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:

What White Blood Cell Count Should We Shoot for?

At the start of my video What Does a Low White Blood Cell Count Mean?, you can see what it looks like when you take a drop of blood, smear it between two pieces of glass, and view at it under a microscope: a whole bunch of little, round, red blood cells and a few big, white blood cells. Red blood cells carry oxygen, while white blood cells are our immune system’s foot soldiers. We may churn out 50 billion new white blood cells a day. In response to inflammation or infection, that number can shoot up to a 100 billion or more. In fact, pus is largely composed of: millions and millions of white blood cells.

Testing to find out how many white blood cells we have at any given time is one of the most common laboratory tests doctors order. It’s ordered it hundreds of millions of times a year. If, for example, you end up in the emergency room with abdominal pain, having a white blood cell count above about 10 billion per quart of blood may be a sign you have appendicitis. Most Americans fall between 4.5 and 10, but most Americans are unhealthy. Just because 4.5 to 10 is typical doesn’t mean it’s ideal. It’s like having a “normal” cholesterol level in a society where it’s normal to die of heart disease, our number-one killer. The average American is overweight, so if your weight is “normal,” that’s actually a bad thing.

In fact, having excess fat itself causes inflammation within the body, so it’s no surprise that those who are obese walk around with two billion more white cells per quart of blood. Given that, perhaps obese individuals should have their own “normal” values. As you can see at 2:06 in my video, if someone with a 47-inch waist walks into the ER with a white blood cell count of 12, 13, or even 14, they may not have appendicitis or an infection. That may just be their normal baseline level, given all the inflammation they have in their body from the excess fat. So, normal levels are not necessarily healthy levels.

It’s like smoking. As you can see at 2:31 in my video, if you test identical twins and one smokes but the other doesn’t, the smoker is going to end up with a significantly higher white cell count. In Japan, for example, as smoking rates have steadily dropped, so has the normal white count range. In fact, it’s dropped such that about 8 percent of men who have never smoked would now be flagged as having abnormally low white counts if you used a cut-off of 4. But, when that cut-off of 4 was set, most people were smoking. So, maybe 3 would be a better lower limit. The inflammation caused by smoking may actually be one of the reasons cigarettes increase the risk of heart attacks, strokes, and other inflammatory diseases. So, do people who have lower white counts have less heart disease, cancer, and overall mortality? Yes, yes, and yes. People with lower white blood cell counts live longer. Even within the normal range, every one point drop may be associated with a 20 percent drop in the risk of premature death.

As you can see at 3:39 in my video, there is an exponential increase in risk in men as white count goes up, even within the so-called normal range, and the same is found for women. The white blood cell count is a “stable, well-standardized, widely available and inexpensive measure of systemic inflammation.” In one study, half of the women around 85 years of age who had started out with white counts under 5.6 were still alive, whereas 80 percent of those who started out over 7 were dead, as you can see at 4:05 in my video—and white blood cell counts of 7, 8, 9, or even 10 would be considered normal. Being at the high end of the normal range may place one at three times the risk of dying from heart disease compared to being at the lower end.

The same link has been found for African-American men and women, found for those in middle age, found at age 75, found at age 85, and found even in our 20s and 30s: a 17 percent increase in coronary artery disease incidence for each single point higher.

As you can see at 5:00 in my video, the higher your white count, the worse your arterial function may be and the stiffer your arteries may be, so it’s no wonder white blood cell count is a useful predictor of high blood pressure and artery disease in your heart, brain, legs, and neck. Even diabetes? Yes, even diabetes, based on a compilation of 20 different studies. In fact, it may be associated with everything from fatty liver disease to having an enlarged prostate. And, having a higher white blood cell count is also associated with an increased risk of dying from cancer. So, what would the ideal range be? I cover that in my video What Is the Ideal White Blood Cell Count?.

A higher white blood cell count may be an important predictor for cardiovascular disease incidence and mortality, decline in lung function, cancer mortality, all-cause mortality, heart attacks, strokes, and premature death in general. This is no surprise, as the number of white blood cells we have circulating in our bloodstreams are a marker of systemic inflammation. Our bodies produce more white blood cells day to day in response to inflammatory insults.

We’ve known about this link between higher white counts and heart attacks since the 1970s, when we found that higher heart attack risk was associated with higher white blood cell counts, higher cholesterol levels, and higher blood pressures, as you can see at 0:53 in my video What Is the Ideal White Blood Cell Count?. This has been found in nearly every study done since then. There are decades of studies involving hundreds of thousands of patients showing dramatically higher mortality rates in those with higher white counts. But why? Why does white blood cell count predict mortality? It may be because it’s a marker of inflammation and oxidation in the body. In fact, it may even be a biomarker for how fast we are aging. It may be more than just an indicator of inflammation—it may also be an active player, contributing directly to disease via a variety of mechanisms, including the actual obstruction of blood flow.

The average diameter of a white blood cell is about seven and a half micrometers, whereas our tiniest vessels are only about five micrometers wide, so the white blood cell has to squish down into a sausage shape in order to squeeze through. When there’s inflammation present, these cells can get sticky. As you can see at 2:20 in my video, a white blood cell may plug up a vessel as it exits a small artery and tries to squeeze into a capillary, slowing down or even momentarily stopping blood flow. And, if it gets stuck there, it can end up releasing all of its internal weaponry, which is normally reserved for microbial invaders, and damage our blood vessels. This may be why in the days leading up to a stroke or heart attack, you may find a spike in the white cell count.

Whether white count is just a marker of inflammation or an active participant, it’s better to be on the low side. How can we reduce the level of inflammation in our body? Staying away from even second-hand smoke can help drop your white count about half of a point. Those who exercise also appear to have an advantage, but you don’t know if it’s cause and effect unless you put it to the test. In one study, two months of Zumba classes—just one or two hours a week—led to about a point and a half drop in white count. In fact, that may be one of the reasons exercise is so protective. But is that just because they lost weight?

Fitness and fatness both appear to play a role. More than half of obese persons with low fitness—51.5 percent—have white counts above 6.6, but those who are more fit or who have less fat are less likely to have counts that high, as you can see at 3:47 in my video. Of course, that could just be because exercisers and leaner individuals are eating healthier, less inflammatory diets. How do we know excess body fat itself increases inflammation, increases the white count? You’d have to find some way to get people to lose weight without changing their diet or exercise habit. How’s that possible? Liposuction. If you suck about a quart of fat out of people, you can significantly drop their white count by about a point. Perhaps this should get us to rethink the so-called normal reference range for white blood cell counts. Indeed, maybe we should revise it downward, like we’ve done for cholesterol and triglycerides.

Until now, we’ve based normal values on people who might be harboring significant background inflammatory disease. But, if we restrict it to those with normal C-reactive protein, another indicator of inflammation, then instead of “normal” being 4.5 to 10, perhaps we should revise it closer to 3 to 9.

Where do the healthiest populations fall, those not suffering from the ravages of chronic inflammatory diseases, like heart disease and common cancers? Populations eating diets centered around whole plant foods average about 5, whereas it was closer to 7 or 8 in the United States at the time. How do we know it isn’t just genetic? As you can see at 5:38 in my video, if you take those living on traditional rural African diets, who have white blood cell counts down around 4 or 5, and move them to Britain, they end up closer to 6, 7, or even 8. Ironically, the researchers thought this was a good thing, referring to the lower white counts on the “uncivilized” diet as neutropenic, meaning having too few white blood cells. They noted that during an infection or pregnancy, when more white cells are needed, the white count came right up to wherever was necessary. So, the bone marrow of those eating traditional plant-based diets had the capacity to create as many white cells as needed but “suffers from understimulation.”

As you can see at 6:26 in my video, similar findings were reported in Western plant eaters, with an apparent stepwise drop in white count as diets got more and more plant based, but could there be non-dietary factors, such as lower smoking rates, in those eating more healthfully? What we need is an interventional trial to put it to the test, and we got one: Just 21 days of removing meat, eggs, dairy, alcohol, and junk affected a significant drop in white count, even in people who started out down at 5.7.

What about patients with rheumatoid arthritis who started out even higher, up around 7? As you can see at 7:03 in my video, there was no change in the control group who didn’t change their diet, but there was a 1.5 point drop within one month on whole food plant-based nutrition. That’s a 20 percent drop. That’s more than the drop-in inflammation one might get quitting a 28-year pack-a-day smoking habit. The most extraordinary drop I’ve seen was in a study of 35 asthmatics. After four months of a whole food plant-based diet, their average white count dropped nearly 60 percent, from around 12 down to 5, though there was no control group nor enough patients to achieve statistical significance.

If white blood cell count is such a clear predictor of mortality and is so inexpensive, reliable, and available, why isn’t it used more often for diagnosis and prognosis? Maybe it’s a little too inexpensive. The industry seems more interested in fancy new risk factors it can bill for.

I touch on the health of the rural Africans I discussed in How Not to Die from Heart Disease.


For more on fighting inflammation, 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 About the Trans Fat in Animal Fat?

The years of healthy life lost due to our consumption of trans fats are comparable to the impact of conditions like meningitis, cervical cancer, and multiple sclerosis. But, if “food zealots” get their wish in banning added trans fats, what’s next? I explore this in my video Banning Trans Fat in Processed Foods but Not Animal Fat.

Vested corporate interests rally around these kinds of slippery slope arguments to distract from the fact that people are dying. New York Mayor Bloomberg was decried as a “meddling nanny” for his trans fat ban and attempt to cap soft drink sizes. How dare he try to manipulate consumer choice! But isn’t that what the food industry has done? “Soft drink portion sizes have grown dramatically, along with Americans’ waistlines.” In 1950, a 12-ounce soda was the king-sized option. Now, it’s the kiddie size. Similarly, with trans fats, it was the industry that limited our choice by putting trans fats into everything without even telling us. Who’s the nanny now?

New York City finally won its trans fat fight, preserving its status as a public health leader. “For example, it took decades to achieve a national prohibition of lead paint, despite unequivocal evidence of harm,” but New York City’s Board of Health led the way, banning it “18 years before federal action.”

There’s irony in the slippery slope argument: First, they’ll come for your fries; next, they’ll come for your burger. After the trans fat oil ban, one of the only remaining sources of trans fat is in the meat itself. “Trans fats naturally exist in small amounts in the fat in meat and milk,” as I’ve discussed before in my video Trans Fat in Meat and Dairy. Before the trans fat ban, animal products only provided about one fifth of America’s trans fat intake, but since the U.S. trans fat ban exempts animal products, they will soon take over as the leading source. As you can see at 2:09 in Banning Trans Fat in Processed Foods but Not Animal Fat, now that added trans fats are banned in Denmark, for example, the only real trans fat exposure left is from animal products found in the U.S. dairy, beef, chicken fat, turkey meat, lunch meat, and hot dogs, with trace amounts in vegetable oils due to the refining process.

The question is: Are animal trans fats as bad as processed food trans fats? As you can see at 2:38 in my video, a compilation of randomized interventional trials found that they both make bad cholesterol go up and they both make good cholesterol go down. So, both animal trans fats and processed food trans fats make the ratio of bad to good cholesterol go up—which is bad. Therefore, all trans fats cause negative effects “irrespective of their origin.” The researchers suspect that also removing natural trans fats from the diet could prevent tens of thousands of heart attacks, but unlike processed foods, you can’t remove trans fats from milk and meat because trans fats are there naturally.

The livestock industry suggests that a little bit of their trans fats might not be too bad, but you saw the same everything-in-moderation argument coming from the Institute of Shortening and Edible Oils after industrial trans fats were first exposed as a threat. The bottom line is “that intake of all sources of trans fat should be minimized.” The trans fat in processed foods can be banned, and just adhering to the current dietary guidelines to restrict saturated fat intake, which is primarily found in meat and dairy, would automatically cut trans fat intake from animal fats.

The reason no progress may have been made on animal trans fat reduction in Denmark is because The Danish Nutrition Council that pushed for the trans fat ban was a joint initiative of The Danish Medical Association and The Danish Dairy Board. They recognized that “the economic support from The Danish Dairy Council could be perceived as problematic” from a scientific integrity point of view, but, not to worry—“The Danish Medical Association expanded the Executive Board and the funding members to also include the Danish pork industry, the Danish meat industry, The Poultry and Egg Council and The Danish Margarine Industry Association.”

If people want to eat trans fat, isn’t that their right? Yes, but only if they’re informed about the risks—yet The Food Industry Wants the Public Confused About Nutrition.

For more on the industry pushback, see my video Controversy Over the Trans Fat Ban.

There does not appear to be a safe level of exposure to trans fat—or to saturated fat or dietary cholesterol, for that matter. See Trans Fat, Saturated Fat, and Cholesterol: Tolerable Upper Intake of Zero.


If you find these videos about industry influence on public policy compelling, check out my many others, including:

Note that the concept of raising or lowering HDL (the so-called good cholesterol) playing a causal role in heart disease has come into question. See Coconut Oil and the Boost in HDL “Good” Cholesterol.

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: