Meat and Colorectal Cancer: A Concise Review

by George Henderson
http://hopefulgeranium.blogspot.co.nz/

Research Assistant at AUT Human Potential Centre

When you promote a diet that allows people to eat red meat if they want to, while others
recommend that red meat be strictly limited, and people eat what they want anyway, it puts you in
the position of having to answer the familiar question, is meat a cause of disease?
The idea that eating meat causes diseases like cancer was initially driven into the public consciousness by the American temperance crusader, quack doctor and breakfast cereal salesman John Harvey Kellogg, who also popularised the idea of colonic cleanses as a cure for dietary ills. Thus the major ideas about meat and disease that we have to deal with today had a wide currency before any sort of scientific evidence existed that could be used to support them. They grew out of a vegetarian bias, the association between meat eating and alcohol consumption in the Temperance era, and the characteristic American desire to succeed by selling novel products and services.
The phrase “nutritional terrorism”, used by food historian Harvey A. Levenstein, describes a process that has been going on, with regard to meat in the diet, for over a hundred years; a war against eating habits in which the weapons are statements like “eating X causes cancer” and “eating Y prevents cancer” (so, by implication, not eating Y causes cancer too). Implicit in the phrase “nutritional terrorism” is the idea that these statements are themselves harmful, and can be used to manipulate and exploit people.

Limitations of scientific inquiry
How strong, and how plausible is the link between meat eating and cancer?
Most of the data about meat and cancer is gleaned from large cohort studies in which large numbers of more-or-less healthy participants are asked to fill out a food questionnaire. Their medical records and death certificates are then examined at some much later date. An obvious flaw with this method is that people change their diets, more so in recent times perhaps. The British diet researcher Zoe Harcombe took part in one such study (EPIC); she filled in the food questionnaire when she was a vegetarian, but by the time the study was completed she was a meat eater, and had become an eloquent advocate for the low carbohydrate diet. Zoe Harcombe’s experience also illustrates another potential flaw; because vegetarianism and veganism are still rather rare, participants can be sought for studies on meat avoidance through vegetarian clubs, as she was. This introduces an element of volunteerism into some studies which favours the vegetarians, who tend to be be more motivated and interested in diet and health issues than the meat eaters, who are likely to have become involved in a more random fashion that does not depend on their food choices.


Another question is whether other factors that might also explain cancer incidence – what are called confounding variables – have been accounted for and correctly measured. 
Red meat eaters or processed meat eaters might be more likely than vegetarians to work in industries where carcinogenic chemicals are used, to do shift work, or to drink or smoke more heavily. 
Do heavy drinkers or binge drinkers report alcohol intake honestly in food questionnaires? 
How accurately do binge drinkers remember how much they drink? 
How far does the consumption of meat, and especially cheap and “unhealthy” processed meats, reflect one’s class, educational level, occupation, and income status, and how well can these variables be measured and accounted for?


There are no trials that feed people meat to see if they develop cancer, for obvious reasons. There
are animal experiments, from which one thing becomes clear; you cannot give an animal cancer by feeding it meat. You can give an animal cancer by feeding it a carcinogenic chemical, then see if
feeding it meat makes the cancer grow or shrink, but the results are instructive. In one series of tests in rats, beef and chicken had no effect, but ordinary commercial bacon reduced the rate of
cancer.[1] These experiments were repeated with the refinement of a nutrient deficiency (calcium),
and this time the rate of cancer increased when haeminin and haemoglobin, sources of iron found in meat, were fed.[2] Though the conditions might not have reflected what goes on in the gut of the average person, these experiments do suggest that whether meat is harmful or indeed beneficial with regard to cancer might depend on factors such as exposure to carcinogens and nutritional status, that is, factors other than meat.

One can observe that the people who live to be older than most of us – supercentenarians, those
110 or older – are rarely vegetarians, and are often, in the news stories that celebrate their
birthdays, fond of bacon. This may merely reflect the fact that older people are at risk of losing their appetites, to the detriment of their chances of longevity, and bacon is a tasty food. But it also shows that meat eating is not inconsistent with extreme longevity.

Associations between meat eating and colorectal cancer
There is a weak but consistent correlation between meat consumption and colorectal cancer in
most, but not all, large epidemiological studies. New Zealand has one of the world’s highest death
rates from colorectal cancer, yet red meat, a protein-rich food, supplied only about 14% of the total protein in the NZ diet in 2006.

To what extent is meat consumption a factor in colorectal cancer, and what is the contribution of
other dietary and non-dietary factors?
A 2015 systematic review and meta-analysis summarised the evidence for meat in colorectal cancer studies where the subtype of meat was recorded as follows: “Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer.


Overall, given the modest effects observed for highest versus lowest intakes, beef consumption
alone seems unlikely to explain the large international variation of CRC incidence.”[3]


Mechanisms that link meat and colorectal cancer
No one mechanism is favoured in the literature, but strong evidence points to heterocyclic amines
(HCA) and polycyclic aromatic hydrocarbons (PAH), which are formed when meat is “well done” and especially when it is scorched or blackened, as on a barbecue, as carcinogens.[4]
In animal studies HCA and PAH are only carcinogenic at very high intakes. They are only carcinogenic after being activated by enzymes produced by certain bacteria in the gut, whereas probiotic species (including acidophilus and bifidus sp.) reduce the amount of these enzymes and inhibit the carcinogenic effects of HCA and PAH.[5] Other mechanisms that are supported by some evidence are haeme iron, and the nitrates and nitrites used as preservatives in some processed meats. Red meat does not promote cancer in rodents but haeme iron has promoted cancer in rats fed a diet deficient in calcium. Interestingly, adding back calcium, adding antioxidants, or replacing the high-PUFA safflower oil in the experiment (5%E) with olive oil all reversed the cancer-promoting effect of haeme.[2]

Insulin resistance and metabolic syndrome
A further theory is that insulin resistance caused by the high fat content of meat promotes colon
cancer.[6] The evidence for hyperinsulinaemia and hyperglycaemia as factors in colorectal cancer is strong.[7] Dairy fat, which is more saturated than the fat in meat, is not associated with colorectal cancer in epidemiology, and is associated with a reduced risk of type 2 diabetes, unlike fat from meat.[8]
Trans fats have a strong correlation with colon cancer; in early epidemiology trans fats were not separated from saturated fats.[9] Fish has an inverse association with colorectal cancer, and omega 3 fatty acids from fish increase insulin sensitivity. It is not at all obvious why meat itself should cause hyperinsulinaemia, as diets based on meat and fat have long been used to lower the requirement for insulin in type 1 diabetes and reverse hyperinsulinaemia in type 2 diabetes, but it is likely that high meat consumption in epidemiology is often associated with other factors that promote insulin resistance. If one thinks of the ways in which meat can be consumed – on pizza, in ready-to-eat meat pies, sausage rolls, hamburgers, frozen lasagne and so on – it is easier to see its association with insulin resistance and metabolic syndrome.

Confounding variables
In the general population, high meat consumption and low fish and vegetable consumption is associated with people in blue-collar occupations whose dietary patterns may differ from those of professionals and academics. Possible confounders arise from the presence or absence of carcinogens in the workplace, and the effects of night shift work on cancer risk. Night shift workers have significantly increased colorectal cancer rates[10,11], while many different workplace
exposures are also associated with increased risk.[12,13]
In terms of a general overview of the epidemiology, the risk ratios associated with occupational and metabolic factors are greater and more consistent than those associated with red or processed meat per se. Peters et al. (ref. 12, a case-control study of colorectal cancer in young men) is interesting in presenting both occupational and dietary evidence together. Beef was not associated with colorectal cancer, deep fried food but not processed meat was significantly associated with CRC overall (OR 2.1), but significant site-specific correlation was seen with deep fried food and fried and smoked processed meat. The choice of wholemeal bread over white bread had a protective association (OR 0.6) overall. Inactivity in the workplace is a further risk factor.[14,15] Such evidence supports the view that the modern incidence of colorectal cancer is a “disease of civilization”, that is, a disease that is promoted by industrial chemical exposures, industrial food processing, fast food cooking, and the circadian disruptions produced by artificial light and the work demands of life in an industrialised society, which include both night shift work and enforced inactivity. Burkitt’s hypothesis that cereal fibre accounts for the different incidence of CRC between industrialised and non-industrialised peoples lacks strong experimental confirmation, but it is likely that a multifactorial approach to the same question will prove more rewarding.[16,17]

Benefits of meat
Meat is an easily digested food with a high bioavailability of most essential nutrients, as well as many non-essential chemicals which are required in human metabolism and not found in plants, such as carnitine and creatine. Zinc and iron are common nutritional inadequacies in populations that do not eat red meat. Low and suboptimal intake of the micronutrient selenium (Se) as noted in New Zealand has been implicated as a risk factor in CRC.[18] Kidneys from sheep and cattle are among the best dietary sources of selenium, meat is also a source of selenium.
Iron deficiency is common in New Zealand, especially among young people, and meat is an excellent source of this mineral.[19]
Red meat is a good source of vitamin B6, which is required for the metabolism of amino acids. Processed meats are a poor source of this vitamin. Intake of vitamin B6 is inversely associated with, and serum levels of the active co-factor form pyridoxal-5-phosphate (PLP) are strongly inversely associated with, colorectal cancer (RR 0.52). PLP is required for the conversion of dietary selenium (selenomethionine) to the active form (selenocysteine) and may also play a role in the metabolism of nitrite.[20]
Fatty cuts of meat, in the context of a low carbohydrate diet, have a high satiating power and meat, by making the low carbohydrate diet more appetising, helps in maintaining a diet that, like any diet, needs to be maintained to be effective. The main therapeutic mechanism of a low carbohydrate diet is to reverse hyperinsulinaemia, hyperglycaemia, and other markers of the metabolic syndrome and type 2 diabetes that are risk factors for colon cancer. In part risk reduction is achieved by lowering energy intake and the resulting weight loss. However weight loss is not necessarily required for improvements in metabolic risk factors.[21]

Serum lipoproteins, dietary biomarkers, and cancer risk
The EPIC study found that ApoA-1, HDL cholesterol, total cholesterol, and LDL cholesterol were inversely associated with CRC risk, but only the protective association with HDL was strong (RR 0.54, highest quintile compared to lowest).[22] This latter finding has been replicated in other studies, and is consistent with hyperinsulinaemia, which suppresses HDL, being an important factor in the aetiology of CRC.
Serum biomarkers of dietary intake, chemicals that owe their presence in the blood to the consumption of specific foods, may be more reliable than subjects’ recall of the foods they ate. In a case-control study nested within the French EPIC cohort a high serum phospholipid level of the odd-chain saturated fatty acids pentadecanoic acid (15:0) and heptadecanoic acid (17:0), which are considered biomarkers of dairy fat consumption, was inversely associated with advanced colorectal adenomas (OR O.40). A similar correlation was seen for a high level of DHA and EPA, biomarkers of fatty fish consumption (OR 0.50). The ratio between long chain omega 3 PUFA and long chain omega6 PUFA was also inversely associated with advanced colorectal adenomas (OR 0.40). Similar but non-significant trends were seen in regard to non-advanced adenomas.[23] Serum phospholipid pentadecanoate and heptadecanoate levels were inversely associated with serum levels of insulin in a prospective study.[24].

Safety of meat in the LCHF diet
The requirement for protein in the LCHF diet is around 15% of energy, or 1g per Kg of body weight.
The consumption of protein from nuts, seeds, fish, seafood, eggs and poultry is encouraged, as well as dairy and some legumes if these are tolerated. In the context of this, and other, diets, the amount of meat consumed is a matter of taste, of cultural preference, and perhaps regard for one’s family history of disease, or one’s iron status. The use of processed meat is discouraged, with nitrate-free bacon and traditional fermented meats being preferred choices. Bacon is a convenient and popular breakfast food, but the evidence we have reviewed suggests that it should be cooked under a grill so that charring can be prevented, and similarly that red meat should not be overcooked. Boiling, in a stew, casserole, or boil-up, minimises the action of heat, as well as the loss of micronutrients, as does cooking steak to medium rare. Cooking meat slowly in liquid with the bone attached, for example in soups, stews, curries, and casseroles, supplies additional calcium in the meal.
Wholegrains are the only foods considered to be protective against CRC that are not included in the LCHF diet; however the foods eaten by people who do not eat wholegrains in epidemiological
studies include refined grains, which are not eaten on the LCHF diet. There is no study which directly compares intake of wholegrains with that of fibre from non-starchy vegetables, nuts, etc. on a grain-free diet.
The protective effect of fruit and vegetables in the diet may not be restricted to those with low meat intakes, and there may also be a protective effect of full-fat dairy products (perhaps due in part to the competition between calcium and iron).
Fermented foods which are sources of probiotic bacteria, such as yoghurt, sauerkraut, kimchi, and
sour cream, are commonly consumed with red meat in many of the world’s cuisines. A nutritious, varied diet, a healthy microbiome, and good habits of work, sleep and exercise are important determinants of metabolic health, including cancer risk, and should be considered as essential adjuncts to the carbohydrate restriction aspects of the LCHF diet.



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