Tuesday, May 13, 2014

Eat as much starch as you wish

It has been interesting to watch the discussions about safe starches on those rather limited areas of the internet which I frequent. Now, you have to understand that I have always eaten a certain amount of starch. Usually chips deep fried in beef dripping to go with a fairly standard high fat supper. Sweet potatoes and parsnips are the two usual sources. Certainly two or three times a week. I’m not obese and certainly not post-obese, so I have some freedom in this. I’ve never been zero carb though I am very low carb and I run in mild ketosis pretty much all of the time nowadays.

My routes in to LC, other than the initial window through Atkins, were Kwasniewski, Bernstein, Groves and Lutz. Lutz was such a nice chap, certainly in his writing. He was perfectly willing to work at mere LC levels rather than VLC (72g/d was his advice) and he was very up front that LC would not work for everyone. For inflammatory bowel disease (he was a gastroenterologist) he expected progressive improvement over two years, not two weeks. He discussed that people experiencing failure of LC for weight loss might eventually need to go to simple calorie restricted diets (and I guess he knew they would fail on that too). He had an awareness that exposing an immune system, crippled and ineffective through years of hyperglycaemia, to sudden onset normoglycaemia might render if truly functional for the first time in decades and so exacerbate auto immune attack. Being a medic he would just reach for a 5 day prednisolone course as a simple expedient. For MS patients, many of whom respond very well to LC diets, he took them to around 100g/d initially then down to 72g/d after a few weeks. This is old stuff.

For people to convert from any particular macronutrient ratio to what is a modest, rather than very, low carbohydrate diet is fine by me.

What I have found very disturbing is the long list of potentially catastrophic problems reported to be associated with the type of food choices I make, where there is an edge of ketosis present much of the time. I have said before, I like to have a few ketones available.

It is quite possible that I, and virtually every lab rodent ever placed on a ketogenic diet, might be oddities. Or it might be that 12 years on a very low carbohydrate diet is too soon for the scurvy, thyroid deficiency, auto immune attack or glucose deficiency to get me. Perhaps it will happen tomorrow. But imagine how much money you could save on genetically the modified mice needed for auto immunity research if a simple ketogenic diet gave you a virtually free supply.

There is a saying in the medical community (used by those of us with any sense of self questioning) which goes along the lines of “Clinical experience is no guide to therapeutic efficacy”. One has only to look at a cardiologist with a statin prescription in their hand to understand this. My favourite example is that old chestnut from the siege of Turin during 1536 when Paré realised that pouring boiling oil in to gunshot wounds (the Gold Standard medical treatment of the day, to flush out the toxic carbon particles from the gunpowder residue dontchano) was, to put it mildly, a bit of a booboo.

So I had a listen to the AHS panel discussion on safe starches. The first thing I realised was that no one was making a case for metabolically safe starches, the "safe" referred to a lack of specific plant poisons. Metabolic safety seemed to be a given. I rather liked the lady clinician, she sounded just like Lutz. I loved Chris Kessler too, on C. elegans research. The world is full of people who seem to think humans are unique, free from the metabolic constraints which affect mere nematodes. When my own clients query, in wonder, that cats can get Alzheimers, diabetes, hypertension etc, my reply is that there is nothing special about humans. Failure to learn from C. elegans will lead to some interesting booboos, hopefully not as painful as the boiling oil fiasco.

Ron Rosedale was the only person who came over as making any metabolic sense or having any deep understanding of the processes involved in the signalling subsequent to metabolism.

I have an approach to life. I resist insulin. Running on the edge of ketosis, with a major preponderance of long chain saturated fatty acids as metabolic substrate, I expect to be insulin resistant. I am. It is pure physiology. I like to have uncoupled mitochondria running with a relatively low delta psi, high oxygen consumption and low free radical leakage. On isolated occasions, a few times a week, my parsnip chips will spike my blood glucose and delta psi for an hour or so and generate a few extra superoxide/H2O2 molecules above basal levels. I hope that’s enough for generating a decent number of healthy mitochondria. I don't know if I am correct.

So. I think people should feel free to make their own choices about starch intake. I can't see anything convincing in the concerns that very low carb eating will run you in to a host of medical problems. I'm very uncomfortable with the rhetoric. Quote of the year for 2014 comes from Sid Dishes, relating to the rise of auto immunity caused by VLC eating (I'm possibly only approximately accurate): "Hypothyroidism is so 2011". Sid keeps coming up with these lovely phrases on Facebook. Personally I see no need to add extra starches to what I already eat (between 30 and 60g/d of carbs). This is my rut. I like it.

As we all know only too well, we only get one shot at this. As the Red Hot Chili Peppers said “This life is more than just a read-through”.

Peter

121 comments:

Anna K. said...

Peter, thank you for another great blog post. This may be the wrong post to ask you, but I'll try nonetheless as my question is tangentially related.

What do you think of CR (caloric restriction) as a way to extend life span of humans? It seems to work on C. elegant, mice and practically all short living species. The CR research ran into problems when it got to primates. Bad research or primates/humans are indeed different when it comes to CR?

And another point, do you agree with Ron Rosedale and others that protein restriction and carb restriction alone are enough to mimic CR. In other words, does limiting calories produce the same life extension benefits as limiting protein and carbs?

Larcana said...

I like the post and agree, as a mere physician.
I don't eat much starch at all..even though I like the taste of chips!
I get the worst heartburn. I used to just cover it with "Tums' but now I have no time for that crap.
I eat VLC around 20 or less per day, I'm not IR but ketogenic ..I guess all the time. I have Celiac Disease and have been GF for 34 years. What do I tell people to eat, well they won't believe me that GF and low carb are good for them so I stopped trying a while back. SIGH.

Pierre said...

hehe...Bless your heart Peter. Have been following the "safe starch" talk for a while and have been waiting for someone not trying to sell me a book or something to give their take. I was hoping that it would be you. heh...

Anyways, some good has come from it as I discovered that sucralose is probably not a good thing to drink or eat and that aspartame is not much better.

Been reading about the gut and finding out that my excursions with loads of antibiotics for various ear infections was probably not helping my health over the long haul but it did make my ears feel better. The addition of sucralose and aspartame probably finished off the remainder of any good gut bacteria I may have had hiding down there.

For the last week I have stopped all diet sweeteners, and added 4 table spoons of resistant starch with a dash of three different pro-biotic. Not sure if I am wasting my money but wanted to see if that might help me lose that last additional 20 pounds after 55 lost so far in the last 4 years.

At this point I eat VLC once a day.

What are your thoughts regarding gut health?

Nigel Kinbrum said...

What about over-fat people on VLC/keto diets? You're not over-fat, so your adipocytes aren't spewing large amounts of NEFAs into your blood. Over-fat people's adipocytes are.

Lori Miller said...

"...exposing an immune system, crippled and ineffective through years of hyperglycaemia, to sudden onset normoglycaemia might render if truly functional for the first time in decades and so exacerbate auto immune attack."

Interesting! I never thought about this.

altavista said...

Peter, 12 years might be too soon for some, indeed. I might have come under immune system attack after 4 years, with no symptoms before that. I guess Don Matesz wasn't fabulating about his skin lesions after all.

It happened to me once last year and again once this year. (and on my scalp of all places, with hair loss and all) My doctor called it an abscess, but when he tried to grow bugs in it, he came empty handed, which leads me to believe my immune system went haywire.

I think you too mentioned some dermatologic problems at some point?

Spittin'chips said...

I may be missing the point, but I'm having trouble imagining a cat letting you take it's blood pressure.

White coat hypertension must a bitch to 'correct for'.

Cheers.

Peter said...

Anna, my main caveat is that, per unit size, humans live way longer than they should do. So metabolically we may be doing something rather good and there may be less scope for improvement.

The aspect of protein/carb restriction is a non issue. I live in the real world, with a family and a life. If I need a calculator before I eat to avoid dying of a deficiency disease or overdosing on calories it’s not going to happen. LCing appears to be the best option, while maintaining some degree of sanity and eating stuff which resembles food.

Larcana, my blood glucose excursions over the day are minimal. If I crack 6mmol/l even after a starch containing high fat meal that is unusual. But 75g of glucose in an OGTT will give me 14mmol/l for two hours before it drops. If I get a decent walk in the afternoon I’ll run at 3.3mmol/l. Spending an hour cutting my grass gave 2.7mmol/l last week. BTW there is a sweet potato with a very dark skin and pale flesh. Tastes of sweet potato spiked with chestnuts, yummee, for tonight with belly pork carnitas!

Nigel, I hope my adipocytes are spewing FFAs. Otherwise I would have no source of calories once digestion is complete.

Lori, I have a paper somewhere on my old hard drive looking at rate of bacterial ingestion by white blood cells. It goes down with rising glucose and stops at around 11mmol/l. Diabetics get infections…

altavista, I invariably develop a scaly skin reaction on my calves and knuckles on gluten exposure. This is never occurred before LC. There is a similar reaction with peanut agglutinin too, which is a bummer as I have a few rather nice recipes which require peanuts and I’ve stopped eating these. I’m unwilling to chance my health on long term exposure with subsequent oral tolerance. There is anecdote about coffee affecting gut integrity too but no hard data on this that I have been able to find. But it is a bean. Like cocoa, which I seem to be fine with (so far). I’ve always had acne, it’s waaaay better on LC but never goes completely. It would be interesting to see if eating spuds for a few years might stop your lesions developing but you would have a cost to pay for doing this if folks like Dr Rosedale are vaguely correct.

Spittin, not always. You choose your patient. If I can see the retina only with extreme caution (and there are haemorrhage patches all over it) but I’m going to get savaged trying for a full physical exam I’ll skip the blood pressure (no point) and consider amlodipine based on the clinical signs and absence of other possible causes for retinal damage. Cats generally pop their retinae when sustained hypertension is over 180mmHg when measured at the vets. But years ago we ran a study looking at the BP effects of medetomidine ketamine and needed baseline BPs pre GA. In young, fit, healthy cats it came out very tightly clustered around 110mmHg. We use a doppler technique and it underestimates in cats by about 10-20mmHg. Of course none of the cats were aware that I was about to remove their testicles during the subsequent GA…

Peter

Mike said...

"There is anecdote about coffee affecting gut integrity too but no hard data on this that I have been able to find."

What I'd heard was that coffee is in Cyrex Labs' "Cross-Reactive Panel" for gluten sensitivity.

The explanation for that I'd heard was simply that people so often drink coffee when they eat pastries that for some people the body concludes, "If this is coffee, then wheat must be coming".

However, I recently heard Tom O'Bryan say that actually it is only instant coffee that has this "cross-reactive" potential, so perhaps that explanation is bogus.

lifextension said...

Peter, you are so fabulous.

raphi said...
This comment has been removed by the author.
raphi said...

Apparently, anecdotal evidence and clinical evidence are equivalent.

Apparently, because X happened while on diet Y, then diet Y MUST be responsible for X.

Apparently, our physiology is programmed to fail spectacularly (thyroid/autoimmunity issues) if we fail to incorporate 1/4 to 1/3 of our daily calories in the form of carbohydrate, which at the metabolic and cellular level has never been shown to be "essential" - at least not anywhere near the same extent that certain AAs & EFAs were shown to be.

Apparently, high-fat/LC/Keto/whatever is AUTOMATICALLY lacking in fiber. (???)

--------------------
Sarcastic 'rant' finished
--------------------

Study: mTORC1 controls fasting-induced ketogenesis and its modulation by ageing [PMID: 21179166]

"Li-Tsc1-KO [Liver Tsc1 Knock-Out] mice had decreased locomotor activity and body temperature upon fasting, phenotypes also observed in other mutant mice with defective ketogenesis".

So if mice can have defective ketogenic pathways (surprise surprise, lab chow diets amongst other things), it might be interesting to ponder whether the same phenotype seen in humans might have SOME commonalities....maybe maybe maybe?

Galina L. said...

In Russia the standard medical advise given by every GP to the people with allergies, especially for the children with an eczema, is to remove some foods from their diets. Chocolate and cacao are on the list together with strawberries, citrus fruits,smoked meat, very spicy food, honey, even red-colored fruits and vegetables. Wheat is not on that list somehow,( alcohol is for the adults, especially beer and a red wine). I wish it would. Maybe it would save me a lot of grief when I was dealing with a severe eczema my son was having from 1.5 months of his life. It is all in the past, he is 21 now, and a gluten free by the necessity.

Nigel Kinbrum said...

Your body "burns" between 1kcal/min (sedentary) and ~16kcal/min (100% exercise intensity) using a variable mixture of carbs/NEFAs. Your adipocytes release NEFAs as required, so they're not spewing them when you're sedentary or exercising at >85% intensity.

Kindke said...

Lori, I have a paper somewhere on my old hard drive looking at rate of bacterial ingestion by white blood cells. It goes down with rising glucose and stops at around 11mmol/l. Diabetics get infections…

Very interesting peter, I also wonder if similar problems might occur in host defenses against virus's at varying blood sugar levels?


He is the bottom line on starch's for me. If I eat significant whole food starch EVERYDAY, I will slowly and surely gain weight. And its not muscle, or water, its FAT.

On a LC diet, I dont have to count calories at all. My natural appetite regulation works perfectly. Infact I will lose weight if I go under 20g carbs per day without even trying.

Meanwhile, If I want to eat potatoes everyday. I have to monitor and count everything else I eat VERY carefully to avoid weight gain.

Lori Miller said...

@Mike, FWIW, I've found I'm sensitive to certain types of coffee. I don't know if it's cross-reactivity with wheat, but I can't tolerate instant coffee (it tears up my stomach), flavored coffee (many of those flavors are made of solvents), or whatever it is we have at work.

I never started drinking coffee until I started LC--i.e., I never had it with pastries.

Sabine said...

http://www.westonaprice.org/blogs/cmasterjohn/2012/01/22/new-evidence-of-synergy-between-vitamins-a-and-d-protection-against-autoimmune-diseases/

Vitamin A and D protect against autoimmune disease.

Jack Kruse said...

Vitamin A or D do not protect anything.........they are chromophobes in the brain that allow for proper circadian signaling.
When water binds to collagen that is energized by the sun’s photons, water chemistry does some amazing things. Thermodynamically, mass goes down and energy rises. This makes life live longer. Sunlight tightens collagen by electrifying it with photons. Photons actually have no mass. Right next to collagen, an empty space called the exclusion zone is formed. Next to the exclusion zone (EZ), electrons are separated from water molecules. Next to the electron layer, we see a dense layer of protons that come from the hydrogen in water. It appears collagen allows water to separate into its constitutive parts to form groups of charged particles. The EZ absorbs photons best in the 270 nm range. This is in the UVB spectrum. UVB light makes Vitamin D.The DHA double bonds consist of a sigma bond and a pi bond. By subtracting 80 kcal/mole (the sigma bond energy) from 145 kcal/mole (the C=C bond energy) we can calculate that the pi bond has a dissociation energy of about 65 kcal/mole. This is much less than the sigma bond energy, and, therefore, pi bonds are more reactive than sigma bonds. This means that, all things being equal, the pi electron bonds of DHA are more likely to undergo activation by light. Your brain is just like a star. It works optically and photonically. This is why optokinetics works to change neural circuits. The brain is all about light because 35-40% of all lipids in membranes in the brain are DHA. Förster resonance energy transfer (FRET) is a mechanism describing energy transfer between two chromophores.HOW DOES COLOR AFFECT OPTICS IN THE BRAIN?



A chromophore is the part of a molecule responsible for its color. The color arises when a molecule absorbs certain wavelengths of visible light and transmits, or reflects, others. The brain is capable of doing this to all wavelengths of the visible spectrum based upon its variable tissue optics. The chromophore is a region in the molecule where the energy difference between two different molecular orbitals falls within the range of the visible spectrum. Visible light that hits the chromophore can be absorbed by exciting an electron from its ground state into an excited state. An example of a chromophore is Vitamin A, Vitamin D, hemoglobin, retinal, bilirubin. Vitamin A and Vitamin D yoke the brain to the circadian cycles found on Earth. The color is usually tied to a centrally located transition metal. A swollen, inflamed brain has different optics than a brain without swelling. A swollen brain tends to have alterations of Vitamin A, hemoglobin and water within it. Moreover, a leptin resistant brain is filled with protons and lacks electrons and photons. This brain is optically different than a leptin sensitive brain loaded with electrons and photons. A leptin resistant brain can not turn electrons into photons. Masterjohn's understanding of Vitamin A and D cycles is very rudimentary. It is all based on optics of neurons due to how they work as chromophobes. This is why people toxic in Vitamin A get pseudotumor cerebri. That is tied to the photoperiod and blue light, not food. Vitamin D is due to an inability to charge separate water properly. People low in Vitamin D develop autoimmunity because they lack electrons in their GALT where T cells and B cell first mature. T cells get final instructions at the thymus early on in life and B cells get it in an electron depleted bone marrow.

Jack Kruse said...

Peter awesome blog.

Sabine said...

The Treg/Th17 Cell Balance: A New Paradigm for Autoimmunity by Eisenstein and Williams

You may have to be a vet to understand this paper (and others like it) though, us physicians seem to be a bit slow (and weird).

Gearóid said...

I like that article, Peter. I'm a retired histopathologist so I know most of the science as well. My family on both sides are fat. I've found that no matter how it works or why it works, that I (now 64) can have the weight I was at 30, without hunger, on low carb and on nothing else. I imagine that a low insulin and insulin resistance reduction are involved in the mechanism, but who cares why? An eating regime should be measured on its effect, not on bits of it. I'm on 50g carbs by the way and no breakouts as I'm in serious physical training at the moment.

Sabine said...

I am very grateful for this blog, and it has helped me to deepen my understanding in a lot of ways.
I am glad that Peter shares his insights and knowledge with all who are interested, and that many others, be they physiologists, biochemists, microbiologists, veterinarians, biologists, and more, do the same.

I have great respect for Peter and others who take the time to spread their insights.

Many of these people have greater insights and better knowledge than many physicians.

SamAbroad said...

Peter,

What would you say to those of us that suffer serious problems eating VLC or even LC?

I can reliably induce vertigo by cutting carbs below 150g a day. It took me over a year to accept this as I was sure something else had to be to blame and LC had allowed me to manage my weight so effortlessly.

raphi said...

@SamAbroad,

It is conceivable that carbohydrates could directly elicit a response such as vertigo. However, many other factors could explain with it as well, with equal or greater likelihood.

Your microbiota change substantially in a matter of days, so do your enzymes responsible for fat or sugar metabolism, water retention, hunger and so on. Beyond macronutrient partitioning abound many theories eager to shed some light on the why's & how's.

shtove said...

Rosedale's best proposition was that a natural diet only gets you to the point of reproducing - and not necessarily past that point.

I've read elsewhere he admits low carb is not optimal for fertility.

His model of communication within the system is interesting - which I suppose is Peter's "deep understanding" bit.

Mind you, a few years ago Jaminet did post serious evidence on mortality with various carb intakes.
http://perfecthealthdiet.com/2011/11/safe-starches-symposium-dr-ron-rosedale/

bjtemple said...

Great blog Peter
Are there any supplements you are taking with your VLC diet? What about all the carbs in nuts?

Suzanne Looms said...

Great post Peter. The 2014 trend seems to be a discussion of resistant starch. I'm not sure how that differs from fibre, but sounds the same.

Peter said...

Hi SamAbroad,

Your situation is interesting. You have an issue with, let us suggest, a group of neurons in your inner ear or in one of the nuclei processing the information provided by the vestibular apparatus of your inner ear. These cells undoubtedly become dysfunctional when your total carb intake drops below 150g/d.

You make certain assumptions. Be cautious. No one doubts your information (I hope). You have to ask what might be happening. If you consider that your neurons are normal it is clear that very even modest carb restriction is generating some sort of toxicity. Conceptually this needs a set of nerves which are dysfunctional under ketosis or dysfunctional on the level of blood glucose provided by 100g/d of carbs. Of course, an individual nerve cell knows nothing of your carb intake. It knows lots about blood glucose and blood ketone levels. Probably very little about free fatty acid levels, though this latter might not be the case for all neurons.

Ketones and normoglycaemia appear rather unlikely candidates for neural dysfunction, if the neurons are normal.

You may be aware that I consider most CNS neurons run on lactic acid supplied by the glial cells. The neurons themselves convert lactate to pyruvate which enters the mitochondria directly to supply ATP almost exclusively from ox phos via the TCA. Glycolysis, while quite possible for neurons, does not look to be the preferred option. Obviously glycolysis provides the possibility for input at the mtG3Pdh level of the electron transport chain so can generate large amounts of superoxide in much the same way as saturated fats generate a functionally similar input at electron transporting flavoprotein dehydrogenase. Fatty acids are largely excluded from the CNS for this reason and I view the use of lactate as a similar ploy to protect essentially irreplaceable nerve cells from glycolysis.

The question is, what happens if you force neurons to run on hyperglycaemia? They use glycolysis which may well induce the Crabtree effect to shut down mitochondrial function. The cells then become dependent of glycolysis and may well not like normoglycaemia. Even worse, they may input to the CoQ couple of functional mitochondria (via mtG3Pdh) and generate a level of superoxide from complex I which produces extensive free radical damage to the complex itself but also potentially to the mtDNA which codes for core elements of the whole of the ETC.

Usually complex I defects can be bypassed or ameliorated by ketosis. But who is to say that they all can?

So none of us know what sort of issues your neurons and their mitochondria have. I look at this from a metabolic perspective. You could very easily suggest that you simply have immune mediated vestibular syndrome, much like gluten ataxia but without the gluten. It flares when you restrict carbs, possibly through abnormal mucus in your gut through glucose deficiency. And that this is caused by carb restriction. We can all speculate, much as I am doing. I know which makes most sense to me.

None of us know. You may well be carbohydrate dependent, a situation of great misfortune. I would be very uncomfortable with accepting that your problem, while shows under LC, has been directly caused by LC.

One of the worst quotes I’ve ever seen was a Facebook link to some paleo person saying (shouting????) “We are not broken!!!!”.

Defiant, yes, but very unlikely to be true. We all break in the end. Which bits break and how we cope with our breakages has an awful lot of ifs, buts and maybes involved… You may be an example of a less common breakage.

Peter

Peter said...

Shtove,

Care with terminology, “admit” and “optimal” are value loaded terms. Optimal egg yield per day from a chicken is one, commercial year average is around 300 under maximally driven human intervention for productivity. You can dial egg yield with carbs (plus other manipulations), this was done, decades a go, by Lutz (of course). By this token “optimal” fertility on a human might be a child every 9 months… Lower fertility on a fixed food availability may not actually be “sub-optimal”.

Paul does put some very nice points, especially as regards HbA1c. I have already roughed out a post about what I do or do not think HbA1c means, what manipulating it means, and what it may mean on a health basis. I should really get back to it. I, needless to say, look at it somewhat sideways.

I think Ron Rosedale is going a little too far on the zero blood glucose when you take it to human levels. Zero environmental glucose for C elegans yes, I agree. My own interest is not in the lowest possible glucose, though my glucose is frequently very low, my interest is in the lowest levels of signalling induced relative to glucose. This is why I resist insulin. I have a fasting blood glucose of around 5mmol/l because I resist insulin, I’m not processing the glucose and I’m not producing the insulin. On VLC eating you markedly down regulate pancreatic glucokinase. So you secrete less insulin. So (coupled with muscle insulin resistance) you will fail an OGTT. You fail the OGTT because you neither secrete insulin nor process glucose. The issues are not the levels of glucose and insulin per se, the issues are what you do with them, what the signalling is and what the results of the signalling are.

Having an HbA1c below 4% on the SAD suggests chronic blood loss or severe reactive hypoglycaemia. Having an HbA1c > 6% puts you in to the maw of the ADA. Now, the real question is what is the long term effect of dropping your 6% ADA fodder to 4.5% using LC? Do you really repair your f*cked mitochondria? When using LC are you just faking the excellent values obtained from a person with resilient mitochondrial conditions who runs with HbA1c of 4.5% on a diet of utter crap? Does modest starch intake help maintain glucokinase activity at the cost of enhanced insulin signalling?

These are deep questions. I resist insulin.

Peter

Happyviking said...

Anna K: One of the major ways that caloric restriction is thought to affect aging is through methionine restriction: http://www.ncbi.nlm.nih.gov/pubmed/20041736 The same effect has been seen by increasing your intake of glycine (very high levels of this in gelatin): http://www.fasebj.org/cgi/content/meeting_abstract/25/1_MeetingAbstracts/528.2 This is an interesting connection that I hope to see more studies on.

Anyway, great post Peter! I have personally been trying out a higher carb approach the last few months, but I did not find it to be either beneficial or safe. My cognition took a serious hit compared to being mild ketogenic. I suspect it is related to the levels of catecholamines as carbohydrates tend to invoke mild worrying thoughts and some compulsive behavior. Maybe ketones are therapeutic or maybe carbohydrates are pathogenic for me. Genetical analysis shows that I have a lot of Baltic and Scandinavian hunter-gatherer genes and very little neolithic adaptation, so maybe I'm poorly adapted to starch consumption. I also have elevated levels of trypsin, which could maybe explain why I do well on high protein? Anyway, the most striking difference for me with is at my job. I have a part-time job next to my studies in which the temperature is 32 degrees fahrenheit. It is a very physical and job, and when in mild ketosis I will oftentimes work in a t-shirt or sometimes with a sweater on without feeling cold. When running on carbohydrates I need a jacket on and I'm really freezing. I've tested this plenty of times, always with the same outcome. Why is that?

Stipetic said...

Great post and comments, Peter.

shtove,

If you are interested, here's Dr. Rosedale's response to Paul:
http://drrosedale.com/blog/2011/11/22/is-the-term-safe-starches-an-oxymoron/#more-338

Exceptionally Brash said...

Perhaps the people who think that LC somehow causes autoimmunity, perhaps they have it backwards. I found this paper to be interesting.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774636/

Peter said...

EB,

Yup!

Peter

JohnN said...

Regarding PMC1774656: that was my personal observation as well. In my case the aftermath of consuming those pieces of crusty, well-fermented pieces of bread (that I'm still so fond of) are mitigated if used merely as carriers of thick layers of butter or cheese.
That paper illuminates and perhaps explains the puzzling result PMID 23648697.
John

karl said...

@ petro wrote:
"But years ago we ran a study looking at the BP effects of medetomidine ketamine and needed baseline BPs pre GA."

Wondered if you had any comment on the inflammation lowering effects in this regard?

Also - I don't think humans have adapted to eating grass based foods loaded with carbs in the short history comes to mind. We know the difference in lactose tolerance (Asians have problems) and I think that tolerance to starch intake is also varied.

It is my take that todays MD's are AWOL by not teaching people to look at their postprandial BG - modulating diet if BG goes above 110. Simple and cheap in 2014..


@@SamAbroad,
IT takes time to adapt to low carb - one of the effects is it normalizes the retention of sodium - some people need to add more salt.



donny said...

Nigel said; "What about over-fat people on VLC/keto diets? You're not over-fat, so your adipocytes aren't spewing large amounts of NEFAs into your blood. Over-fat people's adipocytes are"


Elevated free fatty acids are normal physiology in the fasted or ketogenic diet-fed state. Over-fat, insulin resistant people have elevated free fatty acids in the carb-fed state. This makes all the difference in the world.

Nigel Kinbrum said...

donny said...
"Elevated free fatty acids are normal physiology in the fasted or ketogenic diet-fed state. Over-fat, insulin resistant people have elevated free fatty acids in the carb-fed state. This makes all the difference in the world."

The over-fat have higher elevated serum NEFAs than the non-over-fat. This is not good. Serum NEFAs are suppressed by insulin, but by less than in the non-over-fat.

See P377 of New perspectives on adipose tissue function.

donny said...

"The over-fat have higher elevated serum NEFAs than the non-over-fat. This is not good. Serum NEFAs are suppressed by insulin, but by less than in the non-over-fat."


Nigel, where did I question this? I only added that in the fasted state, elevated free fatty acids are entirely normal. Peter's blogged sh*tloads of stuff about the difference between elevated free fatty acids paired with elevated glucose and insulin, and not paired. Good luck getting past his filing system :lol: but you've been around long enough that I suspect you've already read at least some of it.

Besides that, you've pretty much said it--many overweight people are spewing out those free fatty acids, and increased insulin doesn't seem to be helping them any.

They don't seem to have easy access to one normal physiological state--the proper response to carbohydrate. Maybe they can better approximate another normal state for humans--fasting--if carbohydrates are taken out of the picture.

"What about over-fat people on VLC/keto diets? You're not over-fat, so your adipocytes aren't spewing large amounts of NEFAs into your blood. Over-fat people's adipocytes are."

This is where you started. Over-fat people are very often spewing NEFAs even when insulin is present. Personally, if it's my choice, I'd rather spew even more, but with blood glucose and insulin that isn't elevated.

donny said...

Here's a study showing free fatty acids in overweight, insulin resistant individuals;

"Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet."

Yes, on a weight-loss high carb diet free fatty acids went down. Yes, on a low carbohydrate diet, free fatty acids went up. You can call this lack of suppression... but free fatty acids in a lean person will also go up when you take carbs out of the equation.

"In this group of healthy adults with normal BMI and no family history of diabetes, we explored the effect of a prolonged fast with and without acipimox on glucose metabolism. The central finding is that 24 h of fasting led to a 2.8-fold increase in circulating FFA levels compared with an overnight fast and was accompanied by decreases in the glucose-stimulated AIR and SIMM and therefore a reduced disposition index."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660143/

That's just a 24 hour fast. In a lean, insulin sensitive subject, fasting or a ketogenic diet may elevate free fatty acids 2, 3, 4, etc. fold depending on activity etc. Maybe this would be a problem if it happened in the obese--2, 3, 4 times already free fatty acids might be a problem.

Here's what happened with the obese people in the first study;

Free fatty acids of 790 micromole/l on high-fat, vs 660 micromole/l on high-carbohydrate. So twenty percent higher on low carb. They get the carbs and most of the elevation of free fatty acids to boot. No thank you.

donny said...

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132068/#!po=41.6667

Whoops, forgot to post the first study.

donny said...

Free fatty acids on the high carb diet--where I said they went down, should have said they went up less. 25 vs 159.

Martin said...

Peter,
Do you have any thoughts on people who over-produce acetoacetate? Phinney and Volek think you just need to eat fewer carbs for a while to adapt more - is that the only way?
The conversion to BOHB seems related to NAD+/NADH which you talk about a lot, but the biochemistry is too hard for me to follow. Do you think there are any other ways of encouraging the conversion to BOHB or is extended VLC the only way?

Peter said...

@ Martin, never looked in to this I'm afraid...

@bjtemple, six egg yolks for breakfast covers most of my supplementation. Occasional liver. Some fish.

Peter

donny said...

I've seen Dr. D'Agostino in interviews saying that urine ketones actually track pretty well with blood ketones, in his experience. Within twenty percent accuracy, I think he said, not perfect, but not as useless as many people say. But he works with people trying to get their blood sugar down into the sixties and sometimes fifties. If ketosis is deep enough, even though a keto-adapted person will tend to convert lots of acetoacetate to beta hydroxybutyrate, maybe there's still lots of acetoacetate left to spill over into the urine.

The fact that he says that urine ketones track reasonably well with blood ketones suggests that, since blood ketones measured are beta hydroxybutyrate and urine acetoacetate, "excess" acetoacetate in the urine doesn't mean that insufficient beta hydroxybutyrate is being produced and preserved for use in the brain.

marie said...

donny,
I agree, urine ketones track pretty well with blood ketones, for most people :)

Two points I don't think the ketostix 'doubters' realize, tell me what you think? :
1. except in very rare cases of interactions with the additives in certain specific drugs, there's no false Positive in proper urine testing
2. false Negatives may be possible, but the conditions seem to be important. The term 'keto adaptation' is heard a lot, but....
I've not met any people who display keto-adaption as a big disparity between blood and urine levels.

