The Ketogenic Diet: A Neurologist’s Warning

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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby Tincup » Fri Dec 27, 2019 8:12 pm

From 1990 to around 2008, I ate at Drs Ayesha and Dean Sherzai suggest. A whole foods, very low fat, plant based diet. I was also reasonably fit, competing in high-altitude endurance races such as the Pikes Peak Ascent which has an elevation gain of 7,800' over 13 miles topping out at over 14,100'. T

The following is my n=1 experience. I'd put on weight to play American football in college. I maintained this weight on this diet. I'd also had autoimmune issues since birth. These were also maintained (including itching mouth & rectum). In 2006, I purchased my first glucometer. I did an oral glucose tolerance test. Knowing what I know today, my result suggested hyperinsulinemia. I recall eating my high carb lunch (like beans, rice & veggies) and being ravenous before dinner. I started trying to eat so as to not spike my blood sugar. Turns out this was very difficult for me. In 2009, I gave up on an entirely plant based approach and keto-adapted myself. Over time, I lost about 40 pounds and now weigh even less, what I did in grade 9 (my body fat is around 10-12% & I'm 64) I also found that I could easily go 12 hours between meals. In 2014, I adopted Dr. Gundry's approach and about 80% of my autoimmune issues cleared up (100% of the mouth & rectum itching). As he tests many different inflammatory markers on his approach, mine are always stellar. In 2015, I found I could easily eat one meal a day as well as do multiday extended water fasts. In 2017, I did 19 cycles of fasting 5 consecutive days out of every 14. This would have not been inconceivable on the low fat, high carb, plant based plan. My approach is not a high saturated fat one, and is primarily pescatarian with lots of monounsaturated fats. I also consume, per Gundry, a lot of DHA including plasmalogen.

For Gundry's benefit, I ran a Cardio IQ fractionated lipid test in Nov. My LDL-P was 909, small LDL-P 103, Tg 49, HDL 61, ApoB 83.

Interestingly, since May I was adding in a lot (200+g)/day of carbs as starches like millet, sorghum, green banana flour and green plantain flour. Even with these carbs, I only had one day in the morning with a Nil ketone reading. Mostly my serum ketones were between 0.5-1.0 mmol. Not high, but given the carbs I was eating, still material. If I did an extended fast, my ketones would be > 4mmol/L by day 3 and my glucose in the 50s (mg/dL).

In the original linked article, "Ketones are different – they are small molecules that waltz right through the blood-brain barrier without receptors, right through the cell wall without having to rely on insulin and then right into the mitochondria. Just like a new connection with a charming suitor, this quick pathway to the mitochondria feels great and is why people who start keto report high energy and fast weight loss results. However, it is also damaging, causing inflammation in cells and creating waste by-product."

I've never seen documentation on the bolded quote. In fact, quite the opposite. From the research I've read, ketones and fat burn cleaner than glucose, creating fewer ROS (reactive oxygen species). Also, it has been noted that as ApoE4's, deficits in glucose metabolism in the brain have been observed in E4's as early as in their 30's. Decades before dementia shows up. Hence ketones "quick pathway to the mitochondria" are a benefit as they use an alternative pathway.

My mother was very bright. She got her first degree in theoretical physics in 1948. At around age 60, she got a second degree in computer programming, just for fun. At 60, she would tell me that her brain worked much more slowly than when she was 19. I didn't take her seriously as she was setting the curve competing with people who were 19. However at around 80, she started to present with memory loss & dementia. She passed at 87 and I learned my ApoE4 status a year later. Now knowing about the glucose processing deficit, her comments of being slow at age 60 now make sense. More recently, her now 87 year old sister was presenting with dementia. Her son, my cousin, chatted with me about it. I suggested supplementing his mother with caprylic acid (C8), a medium chain triglyceride that will stimulate the liver to produce the ketone betahydroxybuterate (BHB). I wasn't sure if he would do it. My aunt lives over 1,000 miles from me, but I usually call her once a week. I started to notice a big difference in our conversations. She would remember the subject of our talks from week to week and bring them up, unprompted. After four or so weeks, I reported what I was observing to my cousin. He confirmed that his mother was very "with it" now.

{ecit} I should also note that my mother ate as Drs Ayesha and Dean Sherzai suggest (plant based, very low fat, whole grains, pulses & veggies) until two years before she passed when I had to put her in assisted living for memory care. She prepared all her food at home from organic sources. If Gundry is correct, her diet maxed out on lectins.
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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby circular » Sun Dec 29, 2019 5:25 am

Tincup wrote:Interestingly, since May I was adding in a lot (200+g)/day of carbs as starches like millet, sorghum, green banana flour and green plantain flour. Even with these carbs, I only had one day in the morning with a Nil ketone reading. Mostly my serum ketones were between 0.5-1.0 mmol. Not high, but given the carbs I was eating, still material. If I did an extended fast, my ketones would be > 4mmol/L by day 3 and my glucose in the 50s (mg/dL).

This is interesting as I've also found I can eat more carbs than I'd expect and still show positive, if relatively low, ketones, especially with carbs high in resistant starch. It's hard to say how much of the ketones present is due to production by gut bacteria from the resistant starch portion of the carbs. Theoretically that would account for some or all of it? It also might be worth mentioning for the record that you exercise a lot more than average, which might well be assisting you keeping your ketones present in the context of this many carbs ... just so some don't assume they can eat this many carbs and be in ketosis. Testing is key.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby circular » Sun Dec 29, 2019 5:31 am

Julie G wrote:Highlights
•Higher dietary saturated fat intake is associated with a decreased overall risk of stroke.

•There is a linear dose–response relation between dietary saturated fat intake and the risk of stroke.

•It is necessary to re-evaluate the restrictions on saturated fat intake for future dietary guidelines.

Do the large sample size and statistics indicate the results would be independent of apoe??? Our primer focuses on low saturated fat for us.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby Julie G » Sun Dec 29, 2019 7:20 am

Do the large sample size and statistics indicate the results would be independent of apoe??? Our primer focuses on low saturated fat for us.

I know. I found the results to be startling. :shock: Statistically, the very large sample size would indicate 20-25% would likely carry ApoE4, although it's not examined as an independent risk factor. See methods below.
Background and aims
Because of the conflicting research results, the association between saturated fatty acid (SFA) consumption and the risk of stroke remains controversial. We conducted a meta-analysis to evaluate potential dose–response relation between SFA intake and stroke.
Methods and results
PubMed, Embase, the Cochrane Library Central Register of Controlled Trials, and Web of Science were searched. Summary relative risks (RRs) of the highest vs. the lowest category of SFA intake and their 95% confidence intervals (CIs) were pooled by random-effects models. Linear or nonlinear dose–response trend estimations were evaluated with data from categories of SFA consumption in each study. Fourteen studies involving a total of 598,435 participants were eligible for high vs. low meta-analysis, and 12 studies involving a total of 462,268 participants were eligible for the dose–response relation assessment. Higher dietary SFA intake was associated with a decreased overall risk for stroke (RR, 0.87; 95% CI, 0.78–0.96; I2 = 37.8%). A linear relation between SFA and stroke was explored (P = 0.01), the pooled RR of stroke per 10 g/day increase in SFA intake was 0.94 (95% CI, 0.89–0.98; P = 0.01).
Conclusion
This meta-analysis further demonstrated that a higher consumption of dietary SFA is associated with a lower risk of stroke, and every 10 g/day increase in SFA intake is associated with a 6% relative risk reduction in the rate of stroke. Further research is needed to explore the influence of specific SFA types and different macronutrient replacement models of SFA on the stroke risk.

I think it's important to read the discussion which acknowledges that replacing some SFA with PUFA reduces the risk of CAD based on this reference: (Nettleton JA, Brouwer IA, Geleijnse JM, Hornstra G. Saturated fat consumption and risk of coronary heart disease and ischemic stroke: a science update. Ann Nutr Metab (2017) 70: 26-33. doi:10.1159/000455681.) This seems to present a conundrum: Higher amounts of SFA protect against stroke while lower amounts protect against CAD. :? As always, I found it very helpful to focus on the possible mechanisms to explain WHY higher SFA was protective:

-increased HDL-C
-increased ApoA1
-improved ApoB-to-ApoA1 ratio
-decreased TGs
-decreased risk of aFib
The popular belief is that high SFA intake is detrimental to arterial health, and a reduction in SFA 
consumption is recommended by current dietary guidelines, probably because of the lower risk of 
arterial disease events (especially coronary heart disease) that were detected when replacing part of  the SFA intake with PUFA [35]. As one of the important manifestations of arterial disease, stroke 
 and its relation to dietary SFA intake have attracted much attention. In general, our study revealed a 
significant reduction of overall stroke risk in relation to higher SFA intake. The result was similar to 
a recent meta-analysis [16] but different from a previous meta-analysis [11], largely because of the 
limited number of included literatures and the inability to cover recently published literatures of the 
earlier meta-analysis. Although the evidence of these biological mechanisms was insufficient and 
complicated, some findings possibly explained the inverse relationship between SFA consumption 
and the risk of stroke. For instance, the concentration of high-density lipoprotein cholesterol (HDL - 
 C) and ApoA1 increased with higher SFA intake, the concentration of total cholesterol and low- 
density lipoprotein cholesterol (LDL - C) decreased with specific type of SFA intake (stearic acid) 
 [36], the concentration of triglycerides and ApoB-to-ApoA1 ratio decreased with higher SFA intake, 
and the risk of atrial fibrillation decreased with high levels of long-chain SFAs (stearic acid, 
arachidic acid, behenic acid, and lignoceric acid) [15, 37]. These changes associated with higher SFA 
 intake may play a role in reducing the risk of stroke. Moreover, we further classified stroke into 
 ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage, rather than ischemic stroke 
and hemorrhagic stroke, because the confusing term hemorrhagic stroke could mean not only primary 
 intracranial hemorrhage or subarachnoid hemorrhage but also hemorrhage after infarction [38]. Then 
we explored specific relationships regarding high SFA intake and its association with a reduction in 
 intracranial hemorrhage risk, rather than the risks of ischemic stroke or subarachnoid hemorrhage. 
For ischemic stroke, the finding was similar to a previous meta-analysis [12] but different from 
another previous meta-analysis [16]. For intracranial hemorrhage, the finding was similar to the 
previous meta-analysis [17]: SFA was a major determinant of total and LDL- C, which were strongly 
inversely associated with intracranial hemorrhage [39-41]. Although no significant association was 
found, this was the first meta-analysis to explore the associations between saturated fat intake and 
subarachnoid hemorrhage. Additionally, consistent with previous studies, we found reduced stroke 
risks in relation to people from Asia rather than Europe or North America. The regional differences 
probably are due to the lower levels of background SFA intake among Asians [16, 17]. Excess 
weight and obesity are thought to be risk factors of stroke, so we used 25 kg/m as a boundary value 
 for body mass index according to WHO standards. The pooled results from studies with a mean or 
median body mass index more than 25 kg/m showed no association between dietary saturated fat 
 intake and risk of stroke. This was similar to previous meta-analyses [16, 17]. Lower risks of stroke 
were found when subgroup studies were high-quality (NOS score no less than seven points), had long
follow-up time (mean or median duration of follow-up no less than 14 years), used validated food 
frequency questionnaire (FFQ), and had male or mixed samples. These findings, too, were consistent 
with previous meta-analyses [15]. In addition, we further considered the effects of study sample size 
on the results. The reduction in stroke risks associated with high SFA intake was found in the number 
of participants less than 10,000 subgroup rather than the number of participants greater than or equal 
to 10,000 subgroup. This was probably because studies with a sample size of less than 10,000 mostly 
 came from Asia. Moreover, considering some controversies about influence factors such as poverty 
diet and regional heterogeneity of the large sample size PURE study, we performed some analyses 
that removed the PURE’ data, but the results were not significantly different (Supplemental Table 4) 
[42-45]. Compared to the previous four meta-analysis [11, 12, 16, 17] on this topic, this meta-analysis was 
based on many prospective cohorts from various populations, and incorporated a much larger number 
of individuals, and the inclusion of the PURE study [15] including 135,335 individuals from 18 
countries made the conclusions more convincing. More subgroups were analyzed in this study, which 
could partly reduce the heterogeneity between studies and gain more detailed and significative results 
under different conditions. In addition, we conducted dose-response analysis to explore the linear and 
non-linear relations. It is helpful to quantify the relations and test the shape of the possible 
associations. To our knowledge, it was the first time the dose-response association between dietary 
SFA intake and risk of stroke has been assessed. 


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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby PBW » Sun Dec 29, 2019 12:58 pm

Thanks Slacker and Julie....The only red flags I have had for the last 20 years are high Ldl and homocysteine. Last year after eliminating all dairy for 6 mo. the ldl's went down slightly but small dense ldl went up for the first time in 15 years....concerning. Arterioschlerosis has been my #1 concern as it is common in my family. Alzheimers has not ever been a diagnosis of relatives. I have no information of any health history other than arteriosclerosis and dementia of my blood relatives and I am a 4/4 and the only of my relatives to have genetic testing. This question of Saturated fat being a positive or negative factor in my diet has been in the back of my mind since I read" Running on Fat". First Dr Gundry had me taking High levels of DHA(1000mg)....in August he switched to Krill oil with600mg Om3, EPA 339mg,DHA 202mg, and Astaxanthin 1700mg...don't really understand why. I have also read research indicating DHA supplementation is not reaching the brain. So I am very interested in how fats reach the arteries in the brain. and what effect they have. Very simplistic but if they are clogging arteries to the heart what keeps them from doing the same in the brain. looking forward to more specific research.

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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby Tincup » Sun Dec 29, 2019 2:09 pm

Julie G wrote: As always, I found it very helpful to focus on the possible mechanisms to explain WHY higher SFA was protective:


I would take issue stating that SFA was protective with the source being a meta-analysis of epidemiological studies. I think reviewing Peter Attia's Studying Studies series, especially the article on epidemiological studies (from his Understanding Science series is instructive. All you can state is that there is an association from the studies. I'm always skeptical of food frequency questionnaires. From the full paper, " Ten cohorts used validated food frequency questionnaires (FFQs, questionnaires for assessment of meal patterns, consumption frequencies and portion sizes of regularly eaten foods) for dietary assessment, and the remaining four cohorts used diet history method or 24-hour dietary recall."

I'm not stating that SFA is not protective, I don't know. I just don't think we can conclude anything more than association from the linked study.

Also interesting that "decreased risk of aFib" was in the list. As someone who's had afib for 15.5 years, and participated in an afib forum for most of that time, I've never seen a study with a strong association between SF and lack of afib. I was able to find this study, which again relies on FFQs. "During a median follow-up of 17 years, 5,175 incident cases of AF occurred. In men, there was a higher hazard of AF when total n-3 polyunsaturated FAs replaced dietary saturated FAs—hazard ratio per 1-g substitution of FAs of 1.08 (95% confidence interval 1.02 to 1.14) in a model adjusted for lifestyle factors. For other substitutions of FAs (monounsaturated, total or n-6 polyunsaturated FAs), no consistent nor statistically significant associations were found. In conclusion, we found a moderately higher risk of AF in men, but not in women, when total n-3 polyunsaturated FAs replaced dietary saturated FAs. Substitution of saturated FAs with monounsaturated, total or n-6 polyunsaturated FAs was not associated with the risk of AF." I can say that my current intake of omega 3's as DHA and EPA is very high --14.7% Omega 3 Index in Nov -- and this has not increased my now infrequent afib (after having a 57% afib burden in the first 4 months of having afib, including a 2.5 month episode). I've had 2 episodes lasting about 1 hour each in the last 20 months. Each of these was associated with me accidentally missing my supplemental magnesium, a key component of my afib remission strategy.
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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby Julie G » Sun Dec 29, 2019 3:01 pm

I would take issue stating that SFA was protective with the source being a meta-analysis of epidemiological studies.

