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.

Key takeaways

Given an otherwise healthy overall lifestyle, moderate red meat consumption is likely fine.

Red meat’s dose makes the poison, so it’s wise to moderate red meat intake (particularly, processed red meat).

Red meat consumption correlates positively with cancer (mainly colorectal cancer). While consuming red meat may cause cancer, research cannot establish causation, given numerous confounders and lack of intervention studies.

Processed red meat and cancer correlate better than 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.

Red meat consumption may be carcinogenic through various mechanisms, but your actions can mitigate these risks.

Red meat’s link to cancer is pragmatically relevant because you control how much red meat you consume. However, red meat consumption is certainly not the primary factor influencing cancer risk (2).

Red meat consumption yields some health benefits, so despite its link to cancer, occasional red meat consumption may improve health.

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 world (41,192). Red meat consumption correlates most meaningfully with colorectal cancer.

Less convincing evidence positively correlates red meat consumption with 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).

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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 consuming 100 grams (~3.53 ounces) of unprocessed red meat per day correlates with 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 correlates with increased risk of 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 (of 25 studies) discovered a linear dose-response relationship between both processed and unprocessed meat and colorectal cancer risk. Consuming 100 grams of unprocessed red meat per day correlated with a 1.12 relative risk, while consumption of 50 grams of processed meat per day correlated with a 1.17 relative risk (228). Consuming 4 servings of red meat per day or 2 servings of processed meat per day correlated with 1.8-fold colorectal cancer risk. This review also reported that low red meat consumption, paired with a high whole grain, vegetable, fruit, and dairy product consumption, correlated with decreased colorectal cancer risk (228).

Further, Grundy et al (2012) reported that red and processed red meat consumption caused roughly 12% of colorectal cancers in Alberta, Canada (1.5% of all cancers) (195). Of note, roughly 1 in 2 men and 1 in 4 of the study’s women exceeded the World Cancer Research Fund’s 500 gram (~17.64 ounces) red and processed meat per week recommendation (195,190).

Wang et al’s (2016) meta-analysis (of 17 prospective cohorts) found that more red and processed meat consumption correlated with increased total, cardiovascular, and cancer mortality risk (202).

The WHO’s report concluded that by not consuming red meat, one’s colorectal cancer risk may decrease by ~18% (3,179). However, it’s very difficult to quantify the correlated risk increase, as meat is one variable in our multifactorial diet. Further, it’s impossible to quantify the exact percentage risk increase, given confounders (e.g. sleep and stress).

Lifestyle factors confounding red meat-consumption-induced colorectal cancer risk include regular smoking, high BMI, and alcohol consumption (6,5,7,9,17,23,25,26,28,35,44-50,190,198,199,212).

Additionally, greater fruit and vegetable consumption correlates with generally reduced cancer risk, confounds red meat’s effects considerably (7,10,11,21,33,36,42,44,51-58,178,198,212). We cannot quantify the degree to which fruit/vegetable consumption (or lack thereof) influences cancer risk in red meat-related trials.

We cannot determine red meat’s carcinogenicity, as observational research lacks the control needed to establish this link (50,59-61). Since many factors alter cancer risk, and cancer takes years to develop, cancer-related randomized trials are difficult to conduct.

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 percentage cancer risk change correlated with consuming ~50 grams (~1.76 ounces) of processed red meat or ~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. As such, compared to baseline (1.0), bladder cancer risk increases by 8% upon consuming ~100 grams of red meat or ~50 grams of processed red meat per day. This doesn’t mean that one’s absolute cancer risk increases by 8%; this means cancer risk increases by 8% of the 2.4% baseline bladder cancer risk. The initial 2.4% absolute risk thus increases by .192% (from 2.4% to 2.592%).

Despite an evident relative risk increase, absolute cancer risk doesn’t increase substantially after consuming 100 grams (~3.53 ounces) of red meat or 50 grams (~1.76 ounces) of processed red meat.

Mechanisms through which red meat may increase cancer risk

In a 2017 paper, Johnson reported several identified mechanisms for meat consumption’s mutagenic effects. Unfortunately, it’s not clear which mechanisms cause cancer in humans. Additionally, the extent to which avoiding red meat decreases cancer risk is unknown (204).

Mechanism 1: NOCs

Processed red meat contains N-nitroso compounds (NOCs). NOCs form endogenously from nitrite and nitrate intake (223).

Upon red meat consumption, heme iron catalyzes N-nitroso compound formation, in a dose-dependent manner (46,63-65,67,74,76,77,131,192). These N-nitroso compounds can potentially damage the gut lining, initiating cell regeneration, which may eventually damage DNA (14,63,78-82,205).

Unprocessed red meat effects gut damage less directly than processed red meat (after curing and smoking). This occurs because processed red meat’s chemicals potentiate faster NOC formation (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 high-vitamin C foods should decrease damage as well, though limiting or abstaining from red or processed red meat consumption may help more.

Mechanism 2: High-Heat Chemicals

Heterocyclic amines (HCAs) and Polyaromatic Hydrocarbons (PAHs) form when meat is cooked at high heat or smoked (less so with white meat) (75,93,100-111,181). These heat compounds can damage the gut, and the International Agency for Research on Cancer considers them potentially carcinogenic (98,113,114). Re-heating meat does not seem to contribute to heat compound content (112).

Several genetic mutations (e.g. those involving enzymes NAT1 and NAT2), given their role in HCA metabolism, correlate with increased cancer risk (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 better explain red/processed meat’s correlation with colorectal cancer risk (210).

Few studies find significant associations between white meat (e.g. poultry or fish) consumption and cancer (181,189,187,213). Since cooking white meat also creates high-heat chemicals, high-heat chemical concentrations alone, cannot explain (processed) red meat’s carcinogenicity.

Additionally, PAH’s bioaccessibility in meat is under-studied (210), thus its carcinogenic potential is unknown.

However, one may still want to cook red meat at a lower heat. Cooking meat at low heat, reduces advanced glycation end product formation, thereby potentially improving 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 HCA and PAH formation; preventing much of the heat-chemical induced 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 contains abundant iron, which intestinal tract cells oxidize easily, as other compounds don’t bind tightly to iron (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 catalyze NOC formation, thus may thereby contribute to cancer risk further (46,63-65,67,74,76,77,131,192,205).

Allison-Sliva highlights that this mechanism isn’t universally relevant to cancer. This is because cooking denatures heme, which creates high plasma hemopexin levels that block its tissue delivery. As such, red meat-derived heme can only contribute to colorectal carcinoma risk, via 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 is high in choline and L-carnitine (amino acid), which gut bacteria may metabolize into TMAO (133,134,194,216,217,218). High TMAO levels correlate with high TMA and DMA levels (216). TMA and DMA risk undergoing nitrosation, which potentially causes cancer (via nitrosated amine formation) (218).

However, TMAO may be a lurking variable, rather than a mechanism causing red meat’s carcinogenicity (218). Evidence of TMAO’s protective effect in carcinogenesis (by correcting mutant protein folding (218,220,221)) supports this assertion.

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), but nearly every other mammal’s blood has N-glycolylneuraminic acid (Neu5Gc) type sugars.

Because Neu5Gc and Neu5Ac differ, red-meat derived Neu5Gc ingestion may trigger an immune response, potentiating inflammation and carcinogenesis (137,208).

Human tumors contain high Neu5Gc levels, and Neu5Gc seems carcinogenic to mice. However, we don’t know the dose at which Neu5Gc proves toxic (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

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).

Non-red meats typically contain fewer organic compounds, so red meat’s baseline carcinogenic potential is higher (181).

In a 2017 review, Domingo and Nadal outline that certain cooking processes modify red meat’s environmental pollutant content (181-186).

What you can do about it:

Environmental pollutants concentrations depend (mostly) on the food’s baseline pollutant contents, rather than the food’s preparation method. Since environmental pollutants are typically organic, fat-releasing cooking procedures should also reduce red meat’s 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 heme’s potential to catalyze endogenous nitrosation are specific to red meat. Though, not even these mechanisms explain red meat’s (unique) carcinogenicity to humans, as other carnivores maintain lower risk (208).

Environmental pollutants and infectious agents from dairy cattle may partially explain this discrepancy in risk (208).

Neu5Gc’s metabolic incorporation into red meat consumers’ bodily tissues, followed by inflammation-provoking antibody interactions, potentially explains red-meat induced cancer risk increase (208).

Multiple studies have discovered carcinogenic compounds (e.g. PCDD/Fs, dioxin-like PCBs or PAHs) in raw red meats, which sometimes contain notable carcinogen concentrations (varying with the meat’s type and origin). Therefore, consuming these meats, processed or not, certainly seems risky. Cooking or processing can only add new carcinogens, or increase concentrations of (e.g. PAHs/HCAs) raw/uncooked meat’s pre-existing carcinogens (181).

Why you may want to consume red meat

Despite processed or unprocessed red meat’s link to cancer, one might still benefit from red meat consumption:

Red meat contains essential nutrients iron, zinc, and vitamin B12 (138-140,190,194,196), thus its consumption helps prevent certain nutrient deficiencies. However, people can obtain these nutrients from other, less potentially carcinogenic sources.

Protein plays a vital role in muscle growth (especially when paired with resistance training) (141-145,159,163). Red meat is a great source of protein. Additionally, red meat has a high thermic effect (146), is highly satiating (difficult to overeat; blunts hunger) (139,147,148), and thus may improve weight loss or maintenance (139,146-148). However, other protein sources (such as white meat) may yield similar benefit with less potential risk.

Red meat is high in (rare) vitamin K2 (150-155), which potentially kills cancer cells through “oncosis” (killing through oxidation) (156), and may prevent cancer cell formation via autophagy (dead cell matter recycling) (157,158). Unfortunately, I doubt vitamin K2’s benefits outweigh the increased cancer risk correlated with red meat consumption. Additionally, few other vitamin K2 sources exist (only other meats, egg yolks, cheeses, or natto (225,226)).

Red meat contains creatine, which might reduce depression (164), enhance brain energetics (165-169), increase muscle growth (161-163, 170,171,180), and improve athletic performance (162, 168,170-175). Vegetarians have lower baseline creatine levels than omnivores (161-163), thus meat consumption likely boosts creatine levels. However, one must consume more red meat than recommended to reap creatine’s benefits, thus I recommend creatine monohydrate supplementation instead.

Certain populations can benefit from red meat consumption: Red meat consumption may tremendously benefit the elderly. Since red meat consumption increases muscle growth when paired with resistance training (159), it helps mitigate sarcopenia (age-related muscle loss). It is prudent to prevent sarcopenia because it contributes to weakness, poor health, and physical ineptitude (160,180). Red meat consumption may enhance growth (mid-arm muscle area), cognitive function (arithmetic performance), and behavior (initiative leadership) in Kenyan children (81). As such, red meat consumption may benefit developing children. Iron deficiency is common (214), and red meat is rich in iron (227), thus red meat consumption may benefit anemics. However, many other dietary iron sources exist.



Conclusion

Most scientific literature indicates a link between red meat and cancer, although we cannot conclude causality without intervention studies. Moreover, there are numerous confounders in this research, making red meat’s carcinogenicity difficult to quantify.

We need more research to establish red meat’s most relevant cancer-inducing mechanisms (specifically for colorectal cancer risk).

Red meat consumption is only one determinant of cancer risk. Reduce general cancer risk by avoiding excessive alcohol consumption, stress, smoking, high BMI, and sleep deprivation. Similarly, it’s prudent to consume fruits and vegetables, while exercising often.

Available evidence indicates that red meat consumption likely increases cancer risk, while processed red meat almost certainly does. However, I doubt red meat increases cancer risk meaningfully if you moderate consumption and maintain healthy lifestyle habits.