Two weeks ago, we discussed the link between red meat consumption and breast cancer risk. This relationship is particularly interesting, given that younger women and those taking birth control pills were at the highest risk for breast cancer, indicating some kind of interaction between sex hormones and eating red meat. What wasn’t so well covered is the actual biological explanation for how red meat may contribute to causing cancer.
Current evidence is from large-scale population studies, which actually cannot tell us much about biological mechanisms. The first way these studies are done is through recruiting people who already have cancer, and matching them to similar people without cancer for comparison. Both groups – the cancer ‘cases’ and the healthy ‘controls’ – are asked about their historical consumption of red meat along other dietary and lifestyle factors that may also affect cancer risk. This is called a ‘case-control’ study. The second strategy involves recruiting a large group of healthy people, assessing their red meat consumption and other risk factors in real time, and following them forward in time to see who gets cancer and who doesn’t. This is called a ‘prospective cohort’ study, and provides more scientific validity than a case-control study because it happens in real time.
Both of these epidemiological strategies tell us a lot about population trends. Several, high-quality case-control and prospective cohort studies have consistently found relationships between red and processed meat intake and risks of breast cancer, colorectal cancer, death from cancer and cardiovascular disease, and overall risk of death. These relationships were independent of major dietary and lifestyle risk factors, which were carefully measured and statistically adjusted for (1-5).
There are hypotheses put forward by epidemiologists and biomedical scientists to explain the link between red meat intake and cancer risk:
1. Carcinogenic by-products of cooking meat at high temperatures
When meat is barbequed, grilled, or otherwise cooked at a high temperature, chemical by-products, which have the potential to cause cancer are formed. They are called heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Both PAHs and HCAs have been found to be carcinogenic in rodents, but the biological evidence for humans is not yet well established (6).
HCAs are formed when nutrients in meat – amino acids, sugars, and creatine – react together at high temperatures (6). PAHs are formed when fat and juices from meat drip onto an open flame, causing PAHs from the flame to stick to the surface of the meat (6). PAHs are also found in cigarette smoke and emissions from diesel fuelled-engines, so they are often studied in relation to air pollution (7). They have been linked to breast cancer in epidemiological studies, and this evidence is supported by biomedical research showing that PAHs are stored in the fat tissue of the breast, that they weakly mimic estrogen, and that they bind to DNA, forming damaging PAH-DNA adducts (7-9).
2. Nitrites and nitrates in processed meats
Nitrites and nitrates are found in processed meats, such as bacon, sausages, and hot dogs. In the large intestine, these compounds react with naturally occurring amines in meat to form carcinogenic N-nitroso compounds (NOCs). NOCs have been found to cause cancer in over 40 different animal species (10). Prospective studies have found a link between NOCs and gastrointestinal cancers, including oesophageal, stomach, and colorectal and rectal cancers (11-13). There is some evidence that the antioxidant vitamins C and E could help counteract the effects of NOCs (12,13), but further research is needed.
3. Hormone residues in meat
This explanation is one of the most worrying, as it would be due to growth hormones fed to cattle during farming. There is the least amount of evidence for this hypothesis, and surely there is strong political resistance from the meat industry against this possibility. In many places, use of growth hormones such recombinant bovine growth hormone (rBGH), which is actually more of a concern for dairy products, is banned or has been reduced in its usage. The Huffington Post has an interesting article on this issue.
4. Heme in red meat
The final hypothesis I will cover here is that of heme. Heme is the iron-containing chemical compound in red meat, also providing its pigment or colour. While dietary iron is crucial to good health, heme is also toxic in the digestive system. It has its own toxicity, but also acts to promote the formation of NOCs (14). Population-based cohort studies have found mixed evidence on the relationship between dietary consumption of heme from red meat and cancer incidence (15).
Another current question is the role of genetics in how red meats are metabolised, and whether genetic differences may make some people more susceptible than others to any potential effects of eating red meat (16,17). An even newer and dynamic avenue of research is how the gut microbiome interacts with foods to produce health conditions (18). It also may be as simple as people who eat excessive amounts of red meat are probably not eating enough of other healthy foods that might help prevent cancer.
A lesson learned here is that science moves forward incrementally. Although the epidemiological evidence shows strong trends, not all of it is in perfect agreement. There is always some degree of human error present in the practice of research (19), which might obscure the truth. And, as we learn more, we also learn how much we don’t know. There are probably variations in metabolic genes and the gut microbiome within human populations that we don’t even know about yet, not to mention the biological and chemical factors in meat itself. Years from now, we may look back on today’s research as clunky and unrefined, unable to pick up more subtle aspects of the diet-cancer relationship.
In any case, the editors of the journal JAMA Internal Medicine have advocated that “Reducing meat consumption has multiple benefits for the world’s health” (20), a bold statement that future research will tell us more about.
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