Book of note: “The Personalized Diet” by Eran Segal and Eran Elinav

I have blogged earlier about the book by neuroscientist Sandra Aamodt and have discussed there in passing the pioneering work by Weizmann Institute scientists Eran Segal and Eran Elinav on the individual microbiome (our “gut bacteria population”) and how it affects blood sugar levels. Now the duo has teamed up with editor Eve Adamson, and together they have put out a popularized book:

I am familiar with some of the original papers in top scientific journals—the book is of course much more readable, and the authors and editors have done a good job of presenting their work in lay language while preserving the broad strokes of their work.

The bottom line of their research is this: each of us carries a whole ecosystem of bacteria in our intestines, which help us digest and absorb food. The specific mix of bacteria varies between individuals, and hence so do our responses to different foods. While weight gain/loss is best seen as an outcome—one aspect of overall health—glycemic response, the changes in blood sugar levels after a meal (“postprandial glucose response”) are sufficiently rapid that they can be monitored in real time (e.g. with a continuous glucose monitor) and correlated with what the person ate (logged in a smartphone app). Doing this for thousands of people is a big-data project par excellence, and this is how computer scientist Segal teamed up with gastroenterologist Elinav.

But this isn’t where it ends. Gut bacteria populations can of course be obtained from stool samples, and subjected to analysis—another aspect of the massive big-data puzzle. Moreover, some of what they infer from the data can be checked in an animal model—for instance, certain gut bacteria can be administered to sterile mice and their weight gain (or lack thereof) in response to certain food mixtures tested on a much shorter time scale than would be possible in slow, relatively large, and long-lived mammals like us.

The duo brought different, complementary perspectives to the problem, not just scientifically but personally. Elinav always loved to take machines apart and see how they fit together (fittingly, he did his military service aboard a submarine), then became fascinated with living organisms. He ended up studying medicine, then specializing in internal medicine. During his residency, he was exposed to the human suffering caused by “metabolic syndrome” (the term given to the combination of severe obesity, adult-onset diabetes, fatty liver, hyperlipidemia, and the complications thereof). He realized that they spent all their time as doctors dealing with the consequences and complications rather than with the root cause.

Segal, on the other hand, was an avid long-distance runner in his spare time. He started experimenting with different nutritional approaches to improve his endurance as a runner, assisted in this pursuit by his wife, a clinical dietitian. As he dove deeper into this and observed diets of fellow runners, it became increasingly clear to him that there was no one-size-fits-all, and that recommendations that were held to be gospel truth (or Torah from Sinai, in our case) were, in fact, counterproductive for some. Why do some runners who eat dates before a run become energized and others exhausted? Who do some do best with carb-loading, and indeed thrive on high-carb diets, while others quickly pack on the pounds and suffer from low energy?

Segal was already involved in the computational study of the human genome at the time and then started reading about the emergent field of study of the microbiome. One thing led to another, a mutual acquaintance put Segal and Elinav in touch with each other, and together they embarked on the collaboration that eventually morphed into the personalized nutrition project.

One factor that facilitated their research was that rapid, reliable, and minimally-invasive blood glucose monitoring technology has become relatively inexpensive. And here some of their first surprises came. Anybody who has followed a Gary Taubes-type diet, or who is trying to manage diabetes, is aware of the ‘glycemic index’ (GI) of foods—the increase in blood sugar levels caused by eating a given amount of the food, compared to the same amount of pure glucose (for which GI=100 by definition). But how uniform are these values really?

Segal and Elinav found that the GI for some foods (e.g., bananas) differed very little between their test subjects (say, 60-65), while others (e.g., apples) were all over the place (40-90). Moreover, the variation was not random but correlated with the person.

One would expect glycemic response to go up more or less linearly with the amount of the food consumed was a given. They found that this is indeed true for smaller amounts, but at some point saturation sets in as the body manufactures more insulin, and the glucose response levels off. (This, of course, does not mean you can just eat ten times as much: the insulin will cause the excess energy to be stored as fat!)

More surprising, however, was that higher fat content in the meal on average caused a minor decrease in glycemic response. For a nontrivial number of their participants, eating toast with butter or olive oil actually did less glycemic harm than eating the toast on its own.

Now trying to keep blood sugar levels on a more even keel has two major benefits. In the short term, yo-yoing blood sugar levels lead to a reduction in energy, a feeling of exhaustion as the body pumps out insulin in response to a sugar spike and blood sugar dips. As for the long term: Segal and Elinav found across their sample that glycemic response after habitual meals is strongly correlated with BMI. Keeping blood sugar levels on a more even keel turns out to be a win-win on all counts.

And here’s the catch—”thanks” to our microbiome, glycemic response is highly individual. Segal himself ‘spikes’ after eating rice, while Elinav does not. One person spikes after ice cream, while another does not—and the same person who spikes after an evening snack of ice cream can safely have chocolate instead, go figure.

This addresses a seeming paradox. It’s not that diets don’t work—in fact, many do for some people, though long-term compliance can be an issue—it’s that there is no diet that will work for everyone, or even for most people.

So the next step, then, was to have a computer analyze the data for some of the participants in depth, and have it plan out a personalized diet that would keep blood sugar levels as steady as possible for that patient. Guess what? Yup, you guessed it.

Now some people might be discouraged by the idea of carrying around a blood sugar monitor for two weeks and carefully logging every meal (and physical activity). But once a large enough dataset has been established, and correlated to analyses of the gut flora composition in all the test persons, it becomes possible to predict glycemic responses to different foods with reasonable accuracy based on a bacterial population analysis of stool samples. A startup company named DayTwo is offering to do exactly that. [Full disclosure: I have no financial interest in DayTwo or in any of Drs. Segal and Elinav’s ventures.]

We are at the dawn of a major revolution in healthcare—a shift away from a paradigm of statistical averages to one of detailed monitoring of individual patients. Call it ‘personalized medicine’ or any other buzzword: it does seem poised to radically change healthcare and individual health outcomes for the better.



On dieting, weight, and reductionist fallacies


Sandra Aamodt, the former editor of Nature Neuroscience, presents a TED talk where she explains something counterintuitive: not only do most diets fail to achieve permanent weight loss, but in some cases the rebound actually overshoots, and the diet actually causes a weight gain in the long run.

As she describes it: the hypothalamus of the brain acts as a kind of ‘weight thermostat’ (that would be a barostat? :)) that tries to adjust body weight to within about 10-15 lb of a set weight by sending chemical signals that up- or down-regulate appetite, that speed up or slow down metabolism, etc. If weight drops “too” far below the set point, signals to increase food intake are sent out, and if no food intake ensues (because no food is available, or because the person is dieting), then metabolism is slowed down to reduce the base metabolic rate (i.e., the number of calories your body needs to keep basic functions going at rest). Unfortunately, the “set point” can be ratcheted up but not trivially ratcheted down.

People who think it is all about the pounds (or about the BMI) will find this a depressing message. But this is a classic example of the “reductionist fallacy”: weight or BMI are but. one metric of health among many. There are many others that matter, such as percentage muscle mass, blood sugar at rest, blood pressure, cholesterol, blood oxygen levels,… A person who is technically overweight (i.e., BMI between 25 and 30) but eats healthily, exercises at least 3 times a week, does not smoke, and only drinks in moderation actually has a better health prognosis than somebody who has an “ideal” weight (BMI around 20) but smokes and drinks heavily and never does any exercise.

To be sure, she shows that among people who do not have any of these four healthy habits, an obese person (BMI=30 or higher) has seven times the mortality risk of somebody with an ideal BMI=20.oo. However, for those who do observe all four healthy habits, the mortality risks with normal, overweight, and obese patient differ only by statistical uncertainty.

Does that mean that a morbidly obese person who cannot fit in an airplane seat does not need to go on a diet? Of course, it doesn’t — that is a straw man, and “set point” normally don’t go that high unless pushed there by unhealthy habits or regular binge eating.

But somebody who, well, has a naturally zaftig built is probably better off making a fixed habit of exercise, and to eat ‘smart’, than to go on some extreme low-carb diet. (Full disclosure: I do restrict my carbohydrate intake, but not all the way down to “ketogenic”.)

There is an additional factor here: in recent years we are increasingly aware of the role the microbiome (“gut bacteria”) plays in food absorption, and particularly in sugar absorption. For instance, in this very recent paper:

ABSTRACT: Bread is consumed daily by billions of people, yet evidence regarding its clinical effects is contradicting. Here, we performed a randomized crossover trial of two 1-week-long dietary interventions comprising consumption of either traditionally made sourdough- leavened whole-grain bread or industrially made white bread. We found no significant differential effects of bread type on multiple clinical parameters. The gut microbiota composition remained person specific throughout this trial and was generally resilient to the intervention. We demonstrate statistically significant interpersonal variability in the glycemic response to different bread types, suggesting that the lack of phenotypic difference between the bread types stems from a person-specific effect. We further show that the type of bread that induces the lower glycemic response in each person can be predicted based solely on microbiome data prior to the intervention. Together, we present marked personalization in both bread metabolism and the gut microbiome, suggesting that understanding dietary effects requires integration of person-specific factors.


We are only beginning to understand how human digestion, food absorption, metabolism, and the microbiome interact. Eventually, genome analysis combined with microbiomics will bring us into the personalized nutrition era.


UPDATE: from the same team, a 2014 paper showing that artificial sweeteners induce glucose intolerance by altering the microbiome.  NATURE’s editorial summary in lay language:

We have been using non-caloric artificial sweeteners for more than a century. Today the food industry is using them in ever-greater quantities in ‘diet’ foodstuffs and they are recommended for weight loss and for individuals with glucose intolerance and type 2 diabetes mellitus. Eran Elinav and colleagues show that consumption of the three most commonly used non-caloric artificial sweeteners saccharin, sucralose and aspartame directly induces a propensity for obesity and glucose intolerance in mice. These effects are mediated by changes in the composition and function of the intestinal microbiota; deleterious metabolic effects can be transferred to germ-free mice by faecal transplantation and can be abrogated by antibiotic treatment. The authors demonstrate that artificial sweeteners can induce dysbiosis and glucose intolerance in healthy human subjects, and suggest that it may be necessary to develop new nutritional strategies tailored to the individual and to variations in the gut microbiota.

Of light and banishing SAD

In honor of the holiday (Christmas if you’re a Western Communion Christian, Isaac Newton Day for everyone else), our Beautiful but Evil Space Mistress has a post up about “living in the light”. She mentions some of the more tasteful and tacky Christmas decorations in her neighborhood, but particularly the abundance of light. (Note that all major winter festivals involve light — be it the pagan Julfest, Christian Christmas, or the Jewish Chanukah/Festival of Lights.)

Our BbESM grew up outside Porto, Portugal, with a single 60W incandescent bulb hanging off the ceiling of her room, plus a 30W lampshade — and even that was a luxury by historical standards. In fact, her editor notes that, adjusted for inflation, a given amount of luminosity has gotten a whopping 500,000 times cheaper in the past few centuries. Just in the past few decades alone, we’ve gone from 60W incandescent to 8 W LED for the same luminosity.

Sarah also notes that she suffered from mild SAD (seasonal affective disorder) and hence appreciated the light. Now actually, while incandescents (with their very “reddish” light — not to mention most of their energy output being infrared, i.e., heat) are probably still better than darkness, they do not help a whole lot with SAD except at very high luminosities. Why?

We actually have three types of photoreceptors: rod cells, cone cells in three colors, and ipRGCs (intrinsically photosensitive retinal ganglion cells). The absorption maxima of rod cells (night vision) and cone cells (daytime color vision) are illustrated below:


(Fish and birds have a fourth “color” of cones in the near-ultraviolet region, with an absorption maximum around 370 nm.)

The ipRGC’s task, on the other hand, is not vision per se but the regulation of circadian rhythm. Their pigment, melanopsin, has an absorption maximum around 480nm, in the bluish region. (Mutations in the gene that expresses melanopsin are one cause for SAD.) SAD is a major issue in arctic countries (close to 10% of the population in Finland, for example). The traditional treatment (review article here) involves full-spectrum lamps at high intensity (10,000 lux and more). However, it was recently found that blue-enriched light sources at more modest luminosities of 750 lux — or even narrow-band blue light at just 100 lux — yield equally good results, as they selectively stimulate the ipRGCs.

Merry Christmas, happy belated Chanukah/Festival of Lights, or happy Isaac Newton Day, as applicable!


Flemish doctor refuses to treat 90-year old Jewish woman with broken rib, tells her to “Go to Gaza”

Having lived in Europe for basically half my life, I’ve grown inured to reports of kid-glove and more overt judeophobia on the part of the “natives”. However, this story managed to shock even me (as it would anybody who is a doctor or ever contemplated becoming one).

