Neuronal Control of Appetite, Metabolism and Weight

Last week, I attended a Keystone conference, "Neuronal Control of Appetite, Metabolism and Weight", in Banff.  Keystone conferences are small, focused meetings that tend to attract high quality science.  This particular conference centered around my own professional research interests, and it was incredibly informative.  This post is a summary of some of the most salient points.

Rapid Pace of Scientific Progress

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Atherosclerosis in Ancient Mummies Revisited

Many of you are already aware of the recent study that examined atherosclerosis in 137 ancient mummies from four different cultures (1).  Investigators used computed tomography (CT; a form of X-ray) to examine artery calcification in mummies from ancient Egypt, Peru, Puebloans, and arctic Unangan hunter-gatherers.  Artery calcification is the accumulation of calcium in the vessel wall, and it is a marker of severe atherosclerosis.  Where there is calcification, the artery wall is thickened and extensively damaged.  Not surprisingly, this is a risk factor for heart attack.  Pockets of calcification are typical as people age.

I'm not going to re-hash the paper in detail because that has been done elsewhere.  However, I do want to make a few key points about the study and its interpretation.  First, all groups had atherosclerosis to a similar degree, and it increased with advancing age.  This suggests that atherosclerosis may be part of the human condition, and not a modern disease.  Although it's interesting to have this confirmed in ancient mummies, we already knew this from cardiac autopsy data in a variety of non-industrial cultures (2, 3, 4, 5).

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Does the Mediterranean Diet Reduce Cardiovascular Risk?

By now, most of you have probably heard about the recent study on the "Mediterranean diet" (1), a diet that was designed by diet-heart researchers and is based loosely on the traditional diet of Crete and certain other Mediterranean regions.  The popular press has been enthusiastically reporting this trial as long-awaited proof that the Mediterranean diet reduces the risk of cardiovascular events-- by a full 30 percent over a 4.8-year period.  I wish I could share their enthusiasm for the study.

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Body Fatness and Cardiovascular Risk Factors

I recently revisited a really cool paper published in the Lancet in 2009 on body fatness, biomarkers, health, and mortality (1). It's a meta-analysis that compiled body mass index (BMI) data from nearly 900,000 individual people, and related it to circulating lipids and various health outcomes.  This is one of the most authoritative papers on the subject.

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New Review Paper by Yours Truly: High-Fat Dairy, Obesity, Metabolic Health and Cardiovascular Disease

My colleagues Drs. Mario Kratz, Ton Baars, and I just published a paper in the European Journal of Nutrition titled "The Relationship Between High-Fat Dairy Consumption and Obesity, Cardiovascular, and Metabolic Disease".  Mario is a nutrition researcher at the Fred Hutchinson Cancer Research Center here in Seattle, and friend of mine.  He's doing some very interesting research on nutrition and health (with an interest in ancestral diets), and I'm confident that we'll be getting some major insights from his research group in the near future.  Mario specializes in tightly controlled human feeding trials.  Ton is an agricultural scientist at the University of Kassel in Germany, who specializes in the effect of animal husbandry practices (e.g., grass vs. grain feeding) on the nutritional composition of dairy.  None of us have any connection to the dairy industry or any other conflicts of interest.

The paper is organized into three sections:

1. A comprehensive review of the observational studies that have examined the relationship between high-fat dairy and/or dairy fat consumption and obesity, metabolic health, diabetes, and cardiovascular disease.
2. A discussion of the possible mechanisms that could underlie the observational findings.
3. Differences between pasture-fed and conventional dairy, and the potential health implications of these differences.

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Does Dietary Saturated Fat Increase Blood Cholesterol? An Informal Review of Observational Studies

The diet-heart hypothesis states three things:

1. Dietary saturated fat increases blood cholesterol
2. Elevated blood cholesterol increases the risk of having a heart attack
3. Therefore, dietary saturated fat increases the risk of having a heart attack

To evaluate the second contention, investigators have examined the relationship between blood cholesterol and heart attack risk. Many studies including MRFIT have shown that the two are related (1):

The relationship becomes much more complex when you consider lipoprotein subtypes, density and oxidation level, among other factors, but at the very least there is an association between habitual blood cholesterol level and heart attack risk. This is what you would want to see if your hypothesis states that high blood cholesterol causes heart attacks.

Now let's turn to the first contention, the hypothesis that dietary saturated fat increases serum cholesterol. This idea is so deeply ingrained in the scientific literature that many authors don't even bother providing references for it anymore. When references are provided, they nearly always point to the same type of study: short-term controlled diet trials, in which volunteers are fed different fats for 2-13 weeks and their blood cholesterol measured (2)*. These studies show that saturated fat increases both LDL cholesterol ("bad cholesterol") and HDL cholesterol ("good cholesterol"), but typically the former more than the latter.  These are the studies on which the diet-heart hypothesis was built.

But now we have a problem. Nearly every high-quality (prospective) observational study ever conducted found that saturated fat intake is not associated with heart attack risk (3). So if saturated fat increases blood cholesterol, and higher blood cholesterol is associated with an increased risk of having a heart attack, then why don't people who eat more saturated fat have more heart attacks?

I'll begin to answer that question with another question: why do researchers almost never cite observational studies to support the idea that dietary saturated fat increases blood cholesterol? Surely if the hypothesis is correct, then people who habitually eat a lot of saturated fat should have high cholesterol, right? One reason may be that in most instances, when researchers have looked for a relationship between habitual saturated fat intake and blood cholesterol, it has been very small or nonexistent. Those findings are rarely cited, but let's have a look...

The Studies

It's difficult to do a complete accounting of these studies, but I've done my best to round them up. I can't claim this post is comprehensive, but I doubt I missed very many, and I certainly didn't exclude any that I came across. If you know of any I missed, please add them to the comments.  [UPDATE 4-2012: I did miss several studies, although they're basically consistent with the conclusion I came to here.  I plan to update this post with the new references at some point.]

The earliest and perhaps most interesting study I found was published in the British Medical Journal in 1963 and is titled "Diet and Plasma Cholesterol in 99 Bank Men" (4). Investigators asked volunteers to weigh all food consumed at home for 1-2 weeks, and describe in detail all food consumed away from home. Compliance was good. This dietary accounting method is much more accurate than in most observational studies today**. Animal fat intake ranged from 55 to 173 grams per day, and blood cholesterol ranged from 154 to 324 mg/dL, yet there was no relationship whatsoever between the two. I'm looking at a graph of animal fat intake vs. blood cholesterol as I write this, and it looks like someone shot it with a shotgun at 50 yards. They analyzed the data every which way, but were never able to squeeze even a hint of an association out of it:

Making the most out of the data in other ways- for example, by analysis of the men very stable in their diets, or in whom weighing of food intake was maximal, or where blood was taken close to the diet [measurement]- did not increase the correlation. Because the correlation coefficient is almost as often negative as positive, moreover, what is being discussed mostly is the absence of association, not merely association that is unexpectedly small.

The next study to discuss is the 1976 Tecumseh study (5). This was a large cardiovascular observational study conducted in Tecumseh, Michigan, which is often used as the basis for comparison for other cardiovascular studies in the literature. Using the 24 hour dietary recall method, including an analysis of saturated fat, the investigators found that:

Cholesterol and triglyceride levels were unrelated to quality, quantity, or proportions of fat, carbohydrate or protein consumed in the 24-hr recall period.

They also noted that the result was consistent with what had been reported in other previously published studies, including the Evans county study (6), the massive Israel Ischemic Heart Disease Study (7) and the Framingham study. One of the longest-running, most comprehensive and most highly cited observational studies, the Framingham study was organized by Harvard investigators and continues to this day. When investigators analyzed the relationship between saturated fat intake, serum cholesterol and heart attack risk, they were so disappointed that they never formally published the results. We know from multiple sources that they found no significant relationship between saturated fat intake and blood cholesterol or heart attack risk***.

The next study is the Bogalusa Heart Study, published in 1978, which studied the diet and health of 10 year old American children (8). This study found an association by one statistical method, and none by a second method****. They found that the dietary factors they analyzed explained no more than 4% of the variation in blood cholesterol. Overall, I think this study lends very little support to the hypothesis.

Next is the Western Electric study, published in 1981 (9). This study found an association between saturated fat intake and blood cholesterol in middle-aged men in Chicago. However, the correlation was small, and there was no association between saturated fat intake and heart attack deaths. They cited two other studies that found an association between dietary saturated fat and blood cholesterol (and did not cite any of the numerous studies that found no association). One was a very small study conducted in young men doing research in Antarctica, which did not measure saturated fat but found an association between total fat intake and blood cholesterol (10). The other studied Japanese (Nagasaki and Hiroshima) and Japanese Americans in Japan, Hawai'i and California respectively (11).

This study requires some discussion. Published in 1973, it found a correlation between saturated fat intake and blood cholesterol in Japan, Hawai'i but not in California. The strongest association was in Japan, where going from 5 to 75 g/day of saturated fat (a 15-fold change!) was associated with an increase in blood cholesterol from about 175 to 200 mg/dL. However, I don't think this study offers much support to the hypothesis upon closer examination. Food intake in Japan was collected by 24-hour recall in 1965-1967, when the diet was roughly 3/4 white rice by calories. The lower limit of saturated fat intake in Japan was 5g/day, 1/12th what was typically eaten in Hawai'i and California, and the Japanese average was 16g, with most people falling below 10g. That is an extraordinarily low saturated fat intake. I think a significant portion of the Japanese in this study, living in the war-ravaged cities of Nagasaki and Hiroshima, were over-reliant on white rice and had a very peculiar and perhaps deficient diet.  Also, what is the difference between a diet with 5 and 75 grams of saturated fat per day?  Those diets are probably very different, in many other ways than their saturated fat content.

In Japanese-Americans living in Hawai'i, over a range of saturated fat intakes between 5 and 110 g/day, cholesterol went from 210 to 220 mg/dL. That was statistically significant but it's not exactly knocking my socks off, considering it's a 22-fold difference in saturated fat intake. In California, going from 15 to 110 g/day of saturated fat (7.3-fold change) was not associated with a change in blood cholesterol. Blood cholesterol was 20-30 mg/dL lower in Japan than in Hawai'i or California at any given level of saturated fat intake (e.g., Japanese eating 30g per day vs. Hawai'ians eating 30g per day). I think it's probable that saturated fat is not the relevant factor here, or at least it's much less influential than other factors. An equally plausible explanation is that people in the very low range of saturated fat intake are the rural poor who eat a  diet that differs in many ways from the diets at the upper end of the range, and other aspects of lifestyle such as physical activity also differ.

The most recent study was the Health Professional Follow-up study, published in 1996 (12). This was a massive, well funded study that found no relationship between saturated fat intake and blood cholesterol.

Conclusion

Of all the studies I came across, only the Western Electric study found a clear association between habitual saturated fat intake and blood cholesterol, and even that association was weak. The Bogalusa Heart study and the Japanese study provided inconsistent evidence for a weak association. The other studies I cited, including the bank workers' study, the Tecumseh study, the Evans county study, the Israel Ischemic Heart study, the Framingham study and the Health Professionals Follow-up study, found no association between the two factors.

Overall, the literature does not offer much support for the idea that long term saturated fat intake has a significant effect on the concentration of blood cholesterol in humans. If it's a factor at all, it must be rather weak. It may be that the diet-heart hypothesis rests in part on an over-reliance on the results of short-term controlled feeding studies.  It would be nice to see this discussed more often (or at all) in the scientific literature.  It is worth pointing out that the method used to collect diet information in most of these studies, the food frequency questionnaire, is not particularly accurate, so it's possible that there is a lot of variability inherent to the measurement that is partially masking an association.  In any case, these controlled studies have typically shown that saturated fat increases both LDL and HDL, so even if saturated fat did have a modest long-term effect on blood cholesterol, as hinted at by some of the observational studies, its effect on heart attack risk would still be difficult to predict.

The Diet-heart Hypothesis: Stuck at the Starting Gate
Animal Models of Atherosclerosis: LDL


* As a side note, many of these studies were of poor quality, and were designed in ways that artificially inflated the effects of saturated fat on blood lipids. For example, using a run-in period high in linoleic acid, or comparing a saturated fat-rich diet to a linoleic acid-rich diet, and attributing the differences in blood cholesterol to the saturated fat. Some of them used hydrogenated seed oils as the saturated fat. Although not always consistent, I do think that overall these studies support the idea that saturated fat does have a modest ability to increase blood cholesterol in the short term.

** Although I would love to hear comments from anyone who has done controlled diet trials. I'm sure this method had flaws, as it was applied in the 1960s.

*** Reference cited in the Tecumseh paper: Kannel, W et al. The Framingham Study. An epidemiological Investigation of Cardiovascular Diseases. Section 24: The Framingham Diet Study: Diet and the Regulation of Serum Cholesterol. US Government Printing Office, 1970.

**** Table 5 shows that the Pearson correlation coefficient for saturated fat intake vs. blood cholesterol is not significant; table 6 shows that children in the two highest tertiles of blood cholesterol have a significantly higher intake of saturated fat, unsaturated fat, total fat and sodium than the lowest tertile. The relationship between saturated fat and blood cholesterol shows no evidence of dose-dependence (cholesterol tertiles= 15.6g, 18.4g, 18.5g saturated fat). The investigators did not attempt to adjust for confounding factors.

Potato Diet Interpretation

If you read my post on December 16th, you know that Chris Voigt saw remarkable fat loss and improvements in health markers as a result of two months of eating almost nothing but potatoes. This has left many people scratching their heads, because potatoes are not generally viewed as a healthy food. This is partially due to the fact that potatoes are very rich in carbohydrate, which also happens to be a quickly digested type, resulting in a high glycemic index. The glycemic index refers to the degree to which a particular food increases blood glucose when it's eaten, and I've questioned the relevance of this concept to health outcomes in the past (1, 2, 3). I think Mr. Voigt's results once again argue against the importance of the glycemic index as a diet-health concept.

It's often pointed out that potatoes are low in vitamins and minerals compared to vegetables on a per-calorie basis, but I think it's a misleading comparison because potatoes are much more calorie-dense than most vegetables. Potatoes compare favorably to other starchy staples such as bread, rice and taro.

Over the course of two months, Mr. Voigt lost 21 pounds. No one knows exactly how much of that weight came out of fat and how much out of lean mass, but the fact that he reported a decrease in waist and neck circumference indicates that most of it probably came out of fat. Previous long-term potato feeding experiments have indicated that it's possible to maintain an athletic muscle mass on the amount of protein in whole potatoes alone (4). So yes, Mr. Voigt lost fat on a very high-carbohydrate diet (75-80% carbohydrate, up to 440g per day).

On to the most interesting question: why did he lose fat? Losing fat requires that energy leaving the body exceed energy entering the body. But of course, that's obvious but it doesn't get us anywhere. In the first three weeks of his diet, Mr. Voigt estimates that he was only eating 1,600 calories per day. Aha! That's why he lost weight! Well, yes. But let's look into this more deeply. Mr. Voigt was not deliberately restricting his calorie intake at all, and he did not intend this as a weight loss diet. In my interview, I asked him if he was hungry during the diet. He said that he was not hungry, and that he ate to appetite during this period, realizing only after three weeks that he was not eating nearly enough calories to maintain his weight*. I also asked him how his energy level was, and he said repeatedly that it was very good, perhaps even better than usual. Those were not idle questions.

Calorie restriction causes a predictable physiological response in humans that includes hunger and decreased energy. It's the starvation response, and it's powerful in both lean and overweight people, as anyone knows who has tried to lose fat by decreasing calorie intake alone. The fact that he didn't experience hunger or fatigue implies that his body did not think it was starving. Why would that be?

I believe Mr. Voigt's diet lowered his fat mass 'setpoint'. In other words, for whatever reason, the diet made his body 'want' to be leaner that it already was. His body began releasing stored fat that it considered excess, and therefore he had to eat less food to complete his energy needs. You see this same phenomenon very clearly in rodent feeding studies. Changes in diet composition/quality can cause dramatic shifts in the fat mass setpoint (5, 6). Mr. Voigt's appetite would eventually have returned to normal once he had stabilized at a lower body fat mass, just as rodents do.

Rodent studies have made it clear that diet composition has a massive effect on the level of fat mass that the body will 'defend' against changes in calorie intake (5, 6). Human studies have shown similar effects from changes in diet composition/quality. For example, in controlled diet trials, low-carbohydrate dieters spontaneously reduce their calorie intake quite significantly and lose body fat, without being asked to restrict calories (7). In Dr. Staffan Lindeberg's Paleolithic diet trials, participants lost a remarkable amount of fat, yet a recent publication from his group shows that the satiety (fullness) level of the Paleolithic group was not different from a non-Paleolithic comparison group despite a considerably lower calorie intake over 12 weeks (8, 9). I'll discuss this important new paper soon. Together, this suggests that diet composition/quality can have a dominant impact on the fat mass setpoint.

One possibility is that cutting the wheat, sugar, most vegetable oil and other processed food out of Mr. Voigt's diet was responsible for the fat loss.  Many people find, for example, that they lose fat simply by eliminating wheat from their diet.

Another possibility that I've been exploring recently is that changes in palatability (pleasantness of flavor) influence the fat mass setpoint. There is evidence in rodents that it does, although it's not entirely consistent. For example, rats will become massively obese if you provide them with chocolate flavored Ensure (a meal replacement drink), but not with vanilla or strawberry Ensure (10). They will defend their elevated fat mass against calorie restriction (i.e. they show a physiological starvation response when you try to bring them down to a lower weight by feeding them less chocolate Ensure) while they're eating chocolate Ensure, but as soon as you put them back on unpurified rodent pellets, they will lose fat and defend the lower fat mass. Giving them food in liquid or paste form often causes obesity, while the same food in solid pellet form will not. Eating nothing but potatoes is obviously a diet with a low overall palatability.

So I think that both a change in diet composition/quality and a decrease in palatability probably contributed to a decrease in Mr. Voigt's fat mass setpoint, which allowed him to lose fat mass without triggering a starvation response (hunger, fatigue).

The rest of his improvements in health markers were partially due to the fat loss, including his decreased fasting glucose, decreased triglycerides, and presumably increased insulin sensitivity. They may also have been partially due to a lack of industrial food and increased intake of certain micronutrients such as magnesium.

One of the most striking changes was in his calculated LDL cholesterol ("bad" cholesterol), which decreased by 41%, putting him in a range that's more typical of healthy non-industrial cultures including hunter-gatherers. Yet hunter-gatherers didn't eat nothing but potatoes, often didn't eat much starch, and in some cases had a high intake of fat and saturated fat, so what gives? It's possible that a reduced saturated fat intake had an impact on his LDL, given the relatively short timescale of the diet. But I think there's something mysterious about this setpoint mechanism that has a much broader impact on metabolism than is generally appreciated. For example, calorie restriction in humans has a massive impact on LDL, much larger than the impact of saturated fat (11). And in any case, the latter appears to be a short-term phenomenon (12). It's just beginning to be appreciated that energy balance control systems in the brain influence cholesterol metabolism.

Mr. Voigt's digestion appeared to be just fine on his potato diet, even though he generally ate the skins. This makes me even more skeptical of the idea that potato glycoalkaloids in common potato varieties are a health concern, especially if you were to eliminate most of the glycoalkaloids by peeling.

I asked Mr. Voigt about what foods he was craving during the diet to get an idea of whether he was experiencing any major deficiencies. The fact that Mr. Voigt did not mention craving meat or other high-protein foods reinforces the fact that potatoes are a reasonable source of complete protein. The only thing he craved was crunchy/juicy food, which I'm not sure how to interpret.

He also stopped snoring during the diet, and began again immediately upon resuming his normal diet, perhaps indicating that his potato diet reduced airway inflammation. This could be due to avoiding food allergies and irritants (wheat anyone?) and also fat loss.

Overall, a very informative experiment! Enjoy your potatoes.


*Until the last 5.5 weeks, when he deliberately stuffed himself beyond his appetite because his rapid weight loss worried him. Yet, even with deliberate overfeeding up to his estimated calorie requirement of 2,200 calories per day, he continued to lose weight. He probably was not quite reaching his calorie goal, or his requirement is higher than he thought.

Diet-Heart Controlled Trials: a New Literature Review

Many controlled studies have measured the cardiovascular effects of replacing animal ("saturated") fats with seed oils (predominantly the omega-6 polyunsaturated fat linoleic acid) in humans. A number of these studies recorded heart attacks and total mortality during the following 1-8 years. Several investigators have done meta-analyses (literature reviews) to try to tease out overall conclusions from these studies.

I'm pleased to point out a new meta-analysis of these controlled trials by Dr. Christopher Ramsden and colleagues (1). This paper finally cleans up the mess that previous meta-analyses have made of the diet-heart literature. One recent paper in particular by Dr. Dariush Mozaffarian and colleagues concluded that overall, the controlled trials show that replacing animal fat with linoleic acid (LA)-rich seed oils reduces heart attack risk (2). I disagreed strongly with their conclusion because I felt their methods were faulty (3).

Dr. Ramsden and colleagues pointed out several fundamental flaws in the review paper by Dr. Mozaffarian and colleagues, as well as in the prevailing interpretation of these studies in the scientific literature in general. These overlap with the concerns that I voiced in my post (4):

1. Omission of unfavorable studies, including the Rose corn oil trial and the Sydney diet-heart trial.
2. Inclusion of weak trials with major confounding variables, such as the Finnish mental hospital trial.
3. Failure to distinguish between omega-6 and omega-3 fatty acids.
4. Failure to acknowledge that seed oils often replaced large quantities of industrial trans fats in addition to animal fat in these trials.
   

Dr. Ramsden and colleagues accounted for all of these factors in their analysis, which has never been done before. They chose inclusion criteria* that made sense, and stuck with them. In addition, they did an impressive amount of historical work, digging up old unpublished data from these trials to determine the exact composition of the control and experimental diets. The paper is published in the British Journal of Nutrition, an excellent journal, and overall is written in a scientific and professional manner.

What did they find?

• Interventions that replaced animal and trans fat with seed oils that were rich in LA but low in omega-3 caused a non-significant trend toward increased heart attacks (13% increase) and overall mortality.
  
• Interventions that replaced animal and trans fat with a combination of LA and omega-3 fats significantly reduced heart attacks (by 22%). The numbers for total mortality followed a similar trend.

In other words, LA-rich seed oils do not prevent heart attacks (and may actually promote them), but correcting an omega-3 deficiency and reducing industrial trans fat intake may be protective. This is similar to what I've been saying for a while now, based on my own interpretation of the same studies and others. However, Dr. Ramsden and colleagues have taken the idea to a new level by their thorough and sophisticated detective work and analysis. For example, I didn't realize that in virtually all of these controlled trials, the intervention group reduced its trans fat intake substantially in addition to reducing animal fat. From the paper:

...experimental diets replaced common ‘hard’ margarines, industrial shortenings and other sources of [trans fat] in all seven of the [controlled trials] included in the meta-analysis by Mozaffarian et al. The mean estimated [trans fat] content of the seven control diets was 3·0 [% of calories] (range 1·5–9·6 [%]).
...the displacement of [trans fat], rather than the substitution of mixed n-3/n-6 [polyunsaturated fat] for [saturated fat], may account for some or all of the 22% reduction in non-fatal [heart attacks and heart attack] death in our meta-analysis. By contrast, the increased [heart attack] risks from n-6 specific [polyunsaturated fat] diets in our meta-analysis may be underestimated as n-6 [polyunsaturated fat] also replaced substantial quantities of [trans fat] (Table 3). The consistent trends towards increased [heart attack] risk of n-6 specific [polyunsaturated fat] diets may have become significant if the n-6 [polyunsaturated fat] replaced only [saturated fat], instead of a combination of [saturated fat] and [trans fat].

In other words, it looks like trans fat is probably the issue, not animal fat, but these trials replaced both simultaneously so we can't know for sure. I will note here that trans fat does not generally promote atherosclerosis (thickening and hardening of arteries) in animal models, so if it does truly increase heart attack risk as many studies suggest, it's probably through a mechanism that is independent of atherosclerosis.

The article also contains an excellent discussion of the Finnish mental hospital trial (5, 6) and why it was excluded from the meta-analysis, in which Dr. Ramsden and colleagues point out major design flaws, some of which I was not aware of. For example, trans fat intake was on average 13 times higher in the control groups than in the experimental groups. In addition, one of the control groups received more than twice as much of the antipsychotic drug thioridazine, which is known to be highly toxic to the heart, as any other group. Ouch. I'm glad to see this study finally discussed in an open and honest manner. I discussed my own problems with the Finnish trial in an earlier post (7).

I was also glad to see an open discussion of the Oslo Diet-heart study (8), in which diet changes led to a reduction in heart attack risk over five years. Dr. Mozaffarian and colleagues included it in their analysis as if it were a controlled trial in which animal fat was replaced by seed oils only. In reality, the investigators changed many variables at once, which I had also pointed out in my critique of Dr. Mozaffarian's meta-analysis (9). Here's what Dr. Ramsden and colleagues had to say about it:

First, experimental dieters were instructed to substitute fish, shellfish and ‘whale beef’ for meats and eggs, and were actually supplied with ‘considerable quantities of Norwegian sardines canned in cod liver oil, which proved to be popular as a bread spread’(32)... Second, the experimental group consumed massive amounts of soybean oil, which provided large quantities of both LA (15·6 en %) and ALA (2·7 en %). ALA consumption was about 4·5 times average US intake(42), or about twelve typical flax oil pills (1 g pill ¼ 560 mg ALA) per d. In addition, the fish and cod liver oil consumption provided Oslo (598N latitude) dieters with 610 IU (15·25 mg) of daily vitamin D3, recently linked to lower blood pressure, plaque stabilisation, and reduced [heart attack risk] (64). Furthermore, experimental dieters were encouraged to eat more nuts, fruits, and vegetables; to limit animal fats; and to restrict their intake of refined grains and sugar.

trans fat intake was also reduced substantially by excluding margarine in the experimental group. Other review papers have used this trial as a justification to replace animal fat with seed oils. Hmm... The only reason they get away with this is because the trial was published in 1966 and almost no one today has actually read it.

One criticism I have of Dr. Ramsden's paper is that they used the Oslo trial in their analysis, despite the major limitation described above. However, they were extremely open about it and discussed the problem in detail. Furthermore, the overall result would have been essentially the same even if they had excluded the Oslo trial from the analysis.

Overall, the paper is an excellent addition to the literature, and I hope it will bring a new level of sophistication to the dialogue on dietary prevention of cardiovascular disease. In the meantime, brace yourselves for an avalanche of criticism from the seed oil brigade.


* Guidelines that determine which studies to include in the analysis. For example, you want to exclude any study that wasn't randomized, because it will not be interpretable from a statistical standpoint. You also want to exclude trials where major variables differ between groups besides the specific variable you're trying to test. The Finnish mental hospital trial fails by both criteria.

The China Study on Wheat

Denise Minger has just put up another great China Study post that's worth reading if you haven't already. Denise has been busy applying her statistics skills to the mountain of data the study collected. She noted in a previous post that wheat intake was strongly associated with coronary heart disease (CHD), the quintessential modern cardiovascular disease. I, and several other people, requested that she work her mathmagic to see if the association could be due to some other factor. For example, wheat is eaten mostly in the Northern regions of China, and CHD rates are generally higher at higher latitudes (vitamin D insufficiency?). This is true in Europe as well, and may be partly responsible for the purported benefits of the Mediterranean diet. You can mathematically determine if the association between wheat and CHD is simply due to the fact that wheat eaters live further North.

To make a long story short, nothing could explain the association except wheat itself, even latitude. Furthermore, she found a strong association between wheat intake and body mass index, typically a predictor of fat mass although we can't say that for sure. That finding echos a previous study in China where wheat eaters were more likely to be overweight than rice eaters (1, 2). Head over to Denise's post for the full story.

The China Study has major limitations built into its basic design, due to the fact that it was observational and pooled the blood samples of many individuals. Therefore, its findings can never prove anything, they can only suggest or be consistent with hypotheses. However, the study also has some unique advantages, such as a diversity of diets and regions, and the fact that people had presumably been eating a similar diet for a long time. I feel that Denise's efforts are really teasing out some useful information from the study that have been de-emphasized by other investigators.

There has been very little serious investigation into the health effects of wheat in the general population. Researchers studying celiac disease and other forms of gluten allergy, and the efforts of the paleolithic diet community in spreading that information (for example, Loren Cordain and Pedro Bastos), have been major contributors to understanding the health effects of wheat. Denise's analysis is one of the strongest pieces of evidence I've come by so far. I think there's enough indirect evidence that investigators should begin taking the idea seriously that wheat, particularly in the form of industrial flour products, may contribute to chronic disease in more than just a small subset of the population.

Tropical Plant Fats: Coconut Oil, Part I

Traditional Uses for Coconut

Coconut palms are used for a variety of purposes throughout the tropics. Here are a few quotes from the book Polynesia in Early Historic Times:

Most palms begin to produce nuts about five years after germination and continue to yield them for forty to sixty years at a continuous (i.e., nonseasonal) rate, producing about fifty nuts a year. The immature nut contains a tangy liquid that in time transforms into a layer of hard, white flesh on the inner surface of the shell and, somewhat later, a spongy mass of embryo in the nut's cavity. The liquid of the immature nut was often drunk, and the spongy embryo of the mature nut often eaten, raw or cooked, but most nuts used for food were harvested after the meat had been deposited and before the embryo had begun to form...

After the nut had been split, the most common method of extracting its hardened flesh was by scraping it out of the shell with a saw-toothed tool of wood, shell, or stone, usually lashed to a three-footed stand. The shredded meat was then eaten either raw or mixed with some starchy food and then cooked, or had its oily cream extracted, by some form of squeezing, for cooking with other foods or for cosmetic or medical uses...

Those Polynesians fortunate enough to have coconut palms utilized their components not only for drink and food-- in some places the most important, indeed life-supporting food-- but also for building-frames, thatch, screens, caulking material, containers, matting, cordage, weapons, armor, cosmetics, medicine, etc.

Mainstream Ire

Coconut fat is roughly 90 percent saturated, making it one of the most highly saturated fats on the planet. For this reason, it has been the subject of grave pronouncements by health authorities over the course of the last half century, resulting in its near elimination from the industrial food system. If the hypothesis that saturated fat causes heart disease and other health problems is correct, eating coconut oil regularly should tuck us in for a very long nap.

Coconut Eaters

As the Polynesians spread throughout the Eastern Pacific islands, they encountered shallow coral atolls that were not able to sustain their traditional starchy staples, taro, yams and breadfruit. Due to its extreme tolerance for poor, salty soils, the coconut palm was nearly the only food crop that would grow on these islands*. Therefore, their inhabitants lived almost exclusively on coconut and seafood for hundreds of years.

One group of islands that falls into this category is Tokelau, which fortunately for us was the subject of a major epidemiological study that spanned the years 1968 to 1982: the Tokelau Island Migrant Study (1). By this time, Tokelauans had managed to grow some starchy foods such as taro and breadfruit (introduced in the 20th century by Europeans), as well as obtaining some white flour and sugar, but their calories still came predominantly from coconut.

Over the time period in question, Tokelauans obtained roughly half their calories from coconut, placing them among the most extreme consumers of saturated fat in the world. Not only was their blood cholesterol lower than the average Westerner, but their hypertension rate was low, and physicians found no trace of previous heart attacks by ECG (age-adjusted rates: 0.0% in Tokelau vs 3.5% in Tecumseh USA). Migrating to New Zealand and cutting saturated fat intake in half was associated with a rise in ECG signs of heart attack (1.0% age-adjusted) (2, 3).

Diabetes was low in men and average in women by modern Western standards, but increased significantly upon migration to New Zealand and reduction of coconut intake (4). Non-migrant Tokelauans gained body fat at a slower rate than migrants, despite higher physical activity in the latter (5). Together, this evidence seriously challenges the idea that coconut is unhealthy.

The Kitavans also eat an amount of coconut fat that would make Dr. Ancel Keys blush. Dr. Staffan Lindeberg found that they got 21% of their 2,200 calories per day from fat, nearly all of which came from coconut. They were getting 17% of their calories from saturated fat; 55% more than the average American. Dr. Lindeberg's detailed series of studies found no trace of coronary heart disease or stroke, nor any obesity, diabetes or senile dementia even in the very old (6, 7).

Of course, the Tokelauans, Kitavans and other traditional cultures were not eating coconut in the form of refined, hydrogenated coconut oil cake icing. That distinction will be important when I discuss what the biomedical literature has to say in the next post.


* Most also had pandanus palms, which are also tolerant of poor soils and whose fruit provided a small amount of starch and sugar.

Can a Statin Neutralize the Cardiovascular Risk of Unhealthy Dietary Choices?

The title of this post is the exact title of a recent editorial in the American Journal of Cardiology (1). Investigators calculated the "risk for cardiovascular disease associated with the total fat and trans fat content of fast foods", and compared it to the "risk decrease provided by daily statin consumption". Here's what they found:

The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder®) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices.

Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.

Wow. Later in the editorial, they recommend "a new and protective packet, “MacStatin,” which could be sprinkled onto a Quarter Pounder or into a milkshake." I'm not making this up!

I can't be sure, but I think there's a pretty good chance the authors were being facetious in this editorial, in which case I think a) it's hilarious, b) most people aren't going to get the joke. If they are joking, the editorial is designed to shine a light on the sad state of mainstream preventive healthcare. Rather than trying to educate people and change the deadly industrial food system, which is at the root of a constellation of health problems, many people think it's acceptable to partially correct one health risk by tinkering with the human metabolism using drugs. To be fair, most people aren't willing to change their diet and lifestyle habits (and perhaps for some it's even too late), so frustrated physicians prescribe drugs to mitigate the risk. I accept that. But if our society is really committed to its own health and well-being, we'll remove the artificial incentives that favor industrial food, and educate children from a young age on how to eat well.

I think one of the main challenges we face is that our current system is immensely lucrative for powerful financial interests. Industrial agriculture lines the pockets of a few large farmers and executives (while smaller farmers go broke and get bought out), industrial food processing concentrates profit among a handful of mega-manufacturers, and then people who are made ill by the resulting food spend an exorbitant amount of money on increasingly sophisticated (and expensive) healthcare. It's a system that effectively milks US citizens for a huge amount of money, and keeps the economy rolling at the expense of the average person's well-being. All of these groups have powerful lobbies that ensure the continuity of the current system. Litigation isn't the main reason our healthcare is so expensive in the US; high levels of chronic disease, expensive new technology, a "kitchen sink" treatment approach, and inefficient private companies are the real reasons.

If the editorial is serious, there are so many things wrong with it I don't even know where to begin. Here are a few problems:

1. They assume the risk of heart attack conveyed by eating fast food is due to its total and trans fat content, which is simplistic. To support that supposition, they cite one study: the Health Professionals Follow-up Study (2). This is one of the best diet-health observational studies conducted to date. The authors of the editorial appear not to have read the study carefully, because it found no association between total or saturated fat intake and heart attack risk, when adjusted for confounding variables. The number they quoted (relative risk = 1.23) was before adjustment for fiber intake (relative risk = 1.02 after adjustment), and in any case, it was not statistically significant even before adjustment. How did that get past peer review? Answer: reviewers aren't critical of hypotheses they like.
   
2. Statins mostly work in middle-aged men, and reduce the risk of heart attack by about one quarter. The authors excluded several recent unsupportive trials from their analysis. Dr. Michel de Lorgeril reviewed these trials recently (3). For these reasons, adding a statin to fast food would probably have a negligible effect on the heart attack risk of the general population.
   
3. "Statins rarely cause negative side effects." BS. Of the half dozen people I know who have gone on statins, all of them have had some kind of negative side effect, two of them unpleasant enough that they discontinued treatment against their doctor's wishes. Several of them who remained on statins are unlikely to benefit because of their demographic, yet they remain on statins on their doctors' advice.
   
4. Industrial food is probably the main contributor to heart attack risk. Cultures that don't eat industrial food are almost totally free of heart attacks, as demonstrated by a variety of high-quality studies (4, 5, 6, 7, 8, 9). No drug can replicate that, not even close.
   

I have an alternative proposal. Rather than giving people statins along with their Big Mac, why don't we change the incentive structure that artificially favors the Big Mac, french fries and soft drink? If it weren't for corn, soybean and wheat subsidies, fast food wouldn't be so cheap. Neither would any other processed food. Fresh, whole food would be price competitive with industrial food, particularly if we applied the grain subsidies to more wholesome foods. Grass-fed beef and dairy would cost the same as grain-fed. I'm no economist, so I don't know how realistic this really is. However, my central point still stands: we can change the incentive structure so that it no longer artificially favors industrial food. That will require that the American public get fed up and finally butt heads with special interest groups.

Saturated Fat Consumption Still isn't Associated with Heart Attack Risk

The American Journal of Clinical Nutrition just published the results of a major Japanese study on saturated fat intake and cardiovascular disease (1). Investigators measured dietary habits, then followed 58,453 men and women for 14.1 years. They found that people who ate the most saturated fat had the same heart attack risk as those who ate the least*. Furthermore, people who ate the most saturated fat had a lower risk of stroke than those who ate the least. It's notable that stroke is a larger public health threat in Japan than heart attacks.

This is broadly consistent with the rest of the observational studies examining saturated fat intake and cardiovascular disease risk. A recent review paper by Dr. Ronald Krauss's group summed up what is obvious to any unbiased person who is familiar with the literature, that saturated fat consumption doesn't associate with heart attack risk (2). In a series of editorials, some of his colleagues attempted to discredit and intimidate him after its publication (3, 4). No meta-analysis is perfect, but their criticisms were largely unfounded (5, 6).


*Actually, people who ate the most saturated fat had a lower risk but it wasn't statistically significant.

China Study Problems of Interpretation

The China study was an observational study that collected a massive amount of information about diet and health in 65 different rural regions of China. It's been popularized by Dr. T. Colin Campbell, who has argued that the study shows that plant foods are generally superior to animal foods for health, and even a small amount of animal food is harmful. Campbell's book has been at the center of the strict vegetarian (vegan) movement since its publication.

Richard from Free the Animal just passed on some information that many of you may find interesting. A woman named Denise Minger recently published a series of posts on the China study. She looked up the raw data and applied statistics to it. It's the most thorough review of the data I've seen so far. She raises some points about Campbell's interpretation of the data that are frankly disturbing. As I like to say, the problem is usually not in the data-- it's in the interpretation.

One of the things Minger points out is that wheat intake had a massive correlation with coronary heart disease-- one of the strongest correlations the investigators found. Is that because wheat causes CHD, or is it because wheat eating regions tend to be further North and thus have worse vitamin D status? I don't know, but it's an interesting observation nevertheless. Check out Denise Minger's posts... if you have the stamina:

The China Study: Fact or Fallacy

Also, see posts on the China study by Richard Nikoley, Chris Masterjohn and Anthony Colpo:

T. Colin Campbell's the China Study
The Truth About the China Study
The China Study: More Vegan Nonsense

And my previous post on the association between wheat intake and obesity in China:

Wheat in China

Tropical Plant Fats: Palm Oil

A Fatal Case of Nutritionism

The concept of 'nutritionism' was developed by Dr. Gyorgy Scrinis and popularized by the food writer Michael Pollan. It states that the health value of a food can be guessed by the sum of the nutrients it contains. Pollan argues, I think rightfully, that nutritionism is a reductionist philosophy that assumes we know more about food composition and the human body than we actually do. You can find varying degrees of this philosophy in most mainstream discussions of diet and health*.

One conspicuous way nutritionism manifests is in the idea that saturated fat is harmful. Any fat rich in saturated fatty acids is typically assumed to be unhealthy, regardless of its other constituents. There is also apparently no need to directly test that assumption, or even to look through the literature to see if the assumption has already been tested. In this manner, 'saturated' tropical plant fats such as palm oil and coconut oil have been labeled unhealthy, despite essentially no direct evidence that they're harmful. As we'll see, there is actually quite a bit of evidence, both indirect and direct, that their unrefined forms are not harmful and perhaps even beneficial.

Palm Oil and Heart Disease

Long-time readers may recall a post I wrote a while back titled Ischemic Heart Attacks: Disease of Civilization (1). I described a study from 1964 in which investigators looked for signs of heart attacks in thousands of consecutive autopsies in the US and Africa, among other places. They found virtually none in hearts from Nigeria and Uganda (3 non-fatal among more than 4,500 hearts), while Americans of the same age had very high rates (up to 1/3 of hearts).

What do they eat in Nigeria? Typical Nigerian food involves home-processed grains, starchy root vegetables, beans, fruit, vegetables, peanuts, red palm oil, and a bit of dairy, fish and meat**. The oil palm Elaeis guineensis originated in West Africa and remains one of the main dietary fats throughout the region.

To extract the oil, palm fruit are steamed, and the oily flesh is removed and pressed. It's similar to olive oil in that it is extracted gently from an oil-rich fruit, rather than harshly from an oil-poor seed (e.g., corn or soy oil). The oil that results is deep red and is perhaps the most nutrient-rich fat on the planet. The red color comes from carotenes, but red palm oil also contains a large amount of vitamin E (mostly tocotrienols), vitamin K1, coenzyme Q10 and assorted other fat-soluble constituents. This adds up to a very high concentration of fat-soluble antioxidants, which are needed to protect the fat from rancidity in hot and sunny West Africa. Some of these make it into the body when it's ingested, where they appear to protect the body's own fats from oxidation.

Mainstream nutrition authorities state that palm oil should be avoided due to the fact that it's approximately half saturated. This is actually one of the main reasons palm oil was replaced by hydrogenated seed oils in the processed food industry. Saturated fat raises blood cholesterol, which increases the risk of heart disease. Doesn't it? Let's see what the studies have to say.

Most of the studies were done using refined palm oil, unfortunately. Besides only being relevant to processed foods, this method also introduces a new variable because palm oil can be refined and oxidized to varying degrees. However, a few studies were done with red palm oil, and one even compared it to refined palm oil. Dr. Suzanna Scholtz and colleagues put 59 volunteers on diets predominating in sunflower oil, refined palm oil or red palm oil for 4 weeks. LDL cholesterol was not different between the sunflower oil and red palm oil groups, however the red palm oil group saw a significant increase in HDL. LDL and HDL both increased in the refined palm oil group relative to the sunflower oil group (2).

Although the evidence is conflicting, most studies have not been able to replicate the finding that refined palm oil increases LDL relative to less saturated oils (3, 4). This is consistent with studies in a variety of species showing that saturated fat generally doesn't raise LDL compared to monounsaturated fat in the long term, unless a large amount of purified cholesterol is added to the diet (5).

Investigators have also explored the ability of palm oil to promote atherosclerosis, or hardening and thickening of the arteries, in animals. Not only does palm oil not promote atherosclerosis relative to monounsaturated fats (e.g., olive oil), but in its unrefined state it actually protects against atherosclerosis (6, 7). A study in humans hinted at a possible explanation: compared to a monounsaturated oil***, palm oil greatly reduced oxidized LDL (8). As a matter of fact, I've never seen a dietary intervention reduce oxLDL to that degree (69%). oxLDL is a major risk factor for cardiovascular disease, and a much better predictor of risk than the typically measured LDL cholesterol (9). The paper didn't state whether or not the palm oil was refined. I suspect it was lightly refined, but still rich in vitamin E and CoQ10.

As I discussed in my recent interview with Jimmy Moore, atherosclerosis is only one factor in heart attack risk (10). Several other factors are also major determinants of risk: clotting tendency, plaque stability, and susceptibility to arrhythmia. Another factor that I haven't discussed is how resistant the heart muscle is to hypoxia, or loss of oxygen. If the coronary arteries are temporarily blocked-- a frequent occurrence in modern people-- the heart muscle can be damaged. Dietary factors determine the degree of damage that results. For example, in rodents, nitrites derived from green vegetables protect the heart from hypoxia damage (11). It turns out that red palm oil is also protective (12, 13). Red palm oil also protects against high blood pressure in rats, an effect attributed to its ability to reduce oxidative stress (14, 15).

Together, the evidence suggests that red palm oil does not contribute to heart disease risk, and in fact is likely to be protective. The benefits of red palm oil probably come mostly from its minor constituents, i.e. the substances besides its fatty acids. Several studies have shown that a red palm oil extract called palmvitee lowers serum lipids in humans (16, 17). The minor constituents are precisely what are removed during the refining process.

Palm Oil and the Immune System

Red palm oil also has beneficial effects on the immune system in rodents. It protects against bacterial infection when compared with soybean oil (18). It also protects against certain cancers, compared to other oils (19, 20). This may be in part due to its lower content of omega-6 linoleic acid (roughly 10%), and minor constituents.

