Friday Favorites: Heme Iron in Impossible Burgers and Cancer Risk

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Is heme just an innocent bystander in the link between meat intake and breast cancer, diabetes, heart disease, stroke, and high blood pressure? Let’s take a look at heme’s carcinogenic effects.

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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.

Impossible burgers have been criticized for containing heme iron. What does that mean for consumers’ health? Check out the video.

In an editorial in the Journal of the American Medical Association, the chair of nutrition at Harvard pointed out that many plant-based meat alternatives, such as Beyond Meat and the Impossible Burger, can be high in sodium. But an issue specific to the Impossible Burger was the heme they add, derived from soybean plants to enhance the product’s meaty flavor and appearance. Safety analyses have failed to find any toxicity risk specific to the soy heme they have yeast churn out. The FDA has agreed, both for use as a flavor and color enhancer: safe. In other words, 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 op-ed, for example, was that higher intake of heme has been associated with an elevated risk of developing type 2 diabetes. But not just diabetes, killer #7 in the United States. Higher dietary intake of heme iron is associated with an increased risk of cardiovascular disease as well: killers #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: three meta-analyses published to date, and they all reported the same link. But there’s lots of reasons why meat may increase diabetes risk, like advanced glycation end products, produced when animal products are baked, broiled, grilled, fried, or barbequed. So, how do we know that heme isn’t just some innocent bystander?

The same issue arises with the link between heme intake and increased breast cancer risk. Since heme iron is coming from animal foods, it could be any of the other meat components––like animal fat or meat mutagens––compounds in meat that can cause DNA mutations. And hey, 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. Here’s the comparison of U.S. beef to Japanese beef. And, “higher consumption of estrogen-rich beef due to hormone [implantation] might facilitate estrogen accumulation in the [human] body and thus affect women’s risk for breast cancer.” So yeah, heme iron intake was associated with breast cancer risk, but maybe that’s just because the heme and the hormones are traveling together in the same package: meat.

This is about as good as any observational study can do. The NIH-AARP study is the largest prospective study on diet and health ever, following more than a half million men and women for over a decade now. With such a huge dataset, they could take advantage of the fact that different meats have different amounts of heme; so, they could try to tease out the heme components by, in effect, comparing people eating different amounts of heme, but the same amount of meat, to see if heme is independently associated with disease. And indeed, that’s what they showed: an independent association not only from nitrites in processed meat, but heme and mortality from almost all causes: death from diabetes, heart disease, stroke, respiratory disease, kidney disease, liver disease, cancer, and all causes put together. They calculated that about one-fifth of the association between, like, eating burgers and the shortening of your lifespan could be statistically accounted for by just the heme itself. But that’s assuming cause and effect. Even 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 sausage to be Group 1 carcinogens, meaning we know these products cause cancer in human beings, who cares if it’s the heme iron, or the heterocyclic aromatic amines, or 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, we should just try to stay away from it, regardless of the mechanism. But with the advent of the Impossible Burger, we really do have to know, because for the first time we have lots 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.

In muscle meat, there’s a heme protein that contributes to the meaty taste of meat. Well, there’s a heme protein in the roots of soybean plants too, 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, their main concern was a potential increased risk of colon cancer. We know meat causes cancer. Processed meat—bacon, ham, hot dogs, lunch meat, and sausage—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 just probably causes cancer in people, kind of like DDT. But what’s the role of heme iron?

I mean, there are all sorts of potential mechanisms to explain the cancer risk. Meat’s got the pro-inflammatory long-chain omega-6 arachidonic acid, more of the aging- and cancer-associated methionine, trans fat, endogenous hormones like IGF-1, not to mention the ones that are implanted in animals as hormonal growth-promoters. Then there are all the toxic pollutants that build up the food chain, like pesticides—I didn’t even know about the formaldehyde.

According to the prestigious IARC, the International Agency for Research on Cancer, there is strong evidence that heterocyclic aromatic amines contribute to the cancer-causing mechanism. 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 contribute to the cancer-causing mechanism. These are carcinogens that can form inside our gut when we eat the meat. But there is also strong evidence, according to the IARC, that heme iron contributes to the cancer-causing mechanism. 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 heme 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 lab animal data such as this, 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 people eating up to 40,000 pounds of meat a day. Even the smallest dose would be like a dozen Impossible Burgers a day.

It’s easy to see how casual readers could get confused, though. In this study, ascribing a central role for heme iron in the colon cancer development associated with meat, the authors claimed they were aimed at determining at nutritional doses, which was the main factor involved in cancer promotion. So, doses of heme were chosen to mimic red meat consumption and… boom! A significant increase in tumor load. The researchers conclude that their findings strongly “suggest that at concentrations that are in line with human red meat consumption, heme iron is associated with the promotion of colon [cancer development].” But if you look at the actual diet they were given and do the math, that’s 500 times the level of heme found in people’s diets, in excess of like 70 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, which we’ll explore next.

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.

Impossible burgers have been criticized for containing heme iron. What does that mean for consumers’ health? Check out the video.

In an editorial in the Journal of the American Medical Association, the chair of nutrition at Harvard pointed out that many plant-based meat alternatives, such as Beyond Meat and the Impossible Burger, can be high in sodium. But an issue specific to the Impossible Burger was the heme they add, derived from soybean plants to enhance the product’s meaty flavor and appearance. Safety analyses have failed to find any toxicity risk specific to the soy heme they have yeast churn out. The FDA has agreed, both for use as a flavor and color enhancer: safe. In other words, 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 op-ed, for example, was that higher intake of heme has been associated with an elevated risk of developing type 2 diabetes. But not just diabetes, killer #7 in the United States. Higher dietary intake of heme iron is associated with an increased risk of cardiovascular disease as well: killers #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: three meta-analyses published to date, and they all reported the same link. But there’s lots of reasons why meat may increase diabetes risk, like advanced glycation end products, produced when animal products are baked, broiled, grilled, fried, or barbequed. So, how do we know that heme isn’t just some innocent bystander?

The same issue arises with the link between heme intake and increased breast cancer risk. Since heme iron is coming from animal foods, it could be any of the other meat components––like animal fat or meat mutagens––compounds in meat that can cause DNA mutations. And hey, 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. Here’s the comparison of U.S. beef to Japanese beef. And, “higher consumption of estrogen-rich beef due to hormone [implantation] might facilitate estrogen accumulation in the [human] body and thus affect women’s risk for breast cancer.” So yeah, heme iron intake was associated with breast cancer risk, but maybe that’s just because the heme and the hormones are traveling together in the same package: meat.

This is about as good as any observational study can do. The NIH-AARP study is the largest prospective study on diet and health ever, following more than a half million men and women for over a decade now. With such a huge dataset, they could take advantage of the fact that different meats have different amounts of heme; so, they could try to tease out the heme components by, in effect, comparing people eating different amounts of heme, but the same amount of meat, to see if heme is independently associated with disease. And indeed, that’s what they showed: an independent association not only from nitrites in processed meat, but heme and mortality from almost all causes: death from diabetes, heart disease, stroke, respiratory disease, kidney disease, liver disease, cancer, and all causes put together. They calculated that about one-fifth of the association between, like, eating burgers and the shortening of your lifespan could be statistically accounted for by just the heme itself. But that’s assuming cause and effect. Even 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 sausage to be Group 1 carcinogens, meaning we know these products cause cancer in human beings, who cares if it’s the heme iron, or the heterocyclic aromatic amines, or 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, we should just try to stay away from it, regardless of the mechanism. But with the advent of the Impossible Burger, we really do have to know, because for the first time we have lots 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.

In muscle meat, there’s a heme protein that contributes to the meaty taste of meat. Well, there’s a heme protein in the roots of soybean plants too, 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, their main concern was a potential increased risk of colon cancer. We know meat causes cancer. Processed meat—bacon, ham, hot dogs, lunch meat, and sausage—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 just probably causes cancer in people, kind of like DDT. But what’s the role of heme iron?

I mean, there are all sorts of potential mechanisms to explain the cancer risk. Meat’s got the pro-inflammatory long-chain omega-6 arachidonic acid, more of the aging- and cancer-associated methionine, trans fat, endogenous hormones like IGF-1, not to mention the ones that are implanted in animals as hormonal growth-promoters. Then there are all the toxic pollutants that build up the food chain, like pesticides—I didn’t even know about the formaldehyde.

According to the prestigious IARC, the International Agency for Research on Cancer, there is strong evidence that heterocyclic aromatic amines contribute to the cancer-causing mechanism. 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 contribute to the cancer-causing mechanism. These are carcinogens that can form inside our gut when we eat the meat. But there is also strong evidence, according to the IARC, that heme iron contributes to the cancer-causing mechanism. 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 heme 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 lab animal data such as this, 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 people eating up to 40,000 pounds of meat a day. Even the smallest dose would be like a dozen Impossible Burgers a day.

It’s easy to see how casual readers could get confused, though. In this study, ascribing a central role for heme iron in the colon cancer development associated with meat, the authors claimed they were aimed at determining at nutritional doses, which was the main factor involved in cancer promotion. So, doses of heme were chosen to mimic red meat consumption and… boom! A significant increase in tumor load. The researchers conclude that their findings strongly “suggest that at concentrations that are in line with human red meat consumption, heme iron is associated with the promotion of colon [cancer development].” But if you look at the actual diet they were given and do the math, that’s 500 times the level of heme found in people’s diets, in excess of like 70 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, which we’ll explore next.

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 sixth in a nine-video series on plant-based meats. Check out the other videos in the series:

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

Does Coffee Inhibit Iron Absorption? What Are the Effects of Having Too Much Iron? Watch the video to find out.

The original videos aired on February 15 and 17, 2021.

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