Monday, January 3, 2011

Paleolithic Diet Clinical Trials, Part V

Dr. Staffan Lindeberg's group has published a new paleolithic diet paper in the journal Nutrition and Metabolism, titled "A Paleolithic Diet is More Satiating per Calorie than a Mediterranean-like Diet in Individuals with Ischemic Heart Disease" (1).

The data in this paper are from the same intervention as his group's 2007 paper in Diabetologia (2). To review the results of this paper, 12 weeks of a Paleolithic-style diet caused impressive fat loss and improvement in glucose tolerance, compared to 12 weeks of a Mediterranean-style diet, in volunteers with pre-diabetes or diabetes and ischemic heart disease. Participants who started off with diabetes ended up without it. A Paleolithic diet excludes grains, dairy, legumes and any other category of food that was not a major human food source prior to agriculture. I commented on this study a while back (3, 4).

One of the most intriguing findings in his 2007 study was the low calorie intake of the Paleolithic group. Despite receiving no instruction to reduce calorie intake, the Paleolithic group only ate 1,388 calories per day, compared to 1,823 calories per day for the Mediterranean group*. That's a remarkably low ad libitum calorie intake in the former (and a fairly low intake in the latter as well).

With such a low calorie intake over 12 weeks, you might think the Paleolithic group was starving. Fortunately, the authors had the foresight to measure satiety, or fullness, in both groups during the intervention. They found that satiety was almost identical in the two groups, despite the 24% lower calorie intake of the Paleolithic group. In other words, the Paleolithic group was just as full as the Mediterranean group, despite a considerably lower intake of calories. This implies to me that the body fat "set point" decreased, allowing a reduced calorie intake while body fat stores were burned to make up the calorie deficit. I suspect it also decreased somewhat in the Mediterranean group, although we can't know for sure because we don't have baseline satiety data for comparison.

There are a few possible explanations for this result. The first is that the Paleolithic group was eating more protein, a highly satiating macronutrient. However, given the fact that absolute protein intake was scarcely different between groups, I think this is unlikely to explain the reduced calorie intake.

A second possibility is that certain potentially damaging Neolithic foods (e.g., wheat and refined sugar) interfere with leptin signaling**, and removing them lowers fat mass by allowing leptin to function correctly. Dr. Lindeberg and colleagues authored a hypothesis paper on this topic in 2005 (5).

A third possibility is that a major dietary change of any kind lowers the body fat setpoint and reduces calorie intake for a certain period of time. In support of this hypothesis, both low-carbohydrate and low-fat diet trials show that overweight people spontaneously eat fewer calories when instructed to modify their diets in either direction (6, 7). More extreme changes may cause a larger decrease in calorie intake and fat mass, as evidenced by the results of low-fat vegan diet trials (8, 9). Chris Voigt's potato diet also falls into this category (10, 11). I think there may be something about changing food-related sensory cues that alters the defended level of fat mass. A similar idea is the basis of Seth Roberts' book The Shangri-La Diet.

If I had to guess, I would think the second and third possibilities contributed to the finding that Paleolithic dieters lost more fat without feeling hungry over the 12 week diet period.

*Intakes were determined using 4-day weighed food records.

**Leptin is a hormone produced by body fat that reduces food intake and increases energy expenditure by acting in the brain. The more fat a person carries, the more leptin they produce, and hypothetically this should keep body fat in a narrow window by this form of "negative feedback". Clearly, that's not the whole story, otherwise obesity wouldn't exist. A leading hypothesis is that resistance to the hormone leptin causes this feedback loop to defend a higher level of fat mass.


SamAbroad said...

Hi Stephan,

I wonder is their any evidence this could work in the opposite direction too? Could a change in sensory cues cause a raise in set-point too? A lot of people seem to pack on a lot of weight when they dramatically change their lives, but that could be stress

Todd Hargrove said...


Do you suspect that set point lowering by factors such as food novelty or palatability will persist long term? Or will they eventually be overwhelmed by other homeostatic mechanisms? My guess is that these factors are to some extent short term tricks (like drinking water before eating to increase satiety) that the body will eventually catch on to and make adjustments.

Robert McLeod said...

I saw a talk on "leptin resistance" (scare quote intended) three weeks ago by Myers. He doesn't seem to believe in leptin-resistance per se either.



His research and some of the follow-up I did suggests it's orexin- and neurotensin-receptors that are messed up and not the leptin-receptors, i.e. that the problem is downstream of leptin.

Might-o'chondri-AL said...
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lightcan said...

Hi Stephan,

what happens after weight loss when leptin is supposedly lower?
'These data are consistent with the idea that the decrease in leptin levels that occurs when an individual loses weight serves to protect the body against the loss of body fat.'

lightcan said...


are you aware of these ideas regarding body weight regulation?

Unknown said...


I'm a little confused though. How do you jump to the conclusion that, because Paleolithic dieters ate less Calories, their body fat "set point" must have decreased. Why wouldn't the first possible conclusion be that their metabolism/REE decreased?

Have a great day,

@NaturalWorkwear said...


An interesting post. If there was a “toxic” effect from grains, would we expect to see patients with celiac disease who stick to s gluten-free (and presumably grain-free) diet have less adiposity? Is there any such data in the literature, one way or another?

Might-o'chondri-AL said...
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David L said...


A little off topic here, but I wondered if you could talk about potential morbidity reductions by taking tea, especially green tea. There seem to be a lot of studies which claim significant positive outcomes.

Your thoughts?

Helen said...


Some people make claims for dairy being hyperphagia-producing due to its insulin-stimulating properties. Do you think its exclusion has anything to do with fat loss and satiety here?

I'm wondering because, due to other food limitations, dairy is a *huge* part of my diet. I'm at a good weight right now, and was actually worried I was losing too much for a while, but I do get concerned when it seems like my diet starts to revolve around a food source too much. On the other hand, with gallbladder trouble afoot, which I find is aggravated by a new list of foods (those high in oxalates, *heavy sigh*) on top of mild diabetes and a variety of other food issues and concerns, I don't have too many other places to go right now.

Stephan Guyenet said...

Hi Sam,

Based on the animal experiments, I would think it could change in the upward direction as well.

Hi Todd,

I think setpoint change based on novelty will lose its efficacy over time. If it's based on palatability, it might not though. Most diet studies show regain after 2 years or so even if compliance remains fairly good. Not all do though.

Hi Robert,

That first paper was co-authored by Myers and my current mentor. The paper is pretty clear that cellular leptin resistance does exist and probably contributes to obesity. However, they propose that another factor is palatability or other related factors.

Hi Might-o'chondri-AL,

I did find your comment stuck in my spam filter. I don't know why they end up there, sorry.

Hi Lightcan,

That study was conducted by Rudy Leibel and Joy Hirsch's group. They use simple calorie restriction to cause weight loss, which does not lower the setpoint. Those results are very interesting, however they do not necessarily apply to interventions where diet is qualitatively altered.

Hi Brandon,

That hypothesis comes from the fact that they were eating fewer calories but were not hungrier.

Hi Fraz,

Not necessarily. Gut damage due to gluten causes malabsorption and in some cases underweight.

Hi David,

I'm planning to write about polyphenols soon. I'll probably touch briefly on green tea, however I'll leave the heavy lifting on that to Chris Masterjohn because it's his area of expertise.

Hi Helen,

The fact that a food increases insulin after a meal does not mean it will increase appetite or cause any other adverse effect. That is a myth as far as I can tell. That being said, I think there's something to be said for moderation when it comes to dairy.

Might-o'chondri-AL said...
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LeonRover said...

I was curious when I read this study about the re-calculation of energy intake from both diets, so I read up the details in the 1st report from study on same set of participants.

I was interested in the energy intake before going on either of Paleo or Consensus diets. I could not find any mention of (to me)this rather important piece of data. This got me thinking it is an ASSUMPTION that the respondents had the same amount of food as observed in the 4 day period and being compliant, during the rest of the time. The amounts of energy intake, even when increased by assuming the weight loss is all from fat stores, does not gibe with estimates of predicted BMR plus oxidation from sedentary activity at these average weights, as may be found in any Sports' Physiology text.

I am prepared to accept as reasonable that Paleo food is more satiating than Consensus food, that the bloods were improved etc., but I am suspicious that BOTH diets have been under-reported and that inferences based on weights of food and consequent daily energy consumption are just too low.

Brandon's query has a point, therefore.

Might-o'chondri-AL said...
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Stephan Guyenet said...

Hi Leon,

I agree it would have been nice to see baseline data. I was talking to a friend who does controlled diet studies yesterday, and he thought the reported calorie intakes were probably an underestimate of their actual intakes. If you make people weigh everything they eat, they think twice about eating it.

However, I think the conclusion still stands because there was a substantial difference between the two groups that's unlikely to be explained by that confounder.

David L said...


I wonder is you have read
"The Decline Effect and the Scientific Method"

It casts profound doubts on many types of research, even double-blind studies. Since most (all?) of the dietary work in humans is not even close to double blind, this type of bias could be even worse.

Any thoughts?

Might-o'chondri-AL said...
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LeonRover said...

David L

It is a nice article by Lehrer - I read his stuff since buying The Decisive Moment.

Personally, I have little time for 1 sample in 20 (P<=0.5) as the cut-off in hypothesis testing.When I read papers I only pay attention to results with P<=.01, at P=.005, now that's cooking.

In a similar vein, I ignore NNTs greater than 20 and Risk Ratios less than 500%.

donny said...

Some of the low fat studies I've read are based on the idea that when switching to a lower-fat diet, people fail to adjust for the decrease in calories (and vice versa, when fat is added they fail to compensate by eating less.) I seem to remember something Yudkin said about carbohydrate, when you take the carbohydrate out of the diet, people fail to make up for the reduction in calories. Both of these observations could be explained by setpoint. But... at the same time, there are satiety mechanisms that seem to be more strongly tailored to fat intake, or to carbohydrate intake or to protein intake. What I'm sort of clumsily working my way towards saying is, protein, fat, and glucose homeostasis are strongly interactive, but also to a certain extent seperate, the appetite might not be a general appetite as such, but rather seperate appetites for protein, fat, and carbohydrate.

Feeding behaviour tends to be triggered by opportunity. Giving the opportunity to eat only fat and protein might fail to trigger appetite for carbohydrate. This is a kind of fast, and fasting is generally easier than trying to eat a little less of something. Given no opportunity to eat fat, protein and carbohydrate might fail to trigger fat appetite. And either of these diets might fail, or at least become less effective eventually, as the various appetites are adjusted to the new diet. The sensory cues are changing, but so is the nature of the food; it seems likely that the sensory cues are closely tied to metabolic recognition of specific nutrients. Shangri-la is all about feeding the body misinformation. Finding a way to give the metabolism a better view of what's really going on seems like a better idea.

THE self-selection of diet experiment had for its
subject infants of weaning age, i.e., from six to eleven months of age, who had never had
supplements of the ordinary foods of adult life. This age was chosen because only at this age could we have individuals who had neither had experience of such foods nor could have been influenced by the ideas of older persons and so
would be without preconceived prejudices and biases with regard to them. The children concerned
were studied for six years.
Me again.

The kids in this study were more capable of feeding themselves properly than the adults of the time. Or this time, probably. As long as the foods they had to choose from didn't suck too badly.


The first infant received for the
study was one of the two with severe rickets, and, bound by a promise to do nothing or leave nothing undone to his detriment, we put a small glass of cod liver oil on his tray for him to take if he chose. This he did irregularly and in varying amounts until his blood calcium and phosphorus became normal and x-ray films
showed his rickets to be healed, after which he did not take it again.

Stephan Guyenet said...

Hi David L,

I haven't read that article but I know the general idea and it makes sense to me. I do think a mature understanding of science requires an appreciation for the pitfalls of the scientific method as it's currently practiced.

I think it's important to draw a distinction between different types of studies though. Human trials where there's one intervention and one primary outcome are not the same as most papers in the biological sciences field, where there are several mutually buttressing lines of investigation in each paper. For example, if you do three experiments that all give a result with a p value of less than 0.05, and all agree with one another, the likelihood that the whole thing is wrong is very, very small.

Then again, that assumes that the experiments were selected, performed, analyzed and presented in a completely unbiased fashion, which in practice is almost never true.

Stephan Guyenet said...

But I think if you see a consistent result from human and animal studies, and there is biological plausibility, it increases your confidence in the result.

edibleevolution said...


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Jay said...

Satiety is a very interesting concept because at the point where we are satiated virtually none of the energy in the food has been absorbed, satiety is a state where the body 'thinks' enough nutrients have been eaten. From the conscious sensors like taste and estimate of volume ingested from the mouth and unconscious ones in the digestive tract (mentioned by mighto chondri AL above) the body makes some kind of estimate of nutrients which can easily be wrong.
Lindeberg uses two rather arbitrary categories but back in 1995 Holt et al at the University of Sydney compared the satiating effects of 38 individual foods giving a much more useful result. They published:
A satiety index of common foods.
in the
European journal of clinical nutrition
this paper is not available online as far as I know but is summarised here:
Their "Satiety Index" (SI) of the foods they tested ranged from 47% to 323% where 100% was the index for white bread.
Not surprisingly the least satisfying foods were:
Croissants 47%
Cake, doughnuts, Mars bar 65%-70%
White bread and white pasta were 100% and 119%
Wholemeal bread and brown pasta 157% and 188%
Meat and fish was satiating at 176% and 225%
but surprisingly
Oatmeal porridge was 209% and boiled potatoes 323% (compared to 116% for french fries)
So a junk food junkie exchanging pastries and confectionery for meat and fish on the Atkins diet is exchanging unsatisfying foods for satisfying ones and is likely to consume fewer calories but a peasant exchanging boiled potatoes for eggs (SI 150%) is likely to consume more.
Chris Voigt on his high potato diet lost weight despite trying to eat beyond satiety:
People who find low carbohydrate diets don't work for them could do worse than to increase their potato intake.
Kitavans and Okinawans and others who eat a lot of starchy roots are slim and healthy despite considerable carbohydrate intake.

Stephan Guyenet said...

Hi Jay,

Thanks very much. I've heard about the satiety index but never read the paper. While I think the data are interesting, I'd like to see how they would play out in the long term. i.e., does the body end up compensating for foods that are more satiating by increasing intake over a longer period of time.

One hypothesis is, as you said, that Voigt just couldn't eat many potatoes because they are so satisfying per calorie. However, a lean person will eat enough potatoes to maintain weight, as demonstrated by the previous potato diet studies nearly 100 years ago, as well as potato-reliant cultures.

My thinking is that it's consistent with the hypothesis that something about the potato diet changed Voigt's fat mass setpoint because he started off overweight. The satiety index of a food could be a factor influencing the setpoint, of course. Or perhaps it's due to lower overall palatability of the diet, or some other reward-related process. All I have right now is a broad outline but that's my current thinking. Seth Roberts has done some thinking along these lines.

Anonymous said...


There are many gut hormones that effect satiety. Cholecystokinin (CCK)is a hormone of the gastric intestinal system responsible for stimulating digestion of fats and protein and which also mediates satiety, acting as a hunger suppressant.

A recent meta review (PMID 19176730) of baseline concentrations and physiologic response to gut hormones found that those with anorexia nervosa had exceptionally high levels baseline CCK.

It follows that if you decrease intake of carbohydrates that concentration of fat and protein in the gut will be greatly increased even if you do not increase fat consumption, and that this in turn will increase secretion of CCK which will suppress appetite. It therefore would be expected decreased carbohydrate consumption will result in a decrease in caloric intake.

I know from personal experience that increased fat consumption and decreased carbohydrate consumption can result in unintended excessive weight loss.

Anonymous said...

Interesting blog I just discovered today. Will have spend some more time here. Anyway I want to make a comment regarding this statement: "The first is that the Paleolithic group was eating more protein, a highly satiating macronutrient. However, given the fact that absolute protein intake was scarcely different between groups, I think this is unlikely to explain the reduced calorie intake." Actually, this is consistent with the Protein Leverage Hypothesis which states that our bodies aim for a certain quantity of dietary protein. I myself have been losing a lot of weight on a paleolithic diet the last six months. I calculated my dietary protein was 22% of my caloric intake. A typical diet has 15-18% calories from protein. If I intake 2000 calories at 22%, I would need to eat about 2500 of an 18% protein diet to get the same amount of protein.