High-Fat Diets, Obesity and Brain Damage

Many of you have probably heard the news this week:

High-fat diet may damage the brain
Eating a high-fat diet may rapidly injure brain cells
High fat diet injures the brain
Brain injury from high-fat foods

Your brain cells are exploding with every bite of butter!  Just kidding.  The study in question is titled "Obesity is Associated with Hypothalamic Injury in Rodents and Humans", by Dr. Josh Thaler and colleagues, with my mentor Dr. Mike Schwartz as senior author (1).  We collaborated with the labs of Drs. Tamas Horvath and Matthias Tschop.  I'm fourth author on the paper, so let me explain what we found and why it's important.  

The Questions

Among the many questions that interest obesity researchers, two stand out:

1. What causes obesity?
2. Once obesity is established, why is it so difficult to treat?

Our study expands on the efforts of many other labs to answer the first question, and takes a stab at the second one as well.  Dr. Licio Velloso and collaborators were the first to show in 2005 that inflammation in a part of the brain called the hypothalamus contributes to the development of obesity in rodents (2), and this has been independently confirmed several times since then.  The hypothalamus is an important brain region for the regulation of body fatness, and inflammation keeps it from doing its job correctly.

The Findings

Read more »

Seed Oils and Body Fatness-- A Problematic Revisit

Anthony Colpo recently posted a discussion of one of my older posts on seed oils and body fat gain (1), which reminded me that I need to revisit the idea.  As my knowledge of obesity and metabolism has expanded, I feel the evidence behind the hypothesis that seed oils (corn, soybean, etc.) promote obesity due to their linoleic acid (omega-6 fat) content has largely collapsed.

Read more »

Food Reward: a Dominant Factor in Obesity, Part III

Low-Fat Diets

In 2000, the International Journal of Obesity published a nice review article of low-fat diet trials.  It included data from 16 controlled trials lasting from 2-12 months and enrolling 1,910 participants (1).  What sets this review apart is it only covered studies that did not include instructions to restrict calorie intake (ad libitum diets).  On average, low-fat dieters reduced their fat intake from 37.7 to 27.5 percent of calories.  Here's what they found:
Read more »

Clarifications About Carbohydrate and Insulin

My statements about carbohydrate and insulin in the previous post seem to have kicked up some dust!  Some people are even suggesting I've gone low-fat!  I'm going to take this opportunity to be more specific about my positions.

I do not think that post-meal insulin spikes contribute to obesity, and they may even oppose it.  I'm not aware of anyone who researches metabolism for a living who thinks post-meal insulin spikes contribute to obesity, and after having looked into it, I understand why.  It's not a controversial issue in my field as far as I can tell. Elevated fasting insulin is a separate issue-- that's a marker of insulin resistance.  It's important not to confuse the two.  Does insulin resistance contribute to obesity?  I don't know, but it's hypothetically possible since insulin acts like leptin's kid brother in some ways.  As far as I can tell, starch per se and post-meal insulin spikes do not lead to insulin resistance.
Read more »

Healthy Skeptic Podcast and Reader Questions

Chris Kresser, Danny Roddy and I just finished recording the podcast that will be released on May 24th.  It went really well, and we think you'll find it informative and maybe even practical!

Unfortunately, we only got around to answering three of the questions I had selected:

1. How does one lose fat?
2. What do I (Stephan) eat?
3. Why do many people gain fat with age, especially postmenopausal women?

I feel guilty about that, so I'm going to answer three more right now.

Read more »

US Omega-6 and Omega-3 Fat Consumption over the Last Century

Omega-6 and omega-3 polyunsaturated fats (PUFA) are essential nutrients that play many important roles in the body. They are highly bioactive, and so any deviation from ancestral intake norms should probably be viewed with suspicion. I've expressed my opinion many times on this blog that omega-6 consumption is currently too high due to our high intake of refined seed oils (corn, soybean, sunflower, etc.) in industrial nations. Although it's clear that the quantity of omega-6 and omega-3 polyunsaturated fat have changed over the last century, no one had ever published a paper that attempted to systematically quantify it until last month (1).

Drs. Chris Ramsden and Joseph Hibbeln worked on this paper (the first author was Dr. Tanya Blasbalg and the senior author was Dr. Robert Rawlings)-- they were the first and second authors of a different review article I reviewed recently (2). Their new paper is a great reference that I'm sure I'll cite many times. I'm going to briefly review it and highlight a few key points.

1. The intake of omega-6 linoleic acid has increased quite a bit since 1909. It would have been roughly 2.3% of calories in 1909, while in 1999 it was 7.2%. That represents an increase of 213%. Linoleic acid is the form of omega-6 that predominates in seed oils.

2. The intake of omega-3 alpha-linolenic acid has also increased, for reasons that I'll explain below. It changed from 0.35% of calories to 0.72%, an increase of 109%.

3. The intake of long-chain omega-6 and omega-3 fats have decreased. These are the highly bioactive fats for which linoleic acid and alpha-linolenic acid are precursors. Arachidonic acid, DHA, DPA and EPA intakes have declined. This mostly has to do with changing husbandry practices and the replacement of animal fats with seed oils in the diet.

4. The ratio of omega-6 to omega-3 fats has increased. There is still quite a bit of debate over whether the ratios matter, or simply the absolute amount of each. I maintain that there is enough evidence from highly controlled animal studies and the basic biochemistry of PUFAs to tentatively conclude that the ratio is important. At a minimum, we know that excess linoleic acid inhibits omega-3 metabolism (3, 4, 5, 6). The omega-6:3 ratio increased from 5.4:1 to 9.6:1 between 1909 and 2009, a 78% increase.

5. The biggest factor in both linoleic acid and alpha-linolenic acid intake changes was the astonishing rise in soybean oil consumption. Soybean oil consumption increased from virtually nothing to 7.4% of total calories, eclipsing all sources of calories besides sugar, dairy and grains! That's because processed food is stuffed with it. It's essentially a byproduct of defatted soybean meal-- the second most important animal feed after corn. Check out this graph from the paper:

I think this paper is an important piece of the puzzle as we try to figure out what happened to nutrition and health in the US over the last century.

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 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 saturated fat intake and blood cholesterol, they haven't found one. Those findings have essentially been ignored, 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.

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 was much more thorough 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 twisted 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 little or no 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 mostly white rice in some areas. 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 perhaps bordering on malnourishment.

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 change 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 being trumped by other factors. An equally plausible explanation is that people in the very low range of saturated fat intake are the rural poor who eat an impoverished diet that differs in many ways from the diets at the upper end of the range.

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 hint of a 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. If it's a factor at all, it must be rather weak, which is consistent with what has been observed in multiple non-human species (13). I think it's likely that the diet-heart hypothesis rests in part on an over-interpretation of short-term controlled feeding studies. I'd like to see a more open discussion of this in the scientific literature. 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 small 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 made no effort to adjust for confounding variables.

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.

Saturated Fat, Glycemic Index and Insulin Sensitivity: Another Nail in the Coffin

Insulin is a hormone that drives glucose and other nutrients from the bloodstream into cells, among other things. A loss of sensitivity to the insulin signal, called insulin resistance, is a core feature of modern metabolic dysfunction and can lead to type II diabetes and other health problems. Insulin resistance affects a large percentage of people in affluent nations, in fact the majority of people in some places. What causes insulin resistance? Researchers have been trying to figure this out for decades.*

Since saturated fat is blamed for everything from cardiovascular disease to diabetes, it's no surprise that a number of controlled trials have asked if saturated fat feeding causes insulin resistance when compared to other fats. From the way the evidence is sometimes portrayed, you might think it does. However, a careful review of the literature reveals that this position is exaggerated, to put it mildly (1).

The glycemic index, a measure of how much a specific carbohydrate food raises blood sugar, is another darling of the diet-health literature. On the surface, it makes sense: if excess blood sugar is harmful, then foods that increase blood sugar should be harmful. Despite evidence from observational studies, controlled trials as long as 1.5 years have shown that the glycemic index does not influence insulin sensitivity or body fat gain (2, 3, 4). The observational studies may be confounded by the fact that white flour and sugar are the two main high-glycemic foods in most Western diets. Most industrially processed carbohydrate foods also have a high glycemic index, but that doesn't imply that their high glycemic index is the reason they're harmful.

All of this is easy for me to accept, because I'm familiar with examples of traditional cultures eating absurd amounts of saturated fat and/or high-glycemic carbohydrate, and not developing metabolic disease (5, 6, 7). I believe the key is that their food is not industrially processed (along with exercise, sunlight exposure, and probably other factors).

A large new study just published in the American Journal of Clinical nutrition has placed the final nail in the coffin: neither saturated fat nor high glycemic carbohydrate influence insulin sensitivity in humans, at least on the timescale of most controlled trials (8). At 6 months and 720 participants, it was both the largest and one of the longest studies to address the question. Participants were assigned to one of the following diets:

1. High saturated fat, high glycemic index
2. High monounsaturated fat, high glycemic index
3. High monounsaturated fat, low glycemic index
4. Low fat, high glycemic index
5. Low fat, low glycemic index

Compliance to the diets was pretty good. From the nature of the study design, I suspect the authors were expecting participants on diet #1 to fare the worst. They were eating a deadly combination of saturated fat and high glycemic carbohydrate! Well to everyone's dismay except cranks like me, there were no differences in insulin sensitivity between groups at 6 months. Blood pressure also didn't differ between groups, although the low-fat groups lost more weight than the monounsaturated fat groups. The investigators didn't attempt to determine whether the weight loss was fat, lean mass or both. The low-fat groups also saw an increase in the microalbumin:creatinine ratio compared to other groups, indicating a possible deterioration of kidney function.

In my opinion, the literature as a whole consistently shows that if saturated fat or high glycemic carbohydrate influence insulin sensitivity, they do so on a very long timescale, as no effect is detectable in controlled trails of fairly long duration. While it is possible that the controlled trials just didn't last long enough to detect an effect, I think it's more likely that both factors are irrelevant.

Fats were provided by the industrial manufacturer Unilever, and were incorporated into margarines, which I'm sure were just lovely to eat. Carbohydrate was also provided, including "bread, pasta, rice, and cereals." In other words, all participants were eating industrial food. I think these types of investigations often run into problems due to reductionist thinking. I prefer studies like Dr. Staffan Lindeberg's paleolithic diet trials (9, 10, 11). The key difference? They focus mostly on diet quality, not calories or specific nutrients. And they have shown that quality is king!


* Excess body fat is almost certainly a major cause. When fat mass increases beyond a certain point, particularly abdominal fat, the fat tissue typically becomes inflamed. Inflamed fat tissue secretes factors which reduce whole-body insulin sensitivity (12, 13). The big question is: what caused the fat gain?

Tropical Plant Fats: Coconut Oil, Part II

Heart Disease: Animal Studies

Although humans aren't rats, animal studies are useful because they can be tightly controlled and experiments can last for a significant portion of an animal's lifespan. It's essentially impossible to do a tightly controlled 20-year feeding study in humans.

The first paper I'd like to discuss come from the lab of Dr. Thankappan Rajamohan at the university of Kerala (1). Investigators fed three groups of rats different diets:

1. Sunflower oil plus added cholesterol
2. Copra oil, a coconut oil pressed from dried coconuts, plus added cholesterol
3. Freshly pressed virgin coconut oil, plus added cholesterol

Diets 1 and 2 resulted in similar lipids, while diet 3 resulted in lower LDL and higher HDL. A second study also showed that diet 3 resulted in lower oxidized LDL, a dominant heart disease risk factor (2). Overall, these papers showed that freshly pressed virgin coconut oil, with its full complement of "minor constituents"*, partially protects rats against the harmful effects of cholesterol overfeeding. These are the only papers I could find on the cardiovascular effects of unrefined coconut oil in animals!

Although unrefined coconut oil appears to be superior, even refined coconut oil isn't as bad as it's made out to be. For example, compared to refined olive oil, refined coconut oil protects against atherosclerosis (hardening and thickening of the arteries) in a mouse model of coronary heart disease (LDL receptor knockout). In the same paper, coconut oil caused more atherosclerosis in a different mouse model (ApoE knockout) (3). So the vascular effects of coconut oil depend in part on the animals' genetic background.

In general, I've found that the data are extremely variable from one study to the next, with no consistent trend showing refined coconut oil to be protective or harmful relative to refined monounsaturated fats (like olive oil) (4). In some cases, polyunsaturated oils cause less atherosclerosis than coconut oil in the context of an extreme high-cholesterol diet because they sometimes lead to blood lipid levels that are up to 50% lower. However, even this isn't consistent across experiments. Keep in mind that atherosclerosis is only one factor in heart attack risk.

What happens if you feed coconut oil to animals without adding cholesterol, and without giving them genetic mutations that promote atherosclerosis? Again, the data are contradictory. In rabbits, one investigator showed that serum cholesterol increases transiently, returning to baseline after about 6 months, and atherosclerosis does not ensue (5). A different investigator showed that coconut oil feeding results in lower blood lipid oxidation than sunflower oil (6). Yet a study from the 1980s showed that in the context of a terrible diet composition (40% sugar, isolated casein, fat, vitamins and minerals), refined coconut oil causes elevated blood lipids and atherosclerosis (7). This is almost certainly because overall diet quality influences the response to dietary fats in rabbits, as it does in other mammals.

Heart Disease: Human Studies

It's one of the great tragedies of modern biomedical research that most studies focus on nutrients rather than foods. This phenomenon is called "nutritionism". Consequently, most of the studies on coconut oil used a refined version, because the investigators were most interested in the effect of specific fatty acids. The vitamins, polyphenols and other minor constituents of unrefined oils are eliminated because they are known to alter the biological effects of the fats themselves. Unfortunately, any findings that result from these experiments apply only to refined fats. This is the fallacy of the "X fatty acid does this and that" type statements-- they ignore the biological complexity of whole foods. They would probably be correct if you were drinking purified fatty acids from a beaker.

Generally, the short-term feeding studies using refined coconut oil show that it increases both LDL ("bad cholesterol") and HDL ("good cholesterol"), although there is so much variability between studies that it makes firm conclusions difficult to draw (8, 9). As I've written in the past, the ability of saturated fats to elevate LDL appears to be temporary; both human and certain animal studies show that it disappears on timescales of one year or longer (10, 11). That hasn't been shown specifically for coconut oil that I'm aware of, but it could be one of the reasons why traditional cultures eating high-coconut diets don't have elevated serum cholesterol.

Another marker of cardiovascular disease risk is lipoprotein (a), abbreviated Lp(a). This lipoprotein is a carrier for oxidized lipids in the blood, and it correlates with a higher risk of heart attack. Refined coconut oil appears to lower Lp(a), while refined sunflower oil increases it (12).

Unfortunately, I haven't been able to find any particularly informative studies on unrefined coconut oil in humans. The closest I found was a study from Brazil showing that coconut oil reduced abdominal obesity better than soybean oil in conjunction with a low-calorie diet, without increasing LDL (13). It would be nice to have more evidence in humans confirming what has been shown in rats that there's a big difference between unrefined and refined coconut oil.

Coconut Oil and Body Fat

In addition to the study mentioned above, a number of experiments in animals have shown that "medium-chain triglycerides", the predominant type of fat in coconut oil, lead to a lower body fat percentage than most other fats (14). These findings have been replicated numerous times in humans, although the results have not always been consistent (15). It's interesting to me that these very same medium-chain saturated fats that are being researched as a fat loss tool are also considered by mainstream diet-heart researchers to be among the most deadly fatty acids.

Coconut Oil and Cancer

Refined coconut oil produces less cancer than seed oils in experimental animals, probably because it's much lower in omega-6 polyunsaturated fat (16, 17). I haven't seen any data in humans.

The Bottom Line

There's very little known about the effect of unrefined coconut oil on animal and human health, however what is published appears to be positive, and is broadly consistent with the health of traditional cultures eating unrefined coconut foods. The data on refined coconut oil are conflicting and frustrating to sort through. The effects of refined coconut oil seem to depend highly on dietary context and genetic background. In my opinion, virgin coconut oil can be part of a healthy diet, and may even have health benefits in some contexts.


* Substances other than the fat itself, e.g. vitamin E and polyphenols. These are removed during oil refining.

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 Cardiovascular Disease

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.

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.

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?

Intervew with Chris Kresser of The Healthy Skeptic

Last week, I did an audio interview with Chris Kresser of The Healthy Skeptic, on the topic of obesity. We put some preparation into it, and I think it's my best interview yet. Chris was a gracious host. We covered some interesting ground, including (list copied from Chris's post):

• The little known causes of the obesity epidemic
• Why the common weight loss advice to “eat less and exercise more” isn’t effective
• The long-term results of various weight loss diets (low-carb, low-fat, etc.)
• The body-fat setpoint and its relevance to weight regulation
• The importance of gut flora in weight regulation
• The role of industrial seed oils in the obesity epidemic
• Obesity as immunological and inflammatory disease
• Strategies for preventing weight gain and promoting weight loss

Some of the information we discussed is not yet available on my blog. You can listen to the interview through Chris's post here.

Saturated Fat and Insulin Sensitivity, Again

A new study was recently published exploring the effect of diet composition on insulin sensitivity and other factors in humans (1). 29 men with metabolic syndrome-- including abdominal obesity, low HDL, high blood pressure, high triglycerides, and high fasting glucose-- were fed one of four diets for 12 weeks:

1. A diet containing 38% fat: 16% saturated (SFA), 12% monounsaturated (MUFA) and 6% polyunsaturated (PUFA)
   
2. A diet containing 38% fat: 8% SFA, 20% MUFA and 6% PUFA
3. A diet high in unrefined carbohydrate, containing 28% fat (8% SFA, 11% MUFA and 6% PUFA)
4. A diet high in unrefined carbohydrate, containing 28% fat (8% SFA, 11% MUFA and 6% PUFA) and an omega-3 supplement (1.24 g/day EPA and DHA)
   

After 12 weeks, insulin sensitivity, fasting glucose, glucose tolerance, and blood pressure did not change significantly in any of the four groups. This is consistent with the majority of the studies that have examined this question, although somehow the idea persists that saturated fat impairs insulin sensitivity. I discussed this in more detail in a recent post (2).

The paper that's typically cited by people who wish to defend the idea that saturated fat impairs insulin sensitivity is the KANWU study (3). In this study, investigators found no significant difference in insulin sensitivity between volunteers fed primarily SFA or MUFA for 12 weeks. You wouldn't realize this from the abstract however; you have to look very closely at the p-values in table 4.

One of the questions one could legitimately ask, however, is whether SFA have a different effect on people with metabolic syndrome. Maybe the inflammation and metabolic problems they already have make them more sensitive to the hypothetical damaging effects of SFA? That's the question the first study addressed, and it appears that SFA are not uniquely harmful to insulin signaling in those with metabolic syndrome on the timescale tested.

It also showed that the different diets did not alter the proportion of blood fats being burned in muscle, as opposed to being stored in fat tissue. The human body is a remarkably adaptable biological machine that can make the best of a variety of nutrient inputs, at least over the course of 12 weeks. Metabolic damage takes decades to accumulate, and in my opinion is more dependent on food quality than macronutrient composition. Once metabolic dysfunction is established, some people may benefit from carbohydrate restriction, however.

Full-fat Dairy for Cardiovascular Health

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.

Contrary to popular belief, full-fat dairy, including milk, butter and cheese, has never been convincingly linked to cardiovascular disease. In fact, it has rather consistently been linked to a lower risk, particularly for stroke. 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. In my opinion, artisanal cheese and butter made from pasture-fed milk are the ultimate dairy foods.

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.

The fat is where the vitamins A, K2, E and D are. The fat is where the medium-chain triglycerides, butyric acid and omega-3 fatty acids are. The fat is where the conjugated linoleic acid is. So the next time someone admonishes you to reduce your dairy fat intake, what are you going to tell them??

New Review of Controlled Trials Replacing Saturated fat with Industrial Seed Oils

Readers Stanley and JBG just informed me of a new review paper by Dr. Dariush Mozaffarian and colleagues. Dr. Mozaffarian is one of the Harvard epidemiologists responsible for the Nurse's Health study. The authors claim that overall, the controlled trials show that replacing saturated fat with polyunsaturated fat from industrial seed oils, but not carbohydrate or monounsaturated fat (as in olive oil), slightly reduces the risk of having a heart attack:

These findings provide evidence that consuming PUFA in place of SFA reduces CHD events in RCTs [how do you like the acronyms?]. This suggests that rather than trying to lower PUFA consumption, a shift toward greater population PUFA consumption in place of SFA would significantly reduce rates of CHD.

Looking at the studies they included in their analysis (and at those they excluded), it looks like they did a very nice job cherry picking. For example:

• They included the Finnish Mental Hospital trial, which is a terrible trial for a number of reasons. It wasn't randomized, appropriately controlled or even semi-blinded*. Thus, it doesn't fit the authors' stated inclusion criteria, but they included it in their analysis anyway**. Besides, the magnitude of the result has never been replicated by better trials, not even close.
  
• They included two trials that changed more than just the proportion of SFA to PUFA. For example, the Oslo Diet-heart trial replaced animal fat with seed oils, but also increased fruit, nut, vegetable and fish intake, while reducing trans fat margarine intake! The STARS trial increased both omega-6 and omega-3, reduced processed food intake, and increased fruit and vegetable intake! These obviously aren't controlled trials isolating the issue of dietary fat substitution. If you subtract the four inappropriate trials from their analysis, which is half the studies they analyzed, the result disappears. Those four just happened to show the largest reduction in heart attack mortality...
  
• They excluded the Rose et al. corn oil trial and the Sydney Diet-heart trial. Both found a large increase in total mortality from replacing animal fat with seed oils, and the Rose trial found a large increase in heart attack deaths (the Sydney trial didn't report CHD deaths, but Dr. Mozaffarian et al. stated in their paper that they contacted authors to obtain unpublished results. Why didn't they contact the authors of this study?).

The authors claim, based on their analysis, that replacing 5% of calories as saturated fat with polyunsaturated fat would reduce the risk of having a heart attack by 10%. Take a minute to think about the implications of that statement. For the average American, that means cutting saturated fat nearly in half to 6% of energy, which is a real challenge if you want to have a semblance of a normal diet. It also means nearly doubling PUFA intake, which will come mostly from seed oils if you follow the authors' advice.

So basically, even if the authors' conclusion were correct, you overhaul your whole diet and replace natural foods with bland unnatural foods, and...? You reduce your 10-year risk of having a heart attack from 10 percent to 9 percent. Without affecting your overall risk of dying! The paper states that the interventions didn't affect overall mortality at all. That's what they're talking about here. Sign me up!


* Autopsies were not conducted in a blinded manner. Physicians knew which hospital the cadavers came from, because autopsies were done on-site. There is some confusion about this point because the second paper states that physicians interpreted the autopsy reports in a blinded manner. But that doesn't make it blinded, since the autopsies weren't blinded. The patients were also not blinded, so the study overall was highly susceptible to bias.

** They refer to it as "cluster randomized". I don't know if that term accurately applies to the Finnish trial or not. The investigators definitely didn't randomize the individual patients: whichever hospital a person was being treated in, that's the food he/she ate. There were only two hospitals, so "cluster randomization" in this case would just refer to deciding which hospital got the intervention first. Can this accurately be called randomized?

Fatty Liver: It's not Just for Grown-ups Anymore

The epidemic of non-alcoholic fatty liver disease (NAFLD) is one of my favorite topics on this blog, due to the liver's role as the body's metabolic "grand central station", as Dr. Philip Wood puts it. The liver plays a critical part in the regulation of sugar, insulin, and lipid levels in the blood. Many of the routine blood tests administered in the doctor's office (blood glucose, cholesterol, etc.) partially reflect liver function.

NAFLD is an excessive accumulation of fat in the liver that impairs its function and can lead to severe liver inflammation (NASH), and in a small percentage of people, liver cancer. An estimated 20-30% of people in industrial nations suffer from NAFLD, a shockingly high prevalence (1).

I previously posted on dietary factors I believe are involved in NAFLD. In rodents, feeding a large amount of sugar or industrial seed oils (corn oil, etc.) promotes NAFLD, whereas fats such as butter and coconut oil do not (2). In human infants, enteric feeding with industrial seed oils causes severe liver damage, whereas the same amount of fat from fish oil doesn't, and can even reverse the damage done by seed oils (3).

So basically, I think sugar and industrial oils are major contributors to NAFLD, and if you look at diet trends in the US over the last 40 years, they're consistent with the idea. Industrial oils are harmful due (at least in part) to their high omega-6 content, which is problematic partially because it disturbs normal omega-3 metabolism. A potential solution to fatty liver is to reduce sugar, replace industrial oils with natural fats, and ensure a regular source of omega-3. I've posted two anecdotes of people rapidly healing their fatty livers using diet changes* (4, 5).

I recently came across a study that examined the diet of Canadian children with NAFLD (6). The children had a high sugar intake, a typical (i.e., high) omega-6 intake, and a low omega-3 intake. The authors claimed that the children also had a high saturated fat intake, but at 10.5% of calories, they were almost eating to the American Heart Association's "Step I" diet recommendations**. Busted! Total fat intake was also low.

High sugar consumption was associated with a larger waist circumference, insulin resistance, lower adiponectin and elevated markers of inflammation. High omega-6 intake was associated with markers of inflammation. Low omega-3 intake was associated with insulin resistance and elevated liver enzymes. Saturated fat intake presumably had no relation to any of these markers, since they didn't mention it in the text.

These children with NAFLD, who were all insulin resistant and mostly obese, had diets high in omega-6, high in sugar, and low in omega-3. This is consistent with the idea that these three factors, which have all been moving in the wrong direction in the last 40 years, contribute to NAFLD.


* Fatty liver was assessed by liver enzymes, admittedly not a perfect test. However, elevated liver enzymes do correlate fairly well with NAFLD.

** Steps I and II were replaced by new diet advice in 2000. The AHA now recommends keeping saturated fat below 7% of calories. Stock up on those skinless chicken breasts! Make sure there isn't any residual fat sticking to the meat, it might kill you. I do have to give the AHA credit however, because their new recommendations focus mostly on eating real food rather than avoiding saturated fat and cholesterol.

Corn Oil and Cancer: Reality Strikes Again

The benefits of corn oil keep rolling in. In a new study by Stephen Freedland's group at Duke, feeding mice a diet rich in butter and lard didn't promote the growth of transplanted human prostate cancer cells any more than a low-fat diet (1).

Why do we care? Because other studies, including one from the same investigators, show that corn oil and other industrial seed oils strongly promote prostate cancer cell growth and increase mortality in similar models (2, 3).

From the discussion section:

Current results combined with our prior results suggest that lowering the fat content of a primarily saturated fat diet offers little survival benefit in an intact or castrated LAPC-4 xenograft model. In contrast to the findings when omega-6 fats are used, these results raise the possibility that fat type may be as important as fat amount or perhaps even more important.

The authors seem somewhat surprised and pained by the result. Kudos for publishing it. However, there's nothing to be surprised about. There's a large body of evidence implicating excess omega-6 fat in a number of cancer models. Reducing omega-6 to below 4% of calories has a dramatic effect on cancer incidence and progression*. In fact, there have even been several experiments showing that butter and other animal fats promote cancer growth to a lesser degree than margarine and omega-6-rich seed oils. I discussed that here.

I do have one gripe with the study. They refer to the diet as "saturated fat based". That's inaccurate terminology. I see it constantly in the diet-health literature. If it were coconut oil, then maybe I could excuse it, because coconut fat is 93% saturated. But this diet was made of lard and butter, the combination of which is probably about half saturated. The term "animal fat" or "low-omega-6 fat" would have been more accurate. At least they listed the diet composition. Many studies don't even bother, leaving it to the reader to decide what they mean by "saturated fat".


* The average American eats 7-8% omega-6 by calories. This means it will be difficult to see a relationship between omega-6 intake and cancer (or heart disease, or most things) in observational studies in the US or other industrial nations, because we virtually all eat more than 4% of calories as omega-6. Until the 20th century, omega-6 intake was below 4%, and usually closer to 2%, in most traditional societies. That's where it remains in contemporary traditional societies unaffected by industrial food habits, such as Kitava. Our current omega-6 intake is outside the evolutionary norm.