Via Spanish Caravan, a frequent commenter with let’s just say a “medical background.”
~~~
Physiological Insulin Resistatnce (PIR) results from glucose deficiency the same way mucin deficiency induces dry eyes, nostrils, colon and anemia like symptoms. They’re both ways of preserving glucose for your brain.
When you VLC, your muscles become insulin resistant to preserve your glucose for the brain. So while your muscles are running on fatty acids, they become insulin resistant. This leaves glucose for your brain but the net result is your BG going up as you’re “physiologically” insulin resistant. There doesn’t really seem to a problem with this state, as there is with mucin deficiency; it’s not known to induce diabetes or make prediabetics diabetic. At least not according to those who advocate VLCing. I have a feeling however, that this is a disease-prone state.
Dietary carbohydrates and insulin action in humans
The effects of low carbohydrate diets on insulin sensitivity depend on what is used to replace the dietary carbohydrate, and the nature of the subjects studied. Dietary carbohydrates may affect insulin action, at least in part, via alterations in plasma free fatty acids. In normal subjects a high-carbohydrate/low-GI breakfast meal reduced free fatty acids by reducing the undershoot of plasma glucose, whereas low-carbohydrate breakfasts increased postprandial free fatty acids.
Why is it disease-prone? Because high serum free fatty acids are implicated in various disease states, especially immune related (and also diabetes in some cases). High serum FFA and very low trigs that we see among those who VLC are associated with nascent autoimmunity, especially rheumatic autoimmunity.
See: Low fasting serum triglyceride level as a precocious marker of autoimmune disorders.
We’re talking about triglycerides as low as 10-20 in some of these guys who are in long-term ketosis; you can only attain those levels in long-term ketosis or in starvation. And starvation is ipso facto ketogenic, a point which most people miss. That’s why the immune related problems that people who undergo starvation apply directly to those who’re in long-term ketosis.
Why do you think antibody-positive hypothyroidism is rampant in those who VLC? I used to think these people were hypothyroid to begin with but began VLCing to relieve their symptoms. The opposite is happening: healthy people are developing hypothyroidism (either euthyroid or later Hashimoto’s) upon going on ketosis or undertaking autoimmune protocols. Why? That’s because antithyroid antibodies like TG and TPO are markers for abnormal T-lymphocyte function. T-lymphocyte dysfunction, as I’ve mentioned elsewhere, can be induced in long-term VLCing through either thymus atrophy or starvation-like immunodeficiency. There is a correlation of something like 70% between thyroid antibodies and rheumatic autoimmunity; that’s why most people develop RA or other diseases after contracting Hashimoto’s or vice versa.
Jaminet made a connection between mucin and stomach cancer; he should have made a larger connection between mucin, secretory igA, which is immunoglobulin A found as secretions in tears, saliva, and secretions from the gastrointestinal tract and other epithelium layers. IgA plays an important immune function and could be behind many of the immune problems being encountered by those VLC, along with obviously gut dysbiosis which eviscerates immune-aiding microbes:
Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut
Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote retro-transport of antigens across the intestinal epithelium to dendritic cell subsets in gut-associated lymphoid tissue, and, finally, to downregulate proinflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships with immunity and intestinal homeostasis.
We keep triangulating this thing: long-term ketosis and VLCing => glucose deficiency symptoms like dry eyes, constipation, anemia symptoms, PIR + immunodeficient symptoms like unexplained food allergies, allergic rhinitis, sinusitis, respiratory infections, runny nose ==> disease state for T lymphocyte dysfunction and low immunoglobulins ==> pathogenesis of immunodeficiency + autoimmunity ==> then, and this is the reason why it’s hard to connect the dots, years down the road, clinical immunodeficiency and autoimmunity. Some people never get diagnosed because these are crypto disease states that are normally referred to specialists only when symptoms become severe. You’ll never suspect you have selectively immunodeficiency; your only symptom might be a mildly runny nose, especially if you supplement with Vit D.
~~~
Hopefully the notion that maintaining very low levels of carbohydrate and persisting in a state of ketosis long term will soon be a thing of the past.
John 
John 
I’ve been saying it all along: The low-carbers are going to have their arteries clogged from all that fat.
That’s not even close to what he said. Way to want to think you’re right based on really old and wrong evidence. There is such a think as good for you fats and bad fats. Don’t like being misinformed then have it change, do ya?
Also this is NOT ketosis, this is ketoacidosis which produces these symptoms including the insulin resistance. You prevent this by eating 20-50 grams of carbs a day and drinking LOTS of water.
There is NO SUCH THING as true ketosis. If you’re producing ketones (no matter the level) then you’re in ketosis and burning fat for fuel. If you have too many excess ketones you can get ketoacidosis. You are not for instance with the urine sticks supposed to be in purple like some people seem to think. That can lead to ketoacidosis.
Keto is not supposed to be about starving yourself. You’re supposed to drink lots of water, eat good for you fats (IE not just bacon and cream, get in avocado, coconut oil and olive oil) moderate protein (too much will cause the body to turn it into glycogen anyway) and low carb. NOT NO CARB.
Why does no one look into ketoacidosis vs ketosis then attack ketosis with out knowing the difference?
ketoacidosis is higher state this here we can name like in diabetes (pre-diabetes) they have the same pathology abnormal keton body levels. Low carb 20-50 is good for some condition but in healhty people can mess with brain and body. The biggest myth is that ancestors eat low carbs.
This is all anecdotal hogwash. Popular opinion is anti-fat/cholesterol, even though there is no evidence to support it. People will believe what they wish.
I’ve been on a keto diet for years, and I have no health issues, quite the opposite in fact. My health has substantially improved. My cholesterol levels are better than perfect. My BMI is ideal. I have not eaten anything that has fiber in it in years. Meat/dairy are my only sources of sustenance. The only plants I consume is in the form of coffee.
I used to have horrible cholesterol, horrible excess body fat, horrible water retention, and chronic inflation.
I don’t have any arthritis, constipation, dehydration, or immune issues. I have not once been sick in any way for years, this includes never having allergies.
The notion that eating low carb contributes to insulin resistance is ludicrous, as nothing a person in ketosis consumes has any insulin changes. There are no spikes, my blood sugar has been perfect without a single spike in years.
Every meal a person who eats plants will have an insulin spike post meal, this cannot happen to a person in ketosis unless they eat a higher proportion of protein than fat in their meal.
Please don’t peddle misinformation about something you don’t have a clue about.
Brett:
Just know you don’t have the Inuit to fall back on. Nor any population ever observed. You and others are conducting an experiment with little basis in observing healthy populations practicing long-term, chronic ketosis.
https://freetheanimal.com/2014/03/reiterate-elevated-ketone.html
https://freetheanimal.com/2014/07/stefansson-experiement-compromised.html
The way to exercise metabolic flexibility is how it’s always been done naturally: periodic, intermittent fasting.
“This is all anecdotal hogwash.”
And in the very next paragraph:
“I’ve been on a keto diet for years, and I have no health issues, quite the opposite in fact. My health has substantially improved. My cholesterol levels are better than perfect. My BMI is ideal.”
So, the only anecdotes that are valid are his and similar.
This email I got yesterday, and the thousands of comments on this blog (and thousands more in Paul Jaminet’s comments and forum) are “hogwash.”
“Hi Richard,
“So, I happened upon you by way of Paul Jaminet’s forum. I have been researching the implications of a vlc diet. I liked your article on Long Term Very Low Carb and Ketogenic Diets = Bad News.