Times of Israel liveblog:

Belgian doctor refuses treatment to Jewish woman
A Belgian physician who refused to treat a Jewish woman with a fractured rib suggests she visit Gaza to get rid of the pain.
The physician makes the remark on Wednesday while manning a medical hotline in Flanders, Belgium’s Flemish region, whose capital, Antwerp, has a sizable Orthodox Jewish population, the local Jewish monthly Joods Actueel reports Thursday.
The woman, Bertha Klein, had her son, who is American, call the hotline at 11 p.m.
“I’m not coming,” the doctor reportedly tells the son and hung up. When the son calls again, the doctor says: “Send her to Gaza for a few hours, then [her pains will be over: corrected translation, NCT]” According to Joods Actueel, the doctor confirmed the exchange, saying he had an “emotional reaction.”
Health ministry officials were looking into the incident, according to the monthly’s online edition. According to Joods Actueel, the doctor knew the patient was Jewish because of Klein’s son’s American accent.
The family calls a friend, Samuel Markowitz, who is an alderman of the Antwerp district council and a volunteer paramedic. He calls the doctor to confirm the exchange, and also records their conversation.
Hershy Taffel, Bertha Klein’s grandson, files a complaint with police for discrimination.
“It reminds me of what happened in Europe 70 years ago,” Taffel tells Joods Actueel. “I never thought those days would once again be repeated.”[…]
While the ToI generally do due diligence about such stories (unlike some of the Hebrew press), I read the original article (in Dutch) and can confirm the story is not as bad as reported, but worse. For one, the poor woman is 90 years old.
Any doctor in Belgium is supposed to have sworn the Hippocratic Oath . Denying treatment to anyone for any reason other than sound medical judgment or lack of specific expertise (the Oath specifically gives the example of surgery by a non-surgeon) is a direct violation of the Oath. 
[Jewish doctors in Israel swear the similar Oath of Assaf the Physician). And no matter how heated the conflict with our neighbors, this oath is taken seriously. Arabs from all over the Middle East — even from countries technically at war with Israel — travel to Israel’s Top Four hospitals for specialist medical treatment. Not to mention countless patients from the West Bank and Gaza that are beyond the help of the local medical facilities.
Even hardened Hamas terrorists for whom a bullet would be too merciful get full and proper medical treatment in hospitals. Why? Because. That. Is. What. A. Fecking. Doctor. Does, No Ifs, No Ands, No Buts. The fact that several Arab patients of the infamous Jewish terrorist Baruch Goldstein (a medical doctor) testified after the Hebron Massacre that he had saved their lives when they were his patients speaks volumes — not in favor of his character, but about the seriousness with which the Oath is taken.]
I do not care how much this “dokter strontzak” will apologize or grovel to keep his/her job. Nothing less than permanent revocation of medical license is an appropriate punishment in this case. Anybody behaving like he/she did — denying treatment to a 90-year old woman for no other reason than being Jewish — is not worthy of the name “doctor”/”doctor”/”geneesheer” and only sullies the title.
Then again, I happen to feel the same way about any “doctor” committing involuntary euthanasia . — another practice in direct violation of the Hippocratic Oath (not to mention murder statutes)…

Some of the worst things imaginable have been done with the best intentions

The front page of the Yediot Achronot had a story (sensationalist as is the wont of that paper) about a family tragedy.

Briefly: The head of the hematology department of a large hospital (I will not spell out his name out of concern for the privacy of the family — bad enough that the gutter press chose to do otherwise) was faced with a 34-year old daughter (he himself was 66) who struggled with cancer for over 3 years. Eventually she gave up and insisted that he put her out of her misery, which he did, and subsequently committed suicide, leaving a wife and two more children behind.

It is written “do not judge your fellowman until you have stood in his place” (Avot 2:4). I have not (G-d spare me) stood in this doctor’s place but have been in a closely related situation, which made me lose all respect for the (euthanasia-happy) medical establishment of the European country involved. (For the political establishment of said country, I lost none since I had none left to lose by then ;-)) Suffice to say that the participants in this “Greek tragedy” have suffered, and continue to suffer, enough without me shooting off my mouth on this specific case.

However, now the usual suspects (hyper-secularists, as well as those emoting rather than thinking) are calling for a law permitting active euthanasia — notwithstanding that Israel calls itself ‘a Jewish state’ last time I checked, that Jewish law prohibits active euthanasia in the strongest terms, and that it is also utterly incompatible not just with the Hippocratic Oath but with the Jewish versions thereof. (The situation regarding passive euthanasia is rather more complex, as has been recognized by a 2005 law.)

There is a well-known legal maxim in English: “terrible cases make for bad law”. Sometimes, moved to pity from a few individual heart-rending cases, lawmakers create laws, or judges legal precedents, that would have addressed these specific cases but have unintended consequences hundreds or thousands of times greater in magnitude for years or even centuries to come. Furthermore, dark forces can manipulate public sentiment on a few such terrible cases to generate public pressure for a change of law that suits their nefarious ends  — in this manner, somewhere in Europe, a nation was made to set the first steps on a slippery slope that led first to mass euthanasia of the mentally ill and special-needs children as having “lives not worth living” and “being too great a burden on those caring for them”, which then turned out to be the dress rehearsal for the murder of one-third of my people (plus an even larger percentage of Roma gypsies, as well as millions of Slavs).

It is, incidentally, interesting that the “T4-Aktion” (as the Nazi euthanasia program was known after the address of the headquarters of the program, Tiergartenstrasse 4 in Berlin) stands alone in the history of the Third Reich as an example where a widespread public outcry (backed, admittedly, by some prominent Catholic and Lutheran clergy) forced the regime to back down and discontinue it at least publicly.

It would be a tragedy on a cosmic scale if, moved by the Greek tragedy of a few individual families, the Jewish state of all countries would set the first steps down this “road to Hell paved with good intentions”. Fortunately, I would imagine that public support for such a law is mostly limited to the ‘Haaretz readers’ audience among the secular public, close to zero among the traditional public and the minority religions, and zero full stop among the Orthodox public.

The hideous face of state-run medicine in the UK

At the risk of going full Godwin, this is an updated version of Pfannmüller’s “natural method” during the Third Reich:
Behold the truly hideous endgame of state-run medicine.

International Liberty

I’m not easily grossed out or nauseated. Heck, I’m on email lists for a half-dozen softball teams and you can only imagine the strange/filthy/nasty things that guys send to each other.

But I read a story about the death panels in the United Kingdom that left me discombobulated. I can’t even begin to describe how I feel.

Here’s the intro of a disturbing report in the Daily Mail.

Sick children are being discharged from NHS hospitals to die at home or in hospices on controversial ‘death pathways’. Until now, end of life regime the Liverpool Care Pathway was thought to have involved only elderly and terminally-ill adults. But the Mail can reveal the practice of withdrawing food and fluid by tube is being used on young patients as well as severely disabled newborn babies.

And here are some of the horrifying details. Read at your own risk.

One doctor…

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Replacing the aristocracy of money by the aristocracy of pull

Ayn Rand is an extremely verbose author, but she could be very concise and to the point when she put her mind to it. Witness this scene from ‘Atlas Shrugged’: the crony-capitalist James Taggart starts on a familiar rant and suddenly gets cut off:

We will liberate our culture from the stranglehold of the profit-chasers. We will build a society dedicated to higher ideals, and we will replace the aristocracy of money by–

“the aristocracy of pull,” interjects d’Anconia.

Bingo. Had she been writing today, she might have said “the aristocracy of clout” or “the aristocracy of connections” or in Israel or Russia “the aristocracy of protektziya“.

Make no mistake: there is no such thing as a purely equal society. As George Orwell had his fictitious Emmanuel Goldstein put it: every society in human history has had a High, a Middle, and a Low. In a capitalist society, the High tend to be those with the most money. In a society of the type envisioned by the ‘social justice’ crowd (a term like “People’s Democratic Republic” in which every word actually means the opposite of its plain meaning) all that will happen is that who is part of the ‘High’ gets determined no longer by one’s net worth, but by the number and quality of one’s connections.

I have seen this first-hand in socialized medicine systems, where indeed money could not buy you access to gold-plated treatment — but being connected to the right people could. As an Israeli friend told me: “I’d go to the hospital and say my name is Yossi Cohen and get one type of treatment; I’d go back and say my name is Prof. Joseph Cohen from [name of famous research university] and get the red carpet. It ought not to be like this but this is reality.” (Or it was, until private medicine started making significant inroads.)

Now guess what kind of people figure they would be the High in such a system? Yes indeed, the New Class. This is what ‘social justice’ is really about: a disaffected group from the (upper) Middle trying to set itself up as the new High, using the Low as mascots or (electoral) cannon fodder.