Saturday, August 21, 2010

Thoughts on problems with high fat diets

Back comments section of the uric acid post _Flo passed on the news of the death, due to stomach cancer, of a prominent long term Optimal Diet follower. This is not the sort of in formation that should be ignored although, from an individual case, I doubt whether there is anything we will every actually find out about causation. The main thing it brings home forcefully is that none of us is immortal and a good diet will not allow us to automatically reach an advanced age. The OD and similar approaches brings marked improvement in many of the diseases of civilisation but clearly not all. For someone who has achieved remission from multiple sclerosis or ankylosing spondylitis it is depressing to accept that those same diet changes might not be cancer protective, or not completely so.

_Flo has made her own modifications to her diet which are sensible in their own right and represent her choices. As regards the type of cancer it quite interesting to note that Poland has one of the highest rates of stomach cancer in the world. This snippet was passed along by another friend on the net and is corroborated by pubmed. It does suggest that speculation based on the location/type of the tumour may not be representative a specific diet related factor, rather the result of living in Poland. Of course it might be diet related.

I have my own personal tweaks to the OD and do not see any clear way of improving what I have already achieved.

So let be set here in print. No one has all of the answers.

I thought I would take this chance to discuss the possibility that there are people for whom low carbohydrate eating might be genuinely problematic. I have picked up a couple of hints along these lines over the years, so here we go with some thoughts.

I discussed a secondary prevention trial for heart disease here. All of these people had glucose regulation problems (that's part of my definition of having a heart attack). Adding 500-600kcal of either corn or olive oil to a very low fat diet precipitated diabetes in two of these individuals. Why? That's a good question. Type two diabetes is intrinsically linked to insulin resistance. Normally people eating a bolus of fat will reduce the rest of their calorie intake to compensate. Anyone who didn't would have placed a significant carbohydrate load on top of fat induced insulin resistance (even vegetable oils induce this, although palmitic acid does a rather better job) and failed to deal with their relatively high carbohydrate intake. Pure speculation but a low fat diet, with 80ml of added vegetable oil, undoubtedly triggered 2 cases of type two diabetes. I found that interesting.

Second hint was Jenny Ruhl's comment that she had come across very, very occasional individuals with diabetes who responded to low carbohydrate eating by deterioration of glycaemic control. Again, I have no details what so ever but anyone's ears should prick up when they hear things like this. Denial is not where it's at.

Then Carb Sane introduced me to the Otsuka Long-Evans Tokushima Fatty strain (OLETF) of rats. These rats are a diabetologists dream. Under fixed isocaloric conditions they gain weight and fat mass in direct proportion to the percentage of fat in an exactly measured 28.7 joule daily ration. Like, wow. Fat really does make you fat!

Of course the OLETF rat is described as a Good Model for human type two diabetes. It explains exactly why all diabetics put on to a LC, high fat diet become obese and hyperglycaemiac. What do you mean, they don't? Oh, not enough testosterone! The OLETF rats only become diabetic if they are male. That's why all type two diabetics are blokes. What do you mean, women get type two diabetes? But out model says only blokes should. And it's a Good Model...

OK facetiousness aside, what is happening in the OLETF rats? Is it possible that there are some humans out there with OLEFT rat style type two diabetes. Well, why not?

Let's have a look at what is happening from the point of view that insulin is the primary hormone in the development of obesity. If you think about someone eating just once a day, essentially all of their calories are going to get stored. Glycogen in the liver and fat in the fat. What determines weight gain is how much of that stored energy fails to be extracted from storage before the next meal arrives.

Summary: No one stores lipids or glucose in their blood stream. It all goes in to short term storage. What comes out determines weight loss. Insulin determines what comes out.

OLETF rats, on high fat, fixed calorie diet of 28.7 joules per day put all of this energy in to storage but fail to extract as many of these calories/joules from storage as those OLETF rats on 28.7 joules of a high starch diet. What is going on?

If you accept the insulin hypothesis of weight gain, the answer is that dietary fat is being trapped in adipocytes by excessive blood insulin. There must be excess insulin.

Why is the insulin elevated when there is a reduced dietary stimulus for insulin production? These rats have peripheral, almost certainly muscle based, insulin resistance. But only on a high fat diet.

High fat diets put lipids in to muscles, muscles full of lipid don't accept glucose. If the system works correctly the muscles run on lipids until there is a balance between fat supply rejecting glucose and fat depletion allowing glucose acceptance. A few billion years is ample time to get this system working correctly to maintain normoglycaemia in the face of varied macronutrient intakes from day to day.

What might be broken in this system in the OLETF rat?

Well, if you can get lipids in to muscle cells but cannot then use that lipid for beta oxidation you would expect to develop muscle insulin resistance in proportion to the amount of fat you supply, ie if the fat enters the muscles but does not go any further those muscles will become insulin resistant and stay insulin resistant. If muscles are not accepting glucose because they are insulin resistant the glucose is going to have to be dealt with by increased levels of insulin. Hyperglycaemia is unacceptable.

The extra insulin needed to maintain normoglycaemia then traps stored dietary fat in adipocytes. The rats get fat because they cannot get fat out of adipocytes. They will also do less running around and will probably feel colder than normal rats because they have no access to their fatty tissue for energy supplies. If they had access to food they would eat more, but 28.7 joules per day was the limit in this experiment. If they had access to more calories they would clearly eat more because no one likes the hunger and shivering produced by sequestering a chunk of your caloric fat intake in your adipocytes and locking it in there with insulin.

Once your fat cells get full enough they will spill free fatty acids because they are now too full to listen to insulin any more. These FFAs join those intra cellular muscle tissue di and tri glycerides from the metabolic defect. Intra myocyte fatty acids still have no where to go, so muscle insulin resistance rockets, plasma glucose rockets and you have a superb model of fat induced obesity and peripheral insulin resistance.

Glucose enters mitochondria as pyruvate. Fatty acids enter mitochondria as acyl CoA moieties. The place to be looking for explanations for the syndrome seen in the OLETF rat is in fatty acid processing. My guess is that lipid molecules get in to myocytes but never get effectively passed to the mitochondria. Quite what testosterone has to do with this is beyond me, it's not me that is suggesting the OLETF rat is a good model for human type 2 diabetes!

You have to ask what would have happened on a ketogenic diet. Would ketosis have side stepped this problem? Ketone bodies enter mitochondria without any need for long chain fatty acid transporters. They use monocarboxylate transporters, just like pyruvate... You don't really think that Kaneko et al would so something as stupid as putting an OLETF rat on a ketogenic diet? But it would have been interesting. I'm not sure it would side step the problem but it might. I'm certainly not expecting a diabetologist to find out for me.

I really enjoyed the OLETF rat. Does it tell me something about type two diabetes? Only that there might be very, very special people who respond to dietary fat with hyperglycaemia.

I never did find any teeth in my chickens. I understand hen's teeth are rare. So are OLETF humans.

But they probably exist (not the hen's teeth!).



Jenny said...


The genetically modified rats are a very poor model for any form of human diabetes. We now have a long list of common human genes associated with human Type 2 diabetes.

NONE of these genes bear any relationship to the broken genes in any of the rodent models used in "diabetes" research.

Given that their blood sugar or IR comes from other causes than that of humans, and the significant metabolic differences between healthy rodents and primates and taking into consideration, too, that rodents have adapted to very different diets by evolution than humans, rodent research is mostly irrelevant.

Byond that, human Type 2 is NOT a single condition and even the insulin resistance common in people diagnosed with it varies hugely in its magnitude. In some it is a result mostly of maintaining high blood sugars. In others it is fundamental and not altered by diet.

Because Type 2 isn't one condition, there is no one cure, diet, or treatment for it.

Sadly, over the 12 years I've been online I have seen enough people who are strict low carbers die young from cancer (including the proprietor of Low Carb Friends) that I am starting to wonder about this myself.

OTOH, I know quite a few organic/low fat/supplement using/herb fanatics who died of cancer young too. I often wonder if it is something about supplements which are what these two groups share that is killing people rather than diet.

It's also worth remembering that many people with very high insulin levels cannot lower insulin to normal levels even with a low carb diet (for example tough cases of PCOS, as Dr. Bernstein discusses at length in his book.)

People with very high insulin levels who eat a lot of fat laced with pesticides, and other environmental pollutants may be upping their exposure to these toxins which are known to cause cancer.

For that matter, people eating a lot of fast food meat as part of a low carb diet or other foods known to be full of chemicals, or fatty meats full of pesticides and herbicides maybe raising their toxin load, too.

This is why the older I get, the more I think that a non-extreme diet which doesn't rely heavily on any single food source, avoids chemical or herbal supplements, fast foods and frankenfoods of all kinds, and which changes food sources from month to month may be safest.

Peter said...

Thanks for the comment and your views Jenny. I feel that when any of us stop thinking there is no chance. All information is grist to the mill.

BTW I love these rats studies. I agree fully that they have nothing to do with human diabetes but they are like jigsaw puzzles.... Not that I ever have time for jigsaw puzzles with more than 24 pieces which have Thomas the Tank Engine pictures on them.


Paul Jaminet said...

Hi Peter,

Re the stomach cancer, it's often triggered by H. pylori infection and is highly sensitive to iodine status. Poland long had very high rates of iodine deficiency and stomach cancer. A substantial decline in stomach cancer rates took place after iodine prophylaxis began, see:

Fixing macronutrient ratios is not enough for health. You have to fix micronutrition also, remove toxic foods (gunther gatherer said on the previous thread the OD does not do this), and defeat infectious diseases. These four steps are the main theme of my blog (

I think the Optimal Diet is on the right track, if a little over-skeptical of glucose/starch. It is just incomplete.

Very nice discussion of the OLETF rats. I've also been following CarbSane's investigation of the pathologies of diabetes/obesity. A lot of leads to pick up, so little time ...

Best, Paul

Peter said...

Nice link Paul. The next post is on a specific food toxin and should be up soon, it was written before the comment from _Flo but go shelved for a while...

On the micronutrient front I take it you are well aware of copper deficiency and collagenopathy association in cvd?


Paul Jaminet said...

Hi Peter,

I'm going to do a post on why the Optimal Diet would be expected to cause gastrointestinal cancers (but might prevent other cancers). The emphasis will be on mucus production as well as iodine/micronutrient levels. I think the limited carbs and fiber probably leads to an insufficient gastrointestinal mucus barrier, which is a major risk factor for gastrointestinal cancers.

Re copper, you may have noticed that copper is among my 8 critical supplements (vitamins D, K2, C; magnesium, copper, chromium, selenium, iodine). The reason is mainly its mortality benefit against heart disease. But I haven't explored the mechanisms much, would like to hear more about collagenopathy.

Best, Paul

Peter said...

The arteriosclerosis series might get there eventually when it finsihes with IMT and atheroma, assuming I get back on to that thread. Too much happening!


Stan Bleszynski said...

Re: Second hint was Jenny Ruhl's comment that she had come across very, very occasional individuals with diabetes who responded to low carbohydrate eating by deterioration of glycaemic control.

My glycemic control also got worse on the Optimal Diet in 1999, temporarily for about 1.5 years.

I wrote more about it here.

I suspect that (a) this is a general phenomenon for people staring on a LC high fat diets, and (b) it becomes the problem only for those people who exceed their carbohydrate and protein threshold which could be quite low, for example in my case it was only 25g of carbs a day for the first 1.5 years! Hyperglycemic effects of exceeding the carbs by somebody with a metabolic syndrome, are identical on the low carb and the high carb diets, except that the threshold is different.


Iodine and stomach ulcer is also a very interesting connection. Goiter symptoms were common in Poland among poor villages, especially in the southern mountanous regions, where the staple food was potatoes and cabbage.

This paper quote "Risk [of stomach cancer in Poland] was also significantly increased among men working in fabricated metal production and among women ever employed as managers and governmental officials. Men ever employed as teaching professionals and women employed as technical and science professionals had significantly decreased risks of stomach cancer."

- Clearly indicates that it may be a stress related phenomenon!

David Moss said...

Hi Peter,

On the stomach cancer question I would have guessed that high salt intake (convincingly linked to stomach cancer) might be the cause, given the polish predilection for processed meat and sauerkraut (cf the increased risk from kimchi), but this paper from Warsaw( seems to disagree with me and links increased risk to lack of fruit and veg and plant chemicals like vit C, E and carotenes.

Peter said...

Hi DM (welcome) and Stan,

Just as a follow on to the salt and the iodine connections we have the relatively high incidence of gastric carcinoma in Japan where salt intake is very high but iodine deficiency is unlikely, though I have not checked the latter (do poor people in Japan eat seafood?)... The link with carbohydrate is interesting as H pylori seems to be a problem if you provide it with excess hydrogen and glucose to turbocharge its reverse Kerbs cycle, so allowing it to become anything other than a beneficial commensal.


Stan Bleszynski said...

Interesting. That Polish paper DM linked blames grains and carbohydrates for stomach cancer!


Risks were positively associated with increased intake of breads/cereals/rice/pasta and other refined grains, as well as a high carbohydrate index. Our findings add to the evidence of a protective effect of fruits and certain vegetables on stomach cancer risk, but do not indicate that high intake of sausage and other preserved foods typical in the Polish diet has contributed to the country's elevated stomach cancer incidence. Our data also suggest that high carbohydrate consumption may influence risk, but further confirmation is needed.

Winalot said...

I try not to be a copycat :-) but can you tell me about : "have my own personal tweaks to the OD and do not see any clear way of improving what I have already achieved."?

The toxins in fat I raised makes sense, but sometimes beggars can't be choosers! Rotating food sources seems a compromise I'll try and implement.

Peter said...

Yes Stan, that's logical. H pylori ferments glucose anaerobically and uses part of the Krebs cycle in reverse to reduce pyruvate with hydrogen as a reducing agent rather than the TCA as we expect it to run. A high fat diet ought to protect. But not always....

Winalot, I always have enough omega three around to allow PPAR gamma activation, never touch gluten with a barge pole and also vary my protein sources to include some sea food. I still think liver is hard to beat as a multivitamin supplement, lots of copper...


Winalot said...

Thanks Peter,

I haven't been able to eat seafood since childhood, nothing medical just can't stomach the stuff! Make up for it with pork though - the new White meat :-)

I stay in ketosis to avoid the depression and suicidal tendencies as much as possible, but lately my personal tweaks have been adding broccoli and leeks to my meals (which are otherwise meat, lettuce and butter).

Working well and I think that's the point a la flo; tweak the general concept so it works for you, but always keep your eyes open.

And a westcountry breakfast followed by Roddas now and then never did any harm!

david said...

glad to see posts/comments like this. keeps one on their toes with regards confirmation bias.

Peter said...

Hi david,

Yes, it is quite difficult when you are a pardigm which doesn't really throw up any major paradoxes. Reality should kick you in the teeth occasionally. No one is correct all the time. But the LC approach in the industrialised world throws up a lot fewer paradoxes than any cardilogist's BS!


Anonymous said...

India diabetes capital of the world.

Have you ever seen a healthy vegetarian? Yes? OK, dig deeper. so he eats a bit of dairy, a bit of eggs, and a bit of animal flesh on the side. So he's not really a vegetarian. Case closed.

What about those populations that eat a traditional diet yet are just as sick as we are? Yes? Dig deeper. They eat loads of sugar, loads of white flour, and generally eat crap. OK, so they don't actually eat a traditional diet. Case closed.

What about that guy who was a long term optimal diet eater? What did he eat before he switched? OK, so he wasn't eating the OD since birth, nor did his mother eat this way when she was pregnant with him. Case closed.

Do you know the term "outlier"? It's the exception. What is the exception with the SAD? A healthy human. What is the exception with the traditional diet? A sick human.

Are you suggesting that this guy died because he switched to a low carb high fat diet? That would seem to oppose the rule about low carb high fat, wouldn't it? It merits a deeper look at the details if only to make sure he was actually eating the way he claimed to be eating.

Every time I look deeper into the singular situation I find something that doesn't fit the claim.

Why did the low carb group do better in all things measured?

Peter said...

Hi Martin,

What I would suggest is that no one should ignore the outliers any more than they should take them as typical. But questioning our hypothesis is paramount. Otherwise you might as well go in to cardiology.


LeenaS said...

But questioning our hypothesis is paramount. Otherwise you might as well go in to cardiology.
Oh Peter,
I love you three <3


LeenaS said...

And b.t.w., the three men in the family heard or will see that too...

So, back to facts: we've been 10 years on lowcarb and the last 3+ with ever more JK's style fats; the guys eat a bit more protein and I have some more carbs, but its not high protein for them, either. And it's well below 100g carbs for me.

I do not know how long our buttery bliss will continue (not to speak about the fact that my mom already had had at least one cancer operation at my age; or that her kin has never lived long, except for the two ladies fond of smoking and alcohol who actually lived past 80), but for a life long chronic like myself, these 10y have been the best and the healthiest in my life. So, any problems in the future have probably already been reimbursed by the chance to live as normal people for these years; without eternal weariness, itch, runny eyes and cough.

Too bad we are doomed :)


Peter said...


The Voices tell me these things...



LeenaS said...

You too?

Must be the bifidoes, which make me zombie-walk to the late night butter snack.

Amazing what those little ones can do to one's head. Nothing will ever be the same again.


Peter said...

Luckily none of the Voices tell me to eat leaves.... #;-P


Anonymous said...

Peter, I agree. But the hypothesis acknowledges that it's not merely about diet. Indeed, it explicitly states that diet is merely one of the agents that disrupts the system. There are many more agents that are not food that act on those same systems. Or rather, we may call it food but if it kills us, is it really food?

In other words, the hypothesis is not so simplistic. Why would we blame diet for this person when we don't for the rest of the world? Occam's would suggest that it's not the diet but something else. Indeed, diet may have mitigated the disease. Had it been followed as claimed.

Why would a diet help the brain but kill the stomach? Why would a diet clean the cells but kill the stomach? Why would a diet help the liver but kill the heart and stomach? It's not consistent.

blogblog said...

There was an article in New Scientist a few months back which argued that most experiments on rats were worthless because they don't exercise the rats sufficiently.

A rat has at least twice the aerobic exercise capacity of the world's best marthon runners. Rats can effortlessly run the equivalent of a world-record marathon every day with a bit of training.

blogblog said...

The reality is that LC in most cases isn't true LC at all. The Inuit diet used by Stefansson and Anderson in 1928 was 18% protein: 2% carb :78% fat. It consisted of nothing but 1.5kg of red meat/organ meat each day. Carbohydrate content was <20g/day in the form of glycogen.

Peter said...


This has happened. We none of us know why. My own feeling is that we must watch and not explain it away as a paradox.

The points you make are potentially valid but cannot be tested.

Observe, wait, consider. Do not explain away unless the explanation is clear cut.


Peter said...


I have the greatest respect for rats but I didn't know they were that good.

I would disagree with the gist ot the New Scientist idea. The main problem with rat studies is that they are very carefully designed by very clever people to maximise funding success.

Bugger the truth but don't lie directly.


CarbSane said...


While I don't believe rodent models are completely relevant to humans, this particular rat is not "genetically modified" (aka a knockout rat), but appears to be a strain that has a propensity towards "spontaneous" diabetes -- at least in the males.

Not perfect, but much of the research done on the effects of hyperglycemia have originated in rodent models. So I see no reason to discount out of hand research on the impact of dietary fats and/or NEFA.

Elevated NEFA do as much damage as elevated BG, the concurrent effects apparently being worse than each on their own. Here is my concern.


I can relate to, if I'm correctly interpreting the underlying gist of this post, a lingering concern over trading one health benefit for another w.r.t. our dietary choices. I've no doubt I'm healthier now than 80-100 lbs ago (physically and psychologically!), but sometimes I wonder if it didn't come at some "cost" trade-off. No doubt while the majority of low carbers find this WOE for weight loss, there are factions for which it is effective for other health reasons -- It is abundantly clear that it is effective for neurologically based issues. Ketones appear to be especially "soothing" to the nerves vs. glucose in various conditions.

My personal thoughts are that, if you are lean and your high fat diet doesn't make you fatter, you're probably A-OK. I also subscribe to the general philosophy that most of us tend to wear our health's on the outside. Yes, there's those seemingly healthy fit folks who drop dead of something, but mostly, if we feel good (and are not ignoring those little tell-tale signs), chances are we're OK too.

Perhaps the entire reason for my blog was the whole elevated NEFA issue, it's correlation to sudden cardiac death, and my own "risk factor" of experiencing the occasional (POUNDING) racing heart. No diagnostic scan or blood test has ever indicated anything even remotely wrong with me, and yet .... ????

As to stomach cancer, etc. I do think that VLC/VHF fails to feed our beneficial bacteria. Soluble fibers like glucomannan and inulin may be something to consider.

CarbSane said...
This comment has been removed by the author.
D1S said...

here is the answer

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

Hi Peter,

I am a newly diagnosed diabetic or prediabetic of unknown type, currently assumed by doctors to be Type II, but awaiting a genetic test to see if I'm something else. (I am on the line between prediabetic and diabetic, would require an oral glucose tolerance test to be sure, which doctor says is unnecessary at this point, just keep doing what I'm doing. My glucose meter says I am diabetic, though.)

If I'm that other type, it's one that does not respond particularly well to a very low carb (60g/day or less) diet, though 120g carbs is good. Or at least, that is what I've found observing myself.

I've greatly benefited from Jenny Ruhl's information and advice, but after several months of low-carb eating changing my blood sugars only transiently while sapping my energy and giving me heart palpitations, I decided to creep up the carbs. My readings actually improved a bit and I felt better. The palpitations disappeared.

Although I haven't been diagnosed, if I do have a glucokinase mutation, this would easily explain the reaction to carbohydrate restriction, as the enzyme glucokinase is produced in proportion to the amount of carbs you take in. Glucokinase tells your beta cells that glucose is coming in, so make some insulin. It will just adjust downward as you go down in carbs, soon giving you the same high reading for 10g that you used to get for 30g, and woe betide if you surprise it with 30g if you've been restricting yourself for a while. This down-regulation happens with everyone, but if you have a half-baked glucokinase enzyme, fasting or carbohydrate restriction impairs it more severely than a normal person's.

Various fats down-regulate it to some degree also, but a reduction in glucose down-regulates it the most. This isn't necessarily a bad thing, but if you're trying to resolve hyperglycemia caused by a faulty glucokinase with carb restriction, you will simply start chasing your tail.

I haven't tried going above 120-140 carbs a day yet, since I feel fine at this level. I don't know whether if I inched it up more I'd level out again at a higher number. My main strategies for glucose control at this point are to keep carbs fairly consistent so as not to overshoot my glucokinase's current effective range and to exercise in the morning to bring my inevitably high morning glucose down.

A lot of exercise, alas, also downshifts this enzyme, which I discovered personally after a day of high sugars following a morning jog that included five sprints.

I am not sure if I'm the type who gets more insulin resistance from an inability to metabolize fat in my cells. It's possible, since I started to get fat for the first time in my life following a highish-fat WAPF-type diet. Additional evidence is that when I was pregnant, and diagnosed with gestational diabetes (a harbinger of current dx), I started cutting fat due to concerns about cholestasis of pregnancy (a whole other issue) in the final four weeks of my pregnancy. To my surprise, my insulin requirements went down and down to almost nothing by the time I delivered - in fact, I used none that morning and was fine. I don't really like how I feel on a 10% fat diet, though - my body seems to like fat in some ways at least. I got really tired of protein and fat on the high-fat, low-carb diet of recent months, though. I like a variety of macronutrients, I guess.

A note about the heart palpitations. I think they may have been due to a thiamine deficiency. Most Type I and Type II diabetics are thiamine-deficient, as we excrete far more thiamine than a healthy person. A low-carb, high-fat diet tends to be low in thiamine, unless you eat a lot of pork or organ meats, which I don't. I started supplementing with 15mg thiamine a day and my heart palpitations started to resolve, even before I started increasing my carbs. I'm not sure it's related, but I'd guess it is.

Helen said...

BTW, Peter, people with hyperglycemia resulting from a glucokinase mutation do not appear to have an elevated risk of heart attack. They usually do not have the fellow-traveler of hyperglycemia, metabolic syndrome. Most importantly, probably, low triglycerides is a hallmark of the breed. This is probably due to glucokinase's role in generating triglycerides from glucose and fructose, which I can't claim to understand, but I know it plays a role. If there's less of it, apparently, there are fewer triglycerides. Note that this effect would also be noticed on a low-carb diet.

Peter said...

Hi Helen,

I'm about to drop in to a tunnel of "no time for blogging", for a few days at least, so I'd just like to put this one liner comment up to say thank you for your input and it has given me a considerable amount to think about.

The impression I have of the world is that there are many thousands of variations in out ability to cope with assorted conditions we are presented with. Under current conditions those people who don't cope with carbohydrate "show" as having "diseases". Does exactly the same apply under high fat conditions? Obviously yes, as you illustrate!

I suspect that fat induced diseases are much less common as we carry our emergency calories around as fat and anyone not coping with fat based metabolism would be highly selected against under conditions of hunger. Surviving transient privation is essential, even today for most of the population outside of the G7 nations.

Thanks for the input. Still thinking about it.


Kuntsa said...

The β-oxidation happens mostly in mitochondria. Wikipedia on β-oxidation:

Fatty acid oxidation also occurs in peroxisomes, when the fatty acid chains are too long to be handled by the mitochondria. However, the oxidation ceases at octanyl CoA. It is believed that very long chain (greater than C-22) fatty acids undergo initial oxidation in peroxisomes which is followed by mitochondrial oxidation.
One significant difference is that oxidation in peroxisomes is not coupled to ATP synthesis. Instead, the high-potential electrons are transferred to O2, which yields H2O2. The enzyme catalase, found exclusively in peroxisomes, converts the hydrogen peroxide into water and oxygen.

However, Wikipedia article on peroxisomes:
A major function of the peroxisome is the breakdown of fatty acid molecules, in a process called beta-oxidation. In this process, the fatty acids are broken down two carbons at a time, converted to Acetyl-CoA, which is then transported back to the cytosol for further use. In animal cells, beta-oxidation can also occur in the mitochondria. In yeast and plant cells, this process is exclusive for the peroxisome.

Acetyl-CoA carries the ketone group (acetyl) into Saint-Georgie-Krebs cycle happening in mitochondria. (Pardon my Hungary.) Alternatively, the ketone bodies may be used elsewhere. Hm, time to dig on ketone metabolism (are they just fed to the Cycle?)

Wikipedia articles about α-oxidation and ω-oxidation are also interesting.

Peter said...

Kuntsa, absolutely.


Gretchen said...


Anyone who limits carbs will become more carb-sensitive. The extreme version of a LC diet is starvation, and there's something called "starvation diabetes." Starving people will test diabetic on a GTT when they're not really diabetic.

When you don't eat carbs, you stop producing enzymes to process carbs. It makes sense.

So as long as you stick to the LC diet, being more sensitive to carbs shouldn't be a big problem. What may be harmful is going on a LC diet but breaking the diet whenever you see a tasty, carby treat.

The mechanisms of the increased sensitivity may be many, but here's a study suggesting that ketones may play a role.

Peter said...

Yes Gretchen, it's very logical that ketones should inhibit glucose uptake, the ketones are only there because there are inadequate supplies of glucose (pax MCTs). At the moment I'm sniffing round pancreatic glucokinase and insulin secretion as a mechanism too. Axen and Axen's rats were only borderline ketogenic but portal glucose (as surrogate for carb intake) does seem to control transcription of mRNA for GK in the pancreas, as does insulin itself...


Gretchen said...

I think for us, the mechanism is not as important as being aware that we become more insulin resistant and understanding that this is not necessarily a bad thing.

Exercise promotes muscle glucose uptake without insulin, so the muscles that need glucose won't be without it.

Paul Jaminet said...

Hi Peter,

I've put up my long delayed post on why I think the Optimal Diet promotes gastrointestinal cancers.

It's here:

Best, Paul

Myrmecia said...

Jenny wrote "...a non-extreme diet which doesn't rely heavily on any single food source, avoids chemical or herbal supplements, fast foods and frankenfoods of all kinds, and which changes food sources from month to month may be safest."

These principles are probably consistent with what most of us believe (and follow), but the big gap in this prescription is that "a non-extreme diet" is left open for each of us to determine. Most people think they consume a non-extreme diet. There is a criterion for determining what "non-extreme": the Evolutionary Health Principle. As formulated by Stephen Boyden it is:

"The principle that if an animal or plant is removed from its natural habitat, or if the environment changes in some significant way, it is likely that it will be less well adapted to the new conditions, and will consequently show some signs of physiological or behavioural maladjustment. This principle applies to all species including Homo sapiens."

The Principle gives one big conceptual hurdle for the average person to leap: "non-extreme" has to be defined in terms of the Palaeolithic hunter-gatherer diet being the norm, not dietary conventions of contemporary western societies.

Ken said...

High fat means more bile acids and bile acids can be turned into cancer promoting substances by intestinal bacteria according to a BBC radio prog on gut bacteria yesterday

Peter said...

Hi Ken,

Full text of the study can be down loaded here

It's not worth the blogging time...


Ken said...

Plasma vitamin D and mortality in older men: a community-based prospective cohort study

"Greatly increased enterohepatic cancer death rates were ob- served with both low and high plasma vitamin D concentrations. This is a particularly intriguing finding, because in addition to its classical role in mineral homeostasis, the vitamin D receptor (VDR) is evolutionarily and functionally linked to a distinct group of nuclear receptors that are involved in the elimination of toxic substances absorbed by the gut (19, 22). Low concentrations of vitamin D could contribute to increased enterohepatic carci- nogenesis by reduced detoxification of secondary toxic bile acids (19, 34). Activation of VDR by these bile acids or vitamin D induces expression in vivo of CYP3A, a cytochrome P450 en- zyme that detoxifies secondary bile acids in the liver and intestine (37). Secondary bile acids are formed in the intestine but enter the bile after enterohepatic circulation (19, 34). In contrast, high concentrations of vitamin D suppress the farnesoid X receptor that detoxifies carcinogenic bile acids (12, 20, 21), suggesting a mechanism for increased cancer risk with high vitamin D concentrations"

Plasma vitamin D and mortality in older men: a community-based prospective cohort study. (a very sophisticated 2010 study ) found that those having vitamin D concentrations over 39 ng/ml have a 50% higher total mortality rate. The Garland brothers recommend 40- 60ng/ml

Frank C. Garland. ", Garland died at age 60 on August 17, 2010, at UCSD Medical Center in La Jolla, San Diego, California, due to cancer of the esophageal junction." (He had been ill for a year).

You know I think Garlands death at 60 is very significant so I don't feel inclined to assume the long term Optimal Diet follower would have died at 64 anyway. 64 ain't that old.

(My latest attempt at warning about about D supplementation in comments at a blog HERE if anyone is interested)

Peter said...

I still read Peter Frost's blog


Ken said...

As I read it high vitamin D levels (which suppress farnesoid X) may be particularly risky for those on high fat diets.

twitchyfirefly said...

CarbSane mentioned "Soluble fibers like glucomannan and inulin may be something to consider."

I use konjac noodles. They're made of glucomannan, have zero carbs and zero calories, and are a nice filler in stir fries and things like that.

If anyone knows of a reason not to eat this, I'd like to know...

Peter said...

Good luck!

James said...

What do you think if virus infections? It seems like a large part of the population is infected (or has antibodies and has been at least once), yet overt symptoms only occur in a few. Are those symptoms more likely to occur under an inadequate diet? The The High-fat Hep C Diet blog (from suggests so. For herpes simplex, there seems to be health - symptoms connection as people report outbreaks getting worse under (lifestyle) stress. I have a opened a blog to gather some practical recommendations, they are all speculative but one has to start from somewhere as conventional medicine offers very little for prevention:

Rattus said...

Paul Jaminet makes an argument above in the comments, as well in a post on his blog, that the higher rates of gastrointestinal cancer in Polish optimal dieters is due to mucin deficiency.

I personally think that the higher rates of stomach cancer are most likely due to the very high consumption of pork among Polish people [probably the highest percentage of meat calories from pork of any country], which would be much higher among optimal dieters than the Polish people in general because they get so many calories from protein/fat.

Pork would be the perfect food for HFLC diets, because so many amazing, high-fat meat products are made from it [sausage, pepperoni, salami, etc.]. Unfortunately, it is pork, and pork is...bad. Based on my n=1 experience, as well as some research I've done, humans just shouldn't be eating it. It is also one of the most universally forbidden foods. Perhaps some gene pools are more susceptible to the negative effects of pork, but generally I think most people would be way better off not eating it.

brunonk said...

Don't forget that Polish people drink a lot of alcohol and eat a lot of sliced meats, sausages etc.