Wednesday, October 03, 2012

Protons: Zero fat

A bit speculative here, read with caution!

How do we lower free fatty acids? Obviously, with nicotinic acid. What does this do to insulin secretion in response to a glucose challenge? I'll just work through this figure from the same paper which gave us the insulinotropic effects of various FFAs a couple of posts ago.

Section A is very simple, it just shows that they succeeded in clamping glucose at just over 200mg/dl, about 12mmol/l, ie just in to supraphysiological levels.

Section B shows FFA levels, which they manipulated very carefully. All rats started at about 0.6mmol/l. Nicotinic acid lowered FFA levels to 0.1mmol/l. These are the black squares. Two other intervention groups were included. The white triangles had their lipolysis shut down using nicotinic acid but then had FFAs clamped back up again using a soyabean oil infusion (mostly omega 6 PUFA) and the black triangle group had an infusion of lard based lipids (a mix of lipids but with a significant palmitic acid content) to restore and hold FFAs at about 0.8mmol/l.

The nicotinic acid group, with FFAs of 0.1mmol/l, cannot secrete insulin in response to glucose. Flat line at the bottom of graph C.

The open squares are the control group. These rats show the normal response to an hyperglycaemic clamp. They reduce FFAs in response to the inhibition of lipolysis from secreted insulin, down to 0.2mmol/l. Insulin inhibits lipolysis. But the reduced FFAs also reduce insulin secretion. There is a balance struck with only a modest rise in insulin, sustained throughout the clamp. You can see this in section C, open squares.

The two lipid infused groups have clamped glucose and clamped FFAs. They secrete insulin in proportion to the amount of palmitate in the lipid infusion. A bit extra over control if you use low F:N ratio omega 6 PUFA, a ton extra when you include some palmitate. Section D is simply a summary of this.

Step by step at the mitochondrial level: The lower fatty acid supply results in decrease reduction of the CoQ couple in beta cells. This reduces the reverse electron transport and associated superoxide triggered by glucose as it feeds NADH in to complex I, so limits insulin secretion. You can virtually ablate the insulin response to glucose by eliminating beta cell fatty acid supply.

Now, nicotinic acid is one way of reducing FFAs. There have to be other, perhaps more physiological, methods. Maybe we could use insulin per se? From food perhaps? Let's try eating around 40g of carbohydrate and look at the Spanish study graph again. Insulin rises from 50pmol/l to 75pmol/l. This is enough to reduce FFAs from 0.5mmol/l to just over 0.1mmol/l. Look at the FFAs, especially the circles between 120 and 300 minutes:

Now (again, sorry!) look carefully at the insulin levels after the small carb load, bottom circles.

By 180 minutes insulin is actually lower than fasting, and FFAs are still well below fasting levels too. The rat model appears to hold in humans, not what the study was looking at, and a small effect. But I think the effect is real.

How about scaling this up to a massive dose of potato induced insulin and limiting dietary fat? Severely limiting dietary fat. And never mind pussy footing around at 40g of mixed carbs and protein. There is a limit to how low FFAs can be driven, and it seems safe to assume that a baked potato or three might just inhibit lipolysis maximally and keep it that low for rather a long time. But if you deprive beta cells of free fatty acids you blunt their ability to secrete insulin. Very, very high carbohydrate diets really ought to be able to inhibit lipolysis to the point where the knock on effect is the inhibition of insulin secretion, provided you don't supply exogenous fat. Look at the nicotinic acid treated rats...

Once you get FFA levels low enough to inhibit insulin secretion you will start to move in to the sort of territory where insulin secretion might be blunted enough to allow hyperglycaemia. But the feedback effect of reduced insulin levels is also the re commencement of lipolysis. This will restore enough FFAs to maintain functional insulin secretion and so avoid potential hyperglycaemia, which the body tries to avoid. Of course you have to throw in the increased insulin sensitivity of muscles deprived of exogenously supplied FFAs too.

So is it possible to eat an ad lib, calorie unrestricted diet based on near pure carbohydrate and lose weight? Working from the premise that lowered insulin is a pre requisite for hunger free weight loss, as I always do, the answer is possibly yes. We all remember Chris Voight on his all potato diet (plus 20ml of olive oil, low in palmitate, per day) who lost a great deal of weight over a few weeks, the rate of weight loss accelerating as the weeks progressed? I had a think about it here, well before I had any inkling as to what might be happening in the electron transport chain.

We need to know what the interaction of insulin and FFAs was during this particular n=1 self experiment, and we don't. The rats suggest to me that insulin levels were initially raised post prandially and FFAs were not then available from peripheral adipocytes. Assuming the fall in lipolysis persisted in to the post-absorptive period (the primary function of insulin, especially at low levels, is the inhibition of lipolysis rather than facilitation of glucose diffusion, we've all read Zierler and Rabinowitz) we have a method for limiting insulin secretion late post prandially using reduced free fatty acid levels.

As an aside I personally wonder it might be the ectopic lipid supplies typically found in muscle, liver and visceral adipocytes which might still be available for metabolism by the tissues when exogenous supplies are shut down.  It reminds me of how metformin most likely depletes ectopic lipid to improve insulin sensitivity, despite having complex I inhibition as its primary action. You need lipid from somewhere. So reducing FFA supply by inhibiting systemic lipolysis may well be a route to lower fasting insulin levels. Especially if you are not far in to metabolic syndrome.

Once ectopic lipid becomes depleted then lipolysis would accelerate in peripheral adipocytes as systemic insulin resistance falls and fasting insulin levels too, which might be what was reported as progressively increasing weight loss by Chris Voight. Insulin levels would be low, especially during fasting, and appetite low at the same time due to hypoinsulinaemia facilitated lipolysis, much as appetite is low under LC induced hypoinsulinaemic eating. There is more than one way to skin a.... Oops let's not complete that phrase!

What would happen to a healthy person under these conditions, long term, is anyone's guess. Chis Voight gave up after a few weeks when weight loss became alarmingly rapid. But we know from the crucial study by the vegan apologist Barnard that, for diabetic people at least, that a long term, whole food, low sucrose and low fat diet is a complete disaster, once the initial weight loss ceases.

This is playing with fire (possibly near literally, at the mitochondrial level) if you are a diabetic. Please don't go there.

But the physiology of weight loss on ultra low fat diets is basically comprehensible, especially once you look at lipids and superoxide at the ETC level, and what the body needs to function effectively. Running your metabolism on pure glucose would induce, theoretically, an infinite glucose sensitivity and low fasting insulin. If we do reductio ad absurdum you would end up with no fat stores and experience death from hypoglycaemia if you ever depleted your glycogen stores. Mitochondria like (saturated) fatty acids. Fatty acids keep them in control.

I think someone in obesity research used Chris Voight's experience to support some cock and bull story about food reward and a set point of body fat. We can wait for the recant on that one, if you could care less about it. The biochemistry is, as always, the fascinating stuff.



donny said...
The prolonged absorption of carbohydrate seen over time will maintain suppression of the free fatty acids (FFA) and the counterregulatory responses, while at the same time achieving lower blood glucose concentrations (Figure 1⇓). Over time, with the reduction in FFA concentrations and the rise in the respiratory quotient with tissue insulinization, glucose is withdrawn from the circulation at a faster rate. Consequently, blood glucose concentrations return toward baseline despite continued glucose absorption from the small intestine. The rise in peak postprandial blood glucose is therefore reduced together with the incremental blood glucose are above baseline. Studies in healthy men have shown this effect after a glucose solution was sipped at an even rate over 180m in a supposed to being consumed as a bolus at zero time(26).A marked economy in insulin secretion with sipping the glucose solution was also seen(Figure 2⇓),together with improved glucose clearance(KG) for intravenous glucose at 4 h. This was coincident with the lower serum FFA concentrations compared with those after the bolus intravenous-glucose-tolerance test.

That's a David Jenkin's study. I think it really shows that the concept of glycemic index is a valid one--if you can just slow down glucose absorption enough, you'll get trivial insulin and glucose responses. Anyways, I've wondered for a while whether the effect of very slow glucose sipping over an extended period could be comparable to niacin in some of its effects.

karl said...

There is a known effect of niacin slightly raising fasting BG - this would support the idea of lowering insulin.


I think there are few bits about GI(glycemic index). IF we eat low GI carbs, there will be a rise in insulin all day long - locking the fat in the adipose tissue. We can only lose weight while in ketosis. I think the failure of low GI diets to preform as well as low-carb diets backs this up.

Also, carbs are addictive. they effect serotonin levels in the brain - down regulate the receptors with long term administration. Eating a low GI may be like having an alcoholic trying to drink just a little.

karl said...


You got me digging a bit - the FFA (free as in not bound up in trygly ) are elevated in the obese - I'm guessing these are what leaks out of adipose tissue once folks with T2D stop gaining? Do we know which FA is in play?

What I'm thinking about - normally the trygly are disassembled into FA to pass into and out of adipose tissue - and reassembled on the other side of the cell wall. What I don't know is if the type of FA gets changed in this process?

And if the bit where the FA is going into or out of trygly is where the FFA come from?

My understanding is there is a constant flux both in and out of fat-cells. The tilt of the flux would be controlled by insulin and a couple of other factors.;jsessionid=W2PWswEUsbClkTXTIu07.2

I'm not finding anything to show which FA is involved with fructose consumption.

Puddleg said...

@ Karl, this should help answer the "which FA" question.

I wouldn't expect fructose FA to be very different from glucose.

karl said...

@George Henderson said:

"I wouldn't expect fructose FA to be very different from glucose."

Fatty acid synthesis is not the same for fructose as it is for glucose via the liver.

The diagram on you can see there is a different pathway in the liver ( vs muscles) for fructose

Further on there is this:

"Carbons from dietary fructose are found in both the FFA and glycerol moieties of plasma TG. Excess dietary fructose can be converted to pyruvate, enter the Krebs cycle and emerges as citrate directed toward free fatty acid synthesis in the cytosol of hepatocytes. The DHAP formed during fructolysis can also be converted to glycerol and then glycerol 3-phosphate for TG synthesis. Thus, fructose can provide trioses for both the glycerol 3-phosphate backbone, as well as the free fatty acids in TG synthesis. Indeed, fructose may provide the bulk of the carbohydrate directed toward de novo TG synthesis in humans"

If this quote from wikapiedia is correct, then not only does fructose spike trygly - it increases citrate that has a different pathway into FA.

What I would like to see is a control of glucose vs sucrose (1/2 fructose ) and look at the type(s) of FA in trygly and FFA over time.

Anonymous said...

Excess carbohydrates in the body are converted to palmitic acid. Palmitic acid is the first fatty acid produced during fatty acid synthesis and the precursor to longer fatty acids. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC), which is responsible for converting acetyl-CoA to malonyl-CoA, which in turn is used to add to the growing acyl chain, thus preventing further palmitate generation.[8]

karl said...

First - I've been saying something that is wrong - fructose is a 6 carbon sugar not a 5 carbon sugar, but fructose forms a 5 carbon ring vs glucose forming a 6 carbon ring.

(see start at 18:20 - then skip to 45 up to 1:10 This is one of the few bits of video on this worth the time of watching)

Here is a bit I think comes from Lustig:

100% of fructose broken down by liver and turned into VLDL, FFA and triglycerides

Alcohol? 80% to liver (30 cal for VLDL), 10% to body and 10% to brain

Glucose? 20% broken down by liver and rest immediately used by body

Fructose is most lipophilic carb. Fructose> glycerol (g-3-p) > triglycerides (fat)
120 calories of fructose? 40 calories stored as fat vs. 1 cal for glucose
FFA stored as fat in liver and skeletal muscles causing insulin resistance
Glucose suppresses ghrelin and increases leptin through insulin. Fructose does NOT do this as no
insulin released.
Fructose metabolism makes waste products including uric acid > increased BP/gout "

So if this is correct then fructose besides spiking trygly increases FFA.

According to
Fructose, weight gain, and the insulin resistance syndrome

"Fructose carbon enters the glycolytic pathway at the triose phosphate level (dihydroxyacetone phosphate and glyceraldehyde-3-phosphate). Thus, fructose bypasses the major control point by which glucose carbon enters glycolysis (phosphofructokinase; EC, where glucose metabolism is limited by feedback inhibition by citrate and ATP..... (and) ....
Infusing small amounts of fructose intraportally in dogs appears to have a catalytic action that increases hepatic glucose uptake (24), an effect likely to be mediated by hepatic glucokinase. More recently, a low-dose infusion of fructose has been shown to increase carbon flux through glycogen synthase...."

So I'm wondering if it is the FFA production from fructose?

Puddleg said...

@ Karl, so the FAs are the same but because fructose, if available, is preferred for glycerol, glucose is the preferred source for palmitate and palmitoleate?

mommymd said...

I need a diagram or flow chart to follow what you are saying. Can anyone help me out?

donny said...

Karl--I don't always get around to saying everything I mean to say. I don't think all that gunk about complex carbohydrates, slow carbs, slowing down carbs with fat, vinegar, sourdough bread etc. is at all practical--if you can slow down sugar absorption to 50 grams over a three and a half hour period, and have all those carbs come in at a steady, controlled rate as they would if sipping glucose over that time, sure. That just won't happen if you eat digestible carbs in any significant amount.

I have wondered with the Jenkins study--insulin ends low with sipping, as does glucose, as do free fatty acids. Is this like slowly heating up the water to boil a frog? with the more intense spike of glucose and insulin, you end up with a postprandial rebound--free fatty acids go up, inducing insulin resistance, around here, do we consider this bad? Maybe only if you plan to have another soda pop.

Jeremiah Dubie said...

Peter. I have to commend you on this excellent series of posts. I've had to go re-learn a lot of biochemistry including the electron transport chain and all that entails. Your insight is brilliant, and I'm gaining a better understanding of the whole interaction among fatty acids, insulin, glucose, etc., and various mechanisms after every post. Very empowering. Thank you Peter!

karl said...

A bit more digging --

I think what happens with sucrose - BG goes up while the fructose increases trygly production in the liver to the point that it actually helps control BG? ( not sure I understand why ).

There is also some FFA produced by the liver from fructose containing sugars. I'm guessing that small amounts of fructose don't matter much, but large amounts end up backing the liver up and triggering the production of FFA ( I would suspect palmitic acid). The combination of palmitic acid and elevated BG is a bad thing.

Sort of a binary toxin - you need both glucose and fructose.

My hunch is that the dose makes the poison applies - at some amount (that varies between people ) the liver backs up and the production of FFA kills cells - which would trigger inflammation responses .. bad things happening.

I'm betting that the niacin Petro is talking about may help with CAD in part by blocking FFA production.

I'm also speculating that putting the palmitic acid into trigly protects us from the effects of the palmitic acid - at least to some degree.

I don't know is if there are also important amounts of circulating FFA produced or removed when trygly are disassembled and reassembled in adipose tissue for cell wall transport?

blogblog said...

A large bolus of complex carbohydrate does not cause continuous elevated insulin levels. It typically causes a modest spike lasting a couple of hours.

After a large meal the food typically spends around 1-2 hours in the small intestine. It then moves to the colon. Any unabsorbed carbohyhdrate in the meal is then fermented in the colon. That is why starcy vegetables, cruciferous vegetables and peanuts make you fart.

In societies where very large amounts of complex carbohydrates (but no simple sugars) are eaten diabetes and obesity are very rare.

blogblog said...

The Irish traditionally ate up to 4kg of potatoes per day containing 800g of starch. The potato fed Irish were also renowned throughout Europe for their excellent health and good looks.

karl said...

@ blogblog

I'm not saying low GI makes insulin go up like sugar does - it only has to go up enough to keep the fat from leaving the the adipose tissue.

One has to enter or at least get close to ketosis to lose weight - this happens during the fast imposed by sleeping (when people wake up in the morning they are normally in ketosis).

If one eats low-carb, the amount of time in ketosis is extended to daytime hours. Conversely, if one eats low GI ketosis is only the time just before 'breakfast' (and eat enough complex carbs before bedtime and night time ketosis is reduced.)

My hunch is that it takes some amount of time exposed to overconsumption of sucrose or HFCS to do the damage that I think causes T2D. Once the damage causes T2D, complex carbs will raise BG to the point that fats become toxic.

Someone that doesn't have T2D may be able to eat some amount of complex carbs with out BG going above 110 ( like my 89 year old father ) - there are others (like myself) that have damaged systems (T2D) and even 30G of complex carbs will spike BG to 165 where fats become toxic. From what I know so far, this damage appears rather permanent.

My take is that people with T2D that try to lose weight via low-GI fail for the most part. It raises the area under the curve for insulin enough that there is no net exit of fat from adipose tissue. Furthermore, I think it reignites the addiction to carbs so they end up failing.

blogblog said...

you can essentially eat as much carbohydrate [in the form of fruit and vegetables] as you want if you fast 16-24 hours a day and are moderately active. This is what HGs and traditional peoples do.

The Western idea of eating regular meals every couple of hours only began around 200 years ago. This coincided with the rise of heavy labouring jobs in factories. Factory workers needed to eat regularly because they were using a huge amount of energy.

Westerners still eat as though we are doing heavy labour. We eat regularly whether we are hungry or not.

If you eat only between 4-8pm you won't have a problem with unrefined fruit and vegetable carbohydrates.

blogblog said...


I find it very hard to accept that the damage is irreversible.

Dietitian (now Professor) Kerin O'Dea normalised the metabolism of 10 diabetic aborigines in a mere seven weeks. She did this simply by returning them to a traditional lifestyle.

O'Dea K: Marked improvement in carbohydrate and lipid metabolism in diabetic Australian aborigines after temporary reversion to traditional lifestyle. Diabetes 1984, 33: 596-603.

Jane said...

I think you're right. If your pancreas is in such bad shape it can't be repaired at all, you're probably dead. Karl needs to concentrate on getting his beta cells repaired. They will do it automatically if he does what you do: fasting, exercise and no nutrient-depleted food.

Jane said...

Should have mentioned, I fast for only 10 hours, not 23 as you do and it seems to work. Big breakfast, nothing except water until 7pm. It makes me high, actually. I'm not sure how. I suspect it's because everything is constantly repairing itself, including my brain.

karl said...


(I read that study in the past )
Yes, you can reverse the symptoms if you stop the carbs - No - youthful BG control in spite of eating carbs does not come back.

One the system is damaged carbohydrate restriction is needed apparently life-long.

I think that the insulin resistance gets reversed to a degree due to weight loss, liver recovers but, there is still damage that does not get repaired.

Perhaps some day via stem-cells?

re: fasting
Fasting reduces the area under the curve of the insulin level - as does avoiding sugar and only eating once a day, BUT if one eats low-GI foods as in complex carbs, several times a day - insulin is elevated most of the day.

I don't think we have evolved to eat grasses (wheat, soy, corn ) - non of this food existed for early man.

Paleontology is hardly an exact science, but there is some evidence that meat eating tribes vs farming tribes had stronger bones. Our teeth rot from eating grains - unlike bovines. Just not food we evolved to eat. There are some carbs in leafy green vegetables - but very little.

My hunch is early man ate meat, fish, eggs (perhaps a lot of eggs), insects, (wild fruits when in season) and when starving ate roots, and plants. ( early many was probably starving a lot of the time!) He also probably was infected with intestinal parasites.

Non of the vegetables you find at the grocery store are natural foods - they have untested pesticides bred into them, selected for increased shelf-life(devoid of nutrients that bacteria like and we need), selected for sweetness and carbohydrate content.

Puddleg said...

It's just as probable that farming peoples were healthier than HG - until they started eating grains.
There is nothing about horticulure or pastoralism that's obviously inferior to HG ways; it's just a more reliable source of the same food - until cereals enter the picture. (Nicely for paleo propaganda purposes, sugar cane is a grass related to rice and corn).

Puddleg said...

Anyone here read "An Epidemic of Absence"? Sept 2012,
A grand introduction to the history of, and latest results from, the hygiene/ "old friends" hypothesis.
Complicated and nuanced enough to be credible. The man understands his subject. It's the GCBC of microbes. I give it 5 stars.

Jane said...

' can reverse the symptoms if you stop the carbs...yourthful BG control in spite of eating carbs does not come back...carbohydrate restriction is apparently needed life-long...there is still damage that does not get repaired...'

If your beta cells are not repairing themselves as they should it's because your diet is too high in iron (look up 'diabetes iron') and too low in other micronutrients. If you have evidence against this idea, let's see it. You are right to blame carbs, but only refined carbs which have had things removed that your gut bacteria need and that your own repair processes need.

Jane said...

'...It's just as probable that farming peoples were healthier than HG - until they started eating grains. ..'

I expect you are thinking of the iron deficiency early farmers are supposed to have had as a result of eating grains. This idea was very popular for many years and has now been disproved.
'The causes of porotic hyperostosis and cribra orbitalia: a reappraisal of the iron-deficiency-anemia hypothesis'

James said...

Ive been following the principles of the optimal diet (more or less) for about a year now. I recently had my blood work done and cholesterol fell into what my doctor said was "fairly" healthy. This of course means that im at an elevated risk for heart disease and all the other things that come from low cholesterol!
Ive read that a compound in unfiltered coffee (see here) may increase cholesterol levels. I read this is as implying better memory levels and better overall health. A side effect it notes is elevated triglycerides. Whats the deal with triglycerides?! If they go up from drinking unfiltered coffee, should i worry? Anyone's input would be helpful.


James said...

The link to the cafestol/coffee paper didnt work, so here it is:

FrankG said...

I think it is a mistake to assume that all damage is reversible... yes some can make dramatic improvements -- even complete reversal -- by changing diet (as in the Australian Aboriginals example) but we should be careful not to generalise from that.

Consider skin held close to a flame... at a far enough distance and/or after only a short time, this can lead to a slight redness that fades in minutes... hold it there longer and/or closer and you can get blistering which may take several days to heal... closer still and/or for even longer and we can end up with burns that can only be patched with scar tissue -- the skin will never be as good as new again.

Speaking from experience, as a person with Type 2 Diabetes (Metabolic Syndrome): despite a significant change in diet four years ago, dramatic weight loss and, by every measure, greatly improved health, I am not "cured" nor do I ever expect to be so.

FrankG said...
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FrankG said...

For something that has been "disproven" it seems that not all researchers agree :-)

Earliest Porotic Hyperostosis on a 1.5-Million-Year-Old Hominin, Olduvai Gorge, Tanzania

Melodie said...

I always love your posts. I haven't been around your blog for quite some time---but I've decided to come back to visit.

I wonder about the body composition of Chris Voigt while he was doing his experiment. I agree with you that one can certainly lose weight with a strictly carb based diet...but to me I consider it more like 'wasting' away rather than 'losing fat'. I have a friend who is suffering this at the moment. After many years of thinking he was healthy by eating lots of grains and legumes he is now suffering from lack of sub q. fat, and he's feeling it now. His musculature is still quite good, but I am afraid that if he doesn't start eating more fat/protein then he will begin to lose that too. Luckily he's not dogmatic so he has asked me for 'help' in advising him what to eat.

After much time spent over at Jack Kruse's blog I've finally found the perfect 'diet' for me. :-D For me, paleo does not make sense in the way it is promoted. I now eat seafood every single day. It is one of the best things to have happened to me. Of course it had to start somewhere, so I'm glad for the journey along the way.

I'm curious Peter, how often do you eat fish/seafood? What's your take on food from the sea? From the readings I've done, it really does seem that many of the paradoxes we encounter whether it's from fat or carbohydrate side seem to be cancelled if fish is considered. That's always a good sign for me.

karl said...


Re: Reversibility of damage

We are on the same page - if someone has a paper that shows a cure of sever T2D - a renewed ability to control postprandial BG in a youthful manner - please send a link.

RE: Earliest Porotic Hyperostosis on a 1.5-Million-Year-Old Hominin, Olduvai Gorge, Tanzania

I also saw this paper the other day. I think the case for humans eating meat is pretty obvious. Humans can live quite well on a pure meat diets - very difficult on pure plant diets available to paleo man.

James said...

I have a follow up to my previous question.

Ive been reading about how the density of LDL and HDL cholesterol can vary. In one post, Peter notes that whats probably more important is lowering glycated haemoglobin levels (by lowering fructose) and letting the liver figure out which way is its preferred method of getting cholesterol to the body's cells. Does this mean that after lowering carbs almost to zilch, as ive done, that further adjusting cholesterol (throug the above method) is pointless? Or do cholesterol ratios still matter? Again, thank you for any insigt. This blog is a great service to humanity!

blogblog said...


you are being rediculous. No one claims that any HGs were strict vegetarians.

No purely carnivorous human society has ever been discovered. Contrary to "paleo" mythology traditional Masai and Inuits made extensive use of available plant foods.

There are no purely carnivorous mammals. Even polar bears and domestic cats eat some plant matter. Polar bears are actually omnivores by choice and will very readily consume fruit and vegtables if they are available.

Stipetic said...

Contrary to "paleo" mythology traditional Masai and Inuits made extensive use of available plant foods.

This is plain silly, blogblog. Neither made/make "extensive" use of available plant matter. I spent three weeks with the Masai in the 90's and the tribe I stayed with made little use of plant matter (quantitatively).

As to the Inuits, there were(are) groups that lived so far north in the Canadian tundra they never saw anything but snow and ice year round. So, I'm unsure where they would get the extensive array of plant foods you claim. Maybe they are so genetically unique they developed the ability to digest cellulose. Who knows, maybe the Hudson Bay Company had some bananas sent up way back when...

Regardless, it seems that if an Inuit flossed his teeth with seaweed, by your definition, he wouldn't be "purely" carnivorous. Semantics aside, I think you would agree that if adjectives were not available to the Inuit they would consider themselves carnivores (actually, they'd likely consider themselves obligate carnivores).

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Jane said...

The paper I linked says this.

'Porosities in the outer table of the cranial vault (porotic hyperostosis) and orbital roof (cribra orbitalia) are among the most frequent pathological lesions seen in ancient human skeletal collections. Since the 1950s, chronic iron-deficiency anemia has been widely accepted as the probable cause of both conditions. ...This iron-deficiency-anemia hypothesis is inconsistent with recent hematological research that shows iron deficiency per se cannot sustain the massive red blood cell production that causes the marrow expansion responsible for these lesions. ..'

The paper you linked says the following.

'...The child's parietal fragments, excavated from 1.5-million-year-old sediments, show porotic hyperostosis, a pathology associated with anemia...Our results suggest...a hominin mother's meat-deficient diet negatively altered the nutritional content of her breast milk to the extent that her nursing child ultimately died from malnourishment. ..'

No, they don't.

DLS said...
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DLS said...
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DLS said...

hi guys,34 today. still doing tons of sucrose, milk, yolks, cheeses, meat, + dif. stats and health the same, as in not dead yet, doing # feeling great. cheers

btw, it seems in Malaysia people are lean eating like shit. what gives...

lol bloger, btw lazy as fk, sleeping a lot +hi fat diet, so no Malaysian workout- diet over here...

karl said...


We didn't evolve LDL to cause heart disease. As it is in much of biology, LDL has more than one role - one of those roles is to kill bacteria.

A correlation with CAD does not show causation - if CAD is a immunological disease - which I think it is - LDL may increase from the immune response. Thus it could be that LDL is a result rather than a cause of CAD.

oxLDL is better correlated with CAD than LDL - and is what gets taken up in the artery walls - the change of LDL => oxLDL appears to be a function of BG and interleukins among other things.

My take is the obsessive focus on LDL, HDL,trygl is misplaced - they probably should be looking at postprandial BG, oxLDL, interleukins (at least IL6 and IL8 ) and trying drugs that modulate immune response.

It should be noted that statins - besides their effects on LDL have about 10 other effects - which are involved in immune reaction. Lowering LDL may simply be a side effect.

There are several dietary things people can do to reduce inflammation, long chain O-3 - avoiding O-6 - keeping postprandial BG below 110 ( means eating low-carb ) avoiding fructose.

There are some drugs that modulate interleukins - some antidepressants, low dose Ketamine, Montelukast (

and )

There is ongoing research into this - IMO they will look back at the cholesterol theory of CAD similar to how we

think of attaching leaches today. The different types of LDL appear to be a function of carbohydrates in the diet - again the association is confounded with BG. I don't think the arrow of causation has been shown.

If you have a bad pattern of LDL - the only treatment I know of is nitric acid and low carb diets. Do you need to run these expensive tests to convince yourself to avoid sugar and keep your BG down?

I don't run cholesterol tests all the time anymore as it wouldn't change the interventions that I'm doing.

blogblog said...

Masai plant foods.

Phytochemicals as Evolutionary Mediators of Human Nutritional Physiology, Int J Pharmacognosy 1996, 34:5:327-34.

Inuit plant foods.

Traditional Plant Foods of Canadian Indigenous Peoples:
Nutrition, Botany and Use.

Unfortunately "paleo" nutrition is mostly based on myths and unsubstantiated dogma. The inconvenient facts are that traditional Masai and Inuits were neither pure carnivores nor exceptionally healthy.

blogblog said...


the common factor in healthy populations is controlled energy intake and physical activity. The macronutrient ratio is essentially irrelevant. You can be very healthy on a diet of 80% carbohydrate.

FrankG said...

Right... "the common factor in healthy populations is controlled energy intake and physical activity." So that explains why: when watching documentaries of newly discovered tribes in the Amazon basin, their fitted-kitchens are replete with weighing scales and calorie charts. And that they don't seem to spend inordinate amounts of time sitting around the camp, or lying in hammocks enjoying each others' company.

I also noted how on nature shows the lionesses are always on at the males to cut back on their massive portions... in between 16 hour naps of course! LOL

But hey... what could I possibly know in the face of Jane and blogblog's authoritative pontifications about what is and isn't true... in all humility of course :-)

James said...


Thanks for your response.

Ive been reading Chris Masterjohn's site a lately and was surprised to hear that cholesterol is the rate limiting factor in dendritic growth in the brain.

If this is true than it seems to me that one naturally wants higher blood cholesterol levels, so as to increase supply to the brain and other organs that need it, but to minimize the instances in which blood cholesterol becomes atherosclerotic (ie when it runs in with an oxygen atom on fructose or glucose).

Like I said i eat low carb so i know im limiting the amount of oxLdl, but just wondering whether my genetics are such that blood cholesterol is remaining low despite the low carb.


DLS said...

search Kathleen McManners and see what she is eating... lol petro owned! j/K

karl said...

@blogblog said:

"You can be very healthy on a diet of 80% carbohydrate."

Perhaps you don't get it - over 40% of the general population now has T2D that is caused by something - my number one suspect is fructose.

Once the damage is done one can not be healthy eating carbs. (Show me a paper that demonstrates a long term cure ). I suspect only a portion of the population that does not consume toxic amounts of sugar can tolerate a 80% carb diet. ( There is some epistemological data linking rice consumption with T2D (rice has no fructose - just carbs))

I once was eating low fat - high carbs - I was always hungry - constantly thinking about food. My fingernails got ripples - I was not healthy - I got heart disease and probably did further serious long term damage.

Eating low-carb on the other hand - I eat once or twice a day, I keep the weight off easily, Interluekins, crp, tnf all show lower inflammation than when eating carbs.

There have been countless studies trying to get people losing weight by exercise - there is not any long term success.

The evidence from quality papers just does not support your positions.

city said...

thanks for posting..

city said...

thanks for posting..

blogblog said...
This comment has been removed by the author.
Stipetic said...

Blogblog, neither of these documents demonstrate that the Maasai and/or Inuit made extensive use of plant foods. Quite the contrary, actually.

You don't seem to understand that both the Maasai and Inuit are composed of heterogeneous populations of tribes/groups with unique eating patterns to each. The Maasai of Kenya are not the same as the Maasai of Tanzania. Even different tribes in close proximity aren't the same. Same with the Inuit. The Inuit of Greenland are not the same as the Inuit of the Yukon or the Inuit of Baffin Island, etc. A generalized statement about either probably gives you an idea of what the population median/mean was eating. It says nothing about the range of eating habits of each tribe/group.

As a Canadian, I'm familiar with the seasons and the history of the indigenous populations (I have Montagnais roots). As previously stated, there are groups of Inuit who lived in a land of constant permafrost, so they never saw plant food, even in the summer; even during their migrations. These populations were at one time fully carnivorous. This is not even debatable. Go see any website from indigenous people.

So, blanket statements may make your case, but it isn't the whole truth.

You might enjoy the Canadian movie My Big Fat Diet--Dr. Wortman put an entire village back on something approaching their traditional diet; high in animal fat--and saw massive improvements in all health markers (especially obesity and diabetes).

Anyway, we are getting off topic. I shall stop.

Scott Russell said...

I wouldn't be concerned with the blood cholesterol number if you are otherwise eating a healthy diet, and don't have any underlying pathology. Most cells produce their own cholesterol. Blood cholesterol is not necessarily an indication of an abundance or lack of cholesterol in the body. Simply increasing blood cholesterol will not necessarily improve dendric growth, nor will decreasing it reduce dendric growth.

There are simply too many factors that affect cholesterol. I would say, simply give your body everything it needs, and it will regulate accordingly. Monitoring the number will not be very informative if you are otherwise healthy. If you have FH or something like that, then the rules change a bit.

Although low-carb seems to be the easier approach overall, blogblog is right that high carb diets can be perfectly healthy. Admittedly, whether or not this is an option for former T2D will depend on the extent of pancreatic cell death. But I think blogblog's point was that, in an environment where energy input matches expenditure, a high carb diet (of real foods) will be perfectly healthy.

karl said...

@cedCoffees said :
"blogblog is right that high carb diets can be perfectly healthy"

Pretty much totally agree - IF the high carb diet is not a high-fructose diet AND IF there is no T2D.

There is some epidemiological evidence (AKA very poor evidence ) of an increase of T2D in rice eating populations - I don't get to excited - it is not unusual to see rice with added sugar today and sugar consumption is increasing just about everywhere.

The trillion dollar question remains - What is causing the T2D epidemic? My prime suspect is fructose - but perhaps it has a cofactor? or something else is confounding the situation? So many things have changed at the same time that epidemiological evidence is useless.

blogblog said...

The evidence against fructose is extremely weak.

From an evolutionary point of view it is extremely implausible that fructose and sucrose would be uniquely problematic. We evolved from frugivores and have been eating vast amounts of the stuff for tens of millions of years.

Kindke said...

There is this report suggesting that small doses of fructose may actually be beneficial to glycemic control, most likely because fructose activates glucokinase ( very important! ).

So, it might be worth having a few teaspoons of honey before you eat your potato's.

Kindke said...

BTW I have my suspicions about Chris Voigt, given that there are many vegans out there following following ultra low fat diets but actually manage to gain weight. Unless you want to say that the fructose complicates this theory? And you need to consume or a diet of almost pure glucose molecules ( potato ).

Jane said...

The cause of diabetes is damage, primarily to pancreatic beta cells. You need to consider what causes cell damage. All the evidence points to excess/deregulated iron, together with deficiencies of nutrients that would normally repair or prevent iron-dependent damage.

One of these nutrients is copper, which is needed for iron to get out of cells and for other aspects of iron regulation, which means that without enough copper, iron-dependent damage is all but unavoidable. The damage can be repaired unless you have destroyed every single one of your beta cells, which is very unlikely.

If your diet is high in meat, and low in phytate-containing foods which limit iron absorption, you probably have iron overload. Meat is very low in manganese, which may be even more important than copper in limiting iron-dependent damage.

I'm sorry I can't do more than make statements here. I know it doesn't sound very convincing. It never helps if I say things like 'I am a scientist and I have spent many years studying this'.

Scott Russell said...

I tend to like the idea of fructose as an epigenetic trigger for fat growth. Aka its a signal of abundance prior to winter, and therefore promotes overconsumption through leptin and insulin resistence. So its not necessarily bad, but long term consumption can be problematic. Although I'm unconvinced if it is fructose per se, or fructose refined and seperated from the minerals its normally packaged with.

I personally just think of t2d as the body's failure to get fatter. There are a couple major causes of this, but I don't know if there is a single causal agent

Funnily enough, I'd say fructose's upregulating glucokinase is one of the key problems.

My understanding of iron metabolism is that intestinal transfer of iron is highly regulated, so excess iron is excreted. Is there some reason this is not the case? Intestinal permeability?

John said...


I think the potato itself may contain enough fructose to activate glucokinase.

I have gained weight on a very low fat diet (small amounts of coconut oil), though it could've been glycogen+water (~175 to ~182). I was eating mostly sweet potatoes, rice, broth+gelatin. It was about 4000kcal per day.

That was from a usual high fat diet of about the same calories (protein was also higher; carbs were ~100g/day), to which I switched back for several reasons.

John said...


Do you think the meat itself is a problem, or does it become a problem due to iron plus ...? You often mention Cu; what if one just eats liver weekly? There are so many things that affect iron absorption as well as its future path. Maybe it is unreasonable to simply worry about how much one is consuming?

I personally have coffee/tea and dairy along with iron-rich foods, liver occasionally, and I donate blood every two months. My hemoglobin is always about the same.

blogblog said...

Hot off the presses:


Higher heme iron intake and increased body iron stores were significantly associated with a greater risk of T2DM. Dietary total iron, non-heme iron, or supplemental iron intakes were not significantly associated with T2DM risk.

Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis

BMC Medicine 2012, 10:119 doi:10.1186/1741-7015-10-119
Published: 10 October 2012

Jane said...

Yes iron absorption is regulated, and a high-iron diet will downregulate iron transporters so less is absorbed. But these transporters are also used by manganese. This may not be a problem in the short term, because if you absorb less manganese you will excrete less, but in the long term it might be. Manganese is excreted in the bile, but there is no similar mechanism for iron excretion, and iron loading has been found to increase with age and to correlate with damage in many diseases.

Manganese does two really important things. It prevents damage to mitochondria, and it activates key enzymes in maintenance and repair pathways.

Jane said...

Hi john
I'm not sure whether meat itself is a problem. Obviously it wasn't a problem for the Inuit, but they ate the whole animal, and the animals were wild.

I'm also not sure whether eating liver once a week will solve the copper problem. Liver is very high in iron. For myself, I would rather rely on grains and nuts for my copper, especially since they are high in manganese as well, but it may be that your strategy is better. I just don't know. All I have to go on is my health, which is excellent after 30 years on a low-meat high-grain high-dairy diet.

blogblog said...

Gut parasites will prevent excess iron accumulation. Virtually all HGs had gut parasites.

Anya said...

This seems to fit in perfectly with my latest dietary experiment : slow drip xylitol.

Xylitol is very slowly absorbed and is capable of adjusting glucose metabolism abnormity. Even without insulin, xylitol is capable of penetrating cell membrane as usual to supply cells with nutrition and energy, thus playing the role of glucose and insulin. Xylitol is capable of lowering fatty acid production in plasma, without increasing blood glucose.
It is the perfect anti-ketone.

I can report back after/during the experiments if you whish.

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

Re: inuit iron levels:

Nutr Rev. 2008 May;66(5):256-71.
The paradox of anemia with high meat intake: a review of the multifactorial etiology of anemia in the Inuit of North America.
Jamieson JA, Kuhnlein HV.


Anemia is a serious concern among indigenous populations in North America, and it appears to be widespread among the Inuit despite abundant intakes of heme iron. It is therefore hypothesized that anemia for the Inuit involves other dietary factors not usually associated with animal foods, such as low intakes of vitamin A and/or folate, riboflavin, and vitamin C. Also, Helicobacter pylori infection and/or parasitosis may result in gastrointestinal blood loss and/or functional iron deficiency. This review aims to describe factors that may cause anemia in Inuit populations despite high meat intakes, abundant bioavailable iron, and other important hematological nutrients.

Jane said...

Very interesting paper. I wonder why it doesn't mention Mg or Mn. Anemia in China (Jiangsu province) is reported to be associated with deficiency of Mg (and not of Fe), and Mn deficiency is supposed to cause anemia although I've never seen data on this.

Mn deficiency is very likely in these people because meat is very low in Mn and so are the refined foods they now eat. Any thoughts?

karl said...


I don't think you get it - fructose can lower glucose because it inspires the liver to pump out tyrgly (some made from glucose) and the liver even starts to leak FFA into circulation.

Small dosages of fructose - like one would get in berries are not what I'm talking about - large dosages - from sugar drinks plus what is added to just about all processed foods today add up to back up the liver.

@blobblog - who said "The evidence against fructose is extremely weak."

I would have to ignore a large body of data going back to the 1960's to agree with you.

My hunch is fructose is toxic only at some critical high dosage. My prime suspect is that the liver reacts by pumping out trygly to speed the reduction of circulating fructose ( circulating fructose is much more damaging than glucose ) - once the liver can no longer keep up - it backs up and spills FFA and kills cells if BG is high (from drinking that 64oz sucrose drink ). My hunch is it initiates an auto immune response that produces T2D.

Dr Lustig is somewhat caviler to some details, but his explanation of what goes on in the liver from eating fructose appears correct. (I disagree with him in that I do not want the government deciding what foods I can buy! )

The effect of fructose on Trygly was discovered by 1970 - there was an earlier paper in 1964 that I can't find a copy - (look up WINITZ M papers).

Fructose just isn't glucose - and causes the liver to do things that it just doesn't do with type of foods we evolved to eat.

There was a claim (but I can't find what it is based on ) that elevated trygly interferes with leptin increasing appetite.

An informal observation I've made is noting the types foods in the cart of obese people ahead of me in line at the grocery store. It is almost without fail that the cart contains sugar foods (sucrose & HFCS ) and carb foods (chips, breads, pasta ). This combination would create circulating FFA and elevated BG - just the combination Petro's blog was about last time.

Puddleg said...

The Algonquin word "eskimo" translates as "meat eater".
The Algonquin themselves were highly carnivorous, but they were impressed by the Inuit diet.

Peter, I'm fascinated by this action of niacin. Niacin acts on ketone body receptors. What message does it convey?
Ketones high = no sugar = start burning fat and resisting insulin?

Puddleg said...

It's easier for cell signalling to respond to a positive input (high ketones) than the very negative (low sugar) it's trying to avoid. So ketones, produced by the liver as sugar and insulin drop, becomes the signal to conserve sugar by burning fat, which niacin mimics.

blogblog said...

virtually all the research that shows fructose is harmful is based on mouse studies. Mice are grain eaters that have evolved to live on (grain-based) high starch diets . Starch is a glucose polymer.

There is very litle evidence of fructose being dangerous to humans except in very large doses of free fructose administered to sedentary individuals.

