Kidney Toxins Created by Meat Consumption

As I discuss in my video How to Treat Heart Failure and Kidney Failure with Diet, one way a diet rich in animal-sourced foods like meat, eggs, and cheese may contribute to heart disease, stroke, and death is through the production of an atherosclerosis-inducing substance called TMAO. With the help of certain gut bacteria, the choline and carnitine found concentrated in animal products can get converted into TMAO. But, wait a second. I thought atherosclerosis, or hardening of the arteries, was about the buildup of cholesterol. Is that not the case?

“Cholesterol is still king,” but TMAO appears to accelerate the process. It seems that TMAO appears to increase the ability of inflammatory cells within the atherosclerotic plaque in the artery walls to bind to bad LDL cholesterol, “which makes the cells more prone to gobble up cholesterol.” So TMAO is just “another piece to the puzzle of how cholesterol causes heart disease.”

What’s more, TMAO doesn’t just appear to worsen atherosclerosis, contributing to strokes and heart attacks. It also contributes to heart and kidney failure. If you look at diabetics after a heart attack, a really high-risk group, nearly all who started out with the most TMAO in their bloodstream went on to develop heart failure within 2,000 days, or about five years. In comparison, only about 20 percent of those starting out with medium TMAO levels in the blood went into heart failure and none at all in the low TMAO group, as you can see at 1:21 in my video.

So, those with heart failure have higher levels of TMAO than controls, and those with worse heart failure have higher levels than those with lesser stage heart disease. If you follow people with heart failure over time, within six years, half of those who started out with the highest TMAO levels were dead. This finding has since been replicated in two other independent populations of heart failure patients.

The question is, why? It’s probably unlikely to just be additional atherosclerosis, since that takes years. For most who die of heart failure, their heart muscle just conks out or there’s a fatal heart rhythm. Maybe TMAO has toxic effects beyond just the accelerated buildup of cholesterol.

What about kidney failure? People with chronic kidney disease are at a particularly “increased risk for the development of cardiovascular disease,” thought to be because of a diverse array of uremic toxins. These are toxins that would normally be filtered out by the kidneys into the urine but may build up in the bloodstream as kidney function declines. When we think of uremic toxins, we usually think of the toxic byproducts of protein putrefying in our gut, which is why specially formulated plant-based diets have been used for decades to treat chronic kidney failure. Indeed, those who eat vegetarian diets form less than half of these uremic toxins.

Those aren’t the only uremic toxins, though. TMAO, which, as we’ve discussed, comes from the breakdown of choline and carnitine found mostly in meat and eggs, may be increasing heart disease risk in kidney patients as well. How? “The cardiovascular implication of TMAO seems to be due to the downregulation of reverse cholesterol transport,” meaning it subverts our own body’s attempts at pulling cholesterol out of our arteries.

And, indeed, the worse our kidney function gets, the higher our TMAO levels rise, and those elevated levels correlate with the amount of plaque clogging up their arteries in their heart. But once the kidney is working again with a transplant, your TMAO levels can drop right back down. So, TMAO was thought to be a kind of biomarker for declining kidney function—until a paper was published from the Framingham Heart Study, which found that “elevated choline and TMAO levels among individuals with normal renal [kidney] function predicted increased risk for incident development of CKD,” chronic kidney disease. This suggests that TMAO is both a biomarker and itself a kidney toxin.

Indeed, when you follow kidney patients over time and assess their freedom from death, those with higher TMAO, even controlling for kidney function, lived significantly shorter lives, as you can see at 4:44 in my video. This indicates this is a diet-induced mechanism for progressive kidney scarring and dysfunction, “strongly implying the need to focus preventive efforts on dietary modulation,” but what might that look like? Well, maybe we should reduce “dietary sources of TMAO generation, such as some species of deep-sea fish, eggs, and meat.”

It also depends on what kind of gut bacteria you have. You can feed a vegan a steak, and they still don’t really make any TMAO because they haven’t been fostering the carnitine-eating bacteria. Researchers are hoping, though, that one day, they’ll find a way to replicate “the effects of the vegetarian diet…by selective prebiotic, probiotic, or pharmacologic therapies.”


For more on this revolutionary TMAO story, see:

For more on kidney failure, see Preventing Kidney Failure Through Diet and Treating Kidney Failure Through Diet.

