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Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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Juliegee
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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby Juliegee » Sat May 02, 2015 12:56 pm

LOL, Stavia- I don't think we even have a site quotation anymore. We may have lost it in our latest upgrade. But, I like "Knowledge is Power" as well. We'll have to search for a new spot.

Richard, I listened to Sarah Ballantyne's talk- 79 mins long. For anyone short on time, you can easily skip the first 30 mins where Ballantyne basically discusses how she FEELS about the topic...without missing any of the content. The remaining talk was informative. This was essentially a preview of a Paleo f(x) talk that goes down tomorrow warning of the dangers of ketosis. I appreciated Ballantyne's intense combing of the literature to find adverse effects...and she did, including death :shock: I certainly want to know everything that I can about any strategy that I'm employing.

I was most intrigued by her assertion that a ketogenic diet suppresses the innate immune system, while stimulating the adaptive. Ballantyne suggests this is positive when fighting cancer, but may not be for other conditions. Research shows that E4 carriers experience impaired immunity which may play a role in the development of Alzheimer's. I want to learn more about how a ketogenic diet mechanistically interacts here.

On the other hand, her message is MUCH more geared towards folks who are using a ketogenic diet because it's cool or trendy rather than to address neuro-degeneration. These are the same folks who might be applying it in an unsafe way with very limited carbs and high SFA without a physician's oversight and regularly checking effects/biomarkers.

Anyone who KNOWS our community can easily recognize that those of us who use this strategy practice it very differently by concurrently employing CR, fasting, and exercise to safely create ketones. Most of us eat enormous quantities of non-starchy vegetables and use MUFAs to stay heart healthy. Additionally, we're interacting with top cardiologists and lipidologists in an effort to keep our members heart healthy.

Dr. Yadong Huang, and others, suggest that our misshapen E4 protein may lead to an impaired mitochondrial function. Indeed, we have a strong body of research (Eric Reiman, Richard Caselli, etc.) demonstrating that E4 carriers, in a dose dependent manner, experience reduced cerebral glucose metabolism per PET/FDG imaging beginning decades before the onset of symptoms. Because our brains are the most metabolically demanding organ, it makes sense that the deficiency would show up there first. At the recent NYC conference, there seemed to be a convergence of scientists acknowledging that this mitochondrial deficiency/cerebral hypometabolism occurs years upstream of amyloid and tau deposition. Dr. Stephen Cunnane’s work has suggested that even mild ketones can help address this deficiency in a high risk population like ours, but it's never been trialed preventatively in a research setting; much less been PROVEN to be effective.

For some of us, already experiencing cognitive symptoms, we don't have time to wait for the Cochrane Report. We're doing the best we can for now. I agree with Ski, Merouleau & Stavia. Until science can catch up, N=1 rules.

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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby RichardS » Sat May 02, 2015 4:40 pm

Julie wrote:
On the other hand, her message is MUCH more geared towards folks who are using a ketogenic diet because it's cool or trendy rather than to address neuro-degeneration. These are the same folks who might be applying it in an unsafe way with very limited carbs and high SFA without a physician's oversight and regularly checking effects/biomarkers.

Anyone who KNOWS our community can easily recognize that those of us who use this strategy practice it very differently by concurrently employing CR, fasting, and exercise to safely create ketones. Most of us eat enormous quantities of non-starchy vegetables and use MUFAs to stay heart healthy. Additionally, we're interacting with top cardiologists and lipidologists in an effort to keep our members heart healthy.


You made some good points, but I want to address some of what you said directly. Those "applying it in an unsafe way with very limited carbs" is really how ketosis is generally induced whether it is through HFLC diet, CR or fasting - carbs are very limited. As for high SFA, I would say probably, but I don't have enough information to comment. I can tell you from the experience that my wife, a pediatric neurologist who treats a lot of epilepsy in a large urban center, has had with ketogenic diets that very few physicians seem to be equipped to track and guide patients on the ketogenic diet. Maybe many of the forum members have been fortunate enough to find ketosis-savvy physicians, but that appears to be a challenge to find as best I can tell.

I'm not sure where you are getting the idea about "safely create ketones." Do you have a reason to believe CR, fasting and exercise are safer than a high-fat, low carb, low protein diet? I'm not aware of any data that shows one approach to be safer than another.

I have not seen the references about severe adverse effects, including death, that Dr. Ballantyne is using to support her assertion, though she stated she will post the full literature review she did soon. Still, I would hope those here on the forum using a ketogenic diet don't think themselves exempt from these potential adverse effects. Electrolyte balance, mineral deficiencies, and gut dysbiosis are all important issues to track. Hopefully, a high non-starchy vegetable component to the diet will prevent this, but I think we mostly have anecdotal evidence to go on. I think it is great that Dr. Terry Wahls is pursuing a highly micronutrient-dense ketogenic diet in her clinical trials, but I believe they will be the first in the ketogenic diet literature.

Most of the long-term ketogenic diet research has been conducted with epilepsy, predominantly in children. By long-term, I mean rarely more than a year or two. What may feel like a miracle cure for cognitive problems in the short term by no means ensures ongoing benefit or lack of adverse effects over the long term. If we are looking to a ketogenic diet to prevent dementia, we are clearly in uncharted territory. Just because some are using diet rather than a drug, it does not mean they are inherently safer in this case.

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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby Juliegee » Sat May 02, 2015 7:28 pm

YOU make a lot of good points, Richard. I fully understand the way that traditional ketogenic diets have been applied. Dr. Ballantyne’s warnings come from that data. THAT is precisely why I wanted to make the distinction between those very limited carb/very high fat diets and what some of our members are trying.

Do you have a reason to believe CR, fasting and exercise are safer than a high-fat, low carb, low protein diet? I'm not aware of any data that shows one approach to be safer than another.


I defer to our CR experts here, but my general understanding is that CR, fasting & exercise are less likely to promote CAD/CVD than a high fat diet. Is CR/IF ready for use as a prevention or treatment tool for Alzheimer’s in humans? Just like with ketosis, I’ve never seen any definitive data there…some promising animal studies.

When sharing cautions, I think it’s important to discuss degrees of ketosis. Dr. Cunnane, for instance, has recommended that as little as .3-.5 mmol/L of beta-hydroxybutyrate for E4 carriers may be able to preventatively offset our cerebral glucose hypometabolism. I’m guessing that low of a level would naturally occur during sleep in someone not restricting carbs. Of course, those already experiencing cognitive symptoms would need higher levels. FWIW, as someone who HAS experienced cognitive decline, I personally aim for mild ketosis (.7-1.5mmol/L,) mild CR, a 12-16 hour daily fast, and exercise. The combination has greatly improved my cognition for over two years. Aside from some muscle loss (working on it ;)) I've escaped any detrimental consequences so far...

Most of the long-term ketogenic diet research has been conducted with epilepsy, predominantly in children. By long-term, I mean rarely more than a year or two. What may feel like a miracle cure for cognitive problems in the short term by no means ensures ongoing benefit or lack of adverse effects over the long term. If we are looking to a ketogenic diet to prevent dementia, we are clearly in uncharted territory. Just because some are using diet rather than a drug, it does not mean they are inherently safer in this case.


Of course, there is no drug that can prevent or treat Alzheimer's. And, I fully agree that we are most definitely in unchartered territory with any of these strategies to promote ketosis. BUT, not addressing our reduced cerebral hypometabolism is also making a choice. We may escape unscathed, but for those already showing symptoms; the alternate is progressive neurodegeneration that ultimately results in death. So yeah…some of us are in a tough spot. It sucks.

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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby GenePoole0304 » Sun May 03, 2015 7:32 pm

RichardS said

"Electrolyte balance, mineral deficiencies, and gut dysbiosis are all important issues to track"

all things I have said and agree with your points... from what I have seen here no one has been tracking many of the things that can go wrong over time.
ketosis benefits maybe only short term and it is has not been adapted to known long lived practices with E4's.

being off topic I did look at DrP latest book was totally unimpressed.

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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby GeorgeN » Sun May 03, 2015 8:02 pm

Juliegee wrote:I was most intrigued by her assertion that a ketogenic diet suppresses the innate immune system, while stimulating the adaptive. Ballantyne suggests this is positive when fighting cancer, but may not be for other conditions. Research shows that E4 carriers experience impaired immunity which may play a role in the development of Alzheimer's. I want to learn more about how a ketogenic diet mechanistically interacts here.


In this podcast/interview http://body.io/body-io-fm-41-dr-paul-jaminet/ Paul Jaminet (Perfect Health Diet - PHD) said he'd been on a keto diet for about a year and a half with some preexisting immune issues that would not clear up. He finally came up with the PHD to solve these immune issues. I'm not familiar in detail with his program, but he does use "safe starches." In the interview, he talked about eating 80-90 g/day of carbs. He also wanted people to have a fasting window of 16-18 hours. So his approach would be something of a cyclic ketogenic diet.

Keifer (the interviewer in the above podcast) suggests a reason for his "Carb Nite" and "Carb Backloading" approach is to reset the hormones so the body doesn't think it is always in a starvation mode.

For me, I've cycled in and out of mild ketosis - 0.5 - 1.5 mmol/L and remained "keto adapted" for about 4.5 years. The ability to tap keto fuel at will has been very useful.
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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby MarcR » Sun May 03, 2015 11:26 pm

GeorgeN wrote:For me, I've cycled in and out of mild ketosis - 0.5 - 1.5 mmol/L and remained "keto adapted" for about 4.5 years. The ability to tap keto fuel at will has been very useful.

My pattern over 18 months is similar to yours and I too really enjoy never being desperately hungry and always having a steady supply of energy.
(Formerly merouleau)

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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby GeorgeN » Mon May 04, 2015 12:04 pm

Last summer, I did a serum leptin test (LapCorp). Result - 1.1 ng/mL
Did one 3/31 (Singulex). Result <0.8 (Range 0.8-25.2 ng/mL

Leptin The most reliable test for monitoring leptin levels is the radioimmunoassay (RIA), which utilizes an antibody that responds to leptin in a fasting blood sample. This test will tell you whether or not you have leptin resistance. If your level is in a healthy range— the optimal fasting leptin level is between 4 and 6 ng/ dL and up to 9 ng/ dL is acceptable— your cells are sensitive to leptin’s signals. You are a fat burner as nature intended you to be, and it is unlikely that you will have a weight problem. (If you lower your leptin levels to optimal levels, as you most certainly will on the Rosedale Diet, it is highly unlikely that you will continue to have a weight problem even if you started out with one.) Of course, we don’t want leptin levels to go too low. Anything below –4 ng/ dL is a sign of either malnutrition, usually accompanied by very low body fat, or a genetic inability to produce leptin that results in obesity. (If a woman’s leptin level falls below 3, generally caused by very low stores of body fat due to inadequate food intake or intensive exercise, she will stop menstruating.) If your fasting leptin level is 10 ng/ dL or higher, you will most certainly benefit from the leptin-sensitizing program outlined in this book. Most obese people have extremely elevated leptin levels: 20, 30, even 40 ng/ dL! Yet within only two to three weeks on the Rosedale Diet, almost everyone experiences a dramatic decline in leptin levels. At the same time, they eat less because they do not feel hungry as often as they used to. They no longer experience food cravings and have little difficulty following the diet. If your leptin level doesn’t fall as quickly as it should (younger people often have quicker results than older people), you need to be especially careful about following the diet and perhaps add extra nutritional supplements. But if you follow the program, I promise that your leptin sensitivity will improve and your fasting leptin level will fall. Leptin: 4 to 6 ng/ dL optimal; up to 9 ng/ dL acceptable; 10 + ng/ dL high.

Rosedale M.D., Ron; Carol Colman (2009-10-13). The Rosedale Diet (pp. 166-167). HarperCollins. Kindle Edition.


From the LapCorp test last summer:
Male Ranges by Body Mass Index (BMI)
BMI Leptin Range
11 0.1 - 0.4
12 0.1 - 0.6
13 0.1 - 0.7
14 0.1 - 0.9
15 0.1 - 1.1
16 0.2 - 1.3
17 0.2 - 1.7
18 0.2 - 2.1
19 0.3 - 2.6
20 0.4 - 3.2
21 0.4 - 4.0
22 0.5 - 5.0
23 0.8 - 6.2
24 0.9 - 7.7
25 1.1 - 9.6
26 1.3 - 12.0
27 1.6 - 14.9
28 2.0 - 18.6
29 2.5 - 23.2
30 3.2 - 28.9
31 3.9 - 36.0
32 4.9 - 44.9
33 6.1 - 55.8
34 7.6 - 69.6
35 9.5 - 86.7
36 11.8 - 108.0
37 14.8 - 135.0
Blum WF, Juul A, "Reference Ranges of Leptin Levels According to Body Mass Index, Gender and Development Stage" in Leptin: The Voice of Adipose Tissue, Blumm WF, Kiess WF, and Rascher W, eds, 1997, 319-326.

"Anything below –4 ng/ dL is a sign of either malnutrition, usually accompanied by very low body fat, or a genetic inability to produce leptin that results in obesity."

When I searched on low leptin, the thing that keeps coming up is anorexia. I'm 6'0", 168#'s, so BMI is 22.8. My neck size is 15.5" and waist is 33", so according to the US military correlations I'm 14% body fat. http://www.calculator.net/army-body-fat-calculator.html Doesn't seem I'm that thin, however could be a sign that my body is perceiving a state of starvation. In any case, I plan to institute some refeeds or "Carb Nites" & see what changes.

My test last summer was around the time I figured out my E4 status. I was fairly strict then, but became more so later.
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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby RichardS » Mon May 04, 2015 12:30 pm

When sharing cautions, I think it’s important to discuss degrees of ketosis. Dr. Cunnane, for instance, has recommended that as little as .3-.5 mmol/L of beta-hydroxybutyrate for E4 carriers may be able to preventatively offset our cerebral glucose hypometabolism. I’m guessing that low of a level would naturally occur during sleep in someone not restricting carbs. Of course, those already experiencing cognitive symptoms would need higher levels. FWIW, as someone who HAS experienced cognitive decline, I personally aim for mild ketosis (.7-1.5mmol/L,) mild CR, a 12-16 hour daily fast, and exercise. The combination has greatly improved my cognition for over two years. Aside from some muscle loss (working on it ;)) I've escaped any detrimental consequences so far...


Julie-thank you for clarifying the "degree of ketosis" issue. As you know, there is no clear definition as to what identifies as ketosis. Most of the research I've read involves ketosis at higher levels of beta-hydroxybutyrate than what Dr. Cunnane appears to be recommending. While this lower level is almost certainly safer, we also need to be careful in extrapolating the potential benefits of full-on ketosis as found the literature to the potential benefits we hope for when doing a less rigorous ketogenic diet. There is ongoing debate among researchers and clinicians who deal with epilepsy as to whether ketogenic diets need to be 100% of the time or can be more cyclic and/or at a lower level of ketones and still provide benefit. It is that much further removed for clinical experience when we are trying to apply ketogenic diets to other conditions.

I think a lot of what we need to focus on when there is so little human research to guide us is to look at what has the least probability of harm and greatest potential for other benefits. Exercise is definitely in there, so long as you don't get insured, of course. I'm not sold on CR for those already at or below a good level of body fat. From my reading, a moderately constricted eating window seems to be benign so long as there is no significant cortisol disruption. It seems some fasting can do more harm than good if cortisol or other hormones are out of whack.

I'm glad to hear you are working on reversing your muscle loss. As you have undoubtedly heard, it seems the older we get, the more critical to maintain our muscle mass and avoid sarcopenia. Ketogenic diets for neurological conditions have mostly focused on children and younger adults rather than middle-aged to older adults, so we may need to be extra careful about our protein levels. The children who failed to gain as much weight as expected typically caught up after going off the diet. It sounds like some people here are considering this as a life-time dietary manipulation.

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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby ApropoE4 » Mon May 04, 2015 3:13 pm

The trouble with long term ketogenic diets is that we don't know if the risk increases they exhibit in children for kidney stones and bone fractures are additive or multiplicative. That is, if children put on this diet for years end up developing kidney stones ten times more frequently than their peers, nobody can say if it's just that we see an additional 20 cases per 1000 and the same would be true for middle aged folks, or if all of you keto-addicts are going to be getting kidney stone surgery instead of ultrasound treatment because your bones become to brittle to withstand the latter. I don't expect the paleo fad to stick around for much longer but if it does then we could find out one way or the other.

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Re: Ketogenic Diets for AD Prevention: a "Large [and Unwise] Bet"

Postby GeorgeN » Mon May 04, 2015 3:28 pm

ApropoE4 wrote:The trouble with long term ketogenic diets is that we don't know if the risk increases they exhibit in children for kidney stones and bone fractures are additive or multiplicative. That is, if children put on this diet for years end up developing kidney stones ten times more frequently than their peers, nobody can say if it's just that we see an additional 20 cases per 1000 and the same would be true for middle aged folks, or if all of you keto-addicts are going to be getting kidney stone surgery instead of ultrasound treatment because your bones become to brittle to withstand the latter. I


My experience. I had two stones as a VLF vegan from 17 & 15 years ago (probability of a new stone withing 5 years is >80% having had one prior), 0 stones for 5 years as LCHF. I routinely take falls at fairly high speeds on skis, including a double eject at the base of the headwall two weeks ago. No bone issues, only soft tissue trauma. Had one crash at 55 MPH a couple of years ago where my bindings released when they weren't supposed to. Again only soft tissue trauma - had to ski without poles for a while as I had a pretty good soft tissue impact injury on the deltoid.
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