Seth's Blog

Ten years ago researchers finished the first sequencing of an entire human genome. To mark the anniversary, Eric Green, the director of the National Human Genome Research Institute at the National Institutes of Health, spoke to an unnamed reporter at the New York Times. Here is the final question of the interview:

What about the naysayers who [say], “Where are the cures for diseases that we were promised?”

I became director of this institute three and a half years ago, and I remember when I first started going around and giving talks. Routinely I would hear: “You are seven years into this. Where are the wins? Where are the successes?”

I don’t hear that as much anymore. I think what’s happening, and it has happened in the last three years in particular, is just the sheer aggregate number of the success stories. The drumbeat of these successes is finally winning people over.

We are understanding cancer and rare genetic diseases. There are incredible stories now where we are able to draw blood from a pregnant woman and analyze the DNA of her unborn child.

Increasingly, we have more informed ways of prescribing medicine because we first do a genetic test. We can use microbial DNA to trace disease outbreaks in a matter of hours.

These are just game changers. It’s a wide field of accomplishment, and there is a logical story to be told.

There you have it. The head of the Human Genome Project, a very big deal, says in an oblique way that the project has had little practical benefit so far. Note the present tense: “We are understanding cancer”. Nothing about decreasing cancer. In a short discussion of benefits, he mentions microbial DNA. In a short discussion of benefits, he says, “We are able to draw blood from a pregnant woman and analyze the DNA of her unborn child.” Genetic tests of fetuses are not new. I think he means that the number of rare genetic diseases that can be detected has increased (by how much?). Well, yes, not surprising. It is an increase of something that was already happening and helps only a tiny number of people. Not a “game-changer”.

A new BMJ paper looks at Cuban health before and after the economic crisis of 1991-1995, when the Cuban economy nose-dived. There wasn’t enough gasoline for cars. so bike riding greatly increased. In addition, people ate less. What effect did these changes (more exercise, less eating) have on health?

You know what is supposed to happen: Better health. Walter Willett, the Harvard epidemiologist, wrote a commentary about the study that concluded “The current findings add powerful evidence that a reduction in overweight and obesity would have major population-wide [health] benefits.” In other words, Willett said that what happened supports conventional beliefs.

But it didn’t. In several ways, what happened contradicts conventional beliefs.

1. A popular belief is that exercise causes weight loss. However, the percentage of “physically active individuals” doubled from 1985 to 2010 (from about 30% to 60%). In spite of this, the prevalence of obesity considerably increased (from about 13% to 18%) at the same time. Apparently exercise is considerably less important than something else. I have never heard a public health advocate say this.

2. A graph showing rates of heart disease, cancer, and stroke (the three main killers) over the period showed no change in rates of cancer and stroke. In spite of big changes in both exercise and obesity. The rate of heart disease stayed constant during the period when obesity went down. It steadily dropped during the period of time when obesity went up. Apparently the factors that control obesity and the factors that control heart disease are quite different (contradicting the usual view that exercise reduces both).

3. There is no simple connection between diabetes and obesity. During the economic crisis, when the prevalence of obesity went down by half (from 15% to 7%) and exercise greatly increased, the prevalence of diabetes slightly increased. Only after the crisis did the usual correlation (more obesity, more diabetes) emerge.

4. The only lifestyle factor to have its conventional effect: smoking. When you stop smoking, you gain weight is the usual belief (which I also believe). The data definitely support this connection. A huge reduction in the fraction of people who smoke (from 30% to 10%) did not reduce cancer but did coincide with a great increase in obesity.

5. Cubans are doing something right, as shown by the considerable decrease in heart disease and diabetes deaths. Apparently they are also more health-conscious, as shown by much higher rates of exercise and much lower rates of smoking. (Assuming that cigarettes did not become too expensive.) They are getting fatter, too, but apparently that is less damaging than we are told.

