Margarine and Phytosterolemia

Margarine is one of my favorite foods. To rip on. It's just so easy!

The body has a number of ways of keeping bad things out while taking good things in. One of the things it likes to keep out are plant sterols and stanols (phytosterols), cholesterol-like molecules found in plants. The human body even has two enzymes dedicated to pumping phytosterols back into the gut as they try to diffuse across the intestinal lining: the sterolins. These enzymes actively block phytosterols from passing into the body, but allow cholesterol to enter. Still, a little bit gets through, proportional to the amount in the diet.

As a matter of fact, the body tries to keep most things out except for the essential nutrients and a few other useful molecules. Phytosterols, plant "antioxidants" like polyphenols, and just about anything else that isn't body building material gets actively excluded from circulation or rapidly broken down by the liver. And almost none of it gets past the blood-brain barrier, which protects one of our most delicate organs. It's not surprising once you understand that many of these substances are bioactive: they have drug-like effects that interfere with enzyme activity and signaling pathways. For example, the soy isoflavone genistein abnormally activates estrogen receptors. Your body does not like to hand over the steering wheel to plant chemicals, so it actively defends itself.

A number of trials have shown that large amounts of phytosterols in the diet lower total cholesterol and LDL. This has led to the (still untested) belief that phytosterols lower heart attack risk. The main problem with this belief is that statins are the only cholesterol- and LDL-lowering therapy that also lowers mortality (in some specific groups of people), and the survival benefit of statins is probably not even mediated by their cholesterol-lowering effects! See this article by Anthony Colpo for further reading.

Lowering total cholesterol and LDL through diet and drugs other than statins does not reduce mortality in controlled trials. Decades of controlled diet trials showed that replacing saturated fat with polyunsaturated vegetable oil lowers cholesterol, lowers LDL, but doesn't touch total mortality or death from cardiovascular disease. Soy contains a lot of phytosterols, which is one of the reasons it's heavily promoted as a health food.

All right, let's put on our entrepreneur hats. We know phytosterols lower cholesterol. We know soy is being promoted as a healthier alternative to meat. We know butter is being demonized as a source of artery-clogging saturated fat. I have an idea. Let's make a margarine that contains a massive dose of phytosterols and market it as heart-healthy. We'll call it Benecol, and we'll have doctors recommend it to cardiac patients.

Here are the ingredients:

Liquid Canola Oil, Water, Partially Hydrogenated Soybean Oil, Plant Stanol Esters, Salt, Emulsifiers, (Vegetable Mono- and Diglycerides, Soy Lecithin), Hydrogentated Soybean Oil, Potassium Sorbate, Citric Acid and Calcium Disodium EDTA to Preserve Freshness, Artificial Flavor, DL-alpha-Tocopheryl Acetate, Vitamin A Palmitate, Colored with Beta Carotene.

Are you kidding me? Partially hydrogenated soybean oil for cardiac patients? A nice big dose of omega-6 linoleic acid? A mega-dose of "heart-healthy" plant stanols? This stuff is like a molotov cocktail for your coronary arteries!

And I haven't even gotten to the best part yet. There's a little disorder called phytosterolemia that proponents of phytosterols conveniently ignore. These patients have a mutation in one of their sterolin genes that allows phytosterols (including stanols) to pass into their circulation more easily. They end up with 10-25 times more phytosterols in their circulation than a normal individual. What kind of health benefits do these people see? Premature atherosclerosis, an early death from heart attacks, abnormal accumulation of sterols and stanols in the tendons, and liver damage.

Despite the snappy-looking tub, margarine is just another industrial food-like substance that will help you get underground in a hurry. In the U.S., manufacturers can put the statement "no trans fat" on a product's label, and "0 g trans fat" on the nutrition label, if it contains less than 0.5 grams of trans fat per serving. A serving of Benecol is 14 grams. That means it could be up to 3.5 percent trans fat and still labeled "no trans fat". That's a crime. This stuff is being recommended to cardiac patients.

When deciding whether or not a food is healthy, the precautionary principle is in order. Margarine is a food that has not withstood the test of time. Show me a single healthy culture on this planet that eats margarine regularly. Cow juice may not be as flashy as the latest designer food, but it has sustained healthy cultures for generations. The U.S. used to belong to those ranks, when coronary heart disease was a twinkle in a cardiologist's eye. The likelihood of a new industrially processed food being healthy is about the same as a blindfolded monkey making a basket from half court. It's not impossible, but I wouldn't stake my life on it.

Latest Study on Vitamin K and Coronary Heart Disease

A Dutch group led by Dr. Yvonne T. van der Schouw recently published a paper examining the link between vitamin K intake and heart attack (thanks Robert). They followed 16,057 women ages 49-70 years for an average of 8.1 years, collecting data on their diet and incidence of heart attack.

They found no relationship between K1 intake and heart attack incidence. K1 is the form found in leafy greens and other plant foods. They found that each 10 microgram increase in daily vitamin K2 consumption was associated with a 9% lower incidence of heart attack. Participants consumed an average of 29 micrograms K2 per day, with a range of 0.9 to 128 micrograms. That means that participants with the highest intake had a very much reduced incidence of heart attack on average. Vitamin K2 comes from animal foods (especially organs and pastured dairy)and fermented foods such as cheese, sauerkraut, miso and natto. Vitamin K is fat-soluble, so low-fat animal foods contain less of it. Animal foods contain the MK-4 subtype while fermentation produces longer menaquinones, MK-5 through MK-14.

There's quite a bit of evidence to support the idea that vitamin K2 inhibits and possibly reverses arterial calcification, which is possibly the best overall measure of heart attack risk. It began with the observations of Dr. Weston Price, who noticed an inverse relationship between the K2 MK-4 content of butter and deaths from coronary heart disease and pneumonia in several regions of the U.S. You can find those graphs in Nutrition and Physical Degeneration.

The 25% of participants eating the most vitamin K2 (and with the lowest heart attack risk) also had the highest saturated fat, cholesterol, protein and calcium intake. They were much less likely to have elevated cholesterol, but were more likely to be diabetic.

Here's where the paper gets strange. They analyzed the different K2 subtypes individually (MK-4 through MK-9). MK-7 and MK-6 had the strongest association with reduced heart attack risk per microgram consumed, while MK-4 had no significant relationship. MK-8 and MK-9 had a weak but significant protective relationship.

There are a few things that make me skeptical about this result. First of all, the studies showing prevention/reversal of arterial calcification in rats were done with MK-4. MK-4 inhibits vascular calcification in rats whereas I don't believe the longer menaquinones have been tested. Furthermore, they attribute a protective effect to MK-7 in this study, but the average daily intake was only 0.4 micrograms! You could get that amount of K2 if a Japanese person who had eaten natto last week sneezed on your food. I can't imagine that amount of MK-7 is biologically significant. That, among other things, makes me skeptical of what they're really observing.

I'm not convinced of their ability to parse the effect into the different K2 subtypes. They mentioned in the methods section that their diet survey wasn't very accurate at estimating the individual K2 subtypes. Combine that with the fact that the K2 content of foods varies quite a bit by animal husbandry practice and type of cheese, and you have a lot of variability in your data. Add to that the well-recognized variability inherent in these food questionnaires, and you have even more variabiltiy.

I'm open to the idea that longer menaquinones (K2 MK-5 and longer, including MK-7) play a role in preventing cardiovascular disease, but I don't find the evidence sufficient yet. MK-4 is the form of K2 that's made by animals, for animals. Mammals produce it in their breast milk and other animals produce it in eggs all the way down to invertebrates. I think we can assume they make MK-4, and not the longer menaquinones, for a reason.

MK-4 is able to play all the roles of vitamin K in the body, including activating blood clotting factors, a role traditionally assigned to vitamin K1. This is obvious because K2 MK-4 is the only significant source of vitamin K in the diet of infants before weaning. No one knows whether the longer menaquinones are able to perform all the functions of MK-4; it hasn't been tested and I don't know how you could ever be sure. MK-7 is capable of performing at least some of these functions, such as activating osteocalcin and clotting factors.

I do think it's worth noting that the livers of certain animals contain longer menaquinones, including MK-7. So it is possible that we're adapted to eating some of the longer menaquinones. Many cultures also have a tradition of fermented food (probably a relatively recent addition to the human diet), which could further increase the intake of longer menaquinones. The true "optimum", if there is one, may be to eat a combination of forms of K2, including MK-4 and the longer forms. But babies and healthy traditional cultures such as the Masai seem to do quite well on a diet heavily weighted toward MK-4, so the longer forms probably aren't strictly necessary. If you haven't already seen it, check out my post on 20th century butter consumption and coronary heart disease risk in the United States.

Well if you've made it this far, you're a hero (or a nerd)! Now for some humor. From the paper:

The concept of proposing beneficial effects to vitamin K2 seems to have different basis as for vitamin K1. Vitamin K1 has been associated with a heart-healthy dietary pattern in the earlier work in the USA and this attenuated their associations with CHD. Vitamin K2 has different sources and relate to different dietary patterns than vitamin K1. This suggests that the risk reduction with vitamin K2 is not driven by dietary patterns, but through biological effects.

If that reads like gobledygook, it's because it is. They're trying to justify the fact that participants in the highest K2 intake group ate the most saturated fat and cholesterol (since K2 came mostly from cheese, milk and meat), yet had the lowest heart attack incidence and the lowest serum cholesterol. Look at them squirm! Could this "paradox" be the reason the paper was published in an obscure journal? Here's more:

Thus, although our findings may have important practical implications on CVD prevention, it is important to mention that in order to increase the intake of vitamin K2, increasing the portion vitamin K2 rich foods in daily life might not be a good idea. Vitamin K2 might be, for instance more relevant in the form of a supplement or in low-fat dairy. More research into this is necessary.

Translation: "People who ate the most cheese, milk and meat had the lowest heart attack rate, but be careful not to eat those things because they might give you a heart attack. Get your K2 from low-fat dairy (barely contains any) and supplements (same way your ancestors got it). Gimme more money."

What Can Evolution Teach us About the Human Diet?

Vegetarians deserve our respect. They're usually thoughtful, conscientious people who make sacrifices for environmental and ethical reasons. I was vegetarian for a while myself, until I decided I could find ethical meat.

Vegetarianism and especially veganism can get pretty ideological sometimes. People who have strong beliefs like to think that their belief system is best for all aspects of their lives and the world, not just bits and pieces. Many vegetarians believe their way of eating is healthier than omnivory or carnivory. It's easy to believe, since mainstream nutrition research has a distinctly pro-vegetarian slant. One of the classic arguments for vegetarianism goes something like this: our closest living relatives, chimpanzees and bonobos, are mostly vegetarian, therefore that's the diet to which we're adapted as well. Here's the problem with that argument:

Where are chimps (Pan troglodytes) on this chart? They aren't on it, for two related reasons: they aren't in the genus Homo, and they diverged from us about 5 million years ago. Homo erectus diverged from our lineage about 1.5 million years ago. I don't know if you've ever seen a Homo erectus skull, but 1.5 million years is clearly enough time to do some evolving. Homo erectus hunted and ate animals as a significant portion of its diet.

If you look at the chart above, Homo rhodesiensis (typically considered a variant of Homo heidelbergensis) is our closest ancestor, and our point of divergence with neanderthals (Homo neanderthalensis). Some archaeologists believe H. heidelbergensis was the same species as modern Homo sapiens. I haven't been able to find any direct evidence of the diet of H. heidelbergensis from bone isotope ratios, but the indirect evidence indicates that they were capable hunters who probably got a large proportion of their calories from meat. In Europe, they hunted now-extinct megafauna such as wooly rhinos. These things make modern cows look like chicken nuggets, and you can bet their fat was highly saturated.

H. heidelbergensis was a skilled hunter and very athletic. They were top predators in their ecosystems, judged by the fact that they took their time with carcasses, butchering them thoroughly and extracting marrow from bones. No predator or scavenger was capable of driving them away from a kill.

Our closest recent relative was Homo neanderthalensis, the neanderthal. They died out around 30,000 years ago. There have been several good studies on the isotope ratios of neanderthal bones, all indicating that neanderthals were basically carnivores. They relied both on land and marine animals, depending on what was available. Needless to say, neanderthals are much more closely related to humans than chimpanzees, having diverged from us less than 500,000 years ago. That's less than one-tenth the time between humans and chimpanzees.

I don't think this necessarily means humans are built to be carnivores, but it certainly blows away the argument that we're built to be vegetarians. It also argues against the idea that we're poorly adapted to eating animal fat. Historical human hunter-gatherers had very diverse diets, but on average were meat-heavy omnivores. This fits well with the apparent diet of our ancestor H. heidelbergensis, except that we've killed most of the megafauna so modern hunter-gatherers have to eat frogs, bugs and seeds.

Statistics

Ricardo just sent me a link to the British Heart Foundation statistics website. It's a goldmine. They have data on just about every aspect of health and lifestyle in the U.K. I find it very empowering to have access to this kind of information on the internet.

I've just started sifting through it, but something caught my eye. The U.K. is experiencing an obesity epidemic similar to the U.S.:
Here's where it gets interesting. This should look familiar:

Hmm, those trends look remarkably similar. Just like in the U.S, the British are exercising more and getting fatter with each passing year. In fact, maybe exercise causes obesity. Let's see if there's any correlation between the two. I'm going to plot obesity on the X-axis and exercise on the Y-axis to see if there's a correlation. The data points only overlap on three years: 1998, 2003 and 2006. Let's take a look:
By golly, we've proven that exercise causes obesity! Clearly, the more people exercise, the fatter they get. The R-value is a measure of how closely the points fall on the best-fit line. 0.82 isn't bad for this type of data. If only we could get all British citizens to become couch potatoes, obesity would be a thing of the past! OK, I'm kidding. The obesity is obviously caused by something else. I'm illustrating the point that correlation does not equal causation. Even if an association conforms to our preconceived notions of how the world works, that does not justify saying one factor causes another without testing the hypothesis in a controlled experiment.

Dietary Fiber and Mineral Availability

Mainstream health authorities are constantly telling us to eat more fiber for health, particularly whole grains, fruit and vegetables. Yet the only clinical trial that has ever isolated the effect of eating a high-fiber diet on overall risk of death, the Diet and Reinfarction Trial, came up with this graph:



Oops! How embarrassing. At two years, the group that doubled its fiber intake had a 27% greater chance of dying and a 23% greater chance of having a heart attack. The extra fiber was coming from whole grains. I should say, out of fairness, that the result wasn't quite statistically significant (p less than 0.05) at two years. But at the very least, this doesn't support the idea that increasing fiber will extend your life. I believe this the only diet trial that has ever looked at fiber and mortality, without also changing other variables at the same time.

Why might fiber be problematic? I read a paper recently that gave a pretty convincing answer to that question: "Dietary Fibre and Mineral Bioavailability", by Dr. Barbara F. Hartland. By definition, fiber is indigestible. We can divide it into two categories: soluble and insoluble. Insoluble fiber is mostly cellulose and it's relatively inert, besides getting fermented a bit by the gut flora. Soluble fiber is anything that can be dissolved in water but not digested by the human digestive tract. It includes a variety of molecules, some of which are quite effective at keeping you from absorbing minerals. Chief among these is phytic acid, with smaller contributions from tannins (polyphenols) and oxalates. The paper makes a strong case that phytic acid is the main reason fiber prevents mineral absorption, rather than the insoluble fiber fraction. This notion was confirmed here.

As a little side note, polyphenols are those wonderful plant antioxidants that are one of the main justifications for the supposed health benefits of vegetables, tea, chocolate, fruits and antioxidant supplements. The problem is, many of them are actually anti-nutrients. They reduce mineral absorption, reduce growth and feed efficiency in a number of species, and the antioxidant effect seen in human plasma after eating them is due largely to our own bodies secreting uric acid into the blood (a defense mechanism?), rather than the polyphenols themselves. The main antioxidants in plasma are uric acid, vitamin C and vitamin E, with almost no direct contribution from polyphenols. I'm open to the idea that some polyphenols could be beneficial if someone can show me convincing data, but in any case they are not the panacea they're made out to be. Thanks to Peter for cluing me in on this.

Whole grains would be a good source of water-soluble vitamins and minerals, if it weren't for their very high phytic acid content. Even though whole grains are full of minerals, replacing refined grains with whole grains in the diet (and especially adding extra bran) actually reduces the overall absorption of a number of minerals (free text, check out table 4). This has been confirmed repeatedly for iron, zinc, calcium, magnesium and phosphorus. That could well account for the increased mortality in the DART trial.

Refining grains gets rid of the vitamins and minerals but at least refined grains don't prevent you from absorbing the minerals in the rest of your food. Here's a comparison of a few of the nutrients in one cup of cooked brown vs. unenriched white rice (218 vs. 242 calories):

Brown rice would be quite nutritious if we could absorb all those minerals. There are a few ways to increase mineral absorption from whole grains. One way is to soak them in slightly acidic, warm water, which allows their own phytase enzyme to break down phytic acid. This doesn't seem to do much for brown rice, which doesn't contain much phytase.

A more effective method is to grind grains and soak them before cooking, which helps the phytase function more effectively, especially in gluten grains and buckwheat. The most effective method by far, and the method of choice among healthy traditional cultures around the world, is to soak, grind and ferment whole grains. This breaks down nearly all the phytic acid, making whole grains a good source of both minerals and vitamins.

The paper "Dietary Fibre and Mineral Bioavailability" listed another method of increasing mineral absorption from whole grains that I wasn't aware of. Certain foods can increase the absorption of minerals from whole grains high in phytic acid. These include: foods rich in vitamin C such as fruit or potatoes; meat including fish; and dairy.

Another point the paper made was that the phytic acid content of vegetarian diets is often very high, potentially leading to mineral deficiencies. The typical modern vegetarian diet containing brown rice and unfermented soy products is very high in phytic acid and thus very low in absorbable minerals. The more your diet depends on plant sources for minerals, the more careful you have to be about how you prepare your food.

Just a Reminder

I will not tolerate comments that are disrespectful or threatening to other commenters or myself. Feel free to disagree with anyone here, including me, in a courteous tone. I enjoy the intelligent discussions we have here, and I don't want them to degenerate into troll wars.

NASA satellite crashes

The $278-million Orbiting Carbon Observatory was designed to measure greenhouse gas emissions. It plunges into the ocean near Antarctica after a mechanical problem.A NASA satellite designed to measure greenhouse gas emissions and pinpoint global warming dangers crashed Tuesday after a protective covering failed to separate from the craft shortly after launch at Vandenberg Air Force Base in