The Verdict

Yet again, nutritionism has gotten itself into trouble by underestimating the biological complexity of a whole food. Rather than being harmful to human health, red palm oil, an ancient and delicious food, is likely to be protective. It's also one of the cheapest oils available worldwide, due to the oil palm's high productivity. It has a good shelf life and does not require refrigeration. Its strong, savory flavor goes well in stews, particularly meat stews. It isn't available in most grocery stores, but you can find it on the internet. Make sure not to confuse it with refined palm oil or palm kernel oil.


* The approach that Pollan and I favor is a simpler, more empirical one: eat foods that have successfully sustained healthy cultures.

** Some Nigerians are also pastoralists that subsist primarily on dairy.

*** High oleic sunflower oil, from a type of sunflower bred to be high in monounsaturated fat and low in linoleic acid. I think it's probably among the least harmful refined oils. I use it sometimes to make mayonnaise. It's often available in grocery stores, just check the label.

Interview with Jimmy Moore

About two months ago, I did an interview with Jimmy Moore of the Livin' la Vida Low Carb internet empire. I hardly remember what we talked about, but I think it went well. I enjoyed Jimmy's pleasant and open-minded attitude. Head over to Jimmy's website and listen to the interview here.

I do recall making at least one mistake. When discussing heart attacks,I said "atrial fibrillation" when I meant "ventricular fibrillation".

Nitrate: a Protective Factor in Leafy Greens

Cancer Link and Food Sources

Nitrate (NO3) is a molecule that has received a lot of bad press over the years. It is thought to promote digestive cancers, in part due to its ability to form carcinogens when used as a preservative for processed meat. Because of this (1), nitrate was viewed with suspicion and a number of countries imposed strict limits on its use as a food additive.

But what if I told you that by far the greatest source of nitrate in the modern diet isn't processed meat-- but vegetables, particularly leafy greens (2)? And that the evidence linking exposure to nitrate itself has largely failed to materialize? For example, one study found no difference in the incidence of gastric cancer between nitrate fertilizer plant workers and the general population (3). Most other studies in animals and humans have not supported the hypothesis that nitrate itself is carcinogenic (4, 5, 6), but rather that they are only carcinogenic in the context of processed meats due to the formation of carcinogenic nitrosamines. This, combined with recent findings on nitrate biology, has changed the way we think about this molecule in recent years.

A New Example of Human Symbiosis

In 2003, Dr. K. Cosby and colleagues showed that nitrite (NO2; not the same as nitrate) dilates blood vessels in humans when infused into the blood (7). Investigators subsequently uncovered an amazing new example of human-bacteria symbiosis: dietary nitrate (NO3) is absorbed from the gut into the bloodstream and picked up by the salivary glands. It's then secreted into saliva, where oral bacteria use it as an energy source, converting it to nitrite (NO2). After swallowing, the nitrite is reabsorbed into the bloodstream (8). Humans and oral bacteria may have co-evolved to take advantage of this process. Antibacterial mouthwash prevents it.

Nitrate Protects the Cardiovascular System

In 2008, Dr. Andrew J. Webb and colleagues showed that nitrate in the form of 1/2 liter of beet juice (equivalent in volume to about 1.5 soda cans) substantially lowers blood pressure in healthy volunteers for over 24 hours. It also preserved blood vessel performance after brief oxygen deprivation, and reduced the tendency of the blood to clot (9). These are all changes that one would expect to protect against cardiovascular disease. Another group showed that in monkeys, the ability of nitrite to lower blood pressure did not diminish after two weeks, showing that the animals did not develop a tolerance to it on this timescale (10).

Subsequent studies showed that dietary nitrite reduces blood vessel dysfunction and inflammation (CRP) in cholesterol-fed mice (11). Low doses of nitrite also dramatically reduce tissue death in the hearts of mice exposed to conditions mimicking a heart attack, as well as protecting other tissues against oxygen deprivation damage (12). The doses used in this study were the equivalent of a human eating a large serving (100 g; roughly 1/4 lb) of lettuce or spinach.

Mechanism

Nitrite is thought to protect the cardiovascular system by serving as a precursor for nitric oxide (NO), one of the most potent anti-inflammatory and blood vessel-dilating compounds in the body (13). A decrease in blood vessel nitric oxide is probably one of the mechanisms of diet-induced atherosclerosis and increased clotting tendency, and it is likely an early consequence of eating a poor diet (14).

The Long View

Leafy greens were one of the "protective foods" emphasized by the nutrition giant Sir Edward Mellanby (15), along with eggs and high-quality full-fat dairy. There are many reasons to believe greens are an excellent contribution to the human diet, and what researchers have recently learned about nitrate biology certainly reinforces that notion. Leafy greens may be particularly useful for the prevention and reversal of cardiovascular disease, but are likely to have positive effects on other organ systems both in health and disease. It's ironic that a molecule suspected to be the harmful factor in processed meats is turning out to be one of the major protective factors in vegetables.

Pastured Dairy may Prevent Heart Attacks

Not all dairy is created equal. Dairy from grain-fed and pasture-fed cows differs in a number of ways. Pastured dairy contains more fat-soluble nutrients such as vitamin K2, vitamin A, vitamin E, carotenes and omega-3 fatty acids. It also contains more conjugated linoleic acid, a fat-soluble molecule that has been under intense study due to its ability to inhibit obesity and cancer in animals. The findings in human supplementation trials have been mixed, some confirming the animal studies and others not. In feeding experiments in cows, Dr. T. R. Dhiman and colleagues found the following (1):

Cows grazing pasture and receiving no supplemental feed had 500% more conjugated linoleic acid in milk fat than cows fed typical dairy diets.

Fat from ruminants such as cows, sheep and goats is the main source of CLA in the human diet. CLA is fat-soluble. Therefore, skim milk doesn't contain any. It's also present in human body fat in proportion to dietary intake. This can come from dairy or flesh.

In a recent article from the AJCN, Dr. Liesbeth Smit and colleagues examined the level of CLA in the body fat of Costa Rican adults who had suffered a heart attack, and compared it to another group who had not (a case-control study, for the aficionados). People with the highest level of CLA in their body fat were 49% less likely to have had a heart attack, compared to those with the lowest level (2).

Since dairy was the main source of CLA in this population, the association between CLA and heart attack risk is inextricable from the other components in pastured dairy fat. In other words, CLA is simply a marker of pastured dairy fat intake in this population, and the (possible) benefit could just as easily have come from vitamin K2 or something else in the fat.

This study isn't the first one to suggest that pastured dairy fat may be uniquely protective. The Rotterdam and EPIC studies found that a higher vitamin K2 intake is associated with a lower risk of heart attack, cancer and overall mortality (3, 4, 5). In the 1940s, Dr. Weston Price estimated that pastured dairy contains up to 50 times more vitamin K2 than grain-fed dairy. He summarized his findings in the classic book Nutrition and Physical Degeneration. This finding has not been repeated in recent times, but I have a little hunch that may change soon...

Vitamin K2
Cardiovascular Disease and Vitamin K2
Can Vitamin K2 Reverse Arterial Calcification?

Grains as Food: an Update

Improperly Prepared Grain Fiber can be Harmful

Last year, I published a post on the Diet and Reinfarction trial (DART), a controlled trial that increased grain fiber intake using whole wheat bread and wheat bran supplements, and reported long-term health outcomes in people who had previously suffered a heart attack (1). The initial paper found a trend toward increased heart attacks and deaths in the grain fiber-supplemented group at two years, which was not statistically significant.

What I didn't know at the time is that a follow-up study has been published. After mathematically "adjusting" for preexisting conditions and medication use, the result reached statistical significance: people who increased their grain fiber intake had more heart attacks than people who didn't during the two years of the controlled trial. Overall mortality was higher as well, but that didn't reach statistical significance. You have to get past the abstract of the paper to realize this, but fortunately it's free access (2).

Here's a description of what not to eat if you're a Westerner with established heart disease:

Those randomised to fibre advice were encouraged to eat at least six slices of wholemeal bread per day, or an equivalent amount of cereal fibre from a mixture of wholemeal bread, high-fibre breakfast cereals and wheat bran.

Characteristics of Grain Fiber

The term 'fiber' can refer to many different things. Dietary fiber is simply defined as an edible substance that doesn't get digested by the human body. It doesn't even necessarily come from plants. If you eat a shrimp with the shell on, and the shell comes out the other end (which it will), it was fiber.

Grain fiber is a particular class of dietary fiber that has specific characteristics. It's mostly cellulose (like wood; although some grains are rich in soluble fiber as well), and it contains a number of defensive substances and storage molecules that make it more difficult to eat. These may include phytic acid, protease inhibitors, amylase inhibitors, lectins, tannins, saponins, and goitrogens (3). Grain fiber is also a rich source of vitamins and minerals, although the minerals are mostly inaccessible due to grains' high phytic acid content (4, 5, 6).

Every plant food (and some animal foods) has its chemical defense strategy, and grains are no different*. It's just that grains are particularly good at it, and also happen to be one of our staple foods in the modern world. If you don't think grains are naturally inedible for humans, try eating a heaping bowl full of dry, raw whole wheat berries.

Human Ingenuity to the Rescue

Humans are clever creatures, and we've found ways to use grains as a food source, despite not being naturally adapted to eating them**. The most important is our ability to cook. Cooking deactivates many of the harmful substances found in grains and other plant foods. However, some are not deactivated by cooking. These require other strategies to remove or deactivate.

Healthy grain-based cultures don't prepare their grains haphazardly. Throughout the world, using a number of different grains, many have arrived at similar strategies for making grains edible and nutritious. The most common approach involves most or all of these steps:

• Soaking
  
• Grinding
• Removing 50-75% of the bran
  
• Sour fermentation
• Cooking
  

But wait, didn't all healthy traditional cultures eat whole grains? The idea might make us feel warm and fuzzy inside, but it doesn't quite hit the mark. A recent conversation with Ramiel Nagel, author of the book Cure Tooth Decay, disabused me of that notion. He pointed out that in my favorite resource on grain preparation in traditional societies, the Food and Agriculture Organization publication Fermented Cereals: a Global Perspective, many of the recipes call for removing a portion of the bran (7). Some of these recipes probably haven't changed in thousands of years. It's my impression that some traditional cultures eat whole grains, while others eat them partially de-branned.

In the next post, I'll explain why these processing steps greatly improve the nutritional value of grains, and I'll describe recipes from around the world to illustrate the point.


* Including tubers. For example, sweet potatoes contain goitrogens, oxalic acid, and protease inhibitors. Potatoes contain toxic glycoalkaloids. Taro contains oxalic acid and protease inhibitors. Cassava contains highly toxic cyanogens. Some of these substances are deactivated by cooking, others are not. Each food has an associated preparation method that minimizes its toxic qualities. Potatoes are peeled, removing the majority of the glycoalkaloids. Cassava is grated and dried or fermented to inactivate cyanogens. Some cultures ferment taro.

** As opposed to mice, for example, which can survive on raw whole grains.

Copper in Food

Sources of Copper

It isn't hard to get enough copper-- unless you eat an industrial diet. I've compiled a chart showing the copper content of various refined and unrefined foods to illustrate the point. The left side shows industrial staple foods, while the right side shows whole foods. I've incorporated a few that would have been typical of Polynesian and Melanesian cultures apparently free of cardiovascular disease. The serving sizes are what one might reasonably eat at a meal: roughly 200 calories for grains, tubers and whole coconut; 1/4 pound for animal products; 1/2 teaspoon for salt; 1 cup for raw kale; 1 oz for sugar.

Note that beef liver is off the chart at 488 percent of the USDA recommended daily allowance. I don't know if you'd want to sit down and eat a quarter pound of beef liver, but you get the picture. Beef liver is nature's multivitamin: hands down the Most Nutritious Food in the World. That's because it acts as a storage depot for a number of important micronutrients, as well as being a biochemical factory that requires a large amount of B vitamins to function. You can see that muscle tissue isn't a great source of copper compared to other organs.

Beef liver is so full of micronutrients, it shouldn't be eaten every day. Think of it in terms of the composition of a cow's body. The edible carcass is mostly muscle, but a significant portion is liver. I think it makes sense to eat some form of liver about once per week.

Modern Agriculture Produces Micronutrient-poor Foods

The numbers in the graph above come from NutritionData, my main source of food nutrient composition. The problem with relying on this kind of information is it ignores the variability in micronutrient content due to plant strain, soil quality, et cetera.

The unfortunate fact is that micronutrient levels have declined substantially over the course of the 20th century, even in whole foods. Dr. Donald R. Davis has documented the substantial decline in copper and other micronutrients in American foods over the second half of the last century (1). An even more marked decrease has occurred in the UK (2), with similar trends worldwide. On average, the copper content of vegetables in the UK has declined 76 percent since 1940. Most of the decrease has taken place since 1978. Fruits are down 20 percent and meats are down 24 percent.

I find this extremely disturbing, as it will affect even people eating whole food diets. This is yet another reason to buy from artisanal producers, who are likely to use more traditional plant varieties and grow in richer soil. Grass-fed beef should be just as nutritious as it has always been. Some people may also wish to grow, hunt or fish their own food.

Full-fat Dairy for Cardiovascular Health??

[2013 update: a few colleagues and I have published a comprehensive review paper on the association between full-fat dairy consumption and obesity, metabolic health, and cardiovascular disease.  You can find it here.]

I just saw a paper in the AJCN titled "Dairy consumption and patterns of mortality of
Australian adults". It's a prospective study with a 15-year follow-up period. Here's a quote from the abstract:

There was no consistent and significant association between total dairy intake and total or cause-specific mortality. However, compared with those with the lowest intake of full-fat dairy, participants with the highest intake (median intake 339 g/day) had reduced death due to CVD (HR: 0.31; 95% confidence interval (CI): 0.12–0.79; P for trend = 0.04) after adjustment for calcium intake and other confounders. Intakes of low-fat dairy, specific dairy foods, calcium and vitamin D showed no consistent associations.

People who ate the most full-fat dairy had a 69% lower risk of cardiovascular death than those who ate the least. Otherwise stated, people who mostly avoided dairy or consumed low-fat dairy had more than three times the risk of dying of coronary heart disease or stroke than people who ate the most full-fat diary.  This result is an outlier, and also observational so difficult to interpret, but it certainly is difficult to reconcile with the idea that dairy fat is a significant contributor to cardiovascular disease.

Contrary to popular belief, full-fat dairy, including milk, butter and cheese, has never been convincingly linked to cardiovascular disease. What has been linked to cardiovascular disease is milk fat's replacement, margarine. In the Rotterdam study, high vitamin K2 intake was linked to a lower risk of fatal heart attack, aortic calcification and all-cause mortality. Most of the K2 came from full-fat cheese.

From a 2005 literature review on milk and cardiovascular disease in the EJCN:

In total, 10 studies were identified. Their results show a high degree of consistency in the reported risk for heart disease and stroke, all but one study suggesting a relative risk of less than one in subjects with the highest intakes of milk.

...the studies, taken together, suggest that milk drinking may be associated with a small but worthwhile reduction in heart disease and stroke risk.

...All the cohort studies in the present review had, however, been set up at times when reduced-fat milks were unavailable, or scarce.