RHR: The Truth About Red Meat

November 22, 2022

In this episode, we discuss:

What the largest review ever published on the health impacts of red meat found
How the “healthy user bias” has distorted red meat research
Why context is everything when it comes to red meat specifically, and nutrition research in general
Whether you should be concerned about Neu5Gc, TMAO, and heme iron in red meat
Why red meat is a nutritious and health-promoting food when consumed in the context of a whole-food diet

Show notes:

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Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. We’ve been told for decades that eating red meat will give us cancer, heart disease, and all kinds of other health ailments. This idea has become so deeply ingrained in our society that few people even question it anymore. But what if it’s not true? What if the evidence against red meat was never strong to begin with and has become much weaker over time? That’s the topic of today’s episode of Revolution Health Radio.

I’ll discuss the results of a new paper published in Nature Medicine and review several other studies from the past 10 to 20 years. You’ll learn how the healthy user bias has distorted red meat research, why context is everything when it comes to red meat specifically and nutrition research in general, what the largest review ever published on the health impacts of red meat found, whether you should be concerned about [N-glycolylneuraminic acid] (Neu5Gc), [trimethylamine N-oxide] (TMAO), and heme iron in red meat, and why red meat is a nutritious and health-promoting food when consumed in the context of a whole-food diet. I hope this show will help correct the misconceptions that still persist about red meat and alleviate any anxiety you might have about eating it. Let’s dive in.

Recent Reviews on the Health Impacts of Red Meat

A new paper in the journal Nature Medicine is causing quite a stir. The researchers set out to analyze the relationships between unprocessed red meat consumption and six potential health outcomes. They found weak evidence of an association between unprocessed red meat consumption and colorectal cancer, breast cancer, heart disease, and type 2 diabetes. They found no evidence of an association between red meat consumption and stroke.

Let’s take a deeper look and see just how strong the link between red meat and these health outcomes really was. The researchers assigned a risk-outcome score (ROS) for each outcome. The ROS reflects the certainty of evidence that the risk factor is related to the particular health outcome being studied. A higher ROS corresponds to a stronger relationship, and a lower ROS corresponds to a weaker relationship. The ROS for colorectal cancer was 0.057. Breast cancer was 0.027. Heart disease was 0.01, and type 2 diabetes was 0.005. These are really low numbers. They probably don’t mean much to you, so let’s put them in perspective by comparing them with [ROSs] for other risk factors and health outcomes. The ROS for cigarette smoking and larynx cancer is 1.56. That’s 27 times higher than the ROS for red meat and colorectal cancer, and 312 times higher than the ROS for red meat and type 2 diabetes. So, not even remotely in the same ballpark. The ROS for high blood pressure and heart disease is 0.7. That’s 12 times higher than the ROS for red meat and colorectal cancer and 140 times higher than the ROS for red meat and type 2 diabetes. The researchers categorize the ROS for each condition into a star rating in order to evaluate the quality of the evidence. The evidence linking red meat to any of the diseases studied fell into the one- or two-star rating category. A one-star rating indicates no evidence of an association, and a two-star rating indicates only weak evidence of an association. This led the authors to conclude, “While there is some evidence that eating red meat increases the risk of chronic disease, there is insufficient evidence to make stronger or more conclusive recommendations.”

Other recent research on red meat has also shown that the evidence against it is incredibly weak. A rigorous five-paper review published in the journal Annals of Internal Medicine concluded that low or very low certainty evidence existed to show that meat causes any kind of disease, [including] cancer, heart disease, or diabetes. This was the most exhaustive review of evidence published on red meat to date. It analyzed dozens of studies covering millions of participants followed for 34 years, and the results span over 300 pages of content. This review included randomized, controlled trials and observational cohort studies and examined a wide range of outcomes, including all-cause mortality, cardio-metabolic disease, and cancer incidence and mortality. The researchers used the grade system to assess the quality or certainty of evidence, and the possible ratings are high, moderate, low, and very low. The grade rating tells you the likelihood that the effects seen in studies will be substantially different from the real world. For example, say a study suggests you’ll see five fewer cases of cancer per 10,000 people with lower red meat consumption. If the rating was high, the real-world effect is likely close to what the research suggests. If the rating was very low, the effects seen in the real world may be substantially different than the findings. The quality of the evidence in this review, which covered millions of participants over almost 35 years, was either low or very low. That means that the effects in the real world are probably substantially different than the findings in the research study.

An editorial accompanying this paper stated, “This is sure to be controversial, but it’s based on the most comprehensive review of the evidence to date. Because this review is inclusive, those who seek to dispute it will be hard-pressed to find appropriate evidence with which to build an argument.” I really appreciated that editorial, and I appreciated that this paper was published because when it was, there were, as you can imagine, calls for it to be retracted. People were up in arms in the plant-based community, and it contradicted decades of poorly performed and designed research that wrongly implicated red meat. But the editors of the journal stuck to their guns because this was a very carefully designed and executed trial, and the evidence was comprehensive, as they said in their own words. So they decided to go ahead and publish it. And not only that, they published an editorial accompanying the paper that backed up the rigorous nature of the research that was done.

Why is the evidence against red meat so weak? Well, there are many reasons. But in this podcast, I’m going to focus on two of them: the healthy user bias and the importance of context. I’ll also explain briefly why you don’t need to be concerned about Neu5Gc, TMAO, and heme iron, which are the latest proposed mechanisms for why red meat is harmful. Finally, I’ll explain why red meat is such a nutritious and beneficial food when it’s consumed in the context of a whole-food diet.

The Healthy User Bias

Let’s start with the healthy user bias. This is the observation that people who engage in a behavior that’s perceived as healthy are more likely to engage in other behaviors that are also perceived as healthy and vice versa. Red meat has been perceived as unhealthy for many years, decades, in fact, so people [who] eat more red meat are, on average, more likely to smoke, be physically inactive, eat fewer fruits and vegetables, and be less educated. All those factors have a profound impact on health status and the incidence of disease.

Of course, most researchers are well aware of the influence of confounding factors and healthy user bias, and the best papers at least attempt to control for many of these factors. But even in those studies, researchers cannot control for all possible confounding factors because our lives are simply too complex. As Norman Breslow, a former biostatistician at the University of Washington once said, “People think they may have been able to control for things that aren’t inherently controllable.” The healthy user bias has plagued studies on the health impacts of red meat for decades. Most Americans [who] eat red meat [will] eat it with a bun made of white flour [and] with a serving or more of other refined carbohydrates like chips or fries cooked in industrially processed seed oils, [or soda]. How do we know that it’s the red meat and not these other foods that is causing the increase in cancer? This is where context becomes so important. I think it’s plausible that a high intake of processed meat, and possibly even unprocessed red meat, in the context of a Standard American Diet that is rich in highly refined foods, may be harmful. But there’s no evidence that eating red meat in the context of a whole-food diet is harmful, and there’s quite a bit of evidence suggesting that it isn’t.

Why Context Matters

For example, in all studies that found an association between red meat and cancer that controlled for vegetable intake, a greater increase in cancer was seen in people not consuming vegetables. Vegetable consumption seemed to confer a protective effect, and that was especially true in the people [who] were at the highest risk for cancer. While red meat consumption is weakly associated with a variety of cancers, consumption of fruits and vegetables is associated with protection against just as many [types of cancer] and is most protective in cohorts at the highest risk. The best summary I’ve seen of the problems with the evidence on red meat was in a 2015 review paper called “Red Meat and Colorectal Cancer: A Quantitative Update on the State of the Epidemiologic Science.” The authors concluded that, “The state of the epidemiologic science on red meat consumption and colorectal cancer is best described in terms of weak associations, heterogeneity, an inability to disentangle effects from other dietary and lifestyle factors, lack of a clear dose response effect, and weakening evidence over time.”

Let’s move on to some of the individual mechanisms that have been proposed by researchers who claim that red meat is harmful. Historically, we were told that we shouldn’t eat it because it contains cholesterol and saturated fat. But the evidence supporting the claims against saturated fat and cholesterol has really fallen apart over the past two decades, and even researchers [who] are hostile toward red meat don’t use that argument very much anymore. I cover this in detail in my free eBook The Truth About Red Meat, which you can download at ChrisKresser.com/red-meat.

Neu5Gc, TMAO, and Heme Iron

In this episode, I want to focus on some of the newer mechanisms that have been proposed. The first is Neu5Gc. Neu5Gc is a sugar molecule. It’s a monosaccharide that acts as a signaling molecule in mammalian cells, and one of its functions is to help the immune system distinguish between self and not self. Humans lost the ability to produce Neu5Gc millions of years ago through a genetic mutation, although we still produce the closely related compound [N-acetylneuraminic acid] (Neu5Ac). Humans are unique in this respect because most other mammals still produce Neu5Gc, which is why that compound is found in mammalian meat. The theory is that when humans consume red meat and milk products, we incorporate some of this compound into our tissues, especially tissues that grow at a fast pace like fetuses, epithelial and endothelial tissues, and tumors. The concern is that most of us also have anti-Neu5Gc antibodies circulating in our blood, and some researchers have suggested that these antibodies react with the Neu5Gc in our tissues to create chronic inflammation, which then leads to conditions like cancer. The problem is that researchers are nowhere near proving that hypothesis. Research is still in the earliest stages, and while there are some fascinating hypotheses involving this molecule, the studies needed to confirm or refute them are non-existent.

A 2003 paper showed that feeding people large quantities of Neu5Gc didn’t cause their levels of Neu5Gc in the blood to rise from baseline. This suggests that consuming red meat that contains Neu5Gc may not actually increase Neu5Gc levels in our body. In that same paper, researchers speculated that early childhood exposure to Neu5Gc in cow milk or vaccines, transfer of Neu5Gc from mother to baby, or a pre-existing immune response may be required for Neu5Gc to make its way into human cells. In the absence of conclusive evidence one way or another, it can be helpful to remember that red meat has been part of the human diet for the vast majority of our evolutionary history and remains an important dietary element of many healthy cultures. For example, the traditional diet of the Maasai tribe in Africa is composed almost entirely of red meat, blood, and milk, all of which are very high in Neu5Gc. Yet they are [shown to be] completely free from modern inflammatory disease. If Neu5Gc really caused significant inflammation, the Maasai should have been the first to know because they probably couldn’t have designed a diet higher in Neu5Gc if they tried. So while this is an interesting hypothesis, there are already some glaring issues, and it’s nowhere near proven.

The media loves to plaster alarmist headlines about red meat across their front pages, but as you might suspect, these claims are ill-founded and misleading. An impartial review of the evidence reveals the truth about red meat– it’s one of the healthiest foods you can eat. #chriskresser #foodmyths

The next mechanism is heme iron, which is a type of iron that’s found in animal products like red meat. Studies show that heme iron contributes to forming N-nitroso compounds (NOCs) and toxic aldehydes, both of which can initiate the process of colorectal cancer. But again, context is everything. Eating chlorophyll-rich foods like leafy greens and other plant matter along with iron-rich animal foods has been shown to cancel out any potentially harmful effect of heme iron. Eating fruits and vegetables attenuates the oxidative capacity of heme iron and reduces the absorption of iron in the gut. Consumption of dietary antioxidants in fruits and vegetables is shown to reduce the risk of gastric cancer.

The best way to think about heme iron intake is as a proxy for a crappy diet, and non-heme iron intake is often a proxy for a diet that includes plant foods that are rich in antioxidants and other beneficial compounds. So heme iron is really another example of the healthy user bias. This was evident from a comprehensive meta-analysis of heme iron studies published in 2015 by Fang, et al. They looked at all the significant studies that had been done on heme iron up until 2015, and here’s their conclusion: “With respect to heme iron intake, we found a significant association only in the studies that were based on American cohorts.” In the Netherlands, Canada, France, Italy, Japan, and Sweden, there was no association between heme iron intake and cancer. It was only observed in the [United States], where the major heme iron sources are foods like McDonald’s, Burger King, and Kentucky Fried Chicken. The point here is that when you eat heme iron in the context of [an overall] crappy diet, it might be harmful. If you eat it [as part of] a healthier diet, as people in the Netherlands, Canada, France, Italy, Japan, [and] Sweden are, then it’s not an issue.

What’s more, that analysis only showed an association between heme iron intake and cardiovascular disease incidence, not cardiovascular disease mortality or total mortality. It’s also important to note that it’s relatively easy to get your iron levels tested. You can get an iron panel and ferritin [test]. I run this on all my patients. And when iron levels are high, there are many steps you can take to lower it [that] don’t necessarily need to involve avoiding red meat. So for a number of reasons, the heme iron argument doesn’t hold much water, either.

The last mechanism I want to cover is TMAO. A 2013 study published in the New England Journal of Medicine proposed a link between eggs and coronary heart disease that didn’t involve cholesterol. This was a team of researchers led by Dr. Stanley Hazen, [who] showed that dietary choline, a nutrient found largely in eggs, beef liver, and other animal foods, is metabolized by bacteria in our gut and then converted by the liver into TMAO. Dr. Hazen’s group published another paper linking red meat to TMAO production, claiming that eating red meat increases the risk of heart disease because of its effects on TMAO. But, as with heme iron and Neu5Gc, there are many problems with this hypothesis. The first is that you need to be cautious about a mechanism when the research on outcomes doesn’t support it. If red meat consumption elevates TMAO, and elevated TMAO increases the risk of heart disease, we’d expect to see higher rates of heart disease in people who eat more red meat. But most large studies do not show this [outcome] for fresh red meat consumption, as we’ve discussed earlier in the podcast.

Previous studies have shown that free carnitine and choline bitartrate in supplement form do elevate serum TMAO levels. In fact, [in] the study published in 2017 that showed this increase in TMAO, the researchers almost certainly used choline bitartrate because they knew it would maximally increase serum TMAO levels. The average TMAO levels reached something like 27 micromoles per liter in vegans and vegetarians and 37 micromoles per liter in omnivores. However, research has not shown that eating red meat and eggs instead of taking supplements with carnitine or choline significantly increases serum levels of TMAO. A 2014 paper showed that you’d need to eat four eggs to raise TMAO at all, and the maximum rise was less than 3 to 6 micromoles per liter in some subjects and 10 to 15 in the others, which is far lower than the increase seen with the choline supplements used in [the] 2017 study. Two subjects seemed to get a response from two to three eggs, but most did not. And even when they did get a response, it was under 10 micromoles per liter.

A 1999 study tested the effects of 46 different foods on the urinary excretion of TMAO in six human volunteers. Eggs again had no effect on TMAO excretion, compared to a light control breakfast. Yet 19 out of 21 types of seafood tested did. In fact, halibut generated over 53 times as much TMAO as eggs, and many times more TMAO than red meat.

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So, how do we reconcile this with the fact that seafood intake is consistently associated with lower risk of cardiovascular disease and total mortality? If eating foods that increase TMAO is harmful, and seafood increases TMAO far more than red meat or any other food, why don’t we see a huge increase in heart attacks and early death in people who are eating more seafood? Even if eating certain foods temporarily increases TMAO, that doesn’t mean that eating these foods increases TMAO levels persistently over time. In fact, the original TMAO paper published by Dr. Hazen’s group in 2013 said, “The high correlation between urine and plasma levels of TMAO argues for effective urinary clearance of TMAO.” In other words, even if eating a food does increase total TMAO levels temporarily, most people are able to quickly and efficiently clear that TMAO from their blood by excreting it in the urine. This makes it doubtful that dietary factors alone explain chronic elevations in TMAO. So, if dietary factors alone aren’t responsible for those TMAO elevations, what is?

Well, we don’t know for sure, but the gut microbiota likely plays an important role. High serum TMAO levels are more about which gut microbes you have and less about how much choline and carnitine you consume. Previous work by Dr. Hazen’s group has shown that people with higher levels of Prevotella bacteria in their gut produce higher levels of TMAO. In another study by Romano, et al in 2017, mice colonized with choline-metabolized bacteria had much higher levels of TMAO, while mice with the same bacteria unable to metabolize choline had virtually undetectable TMAO levels. Preliminary data from Dr. Federico Rey’s lab [have] shown that, in humans, low serum choline tends to be associated with high TMAO, and vice versa. That’s significant because, according to the Linus Pauling Institute, 92 percent of Americans are not getting enough choline. This suggests that people with high TMAO are very likely harboring some form of bacterial overgrowth in their gut, possibly a condition like [small intestinal bacterial overgrowth] (SIBO). This could further explain the connection between SIBO and cardiovascular disease. A 2017 study confirmed that TMAO is only absorbed in the small intestine, and a dose of rifaximin, which is the antibiotic most commonly used to treat SIBO, can significantly reduce serum levels of TMAO. This also suggests that what you eat along with the red meat impacts TMAO production, and it explains why a study of people who are following a Paleo diet, which, of course, includes red meat, but also many other healthy, nutritious foods, did not see an increase in TMAO levels at all.

Diabetes and metabolic syndrome also likely play a role via at least two mechanisms. The first is an increased conversion of trimethylamine to TMAO in the liver. An enzyme called [flavin-containing monooxygenase 3] (FMO3) carries out that conversion. FMO3 activity is upregulated in cases of insulin resistance and insulin deficiency. The second [mechanism] is poor kidney function. That’s at least partially supported by data in the New England Journal of Medicine paper published by Stan Hazen’s group. The people [who] had the highest levels of TMAO had an average glomerular filtration rate (GFR) of 69. According to the National Kidney Foundation guidelines, a GFR between 60 and 89 is indicative of a reduced capacity to filter blood through the kidneys. It’s essentially an early or mild stage of kidney disease. One in three Americans now have prediabetes, and more than 30 million have full-fledged type 2 diabetes. Many Americans also have disrupted gut microbiota due to their poor diet, antibiotic use, over-the-counter medications, and many other factors. So even if studies show that the average meat eater in the [United States] has higher TMAO levels, that doesn’t mean that it’s the meat that’s causing those higher TMAO levels.

We still have the glaring issue that epidemiological studies do not show an increase in cardiovascular disease in people who eat more fresh red meat or eggs. We already talked about some studies on red meat earlier. For eggs, a meta-analysis of prospective studies involving almost half a million participants followed from eight to 22 years that was published in [The] BMJ found no association between higher egg consumption and coronary heart disease or stroke. An analysis of data from the [National Health and Nutrition Examination Survey] (NHANES) study found an inverse association between egg consumption and stroke, meaning that people who ate more eggs had lower incidence of stroke. And a cohort study from Japan found that consumption of animal products, including eggs, was associated with [a] reduced risk of death from stroke. So this is another case of a mechanism being used to explain a problem that doesn’t exist, i.e., red meat intake causing heart disease.

Why Red Meat Is Healthy in the Context of a Whole-Food Diet

I think at this point, it’s safe to say that red meat has been unfairly accused. But you might wonder, “Okay, if there are all these potential problems that red meat can cause if it’s consumed in the context of an unhealthy Standard American Diet, why not just avoid it entirely and hedge your bets?” That’s a valid question. But there are several reasons that red meat is an extremely healthy and nutrient-dense choice when it’s included in the context of a whole-food diet. It’s a rich source of vitamin B12, which is vital to the proper functioning [of] nearly every system in your body. [Vitamin] B12 deficiency can play a role in everything from aging to neurological disorders, mental illness, cancer, cardiovascular disease, and infertility. Red meat also contains significant levels of other B vitamins [that] are essential to our health, including thiamine, or [vitamin] B1, riboflavin, [or vitamin] B2, pantothenic acid, [or vitamin] B5, folate, [or vitamin] B9, niacin, which is [vitamin] B3, and pyridoxal, which is vitamin B6. Red meat provides a highly bioavailable source of these nutrients. In fact, a recent study on the nutrient density of common foods found that red meats, both muscle meats like steak and organs like liver, comprise six of the 10 most nutrient-dense foods we can eat. Six out of 10. That alone is a really good reason to include at least some red meat in your diet.

For people who don’t eat a lot of oily fish or get a lot of direct sun exposure, red meat can contribute significantly to their overall vitamin D intake. This is a little-known fact. Red meat contains a vitamin D metabolite called 25-hydroxycholecalciferol, which is assimilated much more quickly and easily than other dietary forms of vitamin D. In populations with low sun exposure, red meat has been shown to be protective against rickets, which is a degenerative bone disease caused by severe vitamin D deficiency. Interestingly, drinking milk with the same levels of vitamin D does not provide the same protection, indicating that the vitamin D in meat is uniquely bioavailable and useful to the human body. Red meat contains primarily heme iron, which is far more bioavailable than ferrous iron, the form found in plant foods. And it’s an especially important source of zinc because the other rich sources of zinc like organ meats and shellfish are much less commonly consumed in the United States. As with vitamin D and iron, the zinc present in red meat is highly bioavailable, and even a small amount of red meat in the diet can increase zinc utilization from all sources. Zinc is an essential mineral that is an imperative part of many physiological functions, including structure of certain proteins and enzymes and regulations of gene expression, and those eating meat-free diets are at greater risk of zinc deficiency.

Finally, to round out this impressive nutrient profile, red meat contains significant levels of other minerals like magnesium, copper, cobalt, phosphorus, chromium, nickel, and selenium. Most people today still have the impression that poultry is a healthier choice than red meat. I will often hear people say, “I eat meat, but only chicken and fish.” Here’s why I don’t think that’s a wise choice. Red meat has significantly more [vitamin] B12, iron, and zinc than white meat or poultry. Those things alone are enough to set it apart. But where red meat really shines is in its fatty acid profile. The fat of grass-eating ruminants like cows comprises approximately equal parts of saturated and monounsaturated fat, with only a small amount of polyunsaturated fat. The unique ruminant digestive system ensures that these proportions stay relatively constant regardless of what the animal eats. This makes red meat a better choice than poultry for those [who] cannot afford pasture-raised meat because you’ll still be getting mostly saturated and monounsaturated fat, whereas with poultry, the levels of polyunsaturated fat can be very high. Red meat is also a great dietary source of conjugated linoleic acid (CLA), which is a trans-rumenic acid that is found abundantly in grass-fed meat and dairy products, and to a lesser degree in grain-fed dairy products. I cover the health benefits of CLA in much more detail in my free eBook The Truth About Red Meat, so make sure to download a copy of that at ChrisKresser.com/red-meat.

One more thing about red meat versus poultry: If you’re concerned about the ecological and environmental impact and sustainability of consuming meat, then consuming pasture-raised red meat is a far better choice than consuming chicken. It’s extremely difficult to find truly pasture-raised chicken in the United States. It’s possible if you’re buying directly from a farmer, [and] there might be a select few stores [where] you can buy a truly pasture-raised chicken. But in most cases, even the organic chicken and chicken that says “cage free” in the grocery store might be kept in a small, contained area indoors. They’re not truly roaming outside and foraging for worms and grubs and what you might imagine. They’re still kept in an enclosed area and very rarely get to go outside. Whereas with beef, if you’re choosing 100 percent pasture-raised meat, you can buy that, even in the grocery store, from farms where those cows are roaming 100 percent on pasture. There have been some life cycle analyses from White Oak Pastures, which is a regenerative farm in Georgia, that show that when regenerative methods are used to raise beef, it can not only be carbon neutral, [but] it can actually be a carbon sink. It can remove carbon from the atmosphere. Whereas the same has not been shown with poultry. And if you think about the number of meals that one cow can provide versus [one] chicken, that’s a huge difference, as well. So if you have any ethical concerns about loss of life related to eating animal products, that’s something to consider.

All right, that’s it for today. I know this was a really dense episode with a lot of studies and science, but I felt like I had to do [it] to set the record straight. A lot of the references that I used in the podcast are in the eBook that I mentioned, [which you can download at] ChrisKresser.com/red-meat. We’ll also put them in the show notes [on] the podcast page, which you can find at ChrisKresser.com. I hope this episode has helped clarify some of the misconceptions that still exist about the health impacts of red meat. It’s been wrongly condemned for decades because of the healthy user bias, ignoring the importance of context, and a lot of the other shortcomings of nutritional research that we talked about today. The good news is that more recent and carefully performed studies and the very comprehensive, exhaustive reviews of research that I’ve covered in this show have exposed the flaws of those previous studies and helped set the record straight. So why not go out and buy a delicious steak to celebrate tonight? I think I will. Thanks for listening, and keep sending your questions to ChrisKresser.com/podcastquestion.

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RHR: The Truth About Red Meat

RHR: The Truth About Red Meat