In health,

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

Updating Our Microbiome Software and Hardware

Good bacteria, those living in symbiosis with us, are nourished by fruits, vegetables, grains, and beans, whereas bad bacteria, those in dysbiosis with us and possibly contributing to disease, are fed by meat, junk food and fast food, seafood, dairy, and eggs, as you can see at 0:12 in my video Microbiome: We Are What They Eat. Typical Western diets can “decimate” our good gut flora.

We live with trillions of symbionts, good bacteria that live in symbiosis with us. We help them, and they help us. A month on a plant-based diet results in an increase in the population of the good guys and a decrease in the bad, the so-called pathobionts, the disease-causing bugs. “Given the disappearance of pathobionts from the intestine, one would expect to observe a reduction in intestinal inflammation in subjects.” So, researchers measured stool concentrations of lipocalin-2, “which is a sensitive biomarker of intestinal inflammation.” As you can see at 1:13 in my video, within a month of eating healthfully, it had “declined significantly…suggesting that promotion of microbial homeostasis”—or balance—“by an SVD [strict vegetarian diet] resulted in reduced intestinal inflammation.” What’s more, this rebalancing may have played a role “in improved metabolic and immunological parameters,” that is, in immune system parameters.

In contrast, on an “animal-based diet,” you get growth of disease-associated species like Bilophila wadsworthia, associated with inflammatory bowel disease, and Alistipes putredinis, found in abscesses and appendicitis, and a decrease in fiber-eating bacteria. When we eat fiber, the fiber-munching bacteria multiply, and we get more anti-inflammatory, anti-cancer short-chain fatty acids. When we eat less fiber, our fiber-eating bacteria starve away.

They are what we eat.

Eat a lot of phytates, and our gut flora get really good at breaking down phytates. We assumed this was just because we were naturally selecting for those populations of bacteria able to do that, but it turns out our diet can teach old bugs new tricks. There’s one type of fiber in nori seaweed that our gut bacteria can’t normally breakdown, but the bacteria in the ocean that eat seaweed have the enzyme to do so. When it was discovered that that enzyme was present in the guts of Japanese people, it presented a mystery. Sure, sushi is eaten raw, so some seaweed bacteria may have made it to their colons, but how could some marine bacteria thrive in the human gut? It didn’t need to. It transferred the nori-eating enzyme to our own gut bacteria.

“Consequently, the consumption of food with associated environmental bacteria is the most likely mechanism that promoted this CAZyme [enzyme] update into the human gut microbe”—almost like a software update. We have the same hardware, the same gut bacteria, but the bacteria just updated their software to enable them to chew on something new.

Hardware can change, too. A study titled “The way to a man’s heart is through his gut microbiota” was so named because the researchers were talking about TMAO, trimethylamine N-oxide. As you can see at 3:33 in my video, certain gut flora can take carnitine from the red meat we eat or the choline concentrated in dairy, seafood, and eggs, and convert it into a toxic compound, which may lead to an increase in our risk of heart attack, stroke, and death.

This explains why those eating more plant-based diets have lower blood concentrations of TMAO. However, they also produce less of the toxin even if you feed them a steak. You don’t see the same “conversion of dietary L-carnitine to TMAO…suggesting an adoptive response of the gut microbiota in omnivores.” They are what we feed them.

As you can see at 4:17 in my video, if you give people cyclamate, a synthetic artificial sweetener, most of their bacteria don’t know what to do with it. But, if you feed it to people for ten days and select for the few bacteria that were hip to the new synthetic chemical, eventually three quarters of the cyclamate consumed is metabolized by the bacteria into another new compound called cyclohexylamine. Stop eating it, however, and those bacteria die back. Unfortunately, cyclohexylamine may be toxic and so was banned by the FDA in 1969. In a vintage Kool-Aid ad from 1969, Pre-Sweetened Kool-Aid was taken “off your grocer’s shelves,” but Regular Kool-Aid “has no cyclamates” and “is completely safe for your entire family.”

But, if you just ate cyclamate once in a while, it wouldn’t turn into cyclohexylamine because you wouldn’t have fed and fostered the gut flora specialized to do so. The same thing happens with TMAO. Those who just eat red meat, eggs, or seafood once in a while would presumably make very little of the toxin because they hadn’t been cultivating the bacteria that produce it.


Here’s the link to my video on TMAO: Carnitine, Choline, Cancer, and Cholesterol: The TMAO Connection. For an update on TMAO, see How Our Gut Bacteria Can Use Eggs to Accelerate Cancer, Egg Industry Response to Choline and TMAO, and How to Reduce Your TMAO Levels.

