Health Journal Online

Tag: Heme

  • Heme Iron and Cancer 

    Heme Iron and Cancer 

    Laboratory models suggest that extreme doses of heme iron may be detrimental, but what about the effects of nutritional doses in humans?

    In muscle meat, there is a heme protein that contributes to, well, the meaty taste of meat. There’s also a heme protein in the roots of soybean plants that can be churned out to provide a similar flavor and aroma in plant-based meat, which is used to make the Impossible Burger possible. The question is: Are there any downsides?

    When the European Food Safety Authority was considering the safety of adding heme iron to foods, its main concern was a potential increased risk of colon cancer. As you can see below and at 1:00 in my video Does Heme Iron Cause Cancer?, we know meat causes cancer. Processed meat—bacon, ham, hot dogs, sausages, and lunch meat—is considered a Group 1 carcinogen, meaning we know it causes cancer in people with the same level of certainty that something like smoking causes cancer, whereas something like a burger probably causes cancer in people, kind of like DDT. But what’s the role of heme iron? 

    There are all sorts of potential mechanisms to explain the cancer risk. Meat has the pro-inflammatory long-chain omega-6 arachidonic acid and more of the aging- and cancer-associated methionine, trans fat, and endogenous hormones like IGF-1, not to mention the ones that are implanted in animals as “exogenous hormonal growth-promoters.” Then there are all the toxic pollutants that build up the food chain, like pesticides and formaldehyde.

    According to the prestigious IARC, the International Agency for Research on Cancer, “there is strong evidence that HAAs [heterocyclic aromatic amines], by causing DNA damage, contribute to carcinogenic mechanisms associated with the consumption of red meat.” These DNA-damaging compounds are formed when muscle tissue is exposed to high, dry heat like grilling, roasting, baking, and broiling—basically anything above steaming or stewing. There is also “strong evidence” that the formation of so-called N-nitroso compounds contributes to the cancer-causing mechanism. Those are carcinogens that can form inside our gut when we eat meat. However, there is also “strong evidence that haem [heme] iron contributes to the carcinogenic mechanisms associated with red and processed meat.”

    Normally I might leave it there, but other authoritative bodies I respect, like the American Institute for Cancer Research and the World Cancer Research Fund, are more tentative. While they agree there is some evidence that the “consumption of foods containing haem iron might increase the risk of colorectal cancer,” they consider the evidence suggesting such a connection to be limited.

    Much of the available evidence is based on data from lab animals, such as the study titled “Dietary Heme Induces Gut Dysbiosis, Aggravates Colitis, and Potentiates the Development of Adenomas in Mice,” in which dietary heme was found to disrupt the gut flora, aggravate inflammation, and potentiate the development of intestinal tumors in mice. But it’s critical to note that, in all the laboratory animal models that have been used, the rodents ingested meat or heme equivalent to humans eating up to 40,000 pounds (18,000 kilograms) of meat a day. Even the smallest dose would be about a dozen daily Impossible Burgers.

    In another study, ascribing “a central role for heme iron” in the development of colon cancer associated with meat intake, the authors claimed they “aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat.” So, heme “doses were chosen to mimic red meat consumption,” and, indeed, there was a significant increase in tumor load, as you can see here and at 3:41 in my video. 

    The researchers concluded that their “results strongly suggest that at concentrations that are in line with human red meat consumption, heme iron is associated with the promotion of colon carcinogenesis,” that is, cancer development. However, if you look at the actual diet given to the participants and do the math, it was 500 times the level of heme found in people’s diets, in excess of about 20 pounds of meat a day. Of course, even if they really did use the right doses, they’re still going to end up with data on the wrong species, which brings us to clinical studies that we’ll explore next. 

    This is part of a nine-video series on plant-based meats. If you missed any of the other earlier installments, check out the related posts below.

    The final two videos in the series are coming up next. See Heme-Induced N-Nitroso Compounds and Fat Oxidation and Is Heme the Reason Meat Is Carcinogenic?.



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  • Heme and Impossible Burgers 

    Heme and Impossible Burgers 

    Is heme just an innocent bystander in the link between meat intake and breast cancer, diabetes, heart disease, stroke, and high blood pressure?