“Here’s some background on me. Female, early 40’s. 5’3, 105 lbs. SAD up until the past few years and then I switched to VLC. Let’s say practically no carb. Healthy before switching to vlc. Last year I started getting very cold toes, sore finger joints and a runny nose. Went to several Reumy’s and after testing, a Scleroderma marker came back positive, however I am ana negative. The rheumy’s have said I may never progress to an actual disease. With that said, I am still trying to make sure I don’t progress and maybe even turn things around.
“I have since added back carrots, potatoes and rice…trying to up my carb intake and stave off what may be coming down the pike. I wonder if there is anything else I should reintroduce or supplement? I appreciate that you must be busy but would love to hear any opinion or advice you may have. Love Free the animal.”
Hi Richard,
I am the one that sent you the email you copied and pasted here. I would greatly appreciate any thoughts on how I could at least make an attempt to turn things around. Like I stated in my email to you, I have added back 2 cups of rice a day as well as carrots and potatoes. I will be taking morning basal temps to see if my core heats up after reintroducing carbs. Temp today at waking was 96.0. Keep you posted. Any advice..ie: foods or supplements?
Keep up the good fight.
K.
Also if this is just the start of a disease process is it even possible to turn it around/reverse it?
K.
Have you looked at the posts on RS and Probiotics? Lots of people reported body temp increased after years of chronic low once they added raw potato starch to their diet.
As far as Scleroderma, I know nothing about it.
It’s been rumored that body temp increases when one gets off their ass and moves. I’ve even heard some with the gall to suggest it improves your health!
Sorry, but I find it hard to keep my trap shut when see people anal-ize minutia like body temp, blood glucose levels, insulin, etc., etc. when all you need is a mirror. Go lift something heavy! Lose fat while adding muscle (the body’s largest endocrine organ). The whore-moans will work themselves out.
AHS 2014: The Underappreciated Role of Muscle in Health and Disease
I realize some people have a “broken” metabolism in some way, that perhaps need medical help? But still, you’d be surprised how many problems can be improved if not solved by a change in activity – to high intensity strength training.
RN,
Yes,
I have looked into RS as a way of upping my temp. I have Tatertot to thank for that. Would this have to be added indefinitely in order to maintain the normalized temp?
K.
K,
Ideally, once you are used to raw PS, you should think about eating real foods rich in prebiotic fibers and RS. These foods should be come your staple foods.
Thanks LF.
Potatoes, rice, carrots sound good?
K.
Very much. Add beans and lentils as well!
Very interested in your diet of just protein and dairy, can you tell me your meal plans.
Bullshit. Your meals are meat and dairy products? All day every day? Bullshit. I’d love to see the logistics, cost, and meal planning breakdown of that.
I wonder how many of these idiots proclaiming this garbage are industry shills? I’ll black bag every last one of you assholes and throw you in a meat grinder.
While I have nothing against keto, I achieved the same effect as you just by eating low calorie/high protein and weight lifting. I agree that long term keto is fine though.
Seems good to me, and Leangain-ish, which fucking works. Caloric restriction combined with hyper protein, toss in 18 hours of daily fast (I prefer 2x per week of 30 hour fasts), and heavy lifting.
It fucking works. I can’t imagine how it wouldn’t for everyone, but it’s a tough program to follow.
So right with that keto acidosis. The only bad fat is trams fats which unfortunately is in all mainstream production that my friends is why kills. Even saturated fats are okay.
Very interesting seeing as the most up to date research is showing global inflammation reduction across animals and humans and they have gone so far as to advise that a lot of this is due to genetic down regulation that happens based on Beta Hydroxy-Buterate effect on Histones and other genetic switching mechanisms. If any diet is done without deep knowledge then you get bad results. your success is directly proportional to your effort to understand the subject and apply it. So histamine increases are very doubtful, though it may increase depending on food choices, one must also understand that histamine has less of an effect if other inflammation contributors are lower so, Histamine by it self is not a quality indicator, breathing air effects histamine levels for example.
I have scleroderma, a diseased thyroid, and a positive ANA.
My doctor has *just* put me on a ketogenic diet. I’m to not go nuts with the protein. Eat lots of cooked veggies. (I cannot handle raw veg because of my gut issues) Drink LOTS of water. When I pee on the stick, if it’s purple, then I need to drink water immediately. The goal is to keep me in ketosis – not have high levels of ketones.
He’s also told me to try intermittent fasting. (Skip breakfast)
He told me that all of this would have the effect of reducing inflammation.
When I began this diet a week ago I was ankle to wrist blisters. Incredible itching. Joints swollen and hot. Had been this way (to varying degrees) for two years.
I’m now a week in and the itching has stopped. The blisters are in the process of healing. The ‘hot spots’ finally went away two days ago. Joint pain has reduced significantly and the swelling is already down.
This is my personal experience and it’s very short-term. But I cannot see how this diet can possibly make my situation worse than it was. If I stay where I am and don’t improve one little bit more, I win.
This is the first thing that’s actually helped me since my body went to hell.
Jimmy Moore’s latest total cholesterol: 392. This is (of course) nothing to be concerned about.
I hope I have not missed this in previous posts of yours, but as we talk about these things, what is your definition of VLC and LC? Is it consistent in the literature? Is it in total grams of carbohydrates or sugars only and how many per day. I guess resistant starch doesn’t count towards the total. Perlmutter in Grain Brain talks to do less than 80 g per day of total carbs, which I assume by your definition is VLC?
I’ve been doing some playing around with blood ketone measurements to put numbers to it. The online buzz is about being in ketosis, but in fact it is very hard to get the blood ketones up to the so called true ketosis threshold of 1 mmol/L. The highest I’ve gone is 0.6 and that’s with chugging MCT oil and almost no carbs, which certainly isn’t paleo! So in fact it makes me think that going into full blown ketosis just isn’t meant to be.
I don’t know that VLC is defined. It’s one of those you know it when you see it. I’d say any level of LC that causes phisiological insulin resistance would be a good measure.
If you want to be in deep Ketosis, tack on a good 300 kcal deficit to your VLCing. As we found on the potato hack, even people eating 90% carbs were peeing pink, but it’s because they were in a big caloric deficit because it’s hard to eat enough potato.
Thanks, good point, the body would want a deficit to kick into deep ketosis,which for me means, I think, a lot less protein. Again, is it necessary I wonder. If I, as they say: look, feel and perform well at 51 years of age now why go more extreme unless it is a sure thing to stave off Alzheimers and other aging issues forty or more years from now. But the jury is still out on this.
Mister Ian,
I don’t think you need to be in ketosis. I would in fact say that using ketosis as a preventive measure against Alzheimer, etc, is a little extreme. Just ditch the grains, eat only 2 meals or less / day (maximize inter-prandial time) and make sure you eat also for a good gut flora. Exercise some for fun and for keeping metabolic flexibility. Ketosis is a great survival mechanism if you get stranded somewhere without easy access to foods, but I guess, you are not in survival mode, are you ? :D
Mister Ian,
Just because a ketogenic diet might be a good theraputic measure for Alzheimers, that doesn’t mean that it would prevent it in the first place. The fact that there are many long term complications with VLC diets would argue against it. If Alzheimers is a concern, I would look into other things like reducing bodily iron stores, which basically means donating blood. Blood donation is much safer than a long term ketogenic diet, and worst case scenario, you simply help out another human being in need.
La Frite, what you say is almost exactly what I’m doing. :-)
The question which I continue to ponder is as John says is a ketogenic diet a therapeutic measure or a long term goal for brain health.
And what does it actually mean “ketogenic diet”? That’s why I decided to do the finger pokes and test the blood ketone levels.
Our dietary quantity and type of carbohydrates, protein and fats is only part of the equation. Exercise, overall health, age, gender and individual variability will affect our results. But does a ketogenic diet mean that the blood ketones have to be elevated or only that there is low carbohydrate consumption? Certainly we did not evolve metabolically to need a carb fix every two hours and we also didn’t evolve with such concentrated readily available carbohydrates — except when we raided the bee hives :-)
Question arises: out of all possible variations of VLC diets and additional helpers – eg. supplements, excercise, hormones, drugs, whatever – is there any one that’s working? Or is carbohydrate an “essential” substance, that needs to be consumed from the outside, like let’s say vitamin C?
What I see in Spanish Caravan is reliance on observational studies that check the state of the subject on some example VLC diet, as practiced. Are these “optimal”, the best VLC diets available – including in combination of vitamins, supplements etc.? Now, maybe there’s no such thing as a better VLC diet, than ones that are practiced today? How would we know that?
Overall I’d be reluctant to reject the whole category of VLC diets (including future ones) based on studies obeserving the results of only some of them. But of course the conclusions about this particular subset that was tested can be made, and potential new or not ones have to be quality-tested in those areas that Spanish Caravan mentioned, before being used.
Some example for what I said – Masai eat lots of fat, but supplement with herbs, that lower the negative effects of consuming a lot of fat. Or for recipies with sugar that add cinammon to lower sugar negative effects. You can even eat some MSG and supplement with oxaloacetate to lower the negative effects of the former. Or perhaps some drug can do such thing – drugs are quite effective at blocking or enhancing various biological pathways.
http://donmatesz.blogspot.com/2010/01/masai-use-of-herbs.html
So is there some saving grace for VLC diets? I’d agree that it may not have a sense economically to buy expansive drugs/supplements/hormones rather than just increasing cheap carbs by some grams, but anyway I’m not convinced that we have enough evidence to throw out the entire category “VLC Diets”, rather just a subset “VLC Diets as practiced today”.
By the way, I googled a citation that Spanish Caravan provided “These side effects are consistent with carbohydrate deficiency, because the brain and muscle do not get enough sugar from carbohydrates to maintain their normal function, Astrup said”
The surprise part of what showed up was… the date. It’s from Q3 2004! So the promoters of VLC had over 9 years to solve the problems mentioned with such articles with their diet (perhaps with the types of methods I mentioned earlier), but there seems to be some silence there? On the other hand VLC is not what get the most government grants, so maybe a reason is being underfunded?
VLC is a great way to lose weight without giving up pleasurable foods. Apart from that, unless you have brain seizures or other weird conditions, I am not sure I get the point of being in ketosis all the time. Isn’t it stressful at some level ? It is also hard to keep a good gut flora unless you supplement some RS “artificially ” (raw PS powder, etc).
The Masai never ate a VLC diet. They drank a lot of milk, getting about 100 grams of carbs a day.
@John – the Masai example was not as mach abut VLC, as about a certain framework, where you have some diet that has some downsides, but you compensate these with something else, like Masai compensating their diet negative results with protective supplemental herbs; same with carbs + cinnamon, or even carbs + lots of fiber like in Chinese cusine (high-GI rice + vegetables). Another example may be Ray Peat, who wen eating red meat consumes tea, in order to prevent iron overload, as tea decreases iron absorption. Again – a known disadvantage of a certain food being compensated by something.
So perhaps for VLC there’s some magic potion that eliminates its downsides? VLC promoters don’t seem offer such stuff, preferring to ignore disadvantages of their approach, which makes it even harder to determine if such thing consists.
@La Frite – the criteria that you propose is reasonableness, sense etc. – these are different that the topic of this blog post, which is that the VLC diet is harmful to your health. I don’t think being unreasonable makes a good reason to “kill” a diet that is one of Richard’s stated goas – as written in a previous post. For example a diet that is based on eating only very expansive products might be unreasonable, but that doesn’t necessairly make it harmful.
Lovely, I had been hoping that Spanish Caravan would give his take on Physiological Insulin Resistance (PIR). Unfortunately, I think many people will not take it seriously as a negative indicator until more serious damage is apparent, even though I’ve yet to see a single report of its existence as a norm in a healthy population.
