Interesting Articles in the AJCN

I just received an RSS alert for the American Journal of Clinical Nutrition's latest articles. This upcoming issue is full of very interesting material:

1. Dr. Neil D. Barnard reviews food consumption patterns in the US from 1909 to 2007 (1). This is something I've written about a number of times. The most notable change is that industrial seed oil use has increased by more than 3-fold in the last 40 years, and even more in the last 100 although he doesn't provide those numbers. Butter and lard use declined sharply. Meat consumption is up, but the increase comes exclusively from poultry because we're eating the same amount of red meat we always have. Grain consumption is down, although it peaked around 1900 so it may not be a fair comparison with today:

In the late 1800s, wheat flours became more popular and available due to the introduction of new [high-gluten] wheat varieties, [low extraction] milling techniques, and transport methods, and during this time new breakfast cereals were introduced by John Harvey Kellogg, CW Post, and the Quaker Oats Company. Thereafter, however, per capita availability of flour and cereal products gradually dropped as increased prosperity, improved mechanization, and transport (eg, refrigerated railway cars) increased competition from other food groups. [Then they partially rebounded in the last 40 years]

2. Dr. S.C. Larsson published a paper showing that in Sweden, multivitamin use is associated with a slightly higher risk of breast cancer (2).

3. Soy protein and isoflavones, which have been proposed to do everything from increase bone mineral density to fight cancer, are slowly falling out of favor. Dr. Z.M. Liu and colleagues show that soy protein and/or isoflavone supplementation has no effect on insulin sensitivity or glucose tolerance in a 6 month trial (3). This follows a recent trial showing that isoflavones have no effect on bone mineral density.

4. Dr. Ines Birlouez-Aragon and colleagues showed that high-heat cooked (fried and sauteed) foods increase risk factors for diabetes and cardiovascular disease (insulin resistance, cholesterol, triglycerides), compared to low-heat cooked foods (steamed, stewed) in a one-month trial (4). The high-heat diet also reduced serum levels of long-chain omega-3 fatty acids and vitamins C and E.

5. Dr. Katharina Nimptsch and colleagues showed that higher menaquinone (vitamin K2) intake is associated with a lower cancer incidence and lower cancer mortality in Europeans (5). Most of their K2 came from cheese.

6. And finally, Dr. Zhaoping Li and colleagues showed that cooking meat with an herb and spice blend reduced the levels of oxidized fat during cooking, and reduced serum and urinary markers of lipid oxidation in people eating the meat (6).

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. 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 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, properly controlled, or 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 significant 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 reported total mortality but not CHD deaths).

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 challenge if you want to eat 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 industrial 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.


* Not even single blinded.  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, though this is hard to accomplish with a study like this.

** They refer to it as "cluster randomized", which I feel is a misuse of that term.  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. I don't think this counts as cluster randomization.  An example of cluster randomization would be if you had 10 hospitals, and you randomized which hospital received which treatment first.  It's analogous to individual randomization but on a group scale.

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). [2013 update: obesity is probably the main contributor to NAFLD.  Obesity is associated with ectopic fat deposition in a number of organs, including the liver]

So basically, I think excessive sugar and industrial oils could be involved NAFLD, and if you look at diet trends in the US over the last 40 years, they're consistent with the idea.

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**! 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.  However, the new recommendations focus mostly on eating real food rather than avoiding saturated fat and cholesterol.

Book Review: The Primal Blueprint

Mark Sisson has been a central figure in the evolutionary health community since he began his weblog Mark's Daily Apple in 2006. He and his staff have been posting daily on his blog ever since. He has also written several other books, edited the Optimum Health newsletter, competed as a high-level endurance athlete, and served on the International Triathlon Union as the anti-doping chairman, all of which you can read about on his biography page. Mark is a practice-what-you-preach kind of guy, and if physical appearance means anything, he's on to something.

In 2009, Mark published his long-awaited book The Primal Blueprint. He self-published the book, which has advantages and disadvantages. The big advantage is that you aren't subject to the sometimes onerous demands of publishers, who attempt to maximize sales at Barnes and Noble. The front cover sports a simple picture of Mark, rather than a sunbaked swimsuit model, and the back cover offers no ridiculous claims of instant beauty and fat loss.

The drawback of self-publishing is it's more difficult to break into a wider market. That's why Mark has asked me to publish my review of his book today. He's trying to push it up in the Amazon.com rankings so that it gets a broader exposure. If you've been thinking about buying Mark's book, now is a good time to do it. If you order it from Amazon.com on March 17th, Mark is offering to sweeten the deal with some freebies on his site Mark's Daily Apple. Full disclosure: I'm not getting anything out of this, I'm simply mentioning it because I was reviewing Mark's book anyway and I thought some readers might enjoy it.

The Primal Blueprint is not a weight loss or diet book, it's a lifestyle program with an evolutionary slant. Mark uses the example of historical and contemporary hunter-gatherers as a model, and attempts to apply those lessons to life in the 21st century. He does it in a way that's empowering accessible to nearly everyone. To illustrate his points, he uses the example of an archetypal hunter-gatherer called Grok, and his 21st century mirror image, the Korg family.

The diet section will be familiar to anyone who has read about "paleolithic"-type diets. He advocates eating meats including organs, seafood, eggs, nuts, abundant vegetables, and fruit. He also suggests avoiding grains, legumes, dairy (although he's not very militant about this one), processed food in general, and reducing carbohydrate to less than 150 grams per day. I like his diet suggestions because they focus on real food. Mark is not a drill sergeant. He tries to create a plan that will be sustainable in the long run, by staying positive and allowing for cheats.

We part ways on the issue of carbohydrate. He suggests that eating more than 150 grams of carbohydrate per day leads to fat gain and disease, whereas I feel that position is untenable in light of what we know of non-industrial cultures (including some relatively high-carbohydrate hunter-gatherers). Although carbohydrate restriction (or at least wheat and sugar restriction) does have its place in treating obesity and metabolic dysfunction in modern populations, ultimately I don't think it's necessary for the prevention of those same problems, and it can even be counterproductive in some cases. Mark does acknowledge that refined carbohydrates are the main culprits.

The book's diet section also recommends nutritional supplements, including a multivitamin/mineral, antioxidant supplement, probiotics, protein powder and fish oil. I'm not a big proponent of supplementation. I'm also a bit of a hypocrite because I do take small doses of fish oil (when I haven't had seafood recently), and vitamin D in wintertime. But I can't get behind protein powders and antioxidant supplements.

Mark's suggestions for exercise, sun exposure, sleep and stress management make good sense to me. In a nutshell: do all three, but keep the exercise varied and don't overdo it. As a former high-level endurance athlete, he has a lot of credibility here. He puts everything in a format that's practical, accessible and empowering.

I think The Primal Blueprint is a useful book for a person who wants to maintain or improve her health. Although we disagree on the issue of carbohydrate, the diet and lifestyle advice is solid and will definitely be a vast improvement over what the average person is doing. The Primal Blueprint is not an academic book, nor does it attempt to be. It doesn't contain many references (although it does contain some), and it won't satisfy someone looking for an in-depth discussion of the scientific literature. However, it's perfect for someone who's getting started and needs guidance, or who simply wants a more comprehensive source than reading blog snippets. It would make a great gift for that family member or friend who's been asking how you stay in such good shape.

Vitamin D May Prevent Flu and Asthma

The AJCN just published a new controlled trial evaluating the effectiveness of vitamin D supplements on flu and asthma (1). Dr. Hiroyuki Ida's group gave Japanese schoolchildren (10 years average age) 1,200 IU of vitamin D3 or placebo per day from December through March. They found that children taking vitamin D had a significantly lower incidence of influenza A but not influenza B. These are two strains of flu that each accounted for roughly half the flu incidence in this population. Sadly, if you add the total flu incidence for A and B together (which the authors don't do in their tables), vitamin D supplementation didn't reduce total flu incidence significantly.

They also found that in the subset of children not already taking vitamin D supplements, the effect was greater, with unsupplemented children contracting nearly three times as many influenza A infections as children receiving vitamin D. They didn't analyze the influenza B or total influenza incidence in that way, so we don't know if prior supplementation makes a difference there.

The most striking finding of the paper is that the vitamin D group suffered from 6 times fewer asthma attacks than the placebo group. This needs to be repeated but it's consistent with other data and I find it very encouraging.

The paper did have some limitations. They didn't measure vitamin D status so they have no way to know exactly how effective their pill-based supplements were.

Another problem is that they began collecting data immediately after beginning supplementation. Vitamin D is a fat-soluble vitamin that can take 3 months to reach maximum concentration in the body following supplementation. By the time the children were reaching their maximum serum concentration of vitamin D, the trial was over. It would be nice to see the next trial begin supplementation in the fall and look at flu incidence in the winter.

This paper comes on the heels of another showing that vitamin D is necessary for the activation of an immune cell called the killer T cell (2). These are important for resistance to infections and cancer. Overall, these papers add to the accumulating evidence that vitamin D is important for the proper functioning of the human immune system. However, mice may not be the best model for use in studying vitamin D biology. From the first paper:

The evolution of different mechanisms for the regulation of PLC-γ1 activity in human and mouse T cells parallels the development of divergent VDR-dependent and VDR-independent antimicrobial pathways in human and mouse macrophages31, respectively, and may reflect the fact that mice are nocturnal animals with fur and humans are daytime creatures that synthesize vitamin D in the skin after exposure to ultraviolet light.

In other words, mice don't use vitamin D in the same way as humans because they have a different evolutionary relationship to it.