The Digest

Why might the consumption of red meat and processed meat cause cancer?

On 26 October 2015, the International Agency for Research on Cancer (IARC), a division of the World Health Organisation (WHO), published a Monograph on its evaluation of the ability of red meat and processed meat to cause cancer. Though seized upon – and in some cases sensationalised – by the media, the working group of 22 experts behind the Monograph reported nothing that was not known already: all they did was to review existing epidemiological studies and conclude that red meat should be classified as ‘probably carcinogenic [cancer causing] to humans’ and that processed meat should be classified as ‘carcinogenic to humans’.

The studies evaluated by the IARC experts were statistical in nature and pointed to an increase in the incidence of several cancers in individuals with a high consumption of red meat or processed meat. Specifically, they concluded that each 50-gram portion of processed meat eaten daily increases the risk of colorectal cancer (also known as bowel cancer) by 18 %. Though alarming, this conclusion must be set against the background risk of developing colorectal cancer.

According to Cancer Research UK, the lifetime risk of developing colorectal cancer in the UK in 2010 was 1 in 14 for men and 1 in 19 for women. Put another way, in 2011, there were 41,581 new cases of bowel cancer in the UK, which amounts to more than 110 people diagnosed with the condition every day. Of course, no one knows how many of these cases were caused by the consumption of red meat or processed meat, but 18 % represents a significant increase in risk and translates into a large number of affected people. Given that the incidence of colorectal cancer continues to increase (by 6 % over the past decade), we should certainly pay careful attention to conclusions reported in the IARC Monograph.

What the IARC experts have certainly not done, however, is add anything to our understanding of how red and processed meats might cause cancer. Statistics point only to patterns: they do not prove that a relationship – a correlation – is causal (i.e. cause and effect) in nature, which is one reason why I prefer to base my own dietary decisions on mechanistic evidence. Indeed, much is known already about the chemical and biological mechanisms by which red meat and processed meat may cause cancer. From what we know about the interactions between the components of these meats and living cells, it is not unreasonable to conclude that plausible mechanisms exist for their induction of cancer.

Journalists do seem to seek simple answers to simple questions – sound bites they can put to use in their ‘stories’. In reality, though, it is never that simple; there are always multiple factors at work. For example, although there are known mechanisms by which red and processed meats could cause cancer, there are also processes and mechanisms that act to prevent their leading to cancer.

Below is an extract from my book, Healthy Eating through Informed Choice. This section (from Chapter 6) covers specifically the mechanisms by which processed meats are believed to cause cancer. I selected these pages because the material within them is fairly self-contained in the sense that most of it can be understood without having to read the previous chapters. I have also included the end-of-chapter Summary, which gives explanations of some of the key scientific terms used in the chapter. Of course, I would be delighted if, after reading this extract, you were persuaded to read the book in its entirety!

To prevent the current article from getting too long, complicated and unwieldy, I decided not to cover the mechanisms by which red meat is linked to cancer. Rest assured, though – they exist and involve the promotion of free radical formation by iron, which is contained in high amounts in red meat relative to white meat.

Extract from Chapter 6 of ‘Healthy Eating through Informed Choice’

We are frequently warned by various authorities of the dangers of eating too much meat. Usually distinctions are made between white meat, red meat and processed meats. Although a common reason we are advised to restrict our intake of red meat is because it contains more cholesterol and saturated fat than white meat, it is more likely that the higher haem content in red meat (as myoglobin) is responsible for the increased health risks associated with its consumption, especially colorectal cancer. Indeed we have seen already why iron is believed to increase the risk of this form of cancer in individuals with ulcerative colitis.

One of the problems with advice given about how much of this or that particular food we should be eating is that it rarely takes into account the interactions between nutrients. In Chapter 3, for example, we saw how vitamin E can protect fatty acids from lipid peroxidation. Since polyunsaturated fatty acids are particularly susceptible to lipid peroxidation, it follows that one’s vitamin E requirements are likely to be higher if one’s diet contains large amounts of vegetable oil relative to animal fat. Similarly, a case can be made that red meat is likely to be particularly harmful if one’s diet is rich in polyunsaturated fatty acids, especially if their ‘oxygenated fatty acid’ content has been boosted by frying. So, if you are going to eat steak and chips, do think twice before frying your chips in sunflower oil.

Before moving on to processed meats, it is worth reminding ourselves of the important role played by dietary fibre – complex carbohydrates that we cannot digest and absorb – in protecting us from colorectal cancer. In addition to ‘mopping up’ free radicals by reacting with them (thereby ‘diverting’ the damage away from more critical targets), fibre ensures that material passes through the digestive system relatively quickly, thereby reducing our exposure to harmful species. As well as the various reactive oxygen species and aldehydes described above, fibre is believed to offer protection from many other mutagens present in food, including the PAH and HAA carcinogens produced when meat is charred.108

Epidemiologists – people who use statistics to compare the incidence of diseases between different populations or groups of people, thereby obtaining clues to their causes – often point to the particularly strong link between the consumption of processed meats and the occurrence of various forms of cancer, including those of the colon, breast and prostate. Some number-crunchers in California, for example, concluded:

‘Weekly consumption of three or more servings of red meat, 1.5 or more servings of processed meat, 1 or more servings of grilled red meat, and 1 or more servings of well done red meat were each associated with an approximately 50 % increased risk of developing advanced prostate cancer,.....’109

These risks were variously associated with the levels of particular chemical carcinogens in the meats, including PAH and HCC, the levels of which increase during cooking. Surprisingly, the contribution of haem iron does not appear to have been considered. As the above example illustrates, processed meat is generally considered to carry a greater risk than non-processed meat – unless, it would appear, the levels of PAH and HCC in the latter have been increased through grilling.

When meat is described as ‘processed’, this is usually taken to mean the meat has been ‘cured’ or preserved by the addition of nitrites or nitrates, typically the sodium ‘versions’ of these: sodium nitrite and sodium nitrate.110 Examples include, bacon, cured hams, sausages, salami and tinned meats. Sodium nitrate is also known as ‘saltpetre’ and has been used in the preservation of meats for hundreds of years. Nitrates, including saltpetre, are converted to nitrites during curing. In addition to its inhibition of the growth of bacteria, including the causative agent of botulism, nitrite binds to the haem of the myoglobin in red meat, resulting in an attractive red colouration. (Maybe it’s not that attractive, but without the nitrite the haem would slowly react with oxygen – forming reactive oxygen species – resulting in deterioration and a somewhat duller colouration.)

The first significant indication of the dangers of curing meats in this way came to light on some fish farms in Norway in the Seventies. Fish that had been fed herring meal preserved using particularly large amounts of sodium nitrite began to develop liver problems, including cancer. It did not take scientists long to realize that the nitrite had interacted with chemicals present in the meal to form a family of substances called the nitrosamines, many of which are known to be potent carcinogens. This discovery was disturbing because the chemicals the nitrite reacted with in the fish meal also occur naturally in meat. It has since been established that nitrosamines are indeed present in cured meats, where they are formed during cooking. There is also concern that nitrosamines can be generated in the stomach, where the presence of acid favours the chemical processes that lead to their formation.

The realization that nitrosamines can be formed in processed meats presented something of a dilemma: removing the preservative would prevent its generation of nitrosomines, but would also result in a significant increase in the incidence of botulism, a potentially fatal form of food poisoning. The outcome of this has been the introduction of limits to the permissible amounts of nitrite added to foods.

A panel advising the European Commission concluded that ‘50-100 mg of nitrite per kg meat may suffice for many products; for other products, especially those with a low salt content and having a prolonged shelf life, the addition of 50-150 mg/kg of nitrite is necessary to inhibit Clostridium botulinum’ (the causative agent of botulism).111 Similar measures have been put in place by the Food and Drug Administration in the United States. Such measures have helped to significantly reduce human exposure to nitrosamines, which is now believed to be below one microgram per day.112

Another measure taken by the food industry to reduce our exposure to nitrosamines has been the inclusion vitamin C in processed meats. Take a look at the ingredients declared on a pack of ‘Tesco Everyday Value Smoked Back Bacon’:

Ingredients Pork (87 %), Water, Salt, Preservatives (Sodium Nitrite, Potassium Nitrate), Antioxidant (Sodium Ascorbate)

Sodium ascorbate is a form of vitamin C. Although listed in this product as an antioxidant, the vitamin is often added to processed meats because it can inhibit the formation of nitrosamines. Vitamin C does this by quenching reactive species formed from nitrite. Note that this product also contains potassium nitrate, which is just another chemical form of nitrate – the ‘part’ of the chemical that is converted to nitrite. Using the potassium, rather than sodium, version of nitrate is a means of lowering the sodium content of the product – a high intake of sodium being associated with high blood pressure. Now look at the ingredients listed on a pack of ‘Tesco Smoked Healthy Living Bacon Rashers’:

Ingredients Pork (90 %), Water, Salt, Preservative (Sodium Nitrite)

There is no vitamin C listed: the ‘healthy living’ status of the product presumably reflecting its lower fat content. One hundred grams of the raw product contains 4.0 grams of total fat, compared with 22.5 grams in the ‘Everyday Value’ product. However if you compare the fat contents after grilling, the difference is much smaller, with the latter product containing two-and-a-half times as much fat as the former. No figures are available for the nitrosamine content of each product, but – because it contains added vitamin C – one would expect the ‘Everyday Value’ product to be the lower of the two. No one seriously eats bacon because they believe it to be a low-fat food (one would hope). This clever marketing really serves only to justify the much higher price asked for the lower-fat bacon. From a health point-of-view, by far the biggest factor to be considered when choosing to eat bacon has to be its nitrosamine content, against which standard the ‘Everyday Value’ product must win hands down.

Even if we were to eliminate nitrites altogether from our diets, we would still be exposed to nitrosamines which, for various reasons, are present in a range of other foods and substances. Nitrosamines are formed, for example, during the malting process and therefore find their way into beers and whiskies. They are also present in smoked foods and in certain forms of milk. Back in 1981, researchers reported a study in which they had performed a somewhat limited comparison of the levels of nitrosamines in various milk products.113 The highest levels were found in non-fat dry, condensed and evaporated milks, with smaller amounts detected in pasteurized skimmed, low-fat and whole milks. Interestingly, nitrosamines were not detected in raw (unpasteurized) milk. Although they tested only three samples of raw milk, this finding is consistent with a role of heat in the promotion of nitrosamine formation. Drying processes, in which the chemicals responsible for the formation of nitrosamines become more concentrated, also probably play a role, as reflected by the nitrosamine levels in non-fat dry milk (and indeed in malt).

It should be emphasized that the levels of nitrosamines in dairy products – formed from substances that are present naturally in milk – are extremely low and should not be causing us any real concern. Similarly, changes in the methods used to produce malt have led to a substantial reduction in the amounts of nitrosamines present in beer and whisky. As we will discuss below, nitrosamines are also formed in the stomach from endogenous nitrites and nitrates, so we can never reduce exposure to zero. What we should be doing is avoiding exposure to nitrosamines from sources that are particularly high. As we have seen, a strong case can be made for the avoidance of processed meats.

Although a book on nutrition is perhaps not the place to be warning of the dangers of tobacco products, it is worth mentioning that – of the sixty or so recognized carcinogens present in tobacco smoke – nitrosamines are one of the most important categories. The detection of products derived from tobacco-specific nitrosamines in the urine of non-smokers exposed to second-hand smoke, including children and newborns (exposed via the placenta), has played a significant role in the putting in place of legislation to prohibit smoking in public places.114

There are also other environmental sources of nitrosamines – rubber products being a well known example. Indeed researchers at the Chemical and Veterinary Investigation Institute in Stuttgart created quite a commotion when they reported that carcinogenic nitrosamines were released, in varying amounts, from 32 brands of condoms when tested in contact with an ‘artificial sweat solution’. The findings were reported initially on the Institute’s website and then, more formally, in a scientific paper published in 2005.115 Werner Altkofer and colleagues calculated that nitrosamine exposure from condoms may exceed exposure from the diet by up to three-fold. Germany’s Deutsche Latex Forschungsgemeinschaft Kondome (‘Condom Research Council’ to the rest of us) issued a prompt rebuttal, which was broadcast on television. The Council cited an earlier study by Ehrhardt Proksch, at the University of Kiel, who determined that a person’s lifetime absorption of condom nitrosamines – assuming 1500 ‘contacts to condoms’ over 30 years (each lasting for 10 minutes) – to be an insignificant 0.9 micrograms in total.116 Rubber gloves, balloons, dummies and bottle teats are also potential sources of nitrosamines, but there are guidelines to limit the levels in these materials. In the rebuttal letter it addressed to a national television company, the ‘Condom Research Council of Germany’ pointed out that it was quite appropriate of the European regulatory authorities to omit setting limits on the levels of nitrosamines in condoms, adding: ‘It would be impermissible and unjustifiable to compare condoms and bottle teats or dummies, either with regard to the mode of use or to the duration of use.’ Let’s not go there.

Having diverted somewhat into the vices of sex, tobacco and alcohol, it is time to get back on course and perhaps keep a sense of perspective. As Bruce Ames showed with his test for mutagens, we are exposed to possibly hundreds of potential carcinogens on a daily basis. It would be futile to try to attempt to avoid exposure to such chemicals altogether. This is particularly true of the nitrosoamines because – even if we were to eliminate their entry into the body through ingestion, inhalation or, indeed, routes involving rubber – they are also generated in our bodies. The formation of nitrosamines, whether in meat or inside the human body, requires nitrite and a particular type of chemical called an amine. Not all amines form nitrosamines, but those which do occur naturally in the diet. Indeed all amino acids – the very building blocks of proteins – are amines (which is why they came to be called amino acids). We cannot avoid dietary amines.

Although we should certainly think twice about consuming foods to which nitrite preservatives have been added, these chemicals also occur ‘naturally’ in the stomach, being derived through the actions of bacteria in the mouth on dietary nitrates. Nitrates are prevalent in vegetables and indeed occur naturally in ground water, particularly where this has been polluted by the excessive use of nitrate fertilizers. Nitrates are also present in small amounts in mineral waters – even in the more expensive brands. Legislative measures are in place to ensure nitrate levels in drinking water are below specified limits, which in the European Union is 50 milligrams per litre. This limit was set not so much with nitrosamines in mind, but to prevent a condition called cyanosis (better known as ‘blue baby syndrome’), which can occur when the water used in the preparation of infant formula feeds contains excessive nitrate. The nitrate is converted to nitrite by bacteria in the body; it then enters the bloodstream and interacts with haemoglobin in the red blood cells. This reduces the ability of the red blood cells to transport oxygen to the tissues, resulting in a characteristic blue colouration of the skin around the mouth, eyes, hands and feet from which the condition takes its name.

Though blue baby syndrome is rare, in extreme cases it can be fatal. Infants under six months of age are particularly susceptible. This is because, unlike adults, they have low levels of an enzyme that is able to regenerate functional haemoglobin following its modification by nitrite. Other theories, involving the levels of particular bacteria in their digestive systems, have also been proposed to account for the susceptibility of infants to cyanosis. In fact, there are many reported examples of cyanosis that have occurred without exposure to high levels of nitrate. This has led to suggestions that the condition may be caused by nitrite generated directly by the body during inflammation associated with infections of the digestive system.117

Over the past fifteen years or so, there has been an enormous increase in our understanding of the biological functions of both nitrate and nitrite, many of which involve beneficial effects. It is known, for example, that saliva contains nitrate, which has been ‘recycled’ from the blood. In addition to its interaction with haemoglobin (which requires relatively high amounts), the nitrite formed from the nitrate in saliva can be converted to a small, gaseous free radical called nitric oxide. Whilst the excessive, inappropriate production of nitric oxide is associated with many disease processes, at low levels the species plays an important role in the control of blood pressure and inflammation.118 Nitric oxide is generated in the body for such purposes by a special enzyme. This enzyme does not use nitrite to make the gas, but rather it uses an amino acid. One of the fates of nitric oxide is its conversion to nitrite, which can explain the occurrence of cyanosis in some infants suffering an infection – when excessive nitric oxide generation may occur – in the absence of excessive nitrate intake from the diet.

The nitrate-nitrite-nitric oxide story is still very much an emerging area of research; its precise relevance to nitrosamine formation is still being unravelled. As far as we are concerned, all we need learn from this is that nitrates and nitrites are linked intimately to several important processes in our bodies. As with so many of the potential toxins to which we are exposed, some of these processes are essential to the maintenance of good health, whereas others are potentially harmful – another reminder that all substances are poisons.

Although the nitrates in drinking water, vegetables and those already present in saliva are all potential sources nitrites – and therefore nitrosamines – that we can do little to avoid (if indeed this were desirable), that is not to say we should not avoid the direct ingestion of large quantities of ‘pre-formed’ nitrites from cured meats. Indeed the conditions created by the acid in our stomachs favour the generation of nitrosamines from nitrite and dietary amines. Another sensible measure we can take is to ensure that we have an adequate intake of vitamin C, which we are unable to synthesize for ourselves. Just as the vitamin suppresses the formation of nitrosamines in processed meats, it also blocks their formation in the stomach. That vitamin C may offer protection from nitrosamine formation within the body has indeed been ‘demonstrated’ – albeit statistically, by the analysis of population data – in a study showing that the combination of a low intake of the vitamin and a high intake of meat increases the risk of colorectal cancer in people exposed to high levels of nitrate in their drinking water.119

A particularly intriguing (and highly speculative) link between vitamin C and disorders of the digestive system is also furnished by the finding that people infected with the bacterial organism Helicobacter pylori have abnormally low levels of the vitamin. In the early Nineties, a lot of excitement was caused by the discovery that infection with this organism is strongly associated with disorders of the stomach, including stomach cancer. Indeed the World Health Organization classified H. pylori as a ‘class I carcinogen’. Many people carry this infection, but most have no symptoms, so how it contributes to the development of stomach cancer is far from understood. What appears to be the case, however, is that infection of the stomach wall with H. pylori prevents the secretion of vitamin C into the stomach, which normally contains a higher concentration of the vitamin than the blood. This may allow nitrite to react with amines – a process which is normally inhibited by vitamin C – thereby forming carcinogenic nitrosamines.120

Whatever the merits of this hypothesis, there are other compelling reasons why we should ensure an adequate dietary intake of vitamin C – not least due to its importance as an antioxidant. Indeed it would be most unexpected if the ability of vitamin C to quench free radicals did not also underlie the protection it appears to afford against cancers in the digestive tract – that is, of course, when it is not busy helping iron generate reactive oxygen species through its of ‘recycling’ iron(3+) to iron(2+). Little wonder there are no simple answers when it comes to nutrition, health and disease. All medicines are poisons.

Summary of Chapter 6

Proteins consist of many amino acids joined together in long chains. The amino acids that form each protein are encrypted in DNA – our ‘genes’ – which is the building material of the chromosomes. Genes are, in effect, instructions for the production of proteins.

A mutagen is an agent – usually a chemical, but the definition also includes certain forms of radiation – that causes a change in the genetic code within DNA. This results in cells making ‘faulty’ proteins, containing the wrong amino acids.

Cancer can occur if a mutation leads to the modification of a protein – at the level of its gene – that is involved in the control of cell growth. Cancer is, essentially, a disorder of cell growth in which affected cells reproduce in an uncontrolled manner.

The Ames test has shown that many man-made and naturally-occurring substances are mutagens; indeed we are exposed to hundreds of potential mutagens on a daily basis. Specialized enzymes (proteins), mostly in the liver, detoxify potentially harmful chemicals and promote their excretion from the body. In some cases, however, the actions of these enzymes result in the activation of chemicals into mutagens. Fortunately, most mutations do not result in cancer.

Many chemicals that cause DNA damage (and therefore mutation) do so by promoting the formation of free radicals, often from oxygen. Even in the absence of harmful chemicals, a tiny proportion of the oxygen we inhale is converted to free radicals and other reactive species (including hydrogen peroxide) – known collectively as reactive oxygen species. In addition to the sacrificial antioxidants, which intercept free radicals, there is a whole armoury of enzymes whose role it is to prevent the formation of free radicals from oxygen.

Metals, particularly iron and copper, play a central role in the generation of reactive oxygen species. There are concerns that iron in food supplements may promote such reactions. This could be a particular problem in infant formula feeds, which contain high levels of polyunsaturated fatty acids, including DHA. The breakdown of fatty acids results in the formation of chemicals called aldehydes, which – by adding to proteins and DNA – are potentially harmful.

Haem iron, a form of iron which occurs in red meat, is particularly effective in the promotion of free radical (and aldehyde) formation from polyunsaturated fatty acids. The consumption of red meat is associated with an increased risk of colorectal cancer. This is particularly so for processed meats containing nitrate and nitrite preservatives, which can lead to the formation of a group of potent mutagens called the nitrosamines. Vitamin C inhibits the formation of nitrosamines.

Footnotes quoted in book extract

108 We owe our appreciation of the importance of dietary fibre in the maintenance of good health to the great Denis Burkitt (1911 – 1993), a Presbyterian missionary and surgeon who devoted much of his life to working in Africa. He is also renowned for his pioneering work on the cause of the cancer which now bears his name, Burkitt’s lymphoma. Denis Burkitt’s work on the geographical distribution of this cancer in Africa led to his linking it to a virus. (There is no known family connection, alas.)

109 E. M. John et al. (2011) Meat consumption, cooking practices, meat mutagens and risk of prostate cancer. Nutrition and Cancer, volume 63, pages 525 – 537. doi: 10.1080/01635581.2011

110 In the UK, some processed meats have been discovered to contain horse.

111 EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Statement on nitrites in meat products. EFSA Journal 2010; 8(5):1538. doi: 10.2903/j.efsa.2010.1538. Available online:

112 A microgram (µg) is one-millionth of a gram.

113 L. Lakritz and J. W. Pensabene (1981) Survey of fluid and nonfat dry milks for N-nitrosamines. Journal of Dairy Science, volume 64, pages 371 – 374.

114 J. L. Thomas et al. (2011) Metabolites of tobacco-specific lung carcinogen in children exposed to secondhand or thirdhand tobacco smoke in their homes. Cancer Epidemiology, Biomarkers & Prevention, volume 20, pages 1213 – 1221. doi 10.1158/1055-9965.EPI-10-1027; and E. Avila-Tang et al. (2013) Assessing secondhand smoke using biological markers. Tobacco Control, volume 22, pages 164 – 171. doi: 10.1136/tobaccocontrol-2011-050298

115 W. Altkofer et al. (2005) Migration of nitrosamines from rubber products – are balloons and condoms harmful to the human health? Molecular Nutrition & Food Research, volume 49, pages 235 – 238. doi: 10.1002/mnfr.200400050

116 E. Proksch (2001) Toxicological evaluation of nitrosamines in condoms. International Journal of Hygiene and Environmental Health, volume 204, pages 103 – 110.

117 A. A. Avery (1999) Infantile methemoglobinemia: reexamining the role of drinking water nitrates. Environmental Health Perspectives, volume 107, pages 583 – 586.

118 Nitric oxide is responsible for the actions of Viagra.

119 A. J. De Roos et al. (2003) Nitrate in public water supplies and the risk of colon and rectum cancers. Epidemiology, volume 14, pages 640 – 649.

120 See, for example: G. M. Sobala et al. (1993) Effect of eradication of Helicobacter pylori on gastric juice ascorbic acid concentrations. Gut, volume 34, pages 1038 – 1041.

Mark Burkitt

Westcott Research and Consulting

Article published 30 October 2015

If you would like to learn more about the role of diet in health and disease (including heart disease and cancer), it is recommended you read Dr Burkitt’s book, Healthy Eating through informed Choice (Troubador Publishing, 2014, ISBN: 9781783064793).

Whilst the book is written in non-technical language and is intended primarily for readers with absolutely no background in science, it is hoped that trained scientists and health professionals will also find the material to be of interest. The book is extensive in its scope and challenges some of the conventional views on the role of diet in human disease, questioning – in particular – the wisdom of the mainstream advice to consume a diet high in polyunsaturated vegetable oils. It is explained how the high susceptibility of polyunsaturates to damage by free radicals means they, rather than saturated fats, are likely to be a major cause of human disease (along with sugar, of course!).

Dr Burkitt's book is available for purchase from [Troubador Publishing], [Amazon], [WHSmith], [Blackwell's] and all other good book shops.

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