Interested in more on keeping our gut bugs happy? See:

In health,

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

What Explains the Egg-Cancer Connection

The reason egg consumption is associated with elevated cancer risk may be the TMAO, considered the “smoking gun” of microbiome-disease interactions.

“We are walking communities comprised not only of a Homo sapiens host, but also of trillions of symbiotic commensal microorganisms within the gut and on every other surface of our bodies.” There are more bacterial cells in our gut than there are human cells in our entire body. In fact, only about 10 percent of the DNA in our body is human. The rest is in our microbiome, the microbes with whom we share with the “walking community” we call our body. What do they do?

Our gut bacteria microbiota “serve as a filter for our largest environmental exposure—what we eat”—and, “technically speaking, food is a foreign object that we take into our bodies” by the pound every day. The “microbial community within each of us significantly influences how we experience a meal…Hence, our metabolism and absorption of food occurs through” this filter of bacteria.

However, as you can see at 1:22 in my video How Our Gut Bacteria Can Use Eggs to Accelerate Cancer, if we eat a lot of meat, including poultry and fish, milk, cheese, and eggs, we can foster the growth of bacteria that convert the choline and carnitine in those foods into trimethylamine (TMA), which can be oxidized into TMAO and wreak havoc on our arteries, increasing our risk of heart attack, stroke, and death.

We’ve known about this “troublesome” transformation from choline into trimethylamine for more than 40 years, but that was way before we learned about the heart disease connection. Why were researchers concerned back then? Because these methylamines might form nitrosamines, which have “marked carcinogenic activity”—cancer-causing activity. So where is choline found in our diet? Mostly from meat, eggs, dairy, and refined grains. The link between meat and cancer probably wouldn’t surprise anyone. In fact, just due to the industrial pollutants, like PCBs, children probably shouldn’t eat more than about five servings a month of meats like beef, pork, or chicken combined. But, what about cancer and eggs?

Studies going back to the 1970s hinted at a correlation between eggs and colon cancer, as you can see at 2:45 in my video. That was based just on so-called ecological data, though, showing that countries eating more eggs tended to have higher cancer rates, but that could be due to a million factors. It needed to be put to the test.

This testing started in the 80s, and, by the 1990s, 15 studies had been published, of which 10 suggested “a direct association” between egg consumption and colorectal cancer, “whereas five found no association.” By 2014, dozens more studies had been published, confirming that eggs may indeed be playing a role in the development of colon cancer, though no relationship was discovered between egg consumption and the development of precancerous polyps, which “suggested that egg consumption might be involved in the promotional” stage of cancer growth—accelerating cancer growth—rather than initiating the cancer in the first place.

This brings us to 2015. Perhaps it’s the TMAO made from the choline in meat and eggs that’s promoting cancer growth. Indeed, in the Women’s Health Initiative study, women with the highest TMAO levels in their blood had approximately three times greater risk of rectal cancer, suggesting that TMAO levels “may serve as a potential predictor of increased colorectal cancer risk.”

As you can see at 4:17 in my video, though there may be more evidence for elevated breast cancer risk with egg consumption than prostate cancer risk, the only other study to date on TMAO and cancer looked at prostate cancer and did indeed find a higher risk.

“Diet has long been considered a primary factor in health; however, with the microbiome revolution of the past decade, we have begun to understand how diet can” affect the back and forth between us and the rest of us inside, and the whole TMAO story is “a smoking gun” in gut bacteria-disease interactions.

Since choline and carnitine are the primary sources of TMAO production, the logical intervention strategy might be to reduce meat, dairy, and egg consumption. And, if we eat plant-based for long enough, we can actually change our gut microbial communities such that we may not be able to make TMAO even if we try.

“The theory of ‘you are what you eat’ finally is supported by scientific evidence.” We may not have to eat healthy for long, though. Soon, Big Pharma hopes, “we may yet ‘drug the microbiome’…as a way of promoting cardiovascular health.”

What did the egg industry do in response to this information? Distort the scientific record. See my video Egg Industry Response to Choline and TMAO.


This is not the first time the egg industry has been caught in the act. See, for example:

For background on TMAO see my original coverage in Carnitine, Choline, Cancer, and Cholesterol: The TMAO Connection and then find out How to Reduce Your TMAO Levels. Also, see: Flashback Friday: How to Reduce Your TMAO Levels.

This is all part of the microbiome revolution in medicine, the underappreciated role our gut flora play in our health. For more, see: 

In health,

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations: