Here is Where Low Carb Diets Ultimately Fail

[Hepoberman]

Not too long after I started seeing consistent serum ketones on an 85% fat ketogenic diet, I noticed my serum ffa levels were elevated. HDLab tests for free fatty acids on their advanced metabolic panel. My lipidologist used this evidence to convince me to learn about the glucose-ffa cycle, or the "Randle cycle" as it is known.

It pretty simple to explain. In a nutshell, as free fatty acids increase, our sensitivity to insulin decreases. This happens inside the cell.

This is basic metabolic biology. There is still some debate as to exactly how this happens but no one credible denies the ffa-glucose cycle. Some low-carbers have convinced themselves that this form of "physiological insulin resistance" is OK, but why is it OK? Healthy people have the good insulin sensitivity and low free fatty acids. These markers trend the other way when we are carbohydrate deficient.

Glucose Fatty Acid Cycle and Insulin Resistance

[Gilgamesh]

Some low-carbers have convinced themselves that this form of "physiological insulin resistance" is OK, but why is it OK?

Hep, thanks so much for (again) raising this critical question. I've sort of slipped into low-carb eating (two days out of three) for no well-thought-through reason and the question of the benignity of what low-carbers call "physiological insulin resistance" is something for which I've not been able to find any peer-reviewed evidence. This makes me nervous. Pubmedding [ "physiological insulin resistance" ] (one has to use the quotes) yields mostly articles about a state that occurs in pregnancy and puberty, for ex.:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306909/

Otherwise I can't find much. I trust the reports of our members here that they feel great (and that many health markers remain excellent -- but those aren't the markers in question), but, myself (and probably not just myself), I can feel great but not be great.

G

[circular]

Last night I listened to this podcast with Terry Wahls and Paul Jaminet. I thought it was one of the most balanced I've heard about ketogenesis, with some, to me, newly articulated perspectives (ketogentic diets will feed mitochondria containing pathogens?!, might be used as a temporary/healing diet, might be used diagnostically ...).

I almost settled for just scanning the text on the page, but I was glad I listened and will probably listen again. They don't address the Randle Cycle, but I'd suggest that low carb diets have potential for failing in some people for additional reasons that we should be cognizant of. But that doesn't mean that high carb diets don't also present with avenues to failure from a health perspective. One has to figure out their individual vulnerabilities and proceed to shore them up while maximizing the micronutrient value within their macro balance and with a strong focus on nurturing a healthy biome.

[Julie G]

One has to figure out their individual vulnerabilities and proceed to shore them up while maximizing the micronutrient value within their macro balance and with a strong focus on nurturing a healthy biome.

Wise words. I look forward to the podcast, Circ. From watching diet/biomarker interactions among our members for over 4 years, it's very clear to me that a blanket approach to diet for E4 carriers doesn't exist.

Otherwise I can't find much. I trust the reports of our members here that they feel great (and that many health markers remain excellent -- but those aren't the markers in question), but, myself (and probably not just myself), I can feel great but not be great.

Interestingly, many members don't exhibit PIR on a low carb diet. I wonder about the factors that lead to this phenomenon. G or Hep, I assume I know the biomarkers in question, but can you specify so folks can determine if this phenomenon may apply to them.

[Stavia]

Yes, I'd also like to find out the markers of this IR.
I know Catherine Crofts (the world's top expert in Joseph Krafts work on IR) personally, and she's recommended and gone thru my markers on a 55% to 60% fat diet, and she says I have no IR, physiological or otherwise.

[apod]

Some low-carbers have convinced themselves that this form of "physiological insulin resistance" is OK, but why is it OK?

Hep, thanks so much for (again) raising this critical question. I've sort of slipped into low-carb eating (two days out of three) for no well-thought-through reason and the question of the benignity of what low-carbers call "physiological insulin resistance" is something for which I've not been able to find any peer-reviewed evidence. This makes me nervous. Pubmedding [ "physiological insulin resistance" ] (one has to use the quotes) yields mostly articles about a state that occurs in pregnancy and puberty, for ex.:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306909/

Otherwise I can't find much. I trust the reports of our members here that they feel great (and that many health markers remain excellent -- but those aren't the markers in question), but, myself (and probably not just myself), I can feel great but not be great.

G

I feel like I had reached a state of mild (benign) PIR following a ketogenic diet for several months (which doesn't seem like a long time.) While eating my low-carb, very high-fat foods (averaging over 200g of fat a day, occasionally in the 250-300g range), fasting blood sugar looked great and post-prandial blood sugar looked great, inflammatory markers looked great, and A1C looked great. The issue was when I decided to see "hmm, what happens if I just randomly eat a bunch of oats now instead of fat and vegetables like I've been doing at every single meal." This caused huge blood sugar elevations, but these were still cleared to acceptable levels within 2hrs or so. After just 3 or 4 blood sugar spikes, this effect went away. This transition period was done during my first CGM data collection post.

I'm not sure if there's a minimal amount of refeeds / insulin spikes or some baseline of moderate carbs that's necessary to prevent that from developing, or if you would even want to prevent it. I've heard Jaminet talk about this in the past, recommending bringing net carbs up to 150g or so leading up to a glucose tolerance test. Chris Masterjohn brought the benefits of higher insulin secretion (or at least, the potential negatives of persistent insulin secretion suppression) to my attention.

I look forward to checking out the podcast.

[Stavia]

Hep, I also wanted to state specifically that I am open to learning about your interpretation of the evidence, and I stand by the rights of everyone to interpret the body of evidence differently. I do welcome and support diverse points of view and I trust that you do as well.

There is no certainty in pathogenesis of Alzheimer's disease in E4s and there are many plausible ways to interpret the body of evidence. If you read my primer carefully I state clearly that I believe each person should assess the topic of high fat vs low fat themselves.

I see that as a male 3/4 you might be more focused on coronary artery disease however, the pathogenesis of which is still debated.

I await your answer to my question about the markers of IR, that you believe are affected by a higher fat diet, with interest and an open mind.

[Hepoberman]

Maybe it helps to consider it this way. Without some level of insulin resistance, we would quickly become hypoglycemic, then possibly have a seizure, and probably die. We all MUST have some level of insulin resistance, its a regulatory mechanism. I am curious what markers Catherine Croft uses to determine "no IR at all", OGTT? I assume this is compared to an age matched peer group, I'd would review the data on cohorts. This still doesn't mean you couldn't be more sensitive to insulin than you are now.
Consider our sensitivity to insulin on a cellular level. Technically, every cell can have slightly different hormonal sensitivities (ie. insulin and glucagon) and it varies constantly over time. We all have varying degrees of insulin sensitivity over time, most likely modified by a myriad of factors. We know Free fatty acids are a major mediator.
Insulin is important for more than just glucose uptake. Does insulin resistance of this type make it harder for a cells to uptake nutrients? Does it effect its cell function? We know its an anabolic, of course.

We can't really know who does or does not experience IR on low carb because it isn't an on or off, black or white situation. I think most people end up hypocaloric, I know I did. This changes everything.

[Stavia]

thanks Hep
1. No she has analysed Joseph Krafts' work for her PhD, it uses 5 hour insulin readings after a glucose load, because glucose levels are too insensitive, and miss insulin resistance. Here is a link to Prof Schofield from my neck of the woods discussing her and Kraft's work. I've had some great discussions with their team about the nuances of her work. And about implications for apoe4s and some dangers we might face in following certain paths.
https://profgrant.com/2013/08/16/joseph ... a-matters/

2. We all have varying degrees of insulin sensitivity over time, most likely modified by a myriad of factors. We know Free fatty acids are a major mediator. Agreed, many, many factors.

3. Insulin is important for more than just glucose uptake. Does insulin resistance of this type make it harder for a cells to uptake nutrients? Does it effect its cell function? We know its an anabolic, of course. oh yes, so many possibilities, so many areas of incomplete knowledge.

4. We can't really know who does or does not experience IR on low carb because it isn't an on or off, black or white situation. I think most people end up hypocaloric, I know I did. This changes everything agreed on both points. Individual variation is a big player, and too many variables muddies the waters. I made sure I varied macronutrients or food groups (eg sat fat, dairy etc one at a time) only while keeping calories constant when I was testing and tweaking over about 18 months.

So in this extremely complex field, I do personally try to balance on a knife edge in this regard, the amount of fat in my diet. I eat just enough fat (about 55% with minimal saturated animal fat, 80-100 grams carbs-ish, all unprocessed whole food plant based) to run my ketones at about 0.5mmol/l, because I have brain fog below this level (I am apoe4 and obviously I have 100% broken mitochondria ;( ). I don't have less brain fog at higher levels of ketones, and I know its uncharted waters long term running at high levels, so I hedge my bets by not running so high ketone wise, and I make sure I have as little IR as possible.

[MAC]

I must admit, I didn't do the normal deep dive on ketogenic diet, however I don't see myself practicing a "severe" ketogenic aka "starvation" like diet. I feel FANTASTIC after almost 4 months, significant and ongoing weight loss (which I needed to get to normal BMI), await next biomarkers at 6 months.

http://www.ketogenic-diet-resource.com/ ... fects.html

Keto-Infographic (1).jpg

Re biomarkers and side effects, if one is eating a balanced diet (and consuming Gundry like good fats) for the non carb component, watching markers and nutrient levels, is there that much risk REALLY? There seems to a presumption that the high fat skew is heavy red meat/satfat/dairy/sugar, which is absolutely a false pretense! I eat no red meat/dairy and very little satfat (the min that comes with the high MUSFA/PUSFA of my diet profile) and getting all the nutrients I think I need. I have been running 3 miles intense every day, so for sure my body tells me re fuel load deficiency re lethargy, fogginess, but I don't have those effects. Yes, I certainly feel hungry more often than before...that's also because I am on simultaneous 18-6 IF protocol.

"Failure" is a very strong term for this thread header...I have not read any scientific evidence to support for those practicing mild-ketosis and very carefully watching dietary intake/biomarkers/supplements. Is there scientific evidence of negative IR consequence of low carb (non starvation like, well biomarker managed ketogenic) in humans (CVD or AD)...then I'd like to see it.

As for comments about it being unsustainable, I don't think they capture a highly motivated (and generally highly scientifically informed) E4 cohort who are VERY much mentally driven to prevent neurodegenerative disease! It's funny, when people will comment on my weight loss and ask how/why, they are all dumbfounded/shocked to learn its for neurodegenerative disease prevention, not weight loss as prime motivator.