homocysteine seem to be very strong predictors of Alzheimer's disease risk. The overal risk estimate is also much stronger than the washed-out figures presented in the paper's abstract. This should be of utmost importance for vegans and vegetarians!

See also:


1. Effect of Vegetarian Diet on Homocysteine Levels

2. Plasma Homocysteine Levels in Taiwanese Vegetarians Are Higher than Those of Omnivores

3. BBC Health News: Vitamin B12 link to Alzheimer's backed by study

4. BBC Health News: Vitamin B 'puts off Alzheimer's'

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Alzheimer's 'is brain diabetes'

c a r b o h y d r a t e s c a r b o h y d r a t e s c a r b o h y d r a t e s c a r b o h y d r a t e s

BBC Health article

Quotes:

Treating Alzheimer's with the hormone insulin, or with drugs to boost its effect, may help patients, they claim.
...

The latest study, joint research between Northwestern University in the US and the University of Rio de Janeiro in Brazil, looked at the effects of insulin on proteins called ADDLs, which build up in the brains of Alzheimer's patients and cause damage. They took neurons - brain cells - from the hippocampus, a part of the brain with a pivotal role in memory formation. These were treated with insulin and a drug called rosiglitazone, given to type II diabetics to increase the effect of the hormone on cells. After this, the cells were far less susceptible to damage when exposed to ADDLs, suggesting that insulin was capable of blocking their effects.

Surely it must be all that fat, lack of exercizing and "bad" genes...

c a r b o h y d r a t e s c a r b o h y d r a t e s c a r b o h y d r a t e s c a r b o h y d r a t e s

Coconut fat - proof of no harm and amazing benefits!

No I have not sold out (yet) to coconut marketing, I just think this is important! 8-:)

1. "Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau island studies."

http://www.ncbi.nlm.nih.gov/pubmed/7270479

Prior IA, Davidson F, Salmond CE, Czochanska Z.

Am J Clin Nutr. 1981 Aug;34( 8 ) :1552-61

Quotes:

...Vascular disease is uncommon is both populations and there is no evidence of the high saturated fat intake having a harmful effect in these populations.... ...

... The migration of Tokelau Islanders from their atolls to the very different environment of New Zealand is associated with changes in lipids that indicate increased risk of atherogenesis. This is associated with an actual fall in saturated fat intake to around 41% of energy, an increase in dietary cholesterol intake to 340 mg, and an increase in carbohydrate and sugar. Lipid changes include increased total cholesterol, higher LDLC and triglycerides, and lower HDLC levels (16) ...

2. "Doctor says an oil lessened Alzheimer's effects on her husband". The clock face drawings below are before, after 2weeks and after 37 days.

Dr. Mary Newport and her husband.  Dr. Mary's husband "clock" drawings below, original - left, after coconut treatment - right.  (picture restored from backup) 

http://www.tampabay.com/news/aging/article879333.ece (Note: the original link has died)

Take a look at the following quotes:

"Ketones are a high-energy fuel that nourish the brain," VanItallie said, explaining that when you are starving, the body produces ketones naturally. When digested, the liver converts MCT oil into ketones. In the first few weeks of life, ketones provide about 25 percent of the energy newborn babies need to survive.

Dr. Veech has been working with ketones for more than 40 years and has become a valuable resource to the Newport family. Currently, he is working for the military, looking into ketones as a way to improve the performance of troops in severe conditions.

and from the readers' comments below the article, by Dr. Mary Newport:

by Mary Nov 2, 2008 6:52 PM From Dr. Mary: Any non-hydrogenated coconut oil would have the ketone effect, contains no cholesterol. Steve's total cholesterol has remained [less than] 200, HDL and LDL are better than ever. It's reputation as "oil clogging fat" is a myth from the 1950's.

P.S.

I found those article links on Stephan's blog (highly recommended!). I thought the subject deserves a separate thread. Other good source on the benefits of coconut (and other fats) is Weston A. Price Foundation .


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Follow up after 9 years (better late than never!)
22-March-2017

Article:

http://www.realfarmacy.com/coconut-oil-alzheimers-clinical-study/

by Paul Fassa

Quote:

Dr. Mary Newport, desperate after orthodox medical attempts failed her husband’s dwindling dysfunction from Alzheimer’s, discovered coconut oil and rescued him from having to be put away in a special home.
His remarkable recovery went viral on the internet and Dr. Newport wrote a 2011-12 bestseller, Alzheimer’s Disease: What if There Was a Cure?Both the Internet’s coverage and her book started an international grassroots movement of folks with very early dementia, even just brain fog and senior moments, trying themselves or helping relatives diagnosed with Alzheimer’s. Thus creating a wave of success reports and testimonial videos.

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