Is Heme Iron the Reason Meat Is Carcinogenic?

Is Heme Iron the Reason Meat Is Carcinogenic?
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Rectal biopsies taken before and after eating meat determine the potentially DNA-damaging dose of heme.

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

US Patent No. 9,700,067 was Impossible Food’s dream of improving plant-based meat substitutes to better replicate the aromas and flavors of meat by using plant-based heme. Okay, but what about the heme-induced formation of nitroso compounds? When we eat lots of meat, you can pick up more and more nitroso compounds in people’s poop, a small fraction of which may be due directly to the heme. The toxicological significance of this remains to be established, since only some nitroso compounds are of concern. But should the nitroso compounds formed in the intestine as a result of heme consumption be shown to be mutagenic or carcinogenic, this might help explain the association between red meat consumption and colorectal cancer. But you don’t know, until you put it to the test.

“DNA damage is considered an essential component of the [development] of colonic cancer;” so, researchers looked at “fecal water genotoxicity.” You’ve heard of green tea and black tea? This is more like brown tea, basically like a filtered fecal smoothie. That’s definitely one where you want to double-check the blender lid is on tight.

But what they found was that the DNA-damaging effects of the fecal water was independent of the amount of nitroso compounds they found. Now the lack of correlation between the apparent total nitroso compound concentrations and DNA damage could be due to much lower levels of nitroso compounds found in fecal water compared to the feces themselves. I mean, just looking at the fecal water, the nitroso compounds are the same across meat groups, but the real poop had the real scoop.

Ideally, though, we’d like to know what’s happening in the human colon. So, researchers took biopsies before and after a week that included a few daily servings of beef and veal. Not only did they see more than a “twofold increase in fecal water genotoxicity,” that correlated with pro-carcinogenic gene expression changes in the before-and-after biopsy specimens after just one week.

Still, there has only been “circumstantial evidence that the [N-nitroso compounds] formed in the large bowel after eating [meat]….may be important genotoxins”—until now, or at least until this study. A significant increase in nitroso compounds, significantly correlated with a significant increase in DNA damage characteristic of N-nitroso genotoxicity. You can visualize the DNA damage in rectal biopsies—the brown staining on the right—after a month of three beef and lamb servings a day. The researchers suggest dietary heme as a reasonable explanation, but the lowest dose of heme showing evidence of direct DNA damage, in this case from freshly-resected colon tissue, was 10 micromoles. I contacted Impossible, and they said that’s equivalent to three times the concentration of heme found in their burgers. After completing this deep dive, therefore, it’s not clear to me that heme at typical dietary doses causes harm, and even less clear that heme is a culprit in the meat and cancer connection. If it’s not the heme, though, what is it?

Well, there are “reasons to suspect involvement of bovine infectious factors in colorectal cancer.” There are heat-resistant tumor-causing viruses that could survive meat cooked medium or rare. A specific class of infectious agents that have been isolated from both cows and around human colon cancer tissue, not to mention the brains of MS victims. “What do breast and colorectal cancers and multiple sclerosis have in common?” Several potentially infectious factors from cattle blood and milk, but that’s a whole video topic in and of itself.

Less speculatively, it could just be the saturated and trans fats, or sulfur-containing amino acids concentrated in the meat interacting with our gut microbes, resulting in oxidative stress and inflammation that drives the cancer. If you compare the gut bacteria in stools from cancer patients to healthy subjects, a high meat-to-fruit-and-veggie ratio “appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment.” A hunt for “global microbial signatures that are specific for colorectal cancer” suggested a “metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet.”

Maybe it’s from the meat putrefying in your colon. Putrefaction inside the human gastrointestinal tract pertains to decomposition of undigested proteins in the gut. Some of the products of this putrefaction process, like ammonia, putrescine, and uremic toxins like cresol, indole, and phenol have been implicated in the development of colorectal cancer. But cut out the meat, and levels of some of these compounds may fall by more than half, perhaps because they cultivated fewer putrefying bacteria.

Bad bacteria also produce secondary bile acids, which are associated with both cancer risk and cancer progression as a potential promoter of colorectal tumor enlargement, in part by damaging the intestinal lining––causing a leaky gut. Put people on a diet packed with animal foods, and you get a massive increase in the bacterial production within days, whereas if you cut out meat, you can go the other way. Even just eating more plant-based––swapping out the standard American diet for healthier fare––remarkably reduced secondary bile acids by 70 percent within just two weeks.

There also may be a “strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat.” Maybe that’s the link between what our gut bugs are doing with meat and risk of colorectal cancer. Maybe because of the inflammation caused by TMAO, but if could also be the oxidative stress, or DNA damage, or protein disruption.

Or what about the nonhuman sialic acid known as Neu5Gc that is incorporated into the tissues of meat consumers, and elicits an inflammatory immune reaction. And antibody levels against this foreign compound found in meat are associated with colorectal cancer risk. One could go on and on.

The bottom line health-wise is that while nutrition experts are understandably concerned you’re going to be ordering that Impossible Whopper with fries and a Coke, hey—it’s better than getting fries and a Coke with a regular Whopper.

Please consider volunteering to help out on the site.

Video production by Glass Entertainment

Motion graphics by Avocado Video

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

US Patent No. 9,700,067 was Impossible Food’s dream of improving plant-based meat substitutes to better replicate the aromas and flavors of meat by using plant-based heme. Okay, but what about the heme-induced formation of nitroso compounds? When we eat lots of meat, you can pick up more and more nitroso compounds in people’s poop, a small fraction of which may be due directly to the heme. The toxicological significance of this remains to be established, since only some nitroso compounds are of concern. But should the nitroso compounds formed in the intestine as a result of heme consumption be shown to be mutagenic or carcinogenic, this might help explain the association between red meat consumption and colorectal cancer. But you don’t know, until you put it to the test.

“DNA damage is considered an essential component of the [development] of colonic cancer;” so, researchers looked at “fecal water genotoxicity.” You’ve heard of green tea and black tea? This is more like brown tea, basically like a filtered fecal smoothie. That’s definitely one where you want to double-check the blender lid is on tight.

But what they found was that the DNA-damaging effects of the fecal water was independent of the amount of nitroso compounds they found. Now the lack of correlation between the apparent total nitroso compound concentrations and DNA damage could be due to much lower levels of nitroso compounds found in fecal water compared to the feces themselves. I mean, just looking at the fecal water, the nitroso compounds are the same across meat groups, but the real poop had the real scoop.

Ideally, though, we’d like to know what’s happening in the human colon. So, researchers took biopsies before and after a week that included a few daily servings of beef and veal. Not only did they see more than a “twofold increase in fecal water genotoxicity,” that correlated with pro-carcinogenic gene expression changes in the before-and-after biopsy specimens after just one week.

Still, there has only been “circumstantial evidence that the [N-nitroso compounds] formed in the large bowel after eating [meat]….may be important genotoxins”—until now, or at least until this study. A significant increase in nitroso compounds, significantly correlated with a significant increase in DNA damage characteristic of N-nitroso genotoxicity. You can visualize the DNA damage in rectal biopsies—the brown staining on the right—after a month of three beef and lamb servings a day. The researchers suggest dietary heme as a reasonable explanation, but the lowest dose of heme showing evidence of direct DNA damage, in this case from freshly-resected colon tissue, was 10 micromoles. I contacted Impossible, and they said that’s equivalent to three times the concentration of heme found in their burgers. After completing this deep dive, therefore, it’s not clear to me that heme at typical dietary doses causes harm, and even less clear that heme is a culprit in the meat and cancer connection. If it’s not the heme, though, what is it?

Well, there are “reasons to suspect involvement of bovine infectious factors in colorectal cancer.” There are heat-resistant tumor-causing viruses that could survive meat cooked medium or rare. A specific class of infectious agents that have been isolated from both cows and around human colon cancer tissue, not to mention the brains of MS victims. “What do breast and colorectal cancers and multiple sclerosis have in common?” Several potentially infectious factors from cattle blood and milk, but that’s a whole video topic in and of itself.

Less speculatively, it could just be the saturated and trans fats, or sulfur-containing amino acids concentrated in the meat interacting with our gut microbes, resulting in oxidative stress and inflammation that drives the cancer. If you compare the gut bacteria in stools from cancer patients to healthy subjects, a high meat-to-fruit-and-veggie ratio “appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment.” A hunt for “global microbial signatures that are specific for colorectal cancer” suggested a “metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet.”

Maybe it’s from the meat putrefying in your colon. Putrefaction inside the human gastrointestinal tract pertains to decomposition of undigested proteins in the gut. Some of the products of this putrefaction process, like ammonia, putrescine, and uremic toxins like cresol, indole, and phenol have been implicated in the development of colorectal cancer. But cut out the meat, and levels of some of these compounds may fall by more than half, perhaps because they cultivated fewer putrefying bacteria.

Bad bacteria also produce secondary bile acids, which are associated with both cancer risk and cancer progression as a potential promoter of colorectal tumor enlargement, in part by damaging the intestinal lining––causing a leaky gut. Put people on a diet packed with animal foods, and you get a massive increase in the bacterial production within days, whereas if you cut out meat, you can go the other way. Even just eating more plant-based––swapping out the standard American diet for healthier fare––remarkably reduced secondary bile acids by 70 percent within just two weeks.

There also may be a “strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat.” Maybe that’s the link between what our gut bugs are doing with meat and risk of colorectal cancer. Maybe because of the inflammation caused by TMAO, but if could also be the oxidative stress, or DNA damage, or protein disruption.

Or what about the nonhuman sialic acid known as Neu5Gc that is incorporated into the tissues of meat consumers, and elicits an inflammatory immune reaction. And antibody levels against this foreign compound found in meat are associated with colorectal cancer risk. One could go on and on.

The bottom line health-wise is that while nutrition experts are understandably concerned you’re going to be ordering that Impossible Whopper with fries and a Coke, hey—it’s better than getting fries and a Coke with a regular Whopper.

Please consider volunteering to help out on the site.

Video production by Glass Entertainment

Motion graphics by Avocado Video

Doctor's Note

This is the final installment in a nine-video series on plant-based meats, which includes:

If you want all nine of the videos in the plant-based meat series in one place, you can get them right now in a digital download from my webinar a few months ago.

If you haven’t yet, you can subscribe to my videos for free by clicking here.

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