Coffee Break: Lifestyle Medicine, More Quackitude, Ancient Manuscripts, Gut Health, and the Epstein Class

Part the First: Nutrition and Medicine.  The current Secretary of Health and Human Services is not wrong in his emphasis on nutrition (a stopped analog clock is right twice a day).  I don’t know where Lauren Rice is attending medical school in New York City, but her editorial take seems about half right in I’m a medical student. RFK Jr. is right about medical school and preventive care:

The first patient I met as a medical student was a middle-aged delivery man and a former track athlete. He was recovering from his second amputation due to uncontrolled type 2 diabetes. When he told me he never realized how much his “high sugars” could cost him, I wasn’t sure what to say.

I rotated at four busy New York City hospitals during my medical education. Each day, I saw patients with similar stories — people living with the consequences of poorly controlled chronic disease. I learned to assess for strokes, manage heart failure exacerbations, and explain the vascular impact of diabetes in fancy physiologic terms. I learned to treat the complications of chronic disease well, but I learned little of how to prevent them.

I am now a fourth-year medical student pursuing a career in internal medicine with a focus on chronic disease prevention. I entered medical school eager to learn how I could shape my patients’ health through nutrition, lifestyle, and preventive medicine.

But these topics have largely been absent from my training. Now, as I’m poised to graduate, I feel unprepared to address the chronic diseases that will affect the patients I will soon care for.

It is true that nutrition in medical education has not been taught very well, for a very long time.  A quick search in PubMed using “nutrition medical education” returns about 40,000 hits going back to 1879, with 90% of them from the last fifteen years.  Until very recently most of that would have been first-year metabolic biochemistry with a smattering of second-year physiology thrown into the mix.  But nutrition and social determinants of health have been a major focus at many medical schools.  And these determinants are best considered as a problem of political economy.  Another problem with medical education for another time is that soon-to-be Dr. Rice describes her medical education as “training.”

These conditions share the same upstream drivers: metabolic dysfunction, chronic inflammation, and an obesogenic environment that makes healthy choices difficult. We future physicians are taught to think of chronic diseases as separate entities rather than the result of these shared root causes. For instance, during a three-week outpatient internal medicine rotation, my classmates and I did not receive any formal training on nutrition or lifestyle counseling, despite the fact that primary care visits are a key touchpoint for discussing behavioral changes with patients.

These are missed opportunities to shape trainees into physicians who value and believe in preventive medicine. We cannot solve our chronic disease epidemic, which affects more than 90% of American adults and accounts for 90% of our health care spending, with a health care training model designed for acute crises.

A proactive health care system means training the next generation of doctors to think about how to alter the course of chronic diseases before they present as acute problems, namely through prevention and lifestyle-based practices.

There is no need to repeat that the Great American Food System™ has ill served the people.  I am a member of our institutional working group that will revamp nutrition in our medical curriculum.  But in our tutorial system the social determinants of health, with diet the major determinant, are front and center from the beginning.  Perhaps this is because our mission is to prepare primary care physicians (Family Medicine, Internal Medicine, Pediatrics, OB/GYN, Psychiatry, and General Surgery) who will practice in rural, underserved communities.  But virtually all communities in the United States are medically underserved, including New York City.

Still, when I have pointed to my colleagues out that “lifestyle medicine” (yes, this is really a thing) could seem natural only to physicians who have no clue this does not apply to people who have the “wrong lifestyle” because they live without money in a food desert, rural or urban, I have a hard time getting through.  But the political economy of food is the problem and will remain so until this is fixed.  These Augean Stables are overflowing with stuff, for now.  But maybe the Heracles we need will appear.  Beyond the performativity of MAHA, s/he has not.  Yet.

Part the Second: More Quackitude.  Sorry, a little bit of biochemistry follows.  Leucovorin is a folate (folic acid, vitamin B9) analog that is used primarily during chemotherapy to moderate the side effects of methotrexate, another folate analog that was one of the first effective chemotherapeutic drugs, going back more than seventy years.  Methotrexate is still used in chemotherapy.  This history is covered in The Emperor of All Maladies, highly recommended.  Leucovorin is also used to treat a rare condition that causes folate deficiency in the brain, which is not autism:

The U.S. Food and Drug Administration on Tuesday approved leucovorin, a synthetic form of vitamin B9, as a treatment for a rare genetic condition that causes folate deficiencies in the brain. The decision comes just months after U.S. president Donald Trump, Secretary of Health and Human Services Robert F. Kennedy, Jr., and FDA chief Marty Makary lauded the drug as a treatment for autism. After a scientific review, the FDA, which falls under Kennedy’s oversight, determined that there weren’t enough data to support that use of the drug.

“Autism is not caused by a folate deficiency,” says David Mandell, a professor of psychiatry at the University of Pennsylvania, who studies autism. “The data suggesting so are outdated and weak.”

Leucovorin is typically used to manage cancer patients’ side effects from chemotherapy. But last September Makary said the FDA would move to make the drug “available to children with autism.” Now the agency has approved its use for cerebral folate deficiency—a rare genetic condition that may affect fewer than one in a million people, though its true prevalence is unknown. It is caused by a mutation on the FOLR1 gene and can produce some similar symptoms to autism, such as communication issues. But autism is a separate condition, and a broad diagnosis. Although it can sometimes be tied to specific genetic factors, many researchers believe autism has no single cause.

Suggesting that leucovorin is a medical treatment for autism will only raise false hope in the most vulnerable:

The FDA’s decision is welcome, Mandell says, but it won’t undo the interest the Trump administration has raised in using the drug for treating autism. “Pandora’s box is already open,” he adds. Prescriptions for off-label leucovorin—that is, for using the drug to treat a condition it isn’t approved for—have skyrocketed among children by 71 percent after the officials touted its potential benefits for autism. Tager-Flusberg says that it remains to be seen how the FDA’s decision will affect off-label use.

“RFK, Jr.’s premature and ill-informed announcement that leucovorin can cure autism led many families to pay out of pocket for this drug when they could have been using that money for better purposes,” Mandell says. “Now these families are experiencing the whiplash that happens when politics and untested theories get ahead of science.”

The Current Administration and its MAHA acolytes have gotten a lot of mileage out of what they view as “political meddling” in matters of individual and public health.  I think the clinical term for this is “projection,” even if the pandemic brought out some of the worst in the politico-medical establishment.

Part the Third: Libraries and Museums Are Still Wonders of the World.  “Give me a place to stand on, and I will move the Earth.”  So said Archimedes.  A missing page of a tenth-century manuscript of his work has reappeared:

The Archimedes Palimpsest is one of the treasures of antiquity. This medieval manuscript, dating the to the 10th century, includes copies of the writings of Archimedes of Syracuse, a Greek mathematician and scientist who laid the foundations of modern calculus, geometry and fundamental physics. And now scientists have recovered one of the lost pages of the palimpsest, shedding more light on the great scientist’s mathematical thinking.

The page has been missing for years: we know that in 1906 a historian photographed much of the manuscript—but sometime later, some of the pages mysteriously went missing.

Researchers discovered the missing sheet, page 123, in the Museum of Fine Arts in Blois, France, according to the French National Center for Scientific Research (CNRS). One side of the page includes a writing from Archimedes’ treatise On the Sphere and the Cylinder, much of which is legible, according to the CNRS.

In a previous life I was a semi-regular at the Walters Art Museum in Baltimore, where the rest of the Archimedes Palimpsest is housed.  Perhaps upon the return of the missing page, a return to the museum should be on the agenda.

Part the Fourth: Antibiotics and the Gut Microbiome.  The rise of the microbiome has been one of the more interesting developments in biomedical science over the past fifteen years.  Before its importance was more fully understood, gut bacteria and other “flora” was just there.  Everyone knew the gut is full of bugs, including bacteria, fungi, and protozoa, but no one really paid attention.  Then it was discovered that fecal transplants were the best treatment for persistent Clostridioides difficile infections, especially in older patients.  It turns out that a primary reason C. difficile causes problems is that after antibiotic treatment this bacterium has a growth advantage because its competitors are knocked back.  Replace them with the transplant and C. difficile quietens down:

Antibiotics are designed to wipe out infection-causing bacteria, but even a single course can leave a lasting mark on the gut microbiome, according to a new study of nearly 15,000 adults in Sweden.

The research cross-referenced stool samples with Sweden’s prescribed drug registry to compare the gut microbiomes of people who had taken antibiotics at some point in the previous eight years with those who hadn’t—an “impressive” scope, says Jotham Suez, a microbiome researcher at the Johns Hopkins Bloomberg School of Public Health, who was not involved in the study. The paper was published today in Nature Medicine (open access).

As would be expected, the effects depend on the antibiotics used:

Clindamycin, (a broad-spectrum antibiotic) which is sometimes prescribed for skin and dental infections, was the most disruptive: each course taken in the year before stool sampling was linked to an average of 47 fewer detected species, as well as changes in abundance in almost 300 of the 1,340 species analyzed. Courses of fluoroquinolones, which are often prescribed for urinary tract infections and respiratory infections, and flucloxacillin, which is mainly prescribed for Staphylococcus aureus infections, both corresponded to an average of about 20 fewer species. (Flucloxacillin is not available in the U.S.) They were also linked to changes in the abundance of 172 and 203 species, respectively. Most of the other antibiotics analyzed in the study were linked to decreases in bacterial abundance, but some were linked to increases in bacteria that have been associated with poor cardiometabolic health.

However, this does not mean that antibiotics should not be taken when necessary!  Life expectancy has not improved so much over the past hundred years because the human lifespan has lengthened. Old cemeteries are full of people who died in their 70s, 80s, and 90s.  Life expectancy has improved because people, especially children, do not die of infectious disease so often since Sir Alexander Fleming discovered penicillin and Howard Flory and Ernest Chain figured out how to synthesize it.  Yes, antibiotic abuse is rampant, especially when cows, pigs, and chickens are “finished” or raised in animal concentration camps.  We do not have to do that or overprescribe them.

But you heard it here first.  We can expect that the next MAHA trope will be, “Ignore antibiotics!  They mess with your gut.  If you are healthy (and therefore worthy) your body will fight the pathogens off.”  Both statements are true.  But the risk of dying from a treatable bacterial infection because antibiotics are “not natural” (yes, they are; ask Penicillium chrysogenum) or some such nonsense is poor advice, now and in the MAHA future.

Part the Fifth: Mansplainin’ Is Still a Thing.  The entire Jeffrey Epstein atrocity has been on one level bewildering, as in “How could so many men be so stupid?”  On the other hand, these erstwhile masters of the universe tend to get what they want, even when they are awkward misanthropes despite, or because of, their money.  I never thought I would cross this line, but Susan Pederson’s article in the London Review of Books, Men explain Epstein to me, seems to be one of the best explanations, so far:

As the whole world knows, Epstein was a wizard at drawing in well-heeled, insecure men and serving up what they most wanted: posh holidays, ‘cool’ parties, tips on investments, trips on private planes, dinners with Nobel laureates, donations to their wives’ charities and introductions to girls supposedly eager to spend time with a nerdy guy three times their age. The podcast hosts were keen dissectors of that sordid mess, sometimes because it was their subject of study, and sometimes because they’d been on the fringe of that world themselves. Of course they had. Anyone in the upper reaches of American (or Anglo-American) philanthropy, arts, politics or university administration has had to spend time making nice with donors, trying to turn their harebrained ideas into something the cause or institution could use. That proximity prompted some on-air anxiety. If invited to one of Epstein’s parties, would I have said yes, (Rory) Stewart wondered? Would I, Adam Tooze asked?

…

The scandal lays bare the entitlement felt and impunity enjoyed by the powerful and crass – an impunity so well captured by Trump’s advice to ‘grab them by the…’ (click on the link for the sordid rest of the story)

The remainder of the article explains the why and how of sexual abuse of girls, not underage women.  And as one might expect, the perps tended to be the usual suspects.  Unfortunately, too many of the Epstein Class rule the world, and for all the world are just like many of the misogynist jackasses I knew who were in the select fraternities of my late-teens and early-twenties at our “flagship” state university.  They are still in charge today and are probably doing the same things.  But maybe not for long, on both counts.  One can hope, anyway.

Thank you for reading.  See you next week!