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:

The Role of Meat and Dairy Viruses in Cancer

“Nearly 20% of cancer cases arising worldwide can be linked to infectious agents, including viruses.” Seven viruses are now conclusively tied to human cancers, and, as new viruses enter into human populations, the incidence and causes of cancer will likely change accordingly.

The foundation of modern tumor virology was laid more than a century ago with the discovery of a cancer-causing chicken virus, for which a Nobel Prize was awarded. Another Nobel Prize went to the “medical doctor-turned-virologist” who discovered that the HPV virus was causing cervical cancer. In his acceptance speech, he mused that there may be a bovine polyoma virus—a multiple tumor virus in cattle—that could be playing a role in human colon cancer, lung cancer, and breast cancer, but no polyoma virus had ever been discovered in meat…until now.

As I discuss in my video The Role of Burger Viruses in Cancer, polyomaviruses are a particular concern—not only because they are known to be carcinogenic, but also because they can survive cooking temperatures. Since a single burger these days can contain meat from “many dozens of animals,” researchers felt “this could present an ideal situation for virus-hunting…” Researchers from the National Cancer Institute purchased meat samples from three separate supermarkets and found three different polyomaviruses in ground beef, as you can see at 1:52 in my video. Now, just because three types of “polyomavirus species are commonly detectable in food-grade ground beef” doesn’t necessarily mean they are causing human disease. What made this Nobel laureate suspect them? Well, for one thing, some people got cancer right where they had been vaccinated for smallpox—a whole bunch of different cancers, in fact. The vaccine had been harvested from the skin of calves, so “it is possible” there could have been some cancer-causing cow virus.

“Many people are exposed to potentially virus-contaminated meat and dairy products” through their diets, but those in the industry, “such as farm workers, butchers, veterinarians, and employees in dairies,” would be even more exposed. Do these groups have higher cancer incidence? Indeed, it now appears to be clear “that workers in the meat industry are at increased risk of developing and dying from cancer.”

Another reason to suspect the involvement of some kind of bovine infectious factor in colorectal cancer is the fact that there appear to be relatively low rates of colorectal cancer in countries where not a lot of beef is eaten. And, when meat consumption suddenly increases, rates shoot up, as you can see at 3:15 in my video. “The only exception is Mongolia where they have low rates of colon cancer and eat a lot of red meat, but there they eat yak.” Maybe yaks don’t harbor the same viruses.

Can’t you just avoid steak tartare? Even steak cooked “medium” may not reach internal temperatures above 70° Celsius, and it takes temperatures higher than that to inactivate some of these viruses, so we would expect viruses to survive both cooking and pasteurization. In fact, researchers followed up with a paper suggesting the consumption of dairy products may “represent one of the main risk factors for the development of breast cancer” in humans. The recent discovery of a larger number of presumably new viruses in the blood, meat, and milk of dairy cows should be investigated, since one might speculate that infectious “agents present in dairy products possess a higher affinity to mammary [breast] cells,” since they came from breast cells. The fact that people with lactose intolerance, who tend to avoid milk and dairy throughout their lives, have lower rates of breast and other cancers could be seen as supporting this concept. Though, there are certainly other reasons dairy may increase cancer risk, such as increasing levels of the cancer-promoting growth hormone IGF-1 or adversely affecting our gut microbiome. Or, for that matter, maybe the plant-based milks they’re drinking instead could be protective. That’s the problem with population studies: You can’t tease out cause and effect. It doesn’t matter how many viruses are found in retail beef, pork, and chicken, as you can see at 5:16 in my video, if we can’t connect the dots.  

Can’t we just look for the presence of these viruses within human tumors? Researchers have tried and did find some, but even if you don’t find any, that doesn’t necessarily mean viruses didn’t play a role. There’s a “viral hit-and-run” theory of cancer development that suggests that certain viruses can slip in and out of our DNA to initiate the cancer, but be long gone by the time the tumor matures.

There’s still a lot of work to be done. But, if the link between bovine polyomaviruses and human disease pans out, the National Cancer Institute researchers envision the development of a high potency vaccine. So, just like the HPV vaccine may prevent cervical cancer from unsafe sex, perhaps one day, vaccines may prevent breast and colon cancer from unsafe sirloin.


This reminds me of the story of bovine leukemia virus and breast cancer. For more on that, see:

What about chicken? Check out The Role of Poultry Viruses in Human Cancers and Poultry and Penis Cancer.

One of the problems with eating other animals is that we put ourselves at risk of their diseases. Not once have I diagnosed anyone with Dutch Elm Disease or a really bad case of aphids. See Eating Outside Our Kingdom for more on this concept.

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 Meat and Eggs Do to Our Microbiome

As I’ve explored before, whether young or old, male or female, smoker or non-smoker, with high blood pressure or low blood pressure, high cholesterol or low, having high levels of a toxic compound called TMAO—trimethylamine oxide—in the bloodstream is associated with a significantly higher risk of having a heart attack, stroke, or dying over a three-year period. Where does TMAO come from? As I investigate in my video How to Develop a Healthy Gut Ecosystem, the choline in foods like eggs can be turned by gut bacteria into TMAO, which is then absorbed back into our system. And, the more eggs we eat, the higher the levels climb, as you can see at 0:41 in my video.

Given the similarity in structure between carnitine and choline, Cleveland Clinic researchers wondered if carnitine found in red meat, energy drinks, and supplements might also lead to TMAO production and put it to the test. As you can see at 1:00 in my video, if you feed omnivores, those who regularly eat meat, a steak, their TMAO levels shoot up. Those who eat strictly plant-based may start out with almost no TMAO in their system, presumably because they’re not eating any meat, eggs, or dairy. But, even if vegans eat a sirloin, still almost no TMAO is made. Why? Presumably, they don’t have steak-eating bacteria in their guts. Indeed, it was found that no TMAO is produced if you don’t have TMAO-producing bacteria in your gut. If you don’t regularly eat meat, then you’re not fostering the growth of the meat-eating microbes that produce TMAO.

This suggests that once we develop a plant-based gut ecosystem, our bacteria will not produce TMAO, even if we eat meat every once and awhile. However, we still don’t know how rapidly gut bacteria shift after a shift in our diet—but it does not appear to be all or nothing. If men eating the standard American diet are given two sausage, egg, and cheese biscuits before and after just five days of eating lots of similarly high-fat meals, their TMAO production boosts even higher, as you can see at 2:09 in my video. So, it’s not just whether we have the bad bugs or not. Apparently, we can breed more of them the more we feed them.

Meat-free diets, on the other hand, can also have been “demonstrated to have a profound influence on human metabolism.”Just by analyzing a urine sample, we can tell what kind of diet people eat, based on measurements like how low TMAO levels are in the urine of those eating egg-free vegetarian diets, as you can see at 2:26 in my video. At 2:43 in my video, you’ll see that we can even take the same people rotate them through three different diets, and determine who is on a high-meat diet, low-meat diet, or no-meat diet, based in part on the different compounds churned out by the different gut flora or different flora activity after just about two weeks on the different diets. It’s possible that some of the beneficial effects of whole plant foods may be mediated by the effects they have on our gut bacteria. At the same time, the standard American diet may increase the relative abundance of undesirables that produce toxic compounds including TMAO (as you can see at 3:07 in my video).

Strictly plant-based diets have gained acceptance as a dietary strategy for preventing and managing disease. Perhaps, in part, this is because of their rather unique gut flora, with less of the disease-causing bacteria and more of the protective species. So, all along, we thought the reason those eating plant-based had lower heart disease rates was because they were eating less saturated fat and cholesterol, but maybe their lower TMAO levels may also be contributing to their benefits, thanks to their reduced ingestion of carnitine and choline.

I talked about the egg industry response to the choline revelation in Egg Industry Response to Choline and TMAO. How has the carnitine supplement industry reacted? In response to the research implicating carnitine in TMAO production, the former vice president of AdvoCare—a multilevel marketing company that sells carnitine supplements like AdvoCare Slam while getting slammed with lawsuits finding them guilty of being “engaged in false, misleading or deceptive acts or practices” and forced to pay more than a million dollars—questioned whether there was a secret vegan conspiracy at the Cleveland Clinic. Restricting our intake of meat or carnitine supplements to prevent our gut bacteria from making TMAO, he argued, is like trying to prevent car accidents by restricting the sale of fuel.

Okay…but there are benefits to transportation. We’re talking about TMAO, which may be fueling our epidemic of heart disease, the number-one killer of men and women in this country. As far as I’m concerned, the more we can cut the fuel for that, the better.


For more background on TMAO, see Carnitine, Choline, Cancer, and Cholesterol: The TMAO Connection, then find out How to Reduce Your TMAO Levels.

Our gut flora are what we eat. Check out:

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: