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Concept: Red meat

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Red meat consumption has been associated with an increased risk of chronic diseases. However, its relationship with mortality remains uncertain.

Concepts: Cohort study, Chronic, Medicine, Red meat, Epidemiology, Actuarial science

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Growing evidence suggests that effects of red meat consumption on coronary heart disease (CHD) and type 2 diabetes could vary depending on processing. We reviewed the evidence for effects of unprocessed (fresh/frozen) red and processed (using sodium/other preservatives) meat consumption on CHD and diabetes. In meta-analyses of prospective cohorts, higher risk of CHD is seen with processed meat consumption (RR per 50 g: 1.42, 95 %CI = 1.07-1.89), but a smaller increase or no risk is seen with unprocessed meat consumption. Differences in sodium content (~400 % higher in processed meat) appear to account for about two-thirds of this risk difference. In similar analyses, both unprocessed red and processed meat consumption are associated with incident diabetes, with higher risk per g of processed (RR per 50 g: 1.51, 95 %CI = 1.25-1.83) versus unprocessed (RR per 100 g: 1.19, 95 % CI = 1.04-1.37) meats. Contents of heme iron and dietary cholesterol may partly account for these associations. The overall findings suggest that neither unprocessed red nor processed meat consumption is beneficial for cardiometabolic health, and that clinical and public health guidance should especially prioritize reducing processed meat consumption.

Concepts: White meat, Heart, Saturated fat, Coronary artery disease, Pork, Meat, Red meat, Nutrition

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This paper is based on a workshop held in Oslo, Norway in November 2013, in which experts discussed how to reach consensus on the healthiness of red and processed meat. Recent nutritional recommendations include reducing intake of red and processed meat to reduce cancer risk, in particular colorectal cancer (CRC). Epidemiological and mechanistic data on associations between red and processed meat intake and CRC are inconsistent and underlying mechanisms are unclear. There is a need for further studies on differences between white and red meat, between processed and whole red meat and between different types of processed meats, as potential health risks may not be the same for all products. Better biomarkers of meat intake and of cancer occurrence and updated food composition databases are required for future studies. Modifying meat composition via animal feeding and breeding, improving meat processing by alternative methods such as adding phytochemicals and improving our diets in general are strategies that need to be followed up.

Concepts: Cancer, White meat, Red meat, Saturated fat, Livestock, Pork, Meat, Nutrition

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-Epidemiologic studies of red meat consumption in relation to risk of heart failure (HF) are scarce. We examined the associations of unprocessed and processed red meat consumption with HF incidence and mortality in men.

Concepts: Cultural studies, Meat, Red meat

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Dietary guidelines emphasize selecting lean (low-fat) meats to reduce saturated fat and cholesterol, but growing evidence suggests that health effects may relate to other ingredients, such as sodium, heme iron, or L-carnitine. Understanding how meats influence health, and on which nutrients this relationship depends, is essential to advise consumer choices, set guidelines, and inform food reformulations. A recent study published in BMC Medicine involving 448,568 participants in 10 European countries, provides important evidence in this regard. After multivariate adjustment, intake of unprocessed red meat was not significantly associated with total or cause-specific mortality; conversely, intake of processed meat was associated with a 30% higher rate of cardiovascular disease (CVD) (per 50g/day, relative risk 1.30, 95% confidence interval 1.17 to 1.45) and also higher cancer mortality. These findings are consistent with our previous meta-analysis, based on smaller studies, showing strong associations of processed meats, but not unprocessed meats, with CVD. Preservatives are the notable difference; the calculated blood-pressure effects of sodium differences (around 400% higher in processed meats) explain most of the observed higher risk. Although unprocessed red meats seem to be relatively neutral for CVD, healthier choices are available, including fish, nuts, legumes, fruits, and vegetables. Public-health guidance should prioritize avoidance of processed meats, including the low-fat deli meats currently marketed as healthy choices, and the food industry should substantially reduce sodium and other preservatives in processed meats.

Concepts: White meat, Livestock, Health, Pork, Red meat, Saturated fat, Meat, Nutrition

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Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P’s ≤ 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28-2.05; Ptrend = 8.0×10-5), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05-1.59; Ptrend = 0.05) and null among those with the slow phenotype (Ptrend = 0.45). A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans.

Concepts: White American, American Civil War, N-acetyltransferase, N-acetyltransferase 2, Pork, Race, Red meat, Meat

18

A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term consumption of “red meat” of mammalian origin. Although multiple theories have attempted to explain this human-specific association, none have been conclusively proven. We used an improved method to survey common foods for free and glycosidically bound forms of the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc), showing that it is highly and selectively enriched in red meat. The bound form of Neu5Gc is bioavailable, undergoing metabolic incorporation into human tissues, despite being a foreign antigen. Interactions of this antigen with circulating anti-Neu5Gc antibodies could potentially incite inflammation. Indeed, when human-like Neu5Gc-deficient mice were fed bioavailable Neu5Gc and challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Such mice are already prone to develop occasional tumors of the liver, an organ that can incorporate dietary Neu5Gc. Neu5Gc-deficient mice immunized against Neu5Gc and fed bioavailable Neu5Gc developed a much higher incidence of hepatocellular carcinomas, with evidence of Neu5Gc accumulation. Taken together, our data provide an unusual mechanistic explanation for the epidemiological association between red meat consumption and carcinoma risk. This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption.

Concepts: Liver, Epidemiology, Red meat, Protein, Scientific method, Immune system, Cancer, Inflammation

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Recent evidence suggests dietary advice to limit red meat is unnecessarily restrictive and may have unintended health consequences. As nutrient-rich high quality protein foods, red meats can play an important role in helping people meet their essential nutrient needs. Yet dietary advice to limit red meat remains standard in many developed countries, even though red meat intakes appear to be within current guidelines. Meanwhile, energy intakes from processed foods have increased dramatically at the expense of nutrient-rich foods, such as red meat. Research suggests these food trends are associated with the growing burden of obesity and associated diseases in recent decades. It is time for dietary advice that emphasizes the value of unprocessed red meat as part of a healthy balanced diet.

Concepts: Diet, Malnutrition, Health, Pork, Meat, Red meat, Healthy diet, Nutrition

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Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses' Health Study (n = 87,108 women, 1980-2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986-2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01-1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09-1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68-0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92-1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.

Concepts: Nutrition, Hereditary nonpolyposis colorectal cancer, Ulcerative colitis, Red meat, Sigmoidoscopy, Colon, Cancer, Colorectal cancer

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Habitual red meat consumption was consistently related to a higher risk of type 2 diabetes in observational studies. Potentially underlying mechanisms are unclear.

Concepts: Nutrition, Ammonia, Acid, Amine, Amino acid, Metabolism, Diabetes mellitus type 2, Red meat