Ray Peat wrote something similar, albeit focused on PUFAs: “There is a growing recognition that a persistent increase of free fatty acids in the serum, which is seen in shock, heart failure, and aging, indicates a bad prognosis, but there is no generally recognized explanation for the fact that free fatty acids are harmful. I want to mention some evidence showing that it is the accumulation of polyunsaturated fats in the body that makes them harmful.”
Is this one thing that Peat got right, at least partly, and could it help explain why so many VLCers report improvements upon trying a Peatarian approach (if their glucose tolerance isn’t too badly shot to tolerate the high fruit intake Peat recommends)?
However we have to remember that those who are using resistant starch may be benefiting from intestinal gluconeogenesis.
Nutrition: Short-chain fatty acids regulate intestinal gluconeogenesis.
http://www.ncbi.nlm.nih.gov/pubmed/24445584
Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
http://www.cell.com/abstract/S0092-8674(13)01550-X?
Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
Summary
“Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms. Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3. The metabolic benefits on body weight and glucose control induced by SCFAs or dietary fiber in normal mice are absent in mice deficient for IGN, despite similar modifications in gut microbiota composition. Thus, the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber.”
Art Ayers recently commented that a person can survive well on meat alone as long as the gut flora is adapted. (I would provide a link but I’m on a tablet and have no idea how to copy and paste)
@VW – an exampe of a man who ate only raw meat for 5 years
http://www.vice.com/read/this-guy-has-eaten-nothing-but-raw-meat-for-five-years
An example of a man, who survived on his own fat and supplements for a year:
http://www.abc.net.au/science/articles/2012/07/24/3549931.htm
GTR: wow! Not the guy who eats raw meat, the other dude.
Can the problems of long term VLC be avoided by cyclical ketogenic diet (e.g. carb nite, i.e. one heavy-carb meal a week)?
Jojo
I’d say if you make it a carb heavy day or two you’d be better off.
@Richard, I think I remember you posted something on FB about “met-flex” (Metabolic Flexibility). I would love to see you expand on this subject some time in the future, as it relates directly to the fat/carb macro-war thing. I have a suspicion that what is good about carb cycling, and more generally cycling all macros… carbs, fat, protein, and even calories and all food via IF, as well as you varying of potato starch supplementation, all boils down to keeping one’s metabolism energy substrate flexible. Obviously there is a correlation between obesity and low met-flex since “metabolic syndrome” is, almost by definition, really poor met-flex.
That was a post by J Stanton covering his AHS13 talk. Top of gnolls.org now.
I know that Dave Asprey over at bulletproof recommends carb refeeds once or twice a week. What do you think of his diet recommendations?
@Richard Why, for improved insulin sensitivity earlier during the day? In general I’d appreciate an inquiry into this hack (John Kiefer & Dave Asprey’s recommendations) as thorough as your much-appreciated expose of the dangers of standard VLCing. Thanks.
Ripken
I like Dave. I’ve been on his podcast (search the archives), I’ve met him a few times, had dinner with him and watched him take his block of Kerrygold out of his pocket, and was a co-speaker at a conference.
I don’t really know that much about his actual prescriptions beyond BP coffee, butter on everything, and his insatiable biohacking. I’m devoted to mainstream plain folk, and with limited time, can’t spend much time looking into what Dave is doing.
I trust him to be reasonable, though.
Pagan
I am only cautioning about VLC/Keto as a long term lifestyle. I fully recognize it in an intermittent setting, just like fasting 1-2 times per week for 24-30 hours.
There isn’t enough evidence for anyone to know — it’s all highly experimental. Dave’s recommendations are mainly for brain/performance hacking, while optimizing one’s overall/peripheral health (thyroid, immunity, ability to combat fungal infections, etc) is considered to be of lower priority. But, of course, that’s why they make bullet-proof supplements ;)