 US Paton 9,700,067 was impossible food's dream of improving plant-based meat substances to better replicate the aromas and flavors of meat by using plant-based heme. OK, 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, black tea, this is more like brown tea, basically a filtered fecal smoothie that's definitely one where you want to double check the blender lids on time. 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 kind of 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. And not only did they see more than a two-fold increase in fecal water genotoxicity that correlated with procarcinogenic gene expression changes in the kind of before-and-after biopsy specimens after just one week. Still, there's only been circumstantial evidence that the 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 a nitroso genotoxicity. You can visualize the DNA damage in rectal biopsies. The brown standing 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's 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 for 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 all 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 intransfans 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 fattened 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 putrefocation process, like ammonia, putrescene, and uremic toxins, like cresol, indol, 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 bylases 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 diet packed with animal food didn't get a massive increase in the bacterial production within days, whereas if you cut 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 bylases by 70% within just two weeks. There also might be a strong link between colorectal cancer and trimethylamine anoxide, 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 it could also be the oxidative stress, or DNA damage, or protein disruption. What about the non-human sialic acid known as Nu5GC, which is incorporating the disissues of meat consumers and elicits an inflammatory immune reaction? And antibody levels against this form 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 the regular whopper.