Willett and the authors of the study look at subsets of the data and use theories about “time-lag” to draw reassuring conclusions. In fact, large portions of the data are not easily explained by conventional ideas, as I’ve shown. You can look at the data many ways, but to me the study makes two main points. 1. During a period when everyone was forced to do what doctors recommend (exercise more, eat less), health did not improve. 2. During a period (post-crisis) when obesity got steadily worse, health improved (heart disease rates went down, cancer stayed the same, diabetes mortality went down). Cuba is too poor for the improvement to be due to better high-tech modern medicine. Taken together, these findings suggest we should be more skeptical of what we are told by doctors and health experts such as Willett.

A recent paper from the Cleveland Clinic reports more than a dozen studies that add up, say the authors, to the conclusion that red meat and other meats cause heart disease at least partly by increasing trimethylamine-N-oxide (TMAO), which is made from carnitine by intestinal bacteria. Meat, especially red meat, is high in carnitine.

The results were reported all over the world, including the New York Times. There are several reasons to question the conclusion:

1. The association between meat and heart disease is weak. An epidemiological paper from the Harvard Nurses Study found estimated reductions in heart disease on the order of 10-20% when a “healthy” food was substituted for meat. Conclusions about causality (eating Food X causes Disease Y) based on the Harvard Nurses Study have predicted wrongly over and over when tested in experiments, so even this weak association is questionable. A 2010 meta-analysis found no association between red meat consumption and heart disease. The absence of any correlation is surprising because red meat is widely believed to be unhealthy. People who eat more red meat would presumably do more other “unhealthy” things. (Perhaps the error rate of the underlying epidemiology is high. Errors push associations toward zero.)

2. Within the Cleveland paper, the associations between carnitine and TMAO and heart disease are weak. For example, people with the greatest sign of heart disease (“triple” angiographic evidence of heart disease) had only slightly more carnitine in their blood (about 15% more) than people with the least sign of heart disease. (Maybe it is peak levels of carnitine rather than average levels that matter.)

3. A 1996 epidemiological study (via Chris Kresser) that looked at the correlates of various “healthy” habits among people especially interested in health (e.g., they shop at health food stores) found no detectable effect of being a vegetarian. For example, vegetarians had the same all-cause mortality as non-vegetarians. Other factors were associated with reduced mortality, including eating wholemeal bread daily and eating fruit daily. This study looked at a large number of people (about 11,000) for a long time (17 years), so I consider the lack of difference (vegetarians versus non-vegetarians) strong evidence against the idea that modest amounts of meat are harmful.  (And I am going to start eating wholemeal bread in small amounts.)

I don’t dismiss the paper. Among people who eat more than modest amounts of meat, there may be something to it. Now and then epidemiology turns up a powerful risk factor — something associated with a risk increase by a factor of 4 or more (people at a high level of the risk factor get the disease at least four times more often than people at a low level of the factor). History shows that such correlations are likely to tell us something about causality. With weaker correlations (such as the correlation between red meat and heart disease), it is much more a guessing game.

To me, the important clue about heart disease is that it is very low in both Japan and France, much lower than in countries with high rates of heart disease. The two countries that have little in common besides the fact that in both people eat a lot more fermented food than in most places. In France, they drink wine, eat stinky cheese and yogurt. In Japan, they eat miso, pickles, and natto. Maybe fermented food protects against heart disease.

After learning about the dramatic effects of xylitol on lichen planus, I looked around for a good summary of xylitol research and found this:

Xylitol and other natural sweeteners were tested extensively in Finland as potential replacements for sugar during the early 1970’s. A series of over 20 research reports (edited by Professors Arje Scheinin and Kauko Makinen) was published together in Acta Odontologica Scandinavica, Supplement 70, in 1975. These investigations became known collectively as the “Turku Sugar Studies.”

Sweeteners were tested for their effects on dental and general health. The main trials involved the long-term substitution of either fructose or xylitol for sucrose (ordinary table sugar). This involved a huge cooperative effort between scientists and food producers. Separate fructose and xylitol versions of common food items were provided for the volunteers.

These trials (including blood and urine tests) established the safety of relatively large amounts of xylitol (often 70 grams per day or more) consumed regularly over a period of years. The xylitol group reported that xylitol-sweetened foods were comparable to the familiar sugar flavors.

The control group who consumed normal amounts of sugar continued to experience tooth decay, as would be expected. The fructose group also continued to have tooth decay, although progression appeared to be somewhat slower.

The results of a xylitol diet on oral health were dramatic. New tooth decay was practically eliminated. A therapeutic remineralizing effect was noted where the decay process was reversed. A parallel study achieved similar 90% reduction in tooth decay simply by adding a small amount of xylitol, delivered in chewing gum after meals) to a normal (regular sugar) diet.

Here are some of the major findings of the Turku Sugar Studies:

• Xylitol can be incorporated into a wide variety of food items to directly replace sugar. More than 100 different products were made with xylitol.
• The taste and overall quality of the xylitol products was comparable, and in some cases superior, to regular sugar items.
• Substantial amounts of xylitol can be consumed regularly with no adverse health effects.
• No potentially damaging bacterial adaptations to xylitol occurred.

Especially early on, there were some instances of gastrointestinal discomfort and even osmotic diarrhea in the xylitol group. After a short period of adaptation (few weeks), these symptoms diminished and became no more frequent than in the other groups. A few individuals were more sensitive than the rest of the group. Even exceptionally high intakes of xylitol of over 200 grams in a day did not necessarily cause any problems. Discomfort was more likely to occur with liquid ingestion on an empty stomach.

It is not necessary to eliminate sugar to dramatically reduce tooth decay. Similar results can be obtained simply by adding a small amount of xylitol to a “normal” diet. Xylitol can provide a natural “antidote” for the damaging dental effects of ordinary sugar. A little more than a teaspoon of xylitol per day can provide amazing protection against tooth decay, when used in chewing gum after meals and snacks.

The last point is especially interesting. Xylitol doesn’t work because you eat less sugar. It works, apparently, because it stops/prevents something that sugar starts, perhaps adhesion of certain bacteria to teeth and gums.

Here (video) is coverage of xylitol research in American mainstream media (in this case, ABC News). The useful information (about a xylitol study) is diluted by unhelpful information about xylitol in fruit and brushing and flossing.

Inside Tracker sells blood panels — for example, 20 things measured in your blood (e.g., hemoglobin, magnesium, Vitamin D). It was founded in 2009 in Boston, Mass., by Gil Blander, a biology Ph.D., and two other people. They started offering the service in late 2011. Their main customers are athletes (20% professional, 30% amateur) and many Quantified Selfer’s (20%). I recently interviewed Dr. Blander:

What have you learned from the data you’ve collected?

Around 60% of the population has low Vitamin D.[What's low Vitamin D?] As of today, if you look at the ranges of the diagnostic companies, they are saying that everything below 30 ng/ml is low Vitamin D. We are giving you your optimal zone based on age, gender, athletic activity and ethnicity. We also compare you to your peers. (more…)

• Bone broths may have too much lead. “Broth made from skin and cartilage taken off the bone once the chicken had been cooked with the bones in situ and chicken-bone broth were both found
  to have markedly high lead concentrations.”
• Upcoming discussion of the work of Renata Adler (in New York City)
• Ben Casnocha on Aaron Swartz
• The silence of doctors about bad medicine. “The silence of other doctors apparently gave company executives the upper hand; in meetings with Dr. Nargol, they said that he seemed to be the only doctor having trouble.”
• Dietitians for Professional Integrity. Some dietitians are fed up with their professional organization’s links to junk food makers, such as Coca-Cola

In the 1960s, Edmund Wilson reviewed Vladimir Nabokov’s translation of Eugene Onegin. Wilson barely knew Russian and his review was a travesty. Everything was wrong. Nabokov wondered if it had been written that way to make sense when reflected in a mirror.

I thought of this when I read recent remarks by “celiac experts” in the New York Times. The article, about gluten sensitivity, includes an example of a woman who tried a gluten-free diet:

Kristen Golden Testa could be one of the gluten-sensitive. Although she does not have celiac, she adopted a gluten-free diet last year. She says she has lost weight and her allergies have gone away. “It’s just so marked,” said Ms. Golden Testa, who is health program director in California for the Children’s Partnership, a national nonprofit advocacy group. She did not consult a doctor before making the change, and she also does not know [= is unsure] whether avoiding gluten has helped at all. “This is my speculation,” she said. She also gave up sugar at the same time and made an effort to eat more vegetables and nuts.

Fine. The article goes on to quote several “celiac experts” (all medical doctors) who say deeply bizarre things.

“[A gluten-free diet] is not a healthier diet for those who don’t need it,” Dr. Guandalini [medical director of the University of Chicago’s Celiac Disease Center] said. These people “are following a fad, essentially.” He added, “And that’s my biased opinion.”

Where Testa provides a concrete example of health improvement and refrains from making too much of it, Dr. Guandalini does the opposite (provides no examples, makes extreme claims).

Later, the article says this:

Celiac experts urge people to not do what Ms. Golden Testa did — self-diagnose. Should they actually have celiac, tests to diagnose it become unreliable if one is not eating gluten. They also recommend visiting a doctor before starting on a gluten-free diet.

As someone put it in an email to me, “Don’t follow the example of the person who improved her health without expensive, invasive, inconclusive testing. If you think gluten may be a problem in your diet, you should keep eating it and pay someone to test your blood for unreliable markers and scope your gut for evidence of damage. It’s a much better idea than tracking your symptoms and trying a month without gluten, a month back on, then another month without to see if your health improves.”

Are the celiac experts trying to send a message to Edmund Wilson, who died many years ago?

• Experiments suggest flu shots reduce heart attacks and death. Huge reduction: 50%. The new report (a conference talk, not a paper) is a reanalysis of four earlier experiments. I was surprised to learn that the CDC uses heart attack outbreaks to locate flu outbreaks, implying that the new finding is not a fluke — there really is a strong connection. I already knew heart attacks are more common in the winter, which also supports a connection with flu.
• Une histoire des haines d’écrivains by Boquel Anne and Kern Etienne. Published 2009. About literary feuds. One of my students was reading a Chinese translation.
• Correspondences between sounds and tastes.
• Report on fraudulent Dutch research. “The 108-page report says colleagues who worked with Stapel had not been sufficiently critical. This was not deliberate fraud but ‘academic carelessness’, the report said.” I doubt it. Based on my experience with Chandra, I believe Stapel’s colleagues had doubts but did nothing from some combination of careerism (doing something would have cost too much, for example  a lot of time, and gained them nothing), ignorance (not their field), and decency (they saw no great value in ruining someone).  I wonder if the report considered these other possible explanations (careerism, ignorance, decency).

Thanks to Tim Beneke.

Health experts call bacteria “good” and “bad”. Bad bacteria make us sick. Good bacteria help us digest food, and a few other things. Let me propose another view. Any bacteria (i.e., bacterial species) will make us sick if it becomes too numerous — so all bacteria are “bad”. All bacteria protect us against other bacteria — so all bacteria are “good”. The terms “good” and “bad” are misleading. It is like saying a person is inherently rich or poor. Anyone, given a lot of money, becomes rich. Anyone whose money is taken away becomes poor. Low bacterial diversity or reduction of diversity makes it more likely that one bacterial species can overwhelm its competitors, producing sickness. When this happens, to say that the species (e.g., H. pylori) that became numerous “caused” the sickness (e.g., ulcers) is to seriously misunderstand what happened and how to prevent it from happening. We are taught that our immune system protects us from infection. We should be taught that bacterial diversity does the same thing. (more…)

My personal science taught me that (a) there are useful things health experts don’t know (b) that the rest of us can discover. I am curious how these discoveries are made. When  Patrick Vlaskovits commented

I suffered migraines my whole life until my 30s. I am prescribed meds to help me manage the pain. These meds are better than nothing. Then I quit eating grain-based products, no migraines ever.

I asked him how he discovered the connection. He replied: (more…)