The start of the controversy about red meat and cancer
In October 2015, the World Health Organization (WHO) released a report stating that eating processed red meat causes cancer and eating unprocessed red meat probably causes cancer (3,179,193).
Is there, however, an actual cause and effect relationship between the consumption of red meat and cancer?
What are the mechanisms through which red meat may causes cancer?
Is there anything we can do to reduce the potential cancer risk from red meat consumption without completely giving up red meat?
These are some of the questions answered in this article.
But first, here are some of the key takeaways.
- Red meat consumption is likely fine in the context of a generally healthy overall lifestyle.
- As with most things, the dose makes the poison and it would be wise to moderate your red meat intake (particularly, processed red meat).
- There is a clear association between consuming red meat and cancer (mainly colorectal cancer) but causation cannot be established given the various confounders and lack of intervention studies.
- Processed red meat and cancer are more strongly correlated than are unprocessed red meat and cancer.
- Some authorities recommend consuming “no more than one to two servings per month of processed meats, and no more than one to two servings per week of unprocessed meat” (1); others suggest <300 grams (~10.58 ounces) of red and processed meat per week (187). The World Cancer Research Fund recommends consuming <500 grams (~17.64 ounces) of red meat per week, with very little to no processed red meat (197). There is not sufficient evidence to conclude a definitively safe intake level.
- There are some mechanisms through which red meat consumption may be carcinogenic, but these risks can be substantially mitigated by some interventions on your part.
- The link between red meat and cancer is pragmatically relevant because one can control how much red meat they consume, but red meat consumption is certainly not the primary factor that contributes to cancer risk (2).
- There are some health benefits to consuming red meat, so despite its potential link to cancer, it may be beneficial to consume red meat occasionally.
What type of cancer?
Cancer encompasses a broad number of diseases rather than one uniform condition.
Colorectal cancer (cancer of the colon or rectum) is the third leading cause of cancer-related death in both the United States and the world (41,192). This is the specific cancer that red meat consumption has been meaningfully associated with.
Less convincing evidence has also found relationships between eating red meat and an increased risk of breast, pancreatic, lung, esophageal, gastric, liver, stomach, bladder, head-and-neck, and prostate cancer, as well as non-Hodgkin lymphoma and multiple myeloma (3-40, 45,176,177,187-190, 193,197-204,207).
Differentiating between red meats
According to the WHO, “Red meat refers to all mammalian muscle meat, including, beef, veal, pork, lamb, mutton, horse, and goat.” (43).
“Processed meat refers to meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance flavour or improve preservation.” (43).
The primary difference is that processed red meat undergoes further processing than red meat.
Red meat and cancer risk classifications
The WHO classifies processed red meat as a group 1 carcinogen and classifies red meat as a group 2A carcinogen (43,179,181,191).
A group 1 carcinogen is defined as “carcinogenic to humans” while a group 2A carcinogen “probably” causes cancer (43,179,181,191).
It is important to note that, for group 1 classifications, the International Agency for Research on Cancer (IARC) states that,
“an agent may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent acts through a relevant mechanism of carcinogenicity.” (215).
Moreover, for group 2A classifications, the IARC states that,
“an agent may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.” (215).
How carcinogenic is red meat?
In a 2017 narrative review, Wolk concluded that the consumption of 100 grams (~3.53 ounces) of unprocessed red meat per day was associated with an increased risk for breast cancer (11%), colorectal cancer (17%), and advanced prostate cancer (19%) (194). Wolk also reported that consuming 50 grams (~1.76 ounces) of processed red meat per day was associated with an increased risk for advanced prostate cancer (4%), cancer mortality (8%), breast cancer (9%), colorectal cancer (18%), and pancreatic cancer (19%) (194).
Another meta-analysis from December 2017 reports similar findings to Wolk concerning colorectal cancer (228). This analysis (based on 25 studies) concludes that a linear dose-response relationship exists between both processed and unprocessed meat and colorectal cancer risk. Consumption of 100 grams of unprocessed red meat per day was associated with a relative risk of 1.12, while consumption of 50 grams of processed meat per day was associated with a relative risk of 1.17 (228). Consumption of 2 servings per day of red meat and 4 servings per day of processed meat was associated with a 1.8-fold increased colorectal cancer risk. This review also reported that low red meat consumption combined with a high intake of whole grains, vegetables, fruit, and dairy products was associated with lower risk of colorectal cancer (228).
In a 2012 study, Grundy et al reported that of all cancers detected in Alberta, Canada, roughly 12% of colorectal cancers (1.5% of all cancers) were attributable to red and processed red meat consumption (195). It’s important to note that, in Grundy’s study, roughly half of the men and a quarter of the women exceeded the World Cancer Research Fund’s recommendation of 500 grams (~17.64 ounces) of red and processed meat per week (195,190).
In a 2016 meta-analysis of 17 prospective cohorts, Wang et al found that more total red meat and processed meat consumption is associated with an increased risk of total, cardiovascular, and cancer mortality (202).
The WHO’s report concluded that by not consuming red meat, one’s risk for colorectal cancer may decrease by ~18% (3,179). However, it is very difficult to put an exact number on the associated risk because meat is eaten in the context of an entire diet, rather than in isolation. Further, it is impossible to conclude an exact percentage of risk because sleep, stress levels, and various other contributing lifestyle factors differ significantly from person to person.
Some confounding lifestyle factors that are associated with an increased the risk of colorectal cancer from red meat consumption are regular smoking, high BMI, and alcohol consumption (6,5,7,9,17,23,25,26,28,35,44-50,190,198,199,212).
Additionally, eating more fruits and vegetables is associated with a reduced risk of developing cancer broadly, which presents a considerable dietary confounder (7,10,11,21,33,36,42,44,51-58,178,198, 212).
Causation of cancer cannot truly be determined because the studies examining the link are observational, rather than randomized controlled trials (50,59-61). Since cancer risk is altered by a variety of factors and takes a long time to develop, you can’t truly have cancer-related randomized trials.
Note: All baseline values are derived from the Cancer Statistics Center website.
Baseline cancer risk and absolute risk with red meat consumption
The above graph represents the percent changes in cancer risk associated with consumption of ~50 grams (~1.76 ounces) of processed red meat and ~100 grams (~3.53 ounces) of unprocessed red meat per day (except for ovarian, which is ~50-100 grams/week).
For example, the relative risk (risk compared to baseline; expressed as a decimal) for both unprocessed and processed red meat is 1.08 for bladder cancer. This means that compared to baseline risk (1.0), one has an 8% greater chance of getting bladder cancer if they consume ~100 grams of red meat or ~50 grams of processed red meat per day. This does not mean that one’s absolute chance of contracting cancer would increase by 8%; this means that relative to the 2.4% baseline risk of bladder cancer, one’s chances would increase by 8%. The 2.4% absolute risk thus increases by .192% (from 2.4% to 2.592%).
One’s absolute cancer risk does not increase substantially with the consumption of 100 grams (~3.53 ounces) of red meat or 50 grams (~1.76 ounces) of processed red meat despite an evident relative risk increase.
Mechanisms through which red meat may increase cancer risk
In a 2017 paper, Johnson reported several mechanisms for mutagenic effects of meat consumption that have been identified, but it is not clear which cause cancer in humans. The extent to which avoiding red meat protects against cancer is also unknown (204).
Mechanism 1: NOCs
N-nitroso compounds (NOCs) are found in processed red meat. NOCs form endogenously from the intake of nitrite and nitrate (223).
When one consumes red meat, heme iron in the meat acts as a catalyst to the formation of N-nitroso compounds in a dose-dependent manner (46,63-65, 67,74,76,77,131,192). These N-nitroso compounds can potentially damage the gut lining and initiate cell regeneration, which can lead to DNA damage over time (14,63,78-82,205).
Unprocessed red meat has a less direct effect on gut damage than processed red meat (after curing and smoking), as the chemicals in processed red meats allow NOCs to form at a faster rate (69,181,192).
What you can do about it: The gut damage caused by NOCs can be reduced or eliminated if the meat is consumed with green vegetables (64). This is because green vegetables contain chlorophyll and/or vitamin C, which may prevent NOC formation (83,54-56). Other foods high in vitamin C should decrease damage as well, though one may elect to limit or abstain from consumption of red or processed red meats.
Mechanism 2: High-Heat Chemicals
Heterocyclic amines (HCAs) and Polyaromatic Hydrocarbons (PAHs) form when meat is cooked at high heat or smoked (to a lesser extent with white meat) (75,93,100-111,181). These heat compounds can damage the gut and are considered possibly carcinogenic by the International Agency for Research on Cancer (98,113,114). Re-heating meat does not seem to contribute to heat compound content (112).
Several genetic mutations, especially those involving the NAT1 and NAT2 enzymes, have been associated with an increased risk of cancer, due to their role in the metabolism of the HCAs (118-122).
Some researchers suggest that high-heat compounds cannot completely explain the link between colorectal cancer and red/processed meat intake (192). For example, Van Hecke suggests that NOCs and oxidation products might be a more likely explanation for the association between red or processed meat intake and increased colorectal cancer risk (210).
Several studies have failed to find significant associations between the consumption of white meat, such as poultry or fish, with colorectal or other types of cancer (181,189,187,213). Since high-heat compounds are also made from cooking white meat, this supports the idea that the presence of high-heat compounds cannot fully explain the carcinogenic properties of (processed) red meat.
Additionally, the bioaccessibility of PAHs in meat is under-studied (210), thus the degree to which it can be associated with cancer risk is unknown.
However, there are still other reasons why one may want to cook red meat at a lower heat. Cooking meat at low-heat rather than high-heat can reduce advanced glycation end product formation, and thereby potentially improve insulin resistance in the obese (224).
What you can do about it: Eating meat with cruciferous vegetables (such as broccoli or Brussels sprouts) or marinating the meat in spices (especially Caribbean spices, such as allspice berries) for 20+ minutes before cooking, can reduce the formation of HCAs and PAHs prevent much of this damage (115,11,51-53,179).
One could also simply cook the meat at a lower heat and/or not cook over an open flame (38,43,93,96,101,109,113,114,116,117,209).
Mechanism 3: Iron
Red meat is rich in the mineral iron, which can be easily oxidized in the intestinal tract cells because it isn’t tightly bound to other compounds (64,125,126). Iron oxidation can cause cell damage, and this might explain the link to increased risk of colorectal cancer (127-130).
Heme iron seems to act as a catalyst for NOC formation, and may thereby contribute to cancer risk further (46,63-65,67,74,76,77,131,192,205).
Allison-Sliva highlights that this mechanism is not relevant to all forms of cancer, because if heme is denatured by cooking, then high levels of plasma hemopexin will block its tissue delivery. Therefore, red meat-derived heme could only contribute to colorectal carcinoma risk, via direct local effects (208).
What you can do about it: There is no way to mitigate the effect of excess iron from red meat without simply consuming less red meat.
Mechanism 4: TMAO
Trimethylamine N-oxide (TMAO) is a controversial compound that research has linked to colon and colorectal cancer (132,219).
Red meat contains large amounts of choline and the amino acid L-carnitine, which can be metabolized by gut bacteria and converted into TMAO (133,134, 194,216,217,218). High TMAO levels are also associated with high levels of TMA and DMA (216). TMA and DMA can each be nitrosated and therefore act as a potential carcinogen via formation of nitrosated amines (218).
However, it is possible that TMAO is a lurking variable of red meat consumption, rather than a mechanism through which red meat consumption contributes to cancer risk (218). This is supported by studies indicating a protective effect of TMAO in carcinogenesis, as it corrects the folding of mutant proteins (218,220,221).
What you can do about it: The effects that TMAO has on gut health are still largely unknown, though maintaining a healthy gut (by eating a diet rich in fruits and vegetables) can prevent some potential damage from red meat (44,135,7,10,11,21,33,36,42,44,51-58,178,191).
Mechanism 5: Neu5Gc
Human blood contains N-Acetylneuraminic acid (Neu5Ac) type sugars, but the blood of nearly every other mammal contains N-glycolylneuraminic acid (Neu5Gc) type sugars.
Because Neu5Gc differs slightly from Neu5Ac, ingesting it from red meat (and any other meat) can trigger an immune response that leads to inflammation and possibly cancer progression (137,208).
High levels of Neu5Gc are contained in human tumors and have been shown to be carcinogenic to mice, but the precise level of Neu5Gc that leads to problems is unknown (136,137,222).
What you can do about it: The only way to mitigate the effects of Neu5Gc is to eat less red meat.
Mechanism 6: Environmental Pollutants
In addition to the previously listed mechanisms, other potentially carcinogenic environmental pollutants include: heavy metals, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (PCBs), and other persistent organic contaminants (181).
The content of these pollutants differs depending on the processing or cooking method of the meat (181).
Other meats generally contain less of these organic compounds than red meat, so red meat has greater carcinogenic potential than other meats, even prior to processing (181).
In a 2017 review, Domingo and Nadal report that their findings and those of others suggest certain cooking processes can modify (decreasing or increasing) the levels of environmental pollutants in foods, thus in meats as well (181-186).
What you can do about it:
Concentrations of environmental pollutants are (mostly) dependent on the original contents of these pollutants in the food, rather than the cooking method used to prepare the food. Since most environmental pollutants are organic, cooking procedures that release or remove fat from the meat should also reduce its pollutant concentrations (181,185,186).
A few important notes on the above mechanisms
Allison-Silva (2016) notes that TMAO, heat compounds, and environmental pollutants are not specific to red meat (208).
Additionally, n-nitroso compounds, heme iron, and the potential of heme to catalyze endogenous nitrosation are more specific to red meat, though even these mechanisms fail to explain the unique link to increased cancer risk in humans, because other carnivores aren’t evidently at high risk for these same diseases (208).
Environmental pollutants and infectious agents from dairy cattle may partially explain this discrepancy in risk (208).
The metabolic incorporation of Neu5Gc into the tissues of red meat consumers, followed by interaction with inflammation-provoking antibodies, presents another potential explanation for the increased human cancer risk (208).
A number of studies have analyzed the concentrations of carcinogenic compounds such as PCDD/Fs, dioxin-like PCBs or PAHs (among others) in raw red meats, showing more or less notable levels of these compounds, depending on the kind of red meat and its origin. This indicates that the consumption of these meats, either unprocessed or uncooked, should result in certain risk for meat-eaters. Cooking or processing would only add new carcinogens, or it would increase the amounts (i.e. PAHs/HCAs) that are already present in the same raw/uncooked meat (181).
Why you may want to consume red meat
Despite the link between processed or unprocessed red meat and cancer, there are reasons why you might want to include red meat in your diet:
- Red meat is rich in essential nutrients including iron, zinc, and vitamin B12 (138-140,190,194,196), thus may help ensure that one does not have a nutrient deficiency. However, one could consume other sources of these nutrients which have not been meaningfully associated with cancer risk.
- Red meat is high in protein, which plays a vital role in building muscle (especially when paired with resistance training) (141-145,159,163). Red meat also has a high thermic effect (146), is highly satiating (difficult to overeat; blunts hunger) (139,147,148), and can thus be useful for weight loss or maintenance (139,146-148). However, there are other sources of protein (such as white meat) that may yield similar benefit with less potential risk.
- Red meat is high in the rare vitamin K2 (150-155), which can potentially kill cancer cells through “oncosis” (killing through oxidation) (156), and may prevent formation of cancer cells by promoting autophagy (the recycling of dead cell matter) (157,158). Unfortunately, I am not convinced that the potential cancer risk from consuming red meat is outweighed by the benefits of vitamin K2. Additionally, there are a few other viable sources of vitamin K2 (such as other meats, egg yolks, cheeses, or natto (225,226)).
- Red meat contains creatine, which might help reduce depression (164), enhance brain energetics (165-169), increase muscle growth (161-163, 170,171,180), and improve certain types of athletic performance (162, 168,170-175). Vegetarians tend to have lower baseline creatine levels than omnivores (161-163), thus it seems like meat consumption contributes to one’s creatine levels. However, one would need to consume more red meat than is recommended in order to benefit from its creatine content, therefore it is prudent to supplement creatine monohydrate instead.
- Certain populations can benefit from red meat consumption:
- The elderly can potentially benefit tremendously from red meat consumption because red meat consumption paired with resistance training increases muscle growth in the elderly (159). This helps mitigate sarcopenia (age-related muscle loss). It is prudent to prevent sarcopenia because it contributes to weakness, poor health, and inability to function physically (160,180).
- Developing children may benefit from red meat intake, as meat supplementation has been shown to improve growth (a near-doubling of mid-arm muscle area), cognitive function (arithmetic test performance), and behavior (initiative leadership) in Kenyan children (81).
- Many people are deficient in iron (214) and red meat is one of the best dietary sources of iron (227), thus the anemic can likely benefit greatly from moderate red meat consumption.
The majority of the literature on the topic supports the existence of a link between red meat and cancer, although we cannot conclude causality without intervention studies. Moreover, there are numerous confounders in the literature and this makes the effect of red meat intake on cancer risk more difficult to discern.
Further research is required to establish the mechanisms that could be responsible for an increase in cancer risk, specifically colorectal cancer risk, due to processed and unprocessed red meat consumption.
Regardless of the link between the consumption of red meat and cancer, it seems that living void of excessive alcohol consumption, stress, smoking, high BMI, and sleep deprivation, while consuming fruits and vegetables, and exercising should reduce cancer risk.
Based on the available evidence, it is reasonable to conclude that red meat consumption likely contributes to cancer risk and processed red meat almost certainly does, though I am not convinced that the contribution to risk increase is significant enough to worry about when intake is moderated and the aforementioned lifestyle habits are in place.