I completely agree. I should have said “appears to have been protective.” As I said earlier, I certainly found this paper in turns both refreshing and startling in its conclusion. I was also confused about how higher SFA would protect against aFib, especially given your experience. The other mechanisms, however, fall in line with a growing consensus of strategies that appear to be beneficial for cardiovascular health which was generally encouraging.

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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby Julie G » Sun Dec 29, 2019 3:10 pm

Very simplistic but if they are clogging arteries to the heart what keeps them from doing the same in the brain.

You ask good questions, PBW. I still maintain that the idea that fat “clogs” arteries anywhere in the body to be an unproven hypothesis. Cardiovascular disease, like AD, is turning out to be multifactorial. Most people who get heart attacks have normal levels of cholesterol leading me to think they are probably not eating high levels of fat that clogged their arteries. I’m convinced that the bigger underlying risk factor for both vascular issues in the heart and brain appears to be insulin resistance.

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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby Plumster » Mon Dec 30, 2019 8:48 am

So I am very interested in how fats reach the arteries in the brain. and what effect they have. Very simplistic but if they are clogging arteries to the heart what keeps them from doing the same in the brain. looking forward to more specific research.


Yes, this is the real concern I have and my reason for posting. How do we reconcile that "fat is good for the brain" vs "only omega 3 is good for the brain" (Sherzai's assertion in their article) because of the risks:
the brain has 400 miles of micro-vasculature – aka arteries – that are incredibly sensitive to fat and the damaging inflammation it causes. This we know.


This study finds that "most VRF [vascular risk factors] act to lower CBF [cerebral blood flow] in aging individuals by promoting cerebrovascular dysfunction."

This study concludes that "The presence of moderate or severe intracranial arterial stenosis significantly increased the risk of dementia progression"

This one states that "Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias."

Julie, we have a thread on our forum on Dr. Francisco Gonzalez-Lima, professor of neuroscience and pharmacology & toxicology, who was on Peter Attia's podcast. He argues that amyloid plaque does not cause AD. AD is a vascular disease and endothelial to the brain shown via hardened, thicker arteries. This is in addition to the insulin problem we are so aware of. Health of heart and arterial circulation are very close to the health of the brain, as Slacker also mentioned above. Gonzalez-Lima suggests several things for AD prevention, including methyline blue, near infrared light, and ketone bodies. He states that the ketogenic diet benefits the brain, not so much the heart. Perhaps I just need to revisit the podcast and listen again (and I will do that), but how can a ketogenic diet be good for the brain at the same time that his very own research shows that endothelial damage in the brain causes AD? Is this about saturated fats only? According to MD Caldwell Esselstyn, ALL oils cause cardiovascular clogging. He may be extreme among doctors and especially on this forum, still I'm right back at Drs. Ayesha and Dean Sherzai's assertion, about which I am tempted to contact them directly for their source on "omega 3s only":
Even for those people who believe that the brain needs fat (which it actually doesn’t, it only needs omega 3’s) the brain has 400 miles of micro-vasculature – aka arteries – that are incredibly sensitive to fat and the damaging inflammation it causes. This we know.
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Re: The Ketogenic Diet: A Neurologist’s Warning

Postby Julie G » Mon Dec 30, 2019 9:58 am

Even for those people who believe that the brain needs fat (which it actually doesn’t, it only needs omega 3’s) the brain has 400 miles of micro-vasculature – aka arteries – that are incredibly sensitive to fat and the damaging inflammation it causes. This we know.

Plumster, can you share the link for this quote? FWIW, I completely agree that vascular disease increases the risk of both CVD and dementia. I remain unconvinced, however, that dietary fat is a primary contributor.

Let me respectfully ask you a very important question. I'm very interested in your response. If I had vascular disease, what would the clinical signs and symptoms be? How would I know?


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