I no longer bother reading the nonsense promoted by celebrity extremists like Robert Lustig. They simply select the sliver of evidence that supports their postion and ignore the much larger body of contradictory evidence.

karl said...

@blogblog said...
"virtually all the research that shows fructose is harmful is based on mouse studies."

This simply isn't true. I have quite a few links on fructose and humans at:,_Carbohydrates_and_Weight_Loss#Fructose

Once more - high fructose consumption tells your liver to pump out trygly - full of Palmitic acid.

I will say that the dosage makes the poison - but fructose obviously is not consumed naturally in the dosages we see today.

If you can realize that fructose tells the liver to pump out Palmitic acid and then look at the posts on SDC1 and POA as well and then you can see the connection with fructose.

karl said...

@blogblog said...
"virtually all the research that shows fructose is harmful is based on mouse studies."

This simply isn't true. I have quite a few links on fructose and humans at:,_Carbohydrates_and_Weight_Loss#Fructose

Once more - high fructose consumption tells your liver to pump out trygly - full of Palmitic acid.

I will say that the dosage makes the poison - but fructose obviously is not consumed naturally in the dosages we see today.

If you can realize that fructose tells the liver to pump out Palmitic acid and then look at the posts on SDC1 and POA as well and then you can see the connection with fructose.

Unknown said...

Peter this series is laying the 30 ft view of what I have been writing about for 18 months. Here is my 30,000 ft view from the brain where I see your series leading:

I think this example from a webinar I gave last night will be instructive here:
a point to make here on Cycloset for the ladies: Anti aging docs push optimal Testosterone, Vitamin D, PG/E2 and IGF1 to improve lean muscle mass and decrease body fat. The dopamine receptor (D2R) agonist bromocriptine (cycloset) also decreases body fat in animal and human models and increases lean muscle mass, improves glucose intolerance and insulin resistance, and reduces triglycerides and free fatty acids in the HPA. One of the cardinal features of environmental mismatches and altered epigenetic switches is a low dopamine level in the HPA. This results in an abnormal diurnal pattern of AM and PM cortisol and melatonin. It is often associated with a low vitamin D too. Low dopamine levels are seen in lower light levels and cause autumnal weight gain by the changes seen in the conversion of Vitamin D1 to D2 and to D3. Many people think dopamine is just tied to the reward of food when it is directly responsible for altered light cycles on the skin and at the eye in the SCN. This is how proper circadian signaling keeps our cells growth pattern normalized. This is also why obesity is considered the first step to cancer......step two is T2D, and the final step is cancer generation itself. They are symptoms of declining circadian signaling of dopamine in the brain. Poor sleep is always associated with altered dopamine, cortisol and melatonin cycle issues too. Poor diets also do the same but the effect is different on the brain because of the pathways involved. The worse your dopamine levels are, the more likely it is for you to develop and epithelial cancers too. Poor sleep is also associated with these cancers and a sluggish metabolism. Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women as well. Here is where the PCOS and T2D link enter.
Kok P et al. Am J Physiol Endocrinol Metab. 2006 November; 291(5):E1038-43.

Why do women have a bigger issue with all this than men? Because of the leptin-dopamine link. Leptin is sexually dimorphic and higher in women naturally. It has been previously shown in several papers that there is a negative correlation between D2R receptor and body weight in obese individuals and in rodents . . . . This has made me conclude that; these observations are all consistent with the existence of unique leptin-Dopamine interactions at the hypothalamus level and the hypothesis that there is hyposensitivity of the Dopamine system in obesity, PCOS,T2D, and in cancer. All of these conditions show low dopamine, upside down PG/E2 ratios, low Vitamin D levels, and very alter diurnal cortisol and melatonin levels. The ideal way to modify this in women is to treat the HPA deficit while teach them how to re establish their circadian signaling at the brain level to improve their metabolism.

That is a focus of this webinar for ladies; ie teaching them why they are different than men in regards to weight and circadian biology. For those who believe the reward theory of food let me give you a new perspective and a 30,000 ft view of what got lost in because of a myopic perspective. Reward is directly tied to light levels in humans and not food, because of what I wrote in the Brain Gut 11 blog.

48% of our metabolic pathways are tied to light sensation. Food does not drive reward. Light does, because the food that carries high reward only grows when light cycles are long therefore controlled by sunlight exposure.

Unknown said...

I know that sounds sounds counterintuitive to some, but it is precisely how the brain is wired in humans to couple food and light into our metabolism and sleep. The body collects that data from the eye (SCN) and skin for the brain and the brain senses and correlates that data to set the the metabolic rate and growth cycle by going up or down with dopamine levels at the HPA. Dopamine interacts with the leptin receptor and its pathways directly as mentioned above and this is why women and men are different at a central Nervous system level. This is why sleep, metabolism and the cell cycle are all linked to the dopamine pathways tied to light and not just food. Food reward is a good idea not looked into deep enough by those who buy it 100%. I love your series Peter. I feel like you are digging the same hole I am from different ends of the earth and soon we will meet. Our only difference is our perspective and our digging tools.

donny said...

My sister's dog would be a cake-a-vore by choice.

James said...

Thanks IcedCoffee for your reply!

blogblog said...

we evolved from fruit eating apes. From an evolutionary perspective there is no plausible reason why fructose, sucrose or other sugars in fruit or vegetables would be harmful. As an example wild chimpanzees get around 80% of their calories from fruit.

I respectfully suggest you consult an exercise physiology textbook.

Contrary to what you believe palmitic acid and triglycerides are ESSENTIAL metabolites. eg They provide ~60% of the energy for the heart at rest. High triglyceride levels are a MARKER of metabolic disease not the cause.

The real science surrounding sucrose and fructose is completely banal. It unequivocally doesn't support the hysterical claims of Lustig et al.

I suggest you read the following article by Professor Jenny Brand-Miller (one of the world's leading authorities on the nutrional role of carbohydrates).

The Australian Paradox

karl said...


Not everyone agrees:

Three points:
1- 16% is a big move - Why did it happen if it really did?

2- Not sure I believe it - The statistics may be bad.

3- If it did happen - people that already got T2D (supposing it is caused by fructose ) would continue to get fat.

blogblog said...


the problem is that paleo is a religion not evidence-based. The paleo faithful simply ignore all the facts that don't agree with their dogma.