Animal Foods and Health Risks: Potential Mechanisms in Context

This subsection contextualizes the various potential mechanisms for harm that have been proposed to explain associations between the intake of animal source foods and disease [Hammerling et al. 2016; Jeyakumar et al. 2017; Nordhagen et al. 2020; De Smet & Van Hecke 2024]. As shown below, these mechanisms are largely unproblematic, except for some predisposed populations or when the application of excessive food processing exerts a clear harmful effect. One of the key take-aways is that one needs to be cautious when extrapolating isolated mechanistic outcomes from experimental models to human health, not in the least because data from animal models of metabolic disease need careful evaluation [Klatt et al. 2024]. Moreover, in all cases, a distinction needs to be made between potential hazards and actual risks.

Haem iron from red and processed meat has sometimes been linked in observational studies to higher mortality as well as greater risks of cardiovascular disease, type-2 diabetes and colorectal adenoma. Concerns about cardiometabolic effects centre on the possibility that elevated iron intake raises plasma ferritin and promotes inflammation and insulin resistance, potentially through oxidative stress, ferroptosis, reduced insulin production, foam-cell formation and accelerated ageing. Yet the evidence remains inconsistent: markers of high iron status show no clear association with coronary heart disease, