Saturday, September 12, 2009

Paleolithic Diet Clinical Trials Part IV

Dr. Staffan Lindeberg has published a new study using the "paleolithic diet" to treat type II diabetics (free full text). Type II diabetes, formerly known as late-onset diabetes until it began appearing in children, is typically thought to develop as a result of insulin resistance (a lowered tissue response to the glucose-clearing function of insulin). This is often followed by a decrease in insulin secretion due to degeneration of the insulin-secreting pancreatic beta cells.

After Dr. Lindeberg's wild success treating patients with type II diabetes or glucose intolerance, in which he normalized the glucose tolerance of all 14 of his volunteers in 12 weeks, he set out to replicate the experiment. This time, he began with 13 men and women who had been diagnosed with type II diabetes for an average of 9 years.

Patients were put on two different diets for 3 months each. The first was a "conventional diabetes diet". I read a previous draft of the paper in which I believe they stated it was based on American Diabetes Association guidelines, but I can't find that statement in the final draft. In any case, here are the guidelines from the methods section:
The information on the Diabetes diet stated that it should aim at evenly distributed meals with increased intake of vegetables, root vegetables, dietary fiber, whole-grain bread and other whole-grain cereal products, fruits and berries, and decreased intake of total fat with more unsaturated fat. The majority of dietary energy should come from carbohydrates from foods naturally rich in carbohydrate and dietary fiber. The concepts of glycemic index and varied meals through meal planning by the Plate Model were explained [18]. Salt intake was recommended to be kept below 6 g per day.
The investigators gave the paleolithic group the following advice:
The information on the Paleolithic diet stated that it should be based on lean meat, fish, fruit, leafy and cruciferous vegetables, root vegetables, eggs and nuts, while excluding dairy products, cereal grains, beans, refined fats, sugar, candy, soft drinks, beer and extra addition of salt. The following items were recommended in limited amounts for the Paleolithic diet: eggs (≤2 per day), nuts (preferentially walnuts), dried fruit, potatoes (≤1 medium-sized per day), rapeseed or olive oil (≤1 tablespoon per day), wine (≤1 glass per day). The intake of other foods was not restricted and no advice was given with regard to proportions of food categories (e.g. animal versus plant foods). The evolutionary rationale for a Paleolithic diet and potential benefits were explained.
Neither diet was restricted in calories. After comparing the effects of the two diets for 3 months, the investigators concluded that the paleolithic diet:
  • Reduced HbA1c more than the diabetes diet (a measure of average blood glucose)
  • Reduced weight, BMI and waist circumference more than the diabetes diet
  • Lowered blood pressure more than the diabetes diet
  • Reduced triglycerides more than the diabetes diet
  • Increased HDL more than the diabetes diet
However, the paleolithic diet was not a cure-all. At the end of the trial, 8 out of 13 patents still had diabetic blood glucose after an oral glucose tolerance test (OGTT). This is compared to 9 out of 13 for the diabetes diet. Still, 5 out of 13 with "normal" OGTT after the paleolithic diet isn't bad. The paleolithic diet also significantly reduced insulin resistance and increased glucose tolerance, although it didn't do so more than the diabetes diet.

As has been reported in other studies, paleolithic dieters ate fewer total calories than the comparison group. This is part of the reason why I believe that something in the modern diet causes hyperphagia, or excessive eating. According to the paleolithic diet studies, this food or combination of foods is neolithic, and probably resides in grains, refined sugar and/or dairy. I have my money on wheat and sugar, with a probable long-term contribution from industrial vegetable oils as well.

Were the improvements on the paleolithic diet simply due to calorie restriction? Maybe, but keep in mind that neither group was told to restrict its caloric intake. The reduction in caloric intake occurred naturally, despite the participants presumably eating to fullness. I suspect that the paleolithic diet reset the dieters' body fat set-point, after which fat began pouring out of their fat tissue. They were supplementing their diets with body fat-- 13 pounds (6 kg) of it over 3 months.

The other notable difference between the two diets, besides food types, was carbohydrate intake. The diabetes diet group ate 56% more carbohydrate than the paleo diet group, with 42% of their calories coming from it. The paleolithic group ate 32% carbohydrate. Could this have been the reason for the better outcome of the paleolithic group? I'd be surprised if it wasn't a factor. Advising a diabetic to eat a high-carbohydrate diet is like asking someone who's allergic to bee stings to fetch you some honey from your bee hive. Diabetes is a disorder of glucose intolerance. Starch is a glucose polymer.

Although to be fair, participants on the diabetes diet did improve in a number of ways. There's something to be said for eating whole foods.

This trial was actually a bit of a disappointment for me. I was hoping for a slam dunk, similar to Lindeberg's previous study that "cured" all 14 patients of glucose intolerance in 3 months. In the current study, the paleolithic diet left 8 out of 13 patients diabetic after 3 months. What was the difference? For one thing, the patients in this study had well-established diabetes with an average duration of 9 years. As Jenny Ruhl explains in her book Blood Sugar 101, type II diabetes often progresses to beta cell loss, after which the pancreas can no longer secrete an adequate amount of insulin.

This may be the critical finding of Dr. Lindeberg's two studies: type II diabetes can be prevented when it's caught at an early stage, such as pre-diabetes, whereas prolonged diabetes may cause damage that cannot be completely reversed though diet. I think this is consistent with the experience of many diabetics who have seen an improvement but not a cure from changes in diet. Please add any relevant experiences to the comments.

Collectively, the evidence from clinical trials on the "paleolithic diet" indicate that it's a very effective treatment for modern metabolic dysfunction, including excess body fat, insulin resistance and glucose intolerance. Another way of saying this is that the modern industrial diet causes metabolic dysfunction.

Paleolithic Diet Clinical Trials
Paleolithic Diet Clinical Trials Part II
One Last Thought
Paleolithic Diet Clinical Trials Part III


R K @ Health Matters To Me said...

Your last words sum up the beast we're dealing with quite well:

"...the modern industrial diet causes metabolic dysfunction."

Wheat + sugar + veggie oils = ill health. Any diet that eliminates this potent combination will result in better health, no doubt!

Bryce said...

I think many paleo dieters cling to "lean meats" too much, because wild animals were allegedly leaner than modern cattle. Even if that's true, hunter gatherers would have eaten plenty of fatty organ meat. And any starchy tubers they would have been eating would have been used to replenish glycogen supplies that were being routinely drained through high intensity anaerobic exertion (sprinting, hauling, etc).

Perhaps if the paleolithic dieters in question were given the suggestion to eat all manner of fatty meat, they would reach satiety earlier and feel less of a need to eat a potato every day. Not that potatoes are evil - they do have there place unlike cereal grain or sugar.


Steve Parker, M.D. said...

I can't wait to drill down into the details of the recent study. But your first link doesn't work for me. Maybe just my computer.

Adherence to the assigned diet is always an issue in studies like this, especially if randomized.

I want to see how good was compliance.


epistemocrat said...

First, Dr. Guyenet, job well done, as always.

I read this post in my Google Reader, ventured here to post my thoughts, then I happily discovered that Bryce made my exact same point. Nice work, Bryce.

So, I second Bryce.

Lean meat never made any sense to me.

Where's hyperlipidity when you need it tested in the right manner?

epistemocrat said...

Also, Seth Roberts has a worthwhile addition to the hyperphagia concept map:

Ditto foods.

Same conclusion, different (psychology) and valuable perspective.

Cupcakes said...

Good post, certainly enjoyed this series on Lindeberg's studies.

I also think many people who know of the Paleo or similar Low-Carb diets choose to just keep it as an option if they ever need to lose a bit of weight or whatever, until it's too late and their pancreatic beta cells are destroyed.

Time is of the essence foodies!

Jeff said...

Hey Stephan,

Do you have any experience with fatter people having a tougher time losing weight? Three people I know have struggled with fat loss going Paleo. Does a worse starting point make it harder? This is similar to the more diabetic folks struggling to cure themselves that you mention here.

Also, any idea of an influence of aspartame or other artificial sweeteners? One of my more heavy friends is a heavy diet soda drinker.

thanks and great post,


Unknown said...

I wish they would test a proper paleo diet with lower carbohydrates for its effects on diabetes. This one had lean meats, fruits and nuts. The latter two might not be too good for someone with diabetes. I suspect the results would be a lot better on a true paleo high-fat diet, with low fructose, LA and a decent omega3:6 ratio.

billye said...

The Paleolithic diet you are posting about sounds similar to "The paleo diet" written by Professor L. Cordain. If this is the case, it is not surprising that the experiment had a poor showing relative to diabetes type 2. The two points that I would like to make are the unbelievable recommendation of eating any type of fruit with out limit, along with lean meat. A true paleo diet would have been some fruit (probably not very sweet) and plenty of meat loaded with saturated fat. The recommendation to trim all of the fat you can from the animals that you eat is laughable. Try to imagine a cave person trimming fat from his meat, that has to give you a giggle. If they did that they would not have survived. Under the guidelines laid out for the paleo diet in this experiment, every one should have failed. The wonder is that some improved. I eat as much fat as I can and limit my fruit intake to a cup of berries daily. I had type 2 diabetes for 28 years and my last 3 A1c numbers were 4/7, 4.8, and 5.0.

David said...

I agree with Andy and billye. Paleo carbs may be okay in the right context (e.g. Kitavans), but too many carbs (regardless of the kind) consumed within the context of preexisting metabolic weakness is not good. I'd like to see a lower- carb version of this little experiment.

Robert McLeod said...

The problem, as others have alluded to here, is that if one is insulin sensitive, glucose is just fine, but once one has progressed deep into insulin resistance, it's no longer acceptable in the diet.

Fructose also seems to be very effective at causing leptin resistance in combination with central obesity and that tends to lead into metabolic syndrome.


There was a study published in Nature, I think in 2008, that showed that the total number of fat cells was more or less fixed in adolescence. Dieting simply reduces the average volume of a fat cell. So yes, people who have been badly damaged by the standard American diet are not so likely to fully recover.


I think lean meats are ok for people who are actively trying to lose weight, but satiety must be satisfied. I think avoiding sucrose and eating at regular hours to better regulate ghrelin production is the best way to handle appetite. People should still be looking at the whole animal though, maybe through in some bone broths and beef or lamb heart.

Dr. B G said...

Wonderful thoughts guys! I second them ALL.

For the gals out there, FYI all oral contraceptives and progestins ruin second phase insulin responses and raise CRP (the inflammatory marker). Additionally many synthetic hormones cause depression, libido, and weight gain issues which tranlates to higher insulin and insulin resistance. Weight gain. *urrg* Of course! Is it reversible these effects? I suspect as Robert and others mentioned once enough beta pancreatic islet cells have been damaged, a certain degree is irreversible. Maybe with enough of our own progenitor cells it can be reversed? Hormone replacement improves insulin sensitivity greatly (like vitamin D).

I love this series, Stephan! You totally R O C K .

Adolfo David said...

I am confused about coconut oil after reading advocate Mary Enig and other phyisicians who dont believe so much in Enig's recommendation for any reason:

Dr Andrew Weil, MD:
despite the ongoing internet buzz that coconut oil can promote weight loss, there's no scientific evidence to back up those claims. Lauric acid, the main fatty acid found in coconut oil, has shown positive effects as an anti-viral agent in treating herpes, but all in all, I recommend avoiding dietary sources of coconut oil.

Dr Barry Sears, PhD (who recommends more fats than Weil) says olive oil is far better than coconut oil:

"Coconut oil is rich in tocotrienols, which have significant anti-oxidative potential, but it is composed of saturated fats. Many of those saturated fats consist of short-chain fatty acids that go directly to the liver via the portal vein and rapidly consume stores of liver glycogen. Without adequate levels of liver glycogen, it is difficult to replenish blood sugar levels for optimal brain function and satiety. You will get a far more powerful anti-oxidant effect by consuming extra-virgin olive oil. Coconut oil can be used in moderation since it contains very little, if any, omega-6 fatty acids."

I believe you in USA have so expensive cold-pressed extra virgin olive oil there (here in Spain is so cheap as vegetable oil, 32oz 5$ in mediterranean Europe), and for this reason many nutritionists in US recommend coconut oil. Its my opinion after reading and thinking pros and cons of coconut and olive oils, and I think I prefer clearly olive.

Anonymous said...

Fantastic post, Stephan. And I agree with the comments that were made indicating that I wouldn't consider a Paleo diet (not my brand, anyway) to include fruit (other than as a garnish) and to limit in any way, good fats -- I certainly would not include white potatoes. Would love to see a study performed with a full-on Paleo diet.

Stephan Guyenet said...

Hi Bryce, epistemocrat and Andy,

I'm with you on that.

Hi Steve,

Sorry the URL was incorrect, I fixed it. I seem to have a knack for messing up links.

Hi Jeff,

Some people have a really hard time losing weight no matter what they do. They may want to get their thyroid levels checked and perhaps measure their body temperature. An underactive thyroid will derail the most valiant weight loss effort. Just one possibility. Some damage is reversible, some isn't.

I would definitely be suspicious of the diet soda habit.


Yes, Dr. Lindeberg and Dr. Cordain collaborate quite a bit and Lindeberg's diets are based in part on Cordain's recommendations. Although I did notice that this version didn't include canola oil or mayo-- a step up!

Hi Adolfo David,

There is some evidence to back up the weight loss claims for coconut oil, but I admit it's pretty weak. In rats it has a pretty amazing ability to increase the metabolic rate. I think that may occur in humans as well, at least to a limited extent.

My main reason for liking coconut oil is it has a proven track record in very healthy cultures. But if you like olive oil then I don't see a problem with that.

lightcan said...

Thank you Stephan

For Jeff related to artificial sweeteners from Dr. Briffa's blog

re diabetes and diet. My mother has had T2DM for 20 years and is on a low cal low fat diet with 200g carbs and insulin injections. She is putting on weight despite the restrictions and HbA1c is high enough (glucose control has been terrible in the recent years). Try telling her doctor that. Last year, when she came to our house for 6 weeks, she had to have her carbs as she was taking insulin but they were reduced and she lost weight.(we don't have bread, potatoes or rice with our dinner and eat eggs for breakfast) The doctor was pleasantly surprised but left it at that. If nothing else, on a paleo diet containing fat she would lose weight and her blood glucose would be easier to control.

Carl M. said...

Hmmm, the Paleo diet said no additional salt. Meat tastes a LOT better with salt.

Carl's rule of fad diets: just about any diet that tastes bad (after a time) will cause you to lose weight. Simple calorie reduction. Most limited diets, be they vegetarian or meatarian, will taste less good than a varied diet. After a while you get tired of the same old, same old.

We here in the USA have access to every cuisine imaginable. When tired of Italian, we can eat Chinese or good ole steak and potatoes. Throw in the "natural flavorings" found in most processed and restaurant foods, and we have succeeded in foiling our natural instinct not to eat too much.

This is not to say paleo is not better than the carbo-mush diet. I just think we had better be careful and discount all results based on the fad diet effect.

Robert Andrew Brown said...

Thanks Stephan,

Great post.

No information on long chain Omega 3s, and it is unclear if other vegetable oil intake was allowed on top, so we have little idea as to the 3:6 ratio of the vegetable fats.

Robert McLeod said...

Stephan wrote:
Although I did notice that this version didn't include canola oil or mayo-- a step up!

Rapeseed oil == canola oil.

Canola is just the Canadian cultivar of the rapeseed plant/weed.

Of course they claimed to exclude refined fats? Does that mean rapeseed oil was an exception or did they actually locate non-refined canola for their clients. Cordain recommends refrigerated, unrefined Canola doesn't he? I've never seen such a product, personally.

Stephan Guyenet said...

Ah yes, apparently I missed that. The amount permitted was small though. I think a small amount of unrefined canola oil is probably OK, as long as you don't cook with it.

That's the essential problem with canola oil as far as I see it: either it's unrefined and you can't cook with it because it has too much n-3, or it's refined and it has less n-3 and significant trans fat.

GoEd said...

I read somewhere that some canola crops are GMO. If so that would be a reason by itself to stay away from it.

Does anyone know if that is correct?

Jeff Consiglio said...

I also have a hard time accepting Cordain's take on lean meats and lots of fruit.

But he has data charts on various wild-game's seasonal, average bodyfat percentage which he cites as proof. He's very insistent that the "modern obese cow" (as he puts it) is NOT anything you'd find in the wild. Obese cows are a product of feeding then a totally alien diet of corn.

I'd be curious of any evidence that paleo man was able to eat lots of fat on a regular basis.

LeenaS said...

Have you ever tasted real virgin canola? I'm 99% sure that the canola or rapeseed oil used was not "unrefined" but normal hot-processed stuff that is available here in every store, with very high hype about the healthiness.

So, there is no longer much trans fats, but the micro nutrient content is just as low as in any industrial product - ja with stuff like dihydro-K is present, as well as traces of trans fats.

As for Swedish studies on diabetes, Vesti Nielsen produced much better progress on both DM2 and DM1 (I'll try to send you the references) with more paleoish LCHF (i.e. Low Carb High (animal)Fat. Not as much marketed in academic circles, though, due to fat controversy.

Miki said...

The saga of Cordain and Sat Fat is the ultimate testimony to the existence of a confirmation bias. In one of his papers (that I can't find now) I had to calculate the average SFA percentage of a caribou (or elk)from a yearly month by month table. It came down to 48%! You would not find this number in the paper anywhere only a mention that SFA are not the majority of fats as if this is the most important fact.
In a recent paper ( the tone re SFA is not changed. Believe it or not, the authors cite the Seven Nation Study. I read Cordain is a nice guy and his papers certainly look professional but...

Jenny Light said...


You are correct! Canola is one of the GM crops! The other major ones are soybean, corn and cotton.

Anyone insisting on continuing to use canola oil would be wise to use ORGANIC expeller pressed, as it is the lesser of evils, and will not be sourced from GM crops.

billye said...

Coach Jeff,
You only have to understand that the survival eating habits of cave people were to eat the entire animal from tail to nose and everything in between. By eating this way they consumed the most fat possible including brains, marrow and all other fatty organ meat. The problem with pen fed cattle is the unnatural force feeding of grains instead of natural grass pasture. The so called fat cattle are not the problem, rather it is the upside down omega 3 to omega 6 ratio because of grain feeding. That is the true horror. I do my best to eat as much pastured grass fed meat as I can, including organ meat and marrow that is found in beef shank. I think that the no saturated fat healthy eating mind set that pervades our healthy eating culture has indoctrinated many including Dr. Cordain.

Dr. T "" recently had me tested for AA/EPA Ratio - Plasma. It came back with my inflammatory risk number 10. Good = 3-10, Ideal Is <3.0. I will keep working at it until I reach my goal of an ideal ratio for omega 3 to omega 6.

Billy Oblivion said...

Dr. Guyenet:

My wife has a minor thyroid condition currently controlled with synthroid. You state:

An underactive thyroid will derail the most valiant weight loss effort. Just one possibility. Some damage is reversible, some isn't.

We used to eat a very carb-heavy diet, and I've been trying to get away from that (it's tough out here, the military provides us with plenty of food, but it's not exactly the freshest and most diverse diet possible.), and she's been trying to eat better, but she's not been able to lose much if any weight.

Is there something you're aware of besides the medication that she can try? My mom (and I suspect her mom) is in the same boat, as are at least 1 or 2 of her friends.


Dana Seilhan said...

I think that if you already have beta cell loss, you pretty much need to can the idea that you should ever eat grains or sugar again. A lot of diabetics try the tack of eating these foods in "moderation" but really, they don't need them, and their bodies can no longer process them. Save what insulin you have left for its other functions, I think. So the "paleo" diet would have worked a lot better for these diabetics had they avoided grains and sugars completely.

Hate to tell that to my dad, since he's Cajun and adores rice.

I think one of the factors leading us to eat more is this: After eating, most of what we eat (carbs, fat, and protein) is converted to fatty acids and stored in our adipose tissue, before we ever use it for energy. This was documented in the 1920s using a heavy form of hydrogen as a marker. (See also Gary Taubes.) In healthy people, serum insulin drops between meals and fatty acids are released from adipose tissue to provide between-meal energy.

In people with hyperinsulinism, this doesn't happen. Insulin remains elevated, the fatty acids are locked up and the lean tissue "freaks out" because it's not getting energy. The cells send out chemical signals, your brain goes, "Whoops, I'm still hungry!", and you eat again.

A lot of the research around hunger stems from the notion that hunger is about personal character or miswired brain. It's not. It's a body-wide biochemical response to caloric deprivation.

So it's no big mystery why ketogenic diets reduce hunger, either. Your body is not starving because it's getting the fatty acids it should have gotten long ago, but didn't because your insulin levels were locking them up. For the same reason, as you came close to pointing out, a "low-calorie" low-carb diet isn't really low-calorie. Technically, if you're burning body fat, you're still eating! It's just not going into your mouth.

This is one of the big problems with calorie theory. It assumes the human body is a combustion engine, but we're a lot more complex than that.

Dana Seilhan said...

And Dr B G is absolutely right about oral contraceptives. I got my first weight gain while on the Pill after twenty-one years being lean.

BTW, pregnancy wrecks you too. Now I'm not sure how much of that was the pregnancy hormones themselves or whether I might have had a different experience had I never gone on the Pill, but I had a roughly fifty-pound weight gain with each of two pregnancies that "set" and never went away.

I also had major inflammation with my second pregnancy that had my doctor testing me for autoimmune diseases.

So be very careful if you decide to have kids. Spend some time properly nourishing yourself first--Nourishing Traditions is an excellent primer for that purpose. The other thing that worked against me was I had had no real nutritional education, so I thought things like low-fat meat and pasta were healthy. Oy vey.

Dana Seilhan said...

Carl M.: Stefansson pretty much proved on his all-meat diet that the "need" for a "varied" diet is cultural, not biological. If it's all you know, it tastes just fine. Our access to varied diets is a product of our improved transportation technology and resulting level of travel and food trade. Two hundred years ago and more, we would have had to largely make do with what was available locally.

Let's be careful not to confuse our modern lifestyles and values with what is "good" for us biologically. Look at the context before you decree something "natural."

It took me realizing that Ice Age humans wouldn't have had greenhouses to raise baby lettuce, nor access to ships to import grain, to realize that of course we get along fine without plant food, because that enabled our survival at some point. All you have in winter is animals and maybe the occasional tuber if you have no farming or trade routes.

Robert McLeod said...

I think that a lot of people who are hypothyroid are actually hypopituitary. Weak thyroid function is just a downstream symptom of such. The key clue is when people start to exhibit symptoms related to some of the other major hormones that the pituitary produces but aren't strictly basal metabolic rate. E.g. low sex drive.

Basically if the antibody tests for Ord's and Hashimoto's come back negative, look at getting the autoimmune pituitary antibody test, if possible.

Anonymous said...

As for "curing" diabetics with a long history of the disease, I have some personal experience. As a Type 2 of 24 years, I began eating a pretty paleo diet. After 6 months I was off all my diabetes meds, so even after a long time with the disease, I have gained control for the present time. The fact that I never let diabetes run away with me may be a factor. My highest A1c was a 7.1 I believe. That is very unhealthy, but for many years was considered good control. I'm not "cured" and resist usage of the word. If I eat inappropriately, my blood sugars will explode, but I am capable of maintaining normal blood sugar levels. I don't think it is possible to "cure" diabetes, but I believe it is possible in most instances for a type 2 to normalize blood sugars.

Stephan Guyenet said...

Hi Coach Jeff,

Cordain's own data make it impossible for contemporary HGs to have avoided large amounts of fat.

He found that 1/5 of the known HG groups got 85% or more of their food from animal sources. That's not precisely a measure of calories, but for the sake of this discussion let's be generous and assume it is.

Since our protein ceiling is roughly 30%, that means these groups had to be eating at least 55% fat. Cordain provides "representative" carcass analyses of several game species showing fairly low BF%, but it varies by species, individual and bodypart. HGs know how to exploit the fattest parts of the fattest animals.

Modern cows are only obese relative to wild ruminants in spring and summer. Fall and early winter wild ruminants are easily as fat as modern cows, if not more fat. Their fat is mostly subcutaneous and perirenal, which are both highly saturated. I discussed all that here:

Hi LeenaS,

I have not tasted virgin canola oil, but it is available in stores here. I'd be interested to see the references you mentioned.

Hi Miki,

I agree, the way those data are presented are misleading. I think Cordain has been coming around to a more reasonable stance lately.

Hi Billy,

The only other things I can think of at this point are avoiding problematic foods-- gluten, sugar, vegetable oils, and possibly dairy protein depending on the person-- and an effective exercise routine. Brief and intense, perhaps with strength training thrown in. Also, lots of sleep and stress reduction. Intermittent fasting has worked for some people as well. Just a few ideas.

Hi dmoak,

That's great. I'm curious, did the paleo diet you adopted involve carb restriction? Do you think in your case there's an effect of neolithic food specifically, or was it simply a matter of carb intake?

Anonymous said...

>>>I believe you in USA have so expensive cold-pressed extra virgin olive oil there (here in Spain is so cheap as vegetable oil, 32oz 5$ in Mediterranean Europe) ...


Contrast to the US where a gallon (128 fl oz) of corn or vegetable/soybean oil is 6.99 [1]. That's 32 oz for $1.75. We also sell a lb of margarine for 89 cents.

In poor areas who's going to pass that up? It's such a tragedy.


Colldén said...


Not related to this post, but I was wondering if you had a chance to look at the new study on inducing central insulin resistance in rats with palmitic acid?

What I found sort of interesting are the significant differences in weight gain and insulin/leptin resistance between the diets enriched in butter and olive oil.

Planning to comment it?

Nate said...

In that study can you really call it a high fat diet when 50% of the calories come from carbs and half of which are sugar?
Food Comp

Colldén said...


No, I agree it's a terrible model for human low-carb diets. But like I said, the interesting thing is that only the butter-enriched caused weight gain and insulin/leptin resistence, and not the olive oil-enriched.

Anonymous said...

"That's great. I'm curious, did the paleo diet you adopted involve carb restriction? Do you think in your case there's an effect of neolithic food specifically, or was it simply a matter of carb intake?"

There was definitely carbohydrate restriction. I am very sensitive to carbs. But I think the paleo/low carb worked together for my results. I would not have known about grass-fed meats, avoidance of artificial sweeteners, processed meats and dairy, etc. without the paleo information. I do eat some dairy. I used to eat low-carb desserts sweetened with Splenda. They are a useful tool for diabetics, but my blood sugars improved when I quit eating them. My numbers are still changing. My fasting sugar this morning was a new low for me (without meds) - 79! thanks for all the good info on your site.

Robert Andrew Brown said...

Dr Staffan Lindberg is speaking on Paleo diets, the Kitavans etc at a very reasonably priced 1/2 day conference in Lisbon in October. (Euros 40 or 25 for students)

Paleo and cardiac disease
Paleo v cereal
Paleo and diabetes
Peptides lectins etc

Stephan Guyenet said...


Yes. It's a nicely designed study conducted by collaborators of the lab I'm going to join soon.

Take a look at table 1. Compare the low-fat fed group to the HFS-R group. Same weight, fasting insulin, fat mass, blood glucose. HFS-R is the group which was fed the butter diet at the same number of calories as the low-fat diet rats ate (isocaloric feeding).

Thus, the insulin disturbances and weight gain are mostly due to an increase in calorie intake due to the butter diet. Rats overeat when fed a high-fat diet. In that respect, they appear to be different than humans. We're more like the HFS-R group.

It would have been nice to see the weekly calorie intake of all groups.

In figure 1, they show that the HFS-R diet mice are less responsive to insulin than low-fat fed animals, but they didn't do the oleic control so we can't see if the effect is specific to the saturated fat group. It may have been the same in the oleic group for all we know.

I'm skeptical of the experiments where they infused palmitic acid plus BSA directly i.c.v. I'm not sure how physiological that is. I'll have to look into it. BSA is often contaminated with lipopolysaccharide (LPS), which induces inflammation.

I actually think the diets are much better controlled than most. The sugar content is less than 10% of calories.

Atticus said...

More accurately, I'd say rats (and people) overeat when given a typical Western 40% fat, 10% sugar diet. Rodents on very high fat diets (ketogenic) do not overeat.

Colldén said...


Yes, it looks like the insulin resistence is caused mainly by over-eating, or rather by the increase in adiposity and weight. The olive oil group didn't gain nearly as much weight or fat as the HSF group, so I guess that could account completely for the differential effect on leptin and insulin sensitivity for all we know, good point.

Interesting still that the olive oil group gained so much less weight despite equal caloric intake.

Also, weren't the palmitic and oleic acid infusions BSA-free? Still I'm doubtful about the i.c.v infusions. Can you really be sure that the fatty acids you ingest are the same as those which reach the CNS?

Stephan Guyenet said...


I think you're right about the i.c.v. infusions being BSA-free.

I couldn't find any data on the caloric intake of the four groups in the paper, except for the snapshots in figure 1. That's not sufficient to know what their food intake was on a regular basis. Some groups have reported that caloric intake goes up in high-fat groups and then drops back down after a few weeks. By then, they're already insulin resistant etc. Other groups have reported that caloric intake goes high and stays high. We don't know how the caloric intake compared between the oleic and HSF groups. All we know is that the HSF-R group ate the same amount as the low-fat group.

Rodents will eat less of foods they perceive as bitter, such as foods containing blueberry extracts etc. That accounts at least in part for the beneficial effects of those substances on rodent models of disease. They may simply not have liked the taste of the olive oil. We can't rule that out based on the data they presented.

As far as palmitic acid reducing insulin sensitivity, it actually makes sense. When would you have a bunch of palmitic acid flowing through your bloodstream? Right after the liver generates it from glucose from a carbohydrate meal. By the time palmitic acid hits the bloodstream, blood glucose is declining and you want to conserve it.

Alex said...

Here is Chris Masterjohn's opinion of the "sat-fat makes you hungry" study:

Stephan Guyenet said...


I can see why the abstract would give that impression, but the mice were not force-fed except in one specific part of the study, where they were force-fed the same number of calories in all groups.

Robert Andrew Brown said...

The trial says under results

"The fatty acid composition of the HFS diet was 10% myristate/27% palmitate/12% stearate/25% oleate. The composition of the oleic acid diet was 11% palmitate/ 70% oleate/13% linoleate."

The Omega 6 linolate would impact on insulin levels and metabolism. The do not give an Omega 6 figure for the HFS.

There is also no info on Omega 3.

Colldén said...


I figured the caloric intake listed in Table 2 was actually the total amount fed to the rats throughout the 3 months, but you're right that it doesn't actually say anywhere in the text that the butter and olive oil diets were adjusted to be isocaloric.

And yes, I was thinking that singling out palmitic acid as a cause of insulin/leptin resistance should have worse implications for overeating on carbohydrates than on consuming animal fats.

Stephan Guyenet said...

Hi Robert,

The HFS group was fed soybean oil (2% cal) and butter (38% cal). It may not have a great n-6/n-3 ratio, but it shouldn't be awful either, maybe 5:1 or so (depending on how much the soybean oil is refined).

The oleic group was fed soybean oil (2% cal) and olive oil (38% cal), so its n-6/3 ratio should actually be much worse than the HFS group.

Hi Collden,

Figure 2 refers to the composition of the diets, it doesn't contain information on the actual caloric intake of the groups.

I'm personally not convinced that the effects of palmitate have negative implications for eating either carbohydrate or fat. The response of the brain to palmitic acid may simply be a normal adaptive response to the rise and fall of glucose and lipids in the bloodstream.

Robert Andrew Brown said...

Palmitic acid may impact on pancreatic function direct as well

"Monounsaturated Fatty Acids Prevent the Deleterious Effects of Palmitate and High Glucose on Human Pancreatic β-Cell Turnover and Function"

Jürgen said...


long time lurker, first time poster, I would like to add what I have seen in the last Economist; they published a study about Diabetes Type II - instead of giving you a amateur summary, feel free to head over and read it yourself:

bottom line: you can actually re-program your genes (Mark from Mark's Daily Apple uses those words, too) by proper diet quite obviously, although they are also trying to invent medicine.

But still, good read and glad to see it in the Economist actually.

Thanks again to all for their passionate and helpful comments earlier, Jürgen

Stephan Guyenet said...


Love the quote: "we are not victims of our genes. If anything, our genes are victims of us."

Stan Bleszynski said...

Dana wrote: "In people with hyperinsulinism, this doesn't happen. Insulin remains elevated, the fatty acids are locked up and the lean tissue "freaks out" because it's not getting energy. The cells send out chemical signals, your brain goes, "Whoops, I'm still hungry!", and you eat again."

Totally agree! This is very important point! I think one would fare a lot better making long breaks between the high carbohydrate meals without snacking, to allow fatty metabolism and ketone production to occur. I wrote more on this here:


Colldén said...


Of course, you're right. So the diets were probably not isocaloric and that makes the different results less remarkable.

As for carbs vs fats, I was thinking more in the context of overeating - binging on carbohydrates should contribute more to elevated levels of palmitic acid than binging on animal fats, no?

Tom Jeanne said...

Regarding Coach Jeff's comment on the "modern obese cow", I just want to point out that grass-fed cows are big animals too. Their fat composition is likely different due to the diet but they still have plenty of fat on them. Here's a photo I took of some 100% grass-fed Jerseys and Jersey-crosses at a local farm. It's possible this cow was pregnant, but all of his cows have bellies almost that big, and the meat cuts I get are certainly not lean by any definition.

Cordain has long been promoting his politically correct view that humans are adapted to lean meat, despite lack of evidence, and he probably won't change his tune much.

"A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it." - M. Planck

Anonymous said...

I started from the basis that changing from a lowish fat diet to a lower fat high carb diet just like my dietician told me wrecked my metabolism completely, including causing weight gain for the first time in my life and actually increasing my already appalling LDL.

In Diabetesworld, this is the best strategy

doing that led me to a Paleo/Primal diet by the backdoor: somewhere between Mark Sisson's Primal and Michael Eades Protein Power in macronutrient ratios brought my BG into normal numbers, reduced my BP, doubled my HDL and decimated (literally) my trigs.

My specific carb load is around 60g/day with outliers to around 100g. Type 2 is a series of similar but different diseases IMO, and untreated they are usually progressive at varying speeds, so an individual's specific diet may vary widely, some can get away with more carbs, some need to be down at Bernstein/Atkins Induction levels permanently, but IME all diabetics can do substantially better than the woeful Official Diet, and many if not most can approach normal A1c and lipids.

The secret ingredient as found in most diabetes forums is monitoring your own performance and moderating diet accordingly. Reducing postprandial BG spikes appears to make major improvements to insulin resistance, along with growing and using muscle (and metformin). This is NOT a cure but a long term treatment, fall off the wagon and the destructive processes start up again, but certainly a la Mark Sisson it provides a way to prevent gene expression.

My trigs/HDL ratio came down from nearly 16 to under unity. The bummer is that I hoped the improvements were such that I could dispense with my measly 10mg Simvastatin, but surprisingly without it my LDL jumped up and trigs nearly doubled. I guess 50 years of being "not diabetic yet" have long term consequences: it's a small price to pay for approaching William Davis' 60-60-60 lipids which most diabetes "authorities" would claim like an A1c in the fives to be unreachable - but there are many thousands of us out in the world. Just never in research papers.

JC said...

I don't see any comments on the differences between eating cooked meat or raw meat. Any info on that?

I'm trying to incorporate as much raw meat as I can. But it's hard with kids and sometimes it's kind of nasty. I have been told that it's not just animal fat, but raw animal fat that is key for regeneration.

Anonymous said...

@jc look over at Dr. Harris' blog he addresses your question several times.
I've personally eaten raw without problems. To me it's a decision of personal taste and variety.

Unknown said...

"The reduction in caloric intake occurred naturally, despite the participants presumably eating to fullness."

This mirrors my own observations while on a peleo-lite diet (no wheat, no sugar, no dairy). The deeper I get into it, the less calories I need to feel "satisfied" so the calorie count just naturally drops.