That's not to say they don't exist, there's at least a few credible anecdotal/case reports, under special circumstances.
For example, next time I go on that 50-mile trail run I might test again and see if I convert and suck up all the ketones just as fast as I could make them (tongue-in-cheek; twice a month, on good days, I can do all of 5 miles!)

Personally, by following both my blood and urine values when I've been doing an experiment long-term, I do find evidence that I may be Making less ketones with time, until they level-off. The ketostix are too imprecise to get a real relative percentage of course, but they roughly go down one color grade.

The key there is that both blood and urine levels drop and stabilize, not just urine level.

I consider this keto-adaptation.
Could be affected by the fact that I start with a fast of at least 24hrs (in order to change metabolism earlier than with diet change alone).

I wonder if anyone else here has measured some form of keto-adaptation and under what conditions.

marie said...

Peter,
sorry to go quite so off-topic above, at the slightest opening, but you know I'm always looking at this :)

Great post, a rational perspective. With all the noise lately, it's a calm haven. Thank you!

Given the wide-ranging effects of the gut biome and how easily it changes with diet composition, one idea is that anyone who thinks their VLC prompted some problems might benefit by looking at what they've been using for gut bug food and how much of it, rather than the macro composition itself.

Martin said...

Agree with the comment about no false positives. I know my fat burning has improved, but it would be nice not to stink of acetone lots of the time!

donny said...

Martin--oh. I've seen claims that when urine ketones go down, it's because they're being utilized rather than spilled. That doesn't really work for me because we're perfectly capable of spilling beta-hydroxybutyrate, we just don't have ketostix for those.

.http://ep.physoc.org/content/53/2/181.full.pdf+html

If you look at figures two and three, you'll see some serious beta-hydroxybutyrate spilling.

Not sure what I'd do about the acetone. I either don't have that problem or am oblivious to it.

Marie--

1) I think so. If you show purple any time of the day, even if it doesn't mean you're in a steady state of ketosis, obviously your diet is ketogenic enough for you to be slipping in and out of ketosis on a regular basis, like Peter likes.

2) Peter Attia has reported higher ketones after extended bike rides. When urine acetoacetate goes down later on on a ketogenic diet, it's partly because non-brain tissue like heart and muscle has reduced its use of ketones--it needs it less. Or maybe it was never needed in that tissue, and it's just a matter of it taking time for beta-hydroxybutyrate dehydrogenase to be upregulated. I'll stop here because this is just leading me back around to what Martin said about NAD+/NADH ratio. The NAD/NADH will tend to track with the energy production of a cell--so it comes down to acetoacetone being higher when more tissues in the body need the stuff to support their energy needs.

mnature said...

Peter, I go into hypoglycemia very easily. I eat mostly meat and potatoes (problems with fructose, but that's a long story). However, I was going into hypoglycemia at night, even if I ate potatoes just before going to bed. After thinking about it, I came up with a biscuit recipe that uses a plain white wheat flour (no additives) and beef tallow for the shortening. Eating a few of these biscuits during the day has allowed me to sleep without going into hypoglycemia.
My question is: Can you think of any reason that the complex carbs of flour would be different from the complex carbs of potato? Or is it possibly just some oddness of my metabolism?

George Henderson said...

Nigel, how do you measure these NEFAs? Is it an app on your phone?
Good to hear from you again anyway.

My guess is that autoimmunity has a lot to do with microbes. Immunology trumps metabolism. Get some sauerkraut, eat some dirt, experiment with fibre sources.


Back when this RS thing was just a gleam in Tatertot's eye my mantra was "eat enough fat for me, and enough starch to keep the microbiota happy". Happy, not riotous.

You're not going to get x, y or z in semi-ketosis. That guy who did get x, y, or z was the guy. That guy needed more carbs. Sorted. Better than he was before, actually. It's not crazy to think that some people are designed to perform and feel better at higher glucose inputs, or higher calorie inputs, even if they don't live as long as other people. Evolution is full of such quirks. That lower carb is better is only a statistical trend. Individual data points may very.
Complex 1 problems are overwhelmingly the most common mitochondrial defects, but are certainly not the only ones.

marie said...

Martin, info-rich succinct reply! Thank you.

I have two daughters, we don't call it 'stink of acetone', we call it 'eau de nail-salon' :)

marie said...

donny, thanks for responding.
True, in exercise ketone production will at some point increase, when you run out of glycogen stores for all systems.
It's demand-driven. Up to a point. Demand can exceed supply at some further point beyond that.
Keto-adaptation and athletic endurance training just determines how early/late that happens.
I understand 'adaptation' the same way you do, it's a lowered demand for ketones.

The thing is, aren't the levels of the ketones measured in the blood and the level of specifically acetoacetate excreted in urine both changing in tandem, whether we look at increased or decreased levels?

That is, what I'm looking for is any evidence that there is actually a difference in the conversion % of acetoacetate to hydroxybutyrate when someone stays long-term in ketosis, or that acetoacetate by itslef is utilized less somehow.
I know the reasoning that says it's possible, that's why I called it 'conceivable', but has anyone measured this? The dead give-away is to measure decreased acetoacetate excretion but Unchanged blood ketone levels.

I come from a traditional food culture that champions structured fasting all through the year. So I've been doing IF on-and off since late childhood and continuously for last 10 years or so. Since my 'carbs' just naturally fall at around 100-150g most of the time, of course I drop into ketosis very easily with any water fast over 20hrs.
Well, in the last few years I've been doing some self-experiments to test specific interventions for my family and friends and Peter has helped me understand some of those. He likes my mitochondria :)

Yet, even when I stay in deep ketosis for weeks, I don't change excretion by more than one 'color' and when that happens the blood level has dropped too.
They move together.

If this is true for most people, then there's no good justification for anyone to believe they may still be in ketosis if they show no color change on the stix. That notion can lull someone into complacency "oh, I've been eating ketogenic for a while, it's fine".

So I continue to search...lantern and all ;)

Galina L. said...

Exercising in a fasted state can really train liver to produce glucose, as I noticed.

LeonRover said...

Hercule Poirot, he say:

"Ze best 'iding place is under the light".

https://www.youtube.com/watch?v=D-szCTIE4q0 -

Sláinte

marie said...

Ahaha! Under the light, indeed.
Evil :)
'Wie einst'...und immer

WilliamS said...

"Exercising in a fasted state can really train liver to produce glucose, as I noticed."

Are you saying this is a bad thing and exercising fasted isn't a good idea for you? Or the opposite?

I strength train fasted and it feels great. But I haven't measured anything.

donny said...

I do think a lot of people are kidding themselves when the ketostix don't turn. Not all, because I've seen people report blood ketones as high as three, with negative urine.

I think it's a relatively safe assumption that you're not in ketosis when the ketostix fail to change colour if there's still room to adjust in your diet. Say, you're at 50 grams of carb or even 20. Or if protein is well within a safe range for retention of lean mass etc. I eat about a gram per kilogram of bodyweight myself, which puts me at about 70 grams (I'm now the mythical 154 pound male). My carbs are ten to twenty a day, this keeps the ketostix purple most of the time. But what if it didn't? I think I'd feel okay experimenting a little lower--maybe the .8 grams of protein advised by the mainstream--but much below that, and I might want a second opinion from a blood ketone meter. Or to simply ignore the strips, and cross my fingers.

http://www.dietdoctor.com/experiment-optimal-ketosis-for-weight-loss-and-improved-performance

Andreas Eenfeldt, morning ketones, urine and blood. I think morning might be a bad time to compare the two--that old saw about urine measuring ketones in preceding hours might be more important, most of the urine was produced while the person was sleeping, blood ketones measured after waking, with all of the hormonal consequences of that. Even so--one thing I don't see is much in the way of false negatives. Every time blood ketones show above 1, so do urine ketones.

Jimmy measured in the morning too.

http://livinlavidalowcarb.com/blog/jimmy-moores-n1-experiments-nutritional-ketosis-day-31-60/14669

Not wildly accurate, comparing the blood to the ketones. Not as bad a correlation as he seems to think, to my eye. Especially since you have to deal with the low resolution of the ketostix. Sometimes it's hard to choose just which purple to go with. Looking at it--if Jimmy was consistently not turning those stix purple, I'd say he'd be kidding himself if he thought he might still be in ketosis.

LeonRover said...

"Mit dir .. .. "

Nigel Kinbrum said...

donny said...
"This is where you started. Over-fat people are very often spewing NEFAs even when insulin is present. Personally, if it's my choice, I'd rather spew even more, but with blood glucose and insulin that isn't elevated."
I've read Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. According to Fig 1, HC meals produced a large reduction in postprandial serum NEFAs, resulting in a mean NEFA of ~400umol/L, compared to ~650umol/L for the HF meals.
On a LC diet (~100g/day of low-GI carbs), there's some postprandial suppression of serum NEFAs. That's why I think that the over-fat are better-off going on a LC diet rather than a VLC diet (<=50g/day of low-GI carbs). Focusing solely on glucotoxicity and ignoring lipotoxicity isn't a good idea.

For the non-over-fat, VLC diets are fine.

George Henderson said...
"Nigel, how do you measure these NEFAs? Is it an app on your phone?

Good to hear from you again anyway."
You can't easily measure serum NEFAs. Blood tests for NEFAs are not available on the NHS and, as far as I know, there are no meters available for measuring serum NEFAs at home.

Thanks! It's good to be posting again. Hi to Galina L, marie & LeonRover, too.

Galina L. said...

William,
Being adopted to exercising in a fasted state feel incredible, like you just can't get tired, but I noticed that it elevates blood sugar higher than the number upon waking up. It makes sense, glyconeogenesis is one of ways to provide a body with the necessary energy source during exercise besides ketones production. I personally think that the people who are prone to hypos can benefit from the fasting adaptations, I don't have the migraines triggered by not eating any longer, for example. I think I used to have such cause for a migraine because my BS could drop too low between meals.

@Nige, Hi. I go regularly to your blog to check what is new in your blog-roll. You are still my friend.

marie said...

Hi Nigel! Very good to see you are back ;)

donny said...

Nigel--yes, there's some. Is some enough?

Nigel Kinbrum said...

donny said...
"Nigel--yes, there's some. Is some enough?"
I don't know, but some is better than none.
From the first link I provided:-
"...although there is a longer-term ‘lipotoxic’ effect of fatty acids on the pancreatic β-cell that may be part of the link between obesity, insulin resistance and development of type 2 diabetes (Unger, 1995; Grill & Qvigstad, 2000)." and
"The increased flux of fatty acids (both as NEFA and TG) in the circulation has acute adverse effects on insulin sensitivity, but also leads in the longer
term to accumulation of TG in glucose-metabolizing tissues
such as skeletal muscle, liver and the pancreatic β-cell.
Accumulation of TG in these tissues, by some unknown mechanism, but probably involving local TG hydrolysis and availability of fatty acids or fatty acyl-CoA (Ellis et al.
2000), leads to an impairment of the normal sensitivity of glucose metabolism to insulin (or, in the case of the β-cell, to an impairment of insulin secretion in response to glucose)."
Are you not concerned about any of this? Is 100g/day of low-GI carbs likely to produce glucotoxicity?

mk07 said...

Peter, can you give me your insight on the Autoimmune Protocol? I understand there are no need for safe starches for someone healthy. But what about someone with an autoimmune condition? I have Hashimoto's, and raynauds. I am still not sure what's the best diet to follow for someone with Hashimoto's Thyroiditis. Also I have read that people with hashi's shouldn't do intermitting fasting because it worsens the condition but I've seen Paul Jaminet saying quite the opposite... He also claims that for hypothyroidism 100g of carbs are essential. I'm confused. I am only 23 years old but already have a damaged metabolism.
If you could give me your opinion on the AIP , and when its best to eat carbs, feeding windows, IF, etc I would appreciate it. I find your knowledge trustworthy and I respect and value your work.

donny said...

Nigel--

"Are you not concerned about any of this? Is 100g/day of low-GI carbs likely to produce glucotoxicity?"

In a person with insulin resistance or type II? Maybe. I'd risk free fatty acids being a little higher, rather than glucose being much higher.

Back when they were starving obese patient for up to a year, those free fatty acids must have been flying pretty high. I wonder what their lipotoxicity status was?

There's pathological lipid storage in muscle etc., as well and then there's the accumulation that happens in athletes. In both cases, increased free fatty acids do lead to accumulation of fat. I think we have to establish 1)free fatty acid excess during a low carbohydrate diet leads to excess accumulation of fat in muscle, liver, etc., and 2)that this constitute lipotoxicity in this particular case.

Not really arguing with you, understand, just trying to define the issues.

LeonRover said...

Hey Nigel, were you trying yr luck in the USA like yr female namesake née Lawson ? :))

Good to see that you have decided to use fingers for .. .. .. typing, once more.

That quote re NEFAs is another example of "dose level makes poisonous".

When there are two poisons - ya gotta balance 'em.

Léon R

Jack Kruse said...

Ketoadaption is all about proper protein folding. Metabolic syndrome is the other side of the same mitochondrial coin.

Nigel Kinbrum said...

donny said...
"In a person with insulin resistance or type II? Maybe. I'd risk free fatty acids being a little higher, rather than glucose being much higher."
If somebody's metabolism is so knackered that 100g/day of low-GI carbs results in serum glucose exceeding 140mg/dL (7.8mmol/L) for significant periods of time, then they should try to reduce their insulin resistance (if due to a combination of over-full cells & excessive sedentariness). An IR liver secretes excessive glucose, even in the absence of dietary carbs & IR muscles can't dispose of it. Insulin resistance can also be caused by deficiencies, as I have blogged about.
Resistance is useless/futile! (Borg/Vogons)

"Back when they were starving obese patient for up to a year, those free fatty acids must have been flying pretty high. I wonder what their lipotoxicity status was?"
With starvation, or very-low-calorie diets, energy expenditure is considerably higher than energy intake, so serum NEFAs fall as cells become depleted. It's the over-fat who have a high energy intake from fats whose total energy intake matches (or exceeds) their energy expenditure (because they believe that calories don't matter in the absence of dietary carbs) who are at risk of lipotoxicity.

"There's pathological lipid storage in muscle etc., as well and then there's the accumulation that happens in athletes. In both cases, increased free fatty acids do lead to accumulation of fat. I think we have to establish 1)free fatty acid excess during a low carbohydrate diet leads to excess accumulation of fat in muscle, liver, etc., and 2)that this constitute lipotoxicity in this particular case."
I don't know much about IMTGs. I'm more concerned about the long-term effects of sky-high NEFAs on pancreatic β-cells, 'cos when they're gone, they're gone.

"Not really arguing with you, understand, just trying to define the issues."
That's fine. Discussion is good.

Nigel Kinbrum said...

LeonRover said...
"Hey Nigel, were you trying yr luck in the USA like yr female namesake née Lawson ? :))"
Nope. I got tired of arguing with so many different people, so I decided to spend my time karaokeing/bandaokeing/open mic nighting & jamming.

"Good to see that you have decided to use fingers for .. .. .. typing, once more."
Lol.

"That quote re NEFAs is another example of "dose level makes poisonous".

When there are two poisons - ya gotta balance 'em."
I like to have dietary flexibility. This includes ~100g/day of low-GI carbs.

Peter said...

Nigel, Hi.

We have to be very careful with phrases like “lipotoxicity”.

In cell culture lipootoxicty is easily and VERY frequently demonstrated. All you need is palmitic acid at 400umol/l and cells will pop their clogs, sometimes too promptly to complete the experiments and researchers have to reduce the concentration to 200umol/l.

What is almost never stated is that this ONLY applies at culture glucose concentration of at or just under 25mmol/l. It doesn’t happen at 5mmol/l of glucose,

The second point is that you MUST use pharmaceutical grade palmitic acid in cell culture. Adding virtually any unsaturated fat to the culture medium eliminates the effect, especially oleic acid.

In intact animal lipotoxicity is easily demonstrable too, all you need is to knock out SCD1 so animals can’t desaturate the LCFA produced by DNL and pancreatic beta cells will die in a lab mouse fed standard low fat chow. High glucose, DNL to high palmitic acid. QED.

It’s also possible to show some sort of lipotoxicity in intact animals with heparin/intralipid (omega 6 PUFA) infusions too. Imitate with caution. Thinking this represents a ketogenic diet is a major booboo.

So. Obese people on ketogenic diets don’t run blood glucose levels of 25mmol/l and NEVER feed pharmaceutical grade pure palmitic acid in to their mitochondria.

Looking for gluco-lipotoxicity (a more descriptive term) by adding 100g of rice (should anyone consider this "safe") to what would otherwise be a ketogenic diet could just be a booboo. Made by not reading the fine print in the methods or by not following the references back through three layers of citations to find 25mmol/ of glucose was (probably) what was used. Sometimes you run out of layers of references to trawl through. I have done this many, many times.

It’s unlikely I would view life otherwise. The paper you cited is lovely. Low insulin 24/7, high physiological fatty acids, reduced 24h exposure to hyperglycaemia from the VLC diet. Just lovely. Normoglycaemia with uncoupled mitochondria. But doesn’t drop LDL cholesterol!!!! OMG! Call the cardiologists, Emergency statins required. These wonder drugs should be available for IV use.

Adding the carbs will just spike the glucose. Free choices to all. But care about WHY you want to spike your glucose, booboos can hurt.

Peter

Digby said...

Loved this post! While I don't handle starches well, my spouse like you, never obese, very lean, does sweet potato, squash, etc a few times a week with no problem. I wish people would get over their all-or-nothing views. Vlc works best for mr, lc for my spouse,: we are not all identical. Thanks for your common sense gentleman's approach to health.

Nigel Kinbrum said...

Hi Peter,

75g of glucose as an OGTT produced a blood glucose spike in me that occurred between 30 & 90mins after consumption. By 120mins, my blood glucose level was slightly lower than before consumption.

I doubt that consuming ~100g of low-GI carbs spread over the course of my waking hours produces a blood glucose spike in me.

1) What do you define as a blood glucose spike?

2) What causes the fasting blood glucose of an over-fat* person on a keto diet who is not in caloric deficit to slowly increase? Is that cause for concern?

3) What causes the blood lipids of an over-fat person on a keto diet who is not in caloric deficit to increase to a level that Dr Thomas Dayspring says is dangerous? Is that cause for concern?

Cheers, Nige

*I prefer to use the term over-fat rather than obese, as some non-obese people have full adipocytes due to insufficient adipocyte hyperplasia.

Peter said...

Nigel, I'm no diet guru, make your own choices re carbs. I'm more concerned that you consider elevated FFAs as toxic while ever blood glucose is below 5mmol/l, if that's what you do think...

Peter

Melchior Meijer said...

Peter, thanks for that clear explanation of 'lipotoxicity'.

The folks in the Newcastle Study by Taylor who restored their betacell function on a very low calorie diet must have had done this with 'higher than normal' NEFA-levels.

http://www.ncl.ac.uk/magres/research/diabetes/reversal.htm

Melchior Meijer said...

From Roy Taylor's review paper (free download):

http://www.ncbi.nlm.nih.gov/pubmed/18726585?ordinalpos=183&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

"Farmers are the supreme experts at the practical manipulation of nature. The production of fatty liver in ducks and geese has been honed over at least 2,500 years [24]. Currently, the birds are allowed increasing access to high-carbohydrate feed over a 12 week free-range period. During this phase, rapid weight gain occurs and the livers become fatty, enlarging to 50% of their final size. This is equivalent to severe fatty liver for man. In the final 12 days, gavage is used to administer a large, high-fat energy overload and exacerbate the hepatic fat excess. However, the first phase of fois gras production gives all the necessary clues to the genesis of fatty liver in man."

I find this very funny, because 'that woman' is always using Taylor in her crusade against anything paleo or low carb.

raphi said...

http://www.drperlmutter.com/wp-content/uploads/2014/03/Glucose-Levels-and-Risk-of-Dementia.pdf - Glucose Levels and Risk of Dementia

- “higher glucose levels may be a risk factor for dementia, even among persons without diabetes.”


http://ac.els-cdn.com/S0969996106001409/1-s2.0-S0969996106001409-main.pdf?_tid=dede4140-e582-11e3-835b-00000aab0f27&acdnat=1401183780_7033fd61045e9f397541a8927b55977c - Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer’s disease mouse models with abundant Aβ in plasma

- “We therefore sought to elucidate the relationship between the natural history of plasma lipids relative to amyloid deposition and Aβ levels in three independent murine models of AD compared to nontransgenic littermate controls […]”
- “We found no consistent significant changes in plasma TC levels with respect to amyloid deposition in any of three mouse models of AD examined, demonstrating that elevated TC levels are not likely to represent an inherent aspect of incipient AD neuropathology in these mouse models […]”
- “however, we observed elevated plasma TG levels prior to and concomitant with amyloid deposition in Tg-CRND8 and APP/PS1 mice”
- “elevated TG levels are clearly not required for amyloid deposition in vivo”
- “Our results suggest the possibility that VLDL-TG may represent an alternative marker of altered peripheral lipid metabolism during the natural history of AD.”
- “altered TG metabolism is an independent risk factor not only for coronary events, but also for metabolic syndrome and type II diabetes mellitus, both of which are characterized by elevated TG levels”

http://ac.els-cdn.com/S0003267011000961/1-s2.0-S0003267011000961-main.pdf?_tid=3569678a-e586-11e3-bbef-00000aacb35e&acdnat=1401185213_4bb79c24790384ef3d3c3eb0e078d9f7 - Plasma esterified and non-esterified fatty acids metabolic profiling using gas chromatography–mass spectrometry and its application in the study of diabetic mellitus and diabetic nephropathy

- “term ‘lipotoxicity’ refers to the processes leading to end organ damage and/or dysfunction following excess exposure to NEFAs […]”
- “DM and DN are often accompanied by symptomatic lipid disorders and insulin resistance. In the DM pathological state, impacted by the changing of insulin metabolize, catabolism becomes the leading metabolism. The dominant of catabolism results in decreased synthesis and increased decomposition of fatty acids. Thus, when it was compared with the control group, most of the plasma EFA concentrations reduced, while NEFAs increased significantly.”
- “Based on the above analysis we speculated, understanding the tendency of the disease developing from the angle of fatty acids metabolism may indicate the process of metabolic self-adjusting. In the development of the disease, the fatty acids metabolism go through repeated self-regulation, and ultimately get close to the healthy state, but at the cost of organ damage.”
- “our results uphold the lipotoxicity hypothesis”



http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874689/pdf/zdb1292.pdf - Local Non-Esterified Fatty Acids Correlate With Inflammation in Atheroma Plaques of Patients With Type 2 Diabetes

- “The presence of LPL mRNA in NEFA-rich areas of the atheroma plaque, as well as the lack of correlation between serum and plaque NEFA, suggests a local origin for plaque NEFA.”
- “We hypothesize that NEFA may be produced locally and contribute to local inflammation”
- AGAIN “Other lipids widely regarded as major players on atherosclerotic pathogenesis, such as cholesterol, did not significantly differ in quantity between diabetic and nondiabetic samples (Table3). Furthermore, there was no differences in triglyceride accumulation (Table 3).”
- “We did not find any correlation between plasma NEFA and any of the lipid molecules measured by TOF-SIMS at the arterial wall (supplemental Table 1, available in an online appendix @ http://diabetes.diabetesjournals.org/cgi/content/full/db09-0848/DC1)”

raphi said...

With all of this Nigel - what to worry about?

Considering the opportunity cost of ‘worrying’ about 1 marker over another, @ this point it seems like a no-brainer to keep both eyes on dietary sugars impacting BG & TG levels rather than total dietary fat intake (leaving quality aside for a moment).

Of note: even in the paper ‘upholding’ the lipotoxicity hypothesis, this is not a call to favor sugars over fats as we know that quickest way in most people to elevate TGs is to consumer sugars. So, I fail to see data or even plausible mechanisms supporting an intervention to ameliorate lipotoxicity by….increasing sugars…?



Peter, maybe you can explain why they (Cornell) seem to say this is used in veterinary medicine and not 'human' medicine? What am I missing?

https://ahdc.vet.cornell.edu/sects/ClinPath/modules/chem/NEFA.htm
- "In veterinary medicine, NEFAs are mostly used for energy metabolite assessment of periparturient (transition) dairy cows and for detecting negative energy balance in camelids (llamas and alpacas), both of which are predisposed to hepatic lipidosis. NEFAs can be measured in small animals and are increased in states of negative energy balance (anorexia, inappetance) or where there is increased lipolysis (diabetes mellitus), however testing is rarely performed in these species."

Nigel Kinbrum said...

Peter said...
"Nigel, I'm no diet guru, make your own choices re carbs. I'm more concerned that you consider elevated FFAs as toxic while ever blood glucose is below 5mmol/l, if that's what you do think...

Peter"
This is why I asked the questions in my previous post.

Something is causing the progressive increase of blood glucose & lipids in a certain well-publicised over-fat person who's on a keto diet containing blocks of butter and who isn't losing weight, so he isn't in a caloric deficit. If it's not lipotoxicity that's causing it, then what?

I prefer to maintain a safe weight (that results in normo****aemia) on a diet that contains ~100g/day of low-GI carbs. Dietary & metabolic flexibility FTW.

Where **** = glucose and lipids.

Nige

Nigel Kinbrum said...

Melchior Meijer said...
"Peter, thanks for that clear explanation of 'lipotoxicity'.

The folks in the Newcastle Study by Taylor who restored their betacell function on a very low calorie diet must have had done this with 'higher than normal' NEFA-levels."
Depleting adipocytes results in reducing serum NEFA levels.

Nigel Kinbrum said...

raphi said...
"With all of this Nigel - what to worry about?"
I'm not worried. Being insulin-sensitive, if I eat high-GI carbs (at a party or meal out, say), I'm hyperglycaemic for only a short period of time. Worrying is bad for you!

raphi said...

@Nigel

I am often mildly ketogenic and mostly VLC/LC. For example, after a short but intense work-out followed by a meal containing 1 big sweet potato, 1 pear & 1tbsp of honey my postprandial BG levels are sub 70 (sometimes even measured as sub 60!).

So, my body is disposing of the glucose by shuttling it to my muscles and brain, EFFICIENTLY. How? Via insulins powerful action, aka it 'spikes'. This COSTS the body (to some extent). There is good evidence to suggest that doing this isn't 'free' in terms of longevity. MAYBE this is the type of approach I need for performance/hypertrophy - maybe. It is likely not beneficial for longevity.

TL;DR Maintaining low fasting or post-prandial BG levels when consume 'higher-carb' diets REQUIRES insulin, which in the long-run, is likely not advantageous for survival.

If we could home test insulin as easily as BG....


http://drrosedale.com/blog/2011/11/22/is-the-term-safe-starches-an-oxymoron/#axzz32vK7Nnr7
Dr.Rosedale puts it this way: "I do not believe, nor might Jaminet, that fasting blood glucose is the sine qua non for health, and it should not be used as such. Again, it is the excursions in glucose and effects on corrupting insulin and leptin signaling that are much more significant. [...]"
"However a main point of my argument is that BG levels are only a small part of the story; What higher carb intake does to insulin and leptin is even more important; it raises them promoting insulin and leptin resistance."

This is not easy to disprove. It has not yet been disproven. Until then...

Nigel Kinbrum said...

@raphi:-
The more insulin-sensitive one is, the less insulin is required to "do the job".

The brain contains GLU-T1, which are insulin-independent. The liver contains GLU-T2, which are also insulin-independent. GLU-T4, the insulin-dependent ones, are found in adipose tissues and striated muscle (skeletal muscle and cardiac muscle) Ref: Glucose transporter - types Skeletal muscle can be made extremely insulin-sensitive by doing glycogen-depleting exercise (high-intensity training). Adipose tissues can be made more insulin-sensitive by depleting them (by not getting over-fat, or burning more than you're eating if you are over-fat).

Relying on gluconeogenesis for blood glucose can have snags. See How eating sugar & starch can lower your insulin needs.

Nige

Melchior Meijer said...

Nigel,

A very low calorie diet increases plasma NEFA levels.

LeonRover said...
This comment has been removed by the author.
LeonRover said...

Raphi said:

"what higher carb intake does to insulin and leptin is even more important; it raises them promoting insulin and leptin resistance.

This is not easy to disprove. It has not yet been disproven. Until then."

There are many, & I am one that requires this particular boot on the the other foot.

I require measured evidence to prove something. In the words of that medieval Empiricist Roger Bacon: The horse's teeth need to be counted.

Otherwise it is a mere speculative hypothetical.

Léon

Nigel Kinbrum said...

Melchior Meijer said...
"Nigel,

A very low calorie diet increases plasma NEFA levels."
In the short-term, yes.

In the long-term, as the over-fat become less over-fat, their adipocytes become more insulin-sensitive and "spew" less NEFAs into the blood.

raphi said...

@Nigel

Thus, the more insulin needs to "do the job", the more "the job" is desensitized to insulin. (unnecessary insulin spiking &/or chronic elevations)

Your link offered an N=1 anecdote:
"Even more weird – now that I have introduced the starches into the diet – I have actually got better control now. I thought my insulin needs would go up – but they haven’t. They’ve gone down."

To which your proposed the following explanation/speculation (as there's no public data for this N=1 that I know of):
"You now have a well-controlled glucose input to your circulation via diet, which has suppressed the poorly-controlled glucose input to your circulation via hepatic glucose production."

Your other point was that insulin-independent GLUT transport exists - so what?...Multiple redundancies & feedback loops are perfectly logical & common strategies used in such a fundamental biological processes. This, in and of itself, is not a point for or against starch consumption.

Is "poorly-controlled glucose input to your circulation via hepatic glucose production" implying wacky GNG? Or what specifically?

Peter said...

raphi, it is quite possible to develop hepatic lipidosis during acute fasting in many species. It’s many years since I dealt with cattle in ketosis. Clinically nowadays the small animal worry is cats undergoing weight loss through illness associated anorexia, these can develop severe hepatic lipidosis, most common in obese cats. It carries a very high morality.

In part it appears to be hypoinsulinaemia related. To me insulin secretion requires rising glucose on a fatty acids profile which inputs a reasonable amount of FADH2 to the ETC, i.e. saturated fats work best. Omega 6 PUFA probably work least effectively so may contribute to relative hypoinsulinaemia. There may also be a simple effect of there being so much adipose tissue available that a reasonable drop in insulin produces unreasonable rise in lipolysis. At the signalling level rather small amounts of omega 3 fats have been shown to be protective under controlled low calorie conditions too. All quiet speculative though.

Dogs are nearly immune to the problem. People seem resistant too.

It’s all interesting but may not relate to the combination of hyperglycaemia with elevated FFAs, a serious problem in its own right.

Peter

Peter said...

Hee hee, mortalilty, not morality!

Peter

marie said...

Peter,
don't know if maybe you've seen this. In current issue of Diabetes, there's a critique (http://diabetes.diabetesjournals.org/content/63/6/1831.full ) of the Jain et al (...Hoyner) paper that was first published online earlier this year and used fat-fed rats and mice to look at mechanism of mitochondrial biogenesis.
(rats, Zucker ones at that, but still.... :))
Jain et al had come up with a role for mitochondrial-generated ROS : "High-fat diet–induced mitochondrial biogenesis is regulated by mitochondrial-derived reactive oxygen species activation of CaMKII" (http://diabetes.diabetesjournals.org/content/63/6/1907.full.pdf+html)

I don't think the critique stands well, if you get a chance, have a look?

Leon,
it also reminded me of your comment re. speculation and insulin resistance:

"..skeletal muscle plays an indispensable role in maintaining glucose homeostasis. However, the mechanisms underlying the development of insulin resistance remains poorly understood..."
....and a-speculating we will go... :)

LeonRover said...

Marie

"speculatin is the name of the game an each generation plays the same" :))

https://www.youtube.com/watch?v=8x-NZ7TaoT0&feature=kp -

Léon

"they better" !!

Nigel Kinbrum said...

raphi said...
"@Nigel
Thus, the more insulin needs to "do the job", the more "the job" is desensitized to insulin. (unnecessary insulin spiking &/or chronic elevations)"
In the short-term no. In the long-term, somewhat. I discussed this in Hyperinsulinaemia and Insulin Resistance - An Engineer's Perspective. Are you suggesting that consuming ~100g/day of low-GI carbs causes insulin spikes and/or chronic hyperinsulinaemia?

"Your other point was that insulin-independent GLUT transport exists - so what?"
I wasn't trying to make a point.
I was merely correcting you when you wrote "So, my body is disposing of the glucose by shuttling it to my muscles and brain, EFFICIENTLY. How? Via insulins powerful action, aka it 'spikes'." The brain's transporters don't require insulin.

"Is "poorly-controlled glucose input to your circulation via hepatic glucose production" implying wacky GNG? Or what specifically?"
If hepatic glucose production is excessive, that isn't necessarily wacky. Everybody is different. I presented that n=1 case as an example of how it's possible for increased dietary carbohydrates to result in a reduced insulin requirement for normoglycaemia, as it's contrary to what you would expect. What do you reckon caused it?

Serova said...

The Kwashevsky diet which Peter supports is not totally potato-hostile. Nigel, may be you eat even less starches than K. recommends.

raphi said...

@Nigel,

3 things:

1) “Are you suggesting that consuming ~100g/day of low-GI carbs causes insulin spikes and/or chronic hyperinsulinaemia?”

-Bah! Who the hell knows without case-relevant insight concerning the special snow-flake we’re on about. But otherwise: for more people than not unfortunately, they’d likely do better under 100g rather than over. Yes yes - define better? Longevity or performance? Etc.,…So to make a long sort short, I prefer to think in odds rather than philosophies. Sophistications aside - Gun to my head —> go sub 100g of carbs for most people most of the time, rather than above.

2) Regarding brains and insulin-dependent glucose uptake, no correction needed. Remember how ‘Cocaine is a hell of a drug??”. So is insulin.
—> “Previous studies have demonstrated no change in rate of brain glucose metabolism in response to elevations of circulating insulin above the basal (fasting) range. Our data, examining the effect of basal insulin replacement during somatostatin infusion, show that brain glucose uptake is however partially insulin sensitive, as there was a significant reduction in global brain glucose uptake when circulating insulin levels were reduced below this. Coupled with the published data showing no effect of increasing circulating insulin above fasting levels, we can infer that brain glucose metabolism is maximally stimulated at these fasting insulin concentrations. The magnitude of the effect may not seem large, but this is because it is superimposed on a background of insulin-independent brain glucose uptake. A 15% increase in brain glucose uptake secondary to insulin stimulation may have clinical significance.
…Furthermore —> “The debate as to whether the neuronal energy requirements are fulfilled by glial-supplied lactate or glucose continues and cannot be determined from our study design. In contrast to the glucose transporters, insulin receptors in the brain are widely distributed on neurons and glial. While in culture, glial cells respond to insulin by stimulation of glucose uptake; the neuronal response to insulin is stimulation of neurotransmitter release, so it is possible that the increased glucose uptake we observe is secondary to neuronal activation by insulin. In any event, the net effect of insulin in our study remains an increase in brain glucose uptake, whatever the ultimate fate of the glucose.”
http://diabetes.diabetesjournals.org/content/51/12/3384.full
- So, we’re left with “brain's transporters don't require insulin.” (TRUE!) but WHO CARES (my hand is up), because “the net effect of insulin in our study remains an increase in brain glucose uptake, whatever the ultimate fate of the glucose.”

3) “What do you reckon caused it?” [IT] being “that n=1 case as an example of how it's possible for increased dietary carbohydrates to result in a reduced insulin requirement for normoglycaemia”.
- I don’t think “it’s possible for increased dietary carbohydrates to result in a reduced insulin action” other high-carb diets would treat hyperinsulinemia successfully. They don’t.
- So - nope! So, says you my friend, says you.
- I could SPECULATE. I’d certainly wouldn’t start by hypothesising the opposite of what has so far well been established; that metabolic diseases and hyperinsulinemia are wisely treated by including a restriction of dietary carbohydrates (amongst a ton of other things of course). But I don’t think I will (speculate) as I have an anonymous N=1 with no data to speak of. Some would call that flimsy.

I feel your pain Nigel. I’m one of em’ lucky bastards who likely can’ get away’ with ~100g of carbs a day. But I don’t, because I do better with less - mostly. Some people aren’t interested in “better” because they’re assessment is now is “meh, good enough - don’t hurt enough yet”. I sympathise - I don’t respect that however. I think” “better” is vague-speak for smart bet placement. It’s not about “what ifs” when we get down to “what do I buy tomorrow?”, it’s about betting smart.

Nigel Kinbrum said...

raphi said...
"@Nigel,
3 things:

1) “Bah! Who the hell knows without case-relevant insight concerning the special snow-flake we’re on about. But otherwise: for more people than not unfortunately, they’d likely do better under 100g rather than over. Yes yes - define better? Longevity or performance? Etc.,…So to make a long sort short, I prefer to think in odds rather than philosophies. Sophistications aside - Gun to my head —> go sub 100g of carbs for most people most of the time, rather than above."
Dunno about snowflakes, but I know what postprandial hyperinsulinaemia used to feel like (a warm, sleepy feeling) and I don't get that on my current diet. My n=1 experience suggests that ~100g/day of low-GI carbs isn't currently producing postprandial hyperinsulinaemia in me. This could be due to my improved insulin sensitivity compared to a few years ago.

"2) Regarding brains and insulin-dependent glucose uptake, no correction needed."
I concede that insulin increases uptake of glucose by the brain a bit (15%).

"3) “What do you reckon caused it?” [IT] being “that n=1 case as an example of how it's possible for increased dietary carbohydrates to result in a reduced insulin requirement for normoglycaemia”.
- I don’t think “it’s possible for increased dietary carbohydrates to result in a reduced insulin action” other high-carb diets would treat hyperinsulinemia successfully. They don’t."
By "increased dietary carbohydrates", I think that Jason increased his carb intake from <50g/day (VLC) to ~100g/day (LC). He didn't increase his carb intake to >200g/day (HC).
Whether or not you think that it's possible, it happened! Jason has LADA and has to inject insulin, so he knows exactly how much insulin it takes to achieve a certain BG level.

"I feel your pain Nigel."
What pain? I'm happy with my current diet. My most recent blood tests came back normal. I'm neither hyperglycaemic nor hyperlipidaemic.

Melchior Meijer said...

Nigel, there is generally a complete absence of relationship between BMI (or rather 'fatness') and fasting NEFA concentration. Over fat people release significantly less NEFA than do 'lean' people. The NEFA they do release, comes mainly from subcutanuous belly fat, not from intra abdominal/visceral fat. On a low calorie diet, NEFA levels will inevitably be 'elevated', in both lean and obese (over fat) people. I have not seen any evidence that NEFA levels will decrease below baseline in obese (over fat) people after they have lost a significant amount of adipose tissue. I.e. it's not certain at all (rather, it is unlikely) that the subjects in Taylors experiment lowered their NEFA levels while they were losing adipose tissue. NEFA concentrations can probably not explain the observed restoration of beta cell function and return to normoglycaemia.

The bull dozing lady in New Jersey is likely barking up to the wrong tree.

From this paper

http://diabetes.diabetesjournals.org/content/60/10/2441.full

***As adipose tissue mass expands, NEFA release per kilogram adipose tissue is downregulated, not increased. In many obese individuals, this can lead to normalization of plasma NEFA concentrations. Some elevation of NEFA concentrations is undeniable in certain groups of obese individuals and in type 2 diabetes, and tracer studies tend to show that NEFA delivery to nonfat tissues is increased even if plasma concentrations are not much raised. However, it is clear that insulin resistance, even severe insulin resistance, can exist in obesity without elevation of NEFA concentrations. It is also clear that elevated NEFA concentrations are not necessarily associated with insulin resistance.***

Nigel Kinbrum said...

Melchior Meijer said...
"Nigel, there is generally a complete absence of relationship between BMI (or rather 'fatness') and fasting NEFA concentration."
I know. It all depends on the degree of adipocyte hyperplasia. People with Beradinelli-Seip Syndrome have no adipocyte hyperplasia, so are all extremely thin - and diabetic. See Beradinelli-Seip Syndrome – stick that in your pipe and smoke it - Comment

"Over fat people release significantly less NEFA than do 'lean' people.
Incorrect.
"As adipose tissue mass expands, NEFA release per kilogram adipose tissue is downregulated, not increased."
Correct. See P377 of New perspectives on adipose tissue function:-
"NEFA release per unit fat mass is actually less in obese subjects than in lean subjects (effectively, it is down regulated by the fasting hyperinsulinaemia). However, because of the increased fat mass, total NEFA delivery to the circulation is increased in obesity."

"I have not seen any evidence that NEFA levels will decrease below baseline in obese (over fat) people after they have lost a significant amount of adipose tissue."
Neither have I. However, it's illogical for adipocytes to release NEFAs at a constant rate as they deplete. I think that adipocytes release NEFAs in an exponentially decaying manner as they deplete, as per http://www.wolframalpha.com/input/?i=graph+y%3De^-x%2C++from+0+to+5 This is because adipocytes become increasingly insulin sensitive as they deplete, so basal insulin has an increasing inhibitory effect on NEFA release with increasing depletion.

"However, it is clear that insulin resistance, even severe insulin resistance, can exist in obesity without elevation of NEFA concentrations. It is also clear that elevated NEFA concentrations are not necessarily associated with insulin resistance."
Can means possible, not probable. ~85% of people with type 2 diabetes are over-fat.

Nigel Kinbrum said...

Melchior Meijer said...
"Nigel, there is generally a complete absence of relationship between BMI (or rather 'fatness') and fasting NEFA concentration."
The example that I gave about Beradinelli-Seip Syndrome is about health, rather than NEFAs. See also The surprising science of fat: you can get fatter and become healthier

A better example NEFA-wise would be to compare two people with the same BMI and fat mass, but one has mostly visceral fat and the other has mostly gluteofemoral fat. There would be higher NEFAs in the person with mostly visceral fat. This doesn't change the fact that depleting the contents of fat cells reduces the rate at which they release NEFAs.

Melchior Meijer said...

Nigel, let's assume you are right on all points (some of which are evident, like having no or relatively inadequate numbers of adipose cells being very unhealthy). How do you explain the rapid restoration of betacell function post gastric bypass, when NEFA levels are the same before and after the procedure?

http://www.researchgate.net/publication/5393861_Twenty-four_hour_insulin_secretion_and_beta_cell_NEFA_oxidation_in_type_2_diabetic_morbidly_obese_patients_before_and_after_bariatric_surgery

Melchior Meijer said...

Nigel, plasma NEFA levels never fell below baseline in Taylor's study:

During the study period, fasting NEFA in the participants with diabetes increased significantly at week 1 (0.93±0.05 mmol/l; p=0.03 vs baseline). With continued hypoenergetic intake, plasma NEFA declined steadily towards baseline values (0.81±0.08 and 0.72±0.06 mmol/l at weeks 4 and 8, respectively).

Nigel Kinbrum said...

Melchior Meijer said...
"Nigel, let's assume you are right on all points (some of which are evident, like having no or relatively inadequate numbers of adipose cells being very unhealthy). How do you explain the rapid restoration of betacell function post gastric bypass, when NEFA levels are the same before and after the procedure?"
I think that it's got something to do with enhanced GLP-1 responsiveness, but I don't know much about it.

Nigel Kinbrum said...

Melchior Meijer said...
"Nigel, plasma NEFA levels never fell below baseline in Taylor's study:

During the study period, fasting NEFA in the participants with diabetes increased significantly at week 1 (0.93±0.05 mmol/l; p=0.03 vs baseline). With continued hypoenergetic intake, plasma NEFA declined steadily towards baseline values (0.81±0.08 and 0.72±0.06 mmol/l at weeks 4 and 8, respectively)."
Thanks. I didn't know that.

Melchior Meijer said...

Thanks for reading, Nigel.

The fascinating thing is that people seem to have an individual threshold for the amount of ectopic fat in liver and pancreas. I mean, before it becomes problematic. If you manage to get these excess triglycerides out of the organs, beta cells start to respond properly to glucokinase, alpha cells start to respond properly to the paracrine whisper of insulin, glucagon goes down when it should and normoglycaemia results. The number of beta cells increases, possibly even very late in the disease.

It doesn't seem to matter how you achieve this. Taylor does it with Slim Fast (600 kcal/day + 200 kcal non starchy vegetables) :-) .

ItsTheWooo said...

Starch trend, in a nutshell:

"I like eating carbs, therefore, eating carbs is good"

Furthermore:

"I can't stick to low carb, therefore low carb is unhealthy and kills you dead"

Nothing more to see here, move along. We will justify the biases we want to be true. Like peter, I have no problem with the first behavior (self delusion), it's more the Richard Nikoley-esque justifying fatassery by attacking LC as a health behavior that bothers me.


George Henderson said...

@ Nigel, you say ""The increased flux of fatty acids (both as NEFA and TG) in the circulation has acute adverse effects on insulin sensitivity, but also leads in the longer
term to accumulation of TG in glucose-metabolizing tissues
such as skeletal muscle, liver and the pancreatic β-cell.
Accumulation of TG in these tissues, by some unknown mechanism, but probably involving local TG hydrolysis and availability of fatty acids or fatty acyl-CoA (Ellis et al.
2000), leads to an impairment of the normal sensitivity of glucose metabolism to insulin (or, in the case of the β-cell, to an impairment of insulin secretion in response to glucose)."

However, this is a completely insulin-dependent process.
Dr Roy Taylor, of the "Newcastle diet" (600 calories a day for diabetes) makes this plain in this video presentation - which I thoroughly recommend, and I don't often have the patience for videos. He has it as the result of hepatic DNL too. So VLC really would be the best way to minimise this effect in a long-term eating plan.
Keep insulin low and the pancreas has to burn that fat, I should think. The liver certainly does.

Melchior Meijer said...

Wooo, there is 'something' to this RS thing, I'm afraid. A 70 y.o. type 2 diabetic lady (insulin treated) on my blog saw her BG and HbA1c deteriorating over the past years, despite strict adherence to a very low carb diet. She is very determined, not the cheating kind of person. I suggested to try RS (potato starch), which she did. First her BG's went erratic for a while, very unpredictable. I suggested to stop the experiment, but she decided to give it some more time. Then after about 2 months, fasting and pp readings came down quite dramatically. Long story short, her HbA1c went from 8,2 in december 2013, to 5,8 a few days ago. I assure you, the only thing she changed was adding RS.

She has now embarked on the Taylor approach. I am very curious if she will accomplish unassisted normoglycaemia after 30 years of type 2. It would be quite revolutionary.

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George Henderson said...

Here's the Roy Taylor vid sorry; rattling good stuff.

http://www.fend-lectures.org/index.php?menu=view&id=94

Nigel Kinbrum said...

@Melchior & George: When push comes to shove, if a health problem is caused by overloaded cells in liver and/or fat mass and/or muscle mass, to rectify the problem you have to deplete the overloaded cells one way or another.

A PSMF will achieve this the fastest (1g protein per lb bodyweight + just enough fat to stimulate gallbladder emptying + incidental carbs from non-starchy veggies).

Adding a bit of fat and/or carbs makes the diet easier to bear but slows the rate of depletion.

raphi said...

Hi Melchior Meijer,

In the anecdote you gave, do we have any data on how this persons insulin response changed (or didn't)?

Assuming it was OK before & still is now - then what took care of the added carbohydrate load? This is especially relevant to diabetics (obviously).

Thanks!

Melchior Meijer said...

Hi Raphi,

Before she started the RS intervention, she injected 55 units of Lantus (long acting insulin) once a day. Over the last half year she had to gradually decrease her bolus and is now on 43 units/day.

She tracks her ketones with a ketone meter (plasma) and has been in ketosis more or less constantly since she started very low carb some years ago. First she saw the expected (dramatic) glycaemic improvement, but, as I said, much to her frustration her blood glucoses and A1c's started creeping up after a while. Nothing worked to get a better grip on it, so she is over happy with this apparantly succesful hack.

My feeling is that she has a massively insulin resistant liver and that the ectopic fat which causes this is very stubborn. RS is converted in the colon to butyrate, acetate and propionate. These SCFA's induce enterocytic gluconeogenesis, which in some paradoxical turn puts a brake on hepatic glucose output. Don't ask me how this works, maybe Peter would like to elucidate us :-) .

She is still making some c-peptide (0,31 fasting). Let's assume that her liver and pancreas indeed contain too much fat and that this is indeed causal to her inability to achieve unassisted normoglycaemia. Will the 600 kcal/day Taylor approach be able to get this stubborn surplus moving (and if so, why didn't her very low carb regimen accomplish this)? Will this then be enough to spark more life into the remaining beta cells, as Taylor predicts?

If she persists we will have an answer in August...

Melchior Meijer said...

Rahi says: "then what took care of the added carbohydrate load?"

Sorry, I was not clear enough. The lady didn't consume extra (digestable) carbs, she only took/takes RS. RS doesn't give a glycaemic response.

Peter said...

Melchior, needless to say I am thinking about resistant starch, germ free animals, endotoxin and insulin resistance. Most information I've read appears to be at the very superficial level so far and that tells us very little about what is happening deep within metabolism...

Peter

Melchior Meijer said...

Peter, my rudimentary 'explanation' is that RS can shift an LPS-spewing and thus diabetogenic microbiome into a non or less toxic one. It's interesting that this woman became very ill prior to the onset of glycaemic improvement. She reported all the symptoms of sepsis and I'm afraid that my 'suggestion' almost killed her. After that episode (a battle between 'good' and 'bad' bacteria?) things started to move into he right direction.

If there is some truth to my speculation, we must conclude that very low carb is sometimes not enough to starve and replace a toxic/diabetogenic microbiome.

raphi said...

@Melchior Meijer,

Thanks for the additional info, that’s helpful. I misconstrued what you’d said about her RS experiment & somehow understood she also shifted to a higher-carb diet - my bad!

Absolutely, RS acts as a fiber & not as a digestible carbohydrate.

I share Peter’s skepticism. The KIND of information being presented is inadequate to support the KIND of claims being made. This is where it gets interesting! [as there are multiple plausible mechanisms of action but with contradictory observations]

A lot of the N=1’s floating around suggest that the way it’s so far being used is quite hit n’ miss (unsurprisingly); as it fits well with the picture we have of fibers, where some are preferred by certain bacteria over others. Furthermore, those same strains of bacteria appear to play different roles in different people (aka we’re correlating them to everything, nothing & all in-between). See Mr.Heisenbug's blog for an excellent analysis of the issue.

In the grand scheme of things it’s ‘safe’ & worth trying out (if one is so inclined). I am & have just received my shipment

Beware: ignore the straw-man argument claiming that the successful use of RS is indeed ‘proof’ of LC/VLC/Keto ‘starving’ your gut bugs. A diet in theory & in practice are not the same thing [e.g. evolutionary biology applied to nutrition isn't the same as the "Paleo movement"...]

Melchior Meijer said...

Hi Raphi,

I don't think Peter was referring to this particular case, but to the thin body of science on this matter, correct me if I'm wrong. I merely present her as an interesting anecdote.

I absolutely agree that we know extremely little. And I'm a huge fan of Heisenbug!

kellyt said...

Peter, Thanks for this blog.

I love this, "I like to have uncoupled mitochondria running with a relatively low delta psi, high oxygen consumption and low free radical leakage. On isolated occasions, a few times a week, my parsnip chips will spike my blood glucose and delta psi for an hour or so and generate a few extra superoxide/H2O2 molecules above basal levels. I hope that’s enough for generating a decent number of healthy mitochondria."

Brilliant, and it gives me so much to research. I'm thinking of memorizing that line to use next time I'm on a date and the subject turns to nutrition :)

psychohist said...

There are people who think multiple sclerosis would be exacerbated by low carb? Maybe they should read this thread, from a person whose MS was essentially put in remission by low carb paleo:

http://cavemanforum.com/progress-reports-photos/kyleen%27s-progress/

Getting rid of the carbs gets rid of a substantial contributor to inflammation, reducing susceptibility to MS and other autoimmune diseases.

E-S said...

@Peter:
"There is anecdote about coffee affecting gut integrity too but no hard data on this that I have been able to find."

Darn. I'm long term LC and recently started getting acidemia-related headaches and fatigue which, through thorough testing, I have determined are from hepatic inflammation caused by... the standard issue, machine-brewed coffee I used to get at work.

The idea that years of LC can slowly heal back the immune system to a point where it'll start getting successfully fooled by legume toxins is intriguing.

Galina L. said...

"hepatic inflammation caused by the standard issue, machine-brewed coffee " A lazy googling din't bring an immediate answer, so what is the danger of drinking a machine-brewed coffee coffee(it is what my husband drinks at work), and how you managed to trace a hepatic inflammation to that?

E-S said...

I did a systematic exclusion roundabout. Quite a few surprising things can cause me headaches. At one point last year it was lemon juice. I've had metabolic acidosis and hepatic inflammation before, so those are issues I could identify. Also I know my mom has migraines at times and that those get worse with coffee, unlike with many people. So I included the coffee among the list of things to exclude - and the headaches started subsiding. I don't know why it's happening, I just follow the evidence.