Gut Microbes Could Finally Settle the Debate Over Whether Red Meat Is Unhealthy
Some people can eat red meat without negative health consequences, which may be due to variability between people's gut microbes.
In different countries' national dietary guidelines, red meats (beef, pork, and lamb) are often confined to a very small corner. Swedish officials, for example, advise the population to "eat less red and processed meat". Experts in Greece recommend consuming no more than four servings of red meat — not per week, but per month.
"Humans 100% rely on the microbes to digest this food."
Yet somehow, the matter is far from settled. Quibbles over the scientific evidence emerge on a regular basis — as in a recent BMJ article titled, "No need to cut red meat, say new guidelines." News headlines lately have declared that limiting red meat may be "bad advice," while carnivore diet enthusiasts boast about the weight loss and good health they've achieved on an all-meat diet. The wildly successful plant-based burgers? To them, a gimmick. The burger wars are on.
Nutrition science would seem the best place to look for answers on the health effects of specific foods. And on one hand, the science is rather clear: in large populations, people who eat more red meat tend to have more health problems, including cardiovascular disease, colorectal cancer, and other conditions. But this sort of correlational evidence fails to settle the matter once and for all; many who look closely at these studies cite methodological shortcomings and a low certainty of evidence.
Some scientists, meanwhile, are trying to cut through the noise by increasing their focus on the mechanisms: exactly how red meat is digested and the step-by-step of how this affects human health. And curiously, as these lines of evidence emerge, several of them center around gut microbes as active participants in red meat's ultimate effects on human health.
Dr. Stanley Hazen, researcher and medical director of preventive cardiology at Cleveland Clinic, was one of the first to zero in on gut microorganisms as possible contributors to the health effects of red meat. In looking for chemical compounds in the blood that could predict the future development of cardiovascular disease, his lab identified a molecule called trimethylamine-N-oxide (TMAO). Little by little, he and his colleagues began to gather both human and animal evidence that TMAO played a role in causing heart disease.
Naturally, they tried to figure out where the TMAO came from. Hazen says, "We found that animal products, and especially red meat, were a dietary source that, [along with] gut microbes, would generate this product that leads to heart disease development." They observed that the gut microbes were essential for making TMAO out of dietary compounds (like red meat) that contained its precursor, trimethylamine (TMA).
So in linking red meat to cardiovascular disease through TMAO, the surprising conclusion, says Hazen, was that, "Without a doubt, [the microbes] are the most important aspect of the whole pathway."
"I think it's just a matter of time [before] we will have therapeutic interventions that actually target our gut microbes, just like the way we take drugs that lower cholesterol levels."
Other researchers have taken an interest in different red-meat-associated health problems, like colorectal cancer and the inflammation that accompanies it. This was the mechanistic link tackled by the lab of professor Karsten Zengler of the UC San Diego Departments of Pediatrics and Bioengineering—and it also led straight back to the gut microbes.
Zengler and colleagues recently published a paper in Nature Microbiology that focused on the effects of a red meat carbohydrate (or sugar) called Neu5Gc.
He explains, "If you eat animal proteins in your diet… the bound sugars in your diet are cleaved off in your gut and they get recycled. Your own cells will not recognize between the foreign sugars and your own sugars, because they look almost identical." The unsuspecting human cells then take up these foreign sugars — spurring antibody production and creating inflammation.
Zengler showed, however, that gut bacteria use enzymes to cleave off the sugar during digestion, stopping the inflammation and rendering the sugar harmless. "There's no enzyme in the human body that can cleave this [sugar] off. Humans 100% rely on the microbes to digest this food," he says.
Both researchers are quick to caution that the health effects of diet are complex. Other work indicates, for example, that while intake of red meat can affect TMAO levels, so can intake of fish and seafood. But these new lines of evidence could help explain why some people, ironically, seem to be in perfect health despite eating a lot of red meat: their ideal frequency of meat consumption may depend on their existing community of gut microbes.
"It helps explain what accounts for inter-person variability," Hazen says.
These emerging mechanisms reinforce overall why it's prudent to limit red meat, just as the nutritional guidelines advised in the first place. But both Hazen and Zengler predict that interventions to buffer the effects of too many ribeyes may be just around the corner.
Zengler says, "Our idea is that you basically can help your own digestive system detoxify these inflammatory compounds in meat, if you continue eating red meat or you want to eat a high amount of red meat." A possibly strategy, he says, is to use specific pre- or probiotics to cultivate an inflammation-reducing gut microbial community.
Hazen foresees the emergence of drugs that act not on the human, but on the human's gut microorganisms. "I think it's just a matter of time [before] we will have therapeutic interventions that actually target our gut microbes, just like the way we take drugs that lower cholesterol levels."
He adds, "It's a matter of 'stay tuned', I think."
Here's how one doctor overcame extraordinary odds to help create the birth control pill
Dr. Percy Julian had so many personal and professional obstacles throughout his life, it’s amazing he was able to accomplish anything at all. But this hidden figure not only overcame these incredible obstacles, he also laid the foundation for the creation of the birth control pill.
Julian’s first obstacle was growing up in the Jim Crow-era south in the early part of the twentieth century, where racial segregation kept many African-Americans out of schools, libraries, parks, restaurants, and more. Despite limited opportunities and education, Julian was accepted to DePauw University in Indiana, where he majored in chemistry. But in college, Julian encountered another obstacle: he wasn’t allowed to stay in DePauw’s student housing because of segregation. Julian found lodging in an off-campus boarding house that refused to serve him meals. To pay for his room, board, and food, Julian waited tables and fired furnaces while he studied chemistry full-time. Incredibly, he graduated in 1920 as valedictorian of his class.
After graduation, Julian landed a fellowship at Harvard University to study chemistry—but here, Julian ran into yet another obstacle. Harvard thought that white students would resent being taught by Julian, an African-American man, so they withdrew his teaching assistantship. Julian instead decided to complete his PhD at the University of Vienna in Austria. When he did, he became one of the first African Americans to ever receive a PhD in chemistry.
Julian received offers for professorships, fellowships, and jobs throughout the 1930s, due to his impressive qualifications—but these offers were almost always revoked when schools or potential employers found out Julian was black. In one instance, Julian was offered a job at the Institute of Paper Chemistory in Appleton, Wisconsin—but Appleton, like many cities in the United States at the time, was known as a “sundown town,” which meant that black people weren’t allowed to be there after dark. As a result, Julian lost the job.
During this time, Julian became an expert at synthesis, which is the process of turning one substance into another through a series of planned chemical reactions. Julian synthesized a plant compound called physostigmine, which would later become a treatment for an eye disease called glaucoma.
In 1936, Julian was finally able to land—and keep—a job at Glidden, and there he found a way to extract soybean protein. This was used to produce a fire-retardant foam used in fire extinguishers to smother oil and gasoline fires aboard ships and aircraft carriers, and it ended up saving the lives of thousands of soldiers during World War II.
At Glidden, Julian found a way to synthesize human sex hormones such as progesterone, estrogen, and testosterone, from plants. This was a hugely profitable discovery for his company—but it also meant that clinicians now had huge quantities of these hormones, making hormone therapy cheaper and easier to come by. His work also laid the foundation for the creation of hormonal birth control: Without the ability to synthesize these hormones, hormonal birth control would not exist.
Julian left Glidden in the 1950s and formed his own company, called Julian Laboratories, outside of Chicago, where he manufactured steroids and conducted his own research. The company turned profitable within a year, but even so Julian’s obstacles weren’t over. In 1950 and 1951, Julian’s home was firebombed and attacked with dynamite, with his family inside. Julian often had to sit out on the front porch of his home with a shotgun to protect his family from violence.
But despite years of racism and violence, Julian’s story has a happy ending. Julian’s family was eventually welcomed into the neighborhood and protected from future attacks (Julian’s daughter lives there to this day). Julian then became one of the country’s first black millionaires when he sold his company in the 1960s.
When Julian passed away at the age of 76, he had more than 130 chemical patents to his name and left behind a body of work that benefits people to this day.
Therapies for Healthy Aging with Dr. Alexandra Bause
My guest today is Dr. Alexandra Bause, a biologist who has dedicated her career to advancing health, medicine and healthier human lifespans. Dr. Bause co-founded a company called Apollo Health Ventures in 2017. Currently a venture partner at Apollo, she's immersed in the discoveries underway in Apollo’s Venture Lab while the company focuses on assembling a team of investors to support progress. Dr. Bause and Apollo Health Ventures say that biotech is at “an inflection point” and is set to become a driver of important change and economic value.
Previously, Dr. Bause worked at the Boston Consulting Group in its healthcare practice specializing in biopharma strategy, among other priorities
She did her PhD studies at Harvard Medical School focusing on molecular mechanisms that contribute to cellular aging, and she’s also a trained pharmacist
In the episode, we talk about the present and future of therapeutics that could increase people’s spans of health, the benefits of certain lifestyle practice, the best use of electronic wearables for these purposes, and much more.
Dr. Bause is at the forefront of developing interventions that target the aging process with the aim of ensuring that all of us can have healthier, more productive lifespans.