    In an editorial in the Journal of the American Medical Association, the chair of nutrition at Harvard pointed out that many plant-based meats, such as burgers made by Beyond Meat and Impossible Foods, can be high in sodium. An issue specific to the Impossible burger is the “heme (an iron-containing molecule) from soy plants added to the burger patty to enhance the product’s meaty flavor and appearance.” Safety analyses have failed to find any toxicity risk specific to the soy heme churned out by yeast, and the U.S. Food and Drug Administration has agreed that it is safe, both for use as a flavor and color enhancer. In other words, it’s just as safe as the heme found in blood and muscle in meat—but how much is that really saying?

    The concern raised in the JAMA editorial, for example, was that “higher intake of heme iron has been associated with…elevated risk of developing type 2 diabetes,” killer number seven in the United States. That isn’t all, though. “Higher dietary intake of heme iron is associated with an increased risk of cardiovascular disease,” as well, as killers numbered 1, 4, and 13—heart disease, stroke, and high blood pressure. But since heme is found mostly in meat, heme intake may just be a marker for meat intake. It’s like with diabetes: Four meta-analyses have been published to date, and they all reported the same link, as seen below and at 1:25 in my video What About the Heme in Impossible Burgers?. But there are a lot of reasons meat may increase diabetes risk, like its advanced glycation end-products (AGEs), which are produced when animal products are baked, broiled, grilled, fried, or barbecued. So, how do we know that heme isn’t just an innocent bystander?

    The same issue arises with the link between heme intake and increased breast cancer risk. Since heme iron comes from animal foods, it could be any of the other components in meat, like animal fat or meat mutagens, which are compounds in meat that can cause DNA mutations. And what about all the hormonal steroids implanted into cattle that may play a role in the development of breast cancer? A study in Japan found that beef imported from the United States contained up to 600 times the levels of estrogens like estradiol. You can see the comparison of U.S. beef to Japanese beef below and at 2:20 in my video. “Higher consumption of estrogen-rich beef due to hormone application might facilitate estrogen accumulation in the [human] body and thus affect women’s risk for breast cancer.” So, yes, heme iron intake was associated with breast cancer risk, but maybe that’s just because the heme and the hormones traveled together in the same package—meat.

    The NIH-AARP Diet and Health Study is about as good as any observational study can get. It is the largest prospective study on diet and health ever, following more than half a million men and women for more than a decade now. With such a huge dataset, its researchers could take advantage of the fact that different meats have different amounts of heme, so they could try to tease out the heme components, in effect, by comparing people eating different amounts of heme, but the same amount of meat, to see if heme is independently associated with the disease. And, indeed, that’s what they showed: “independent associations between the intake of heme iron and nitrate/nitrite in processed meat and mortality from almost all causes”—death from diabetes, heart disease, stroke, respiratory disease, kidney disease, liver disease, cancer, and all causes put together, as seen here and a 3:33 in my video. 

    The researchers calculated that about one fifth of the association between eating burgers and the shortening of our lifespan, for example, could be statistically accounted for by just the heme itself, but that’s assuming cause-and-effect. An “independent association” is still an association. You can’t prove cause and effect until you put it to the test in interventional studies. 

    Normally, we don’t necessarily care about the mechanism. When the World Health Organization designated bacon, ham, hot dogs, lunch meat, and sausages to be Group 1 carcinogens, meaning we know these products cause cancer in human beings, who cares if it’s the heme iron, the heterocyclic aromatic amines, the polycyclic aromatic hydrocarbons, or the N-nitrosamines? They’re all wrapped up in the same place—processed meat—which we know causes cancer, so shouldn’t we try to stay away from it, regardless of the mechanism? With the advent of the Impossible Burger, we really do have to know, because, for the first time, we have a lot of heme without any actual meat, so we need to know if the heme itself is harmful. For that, we’ll have to turn to interventional studies, which we’ll cover next.

    This is the sixth in a nine-part series on plant-based meats. If you missed any of the previous installments, see the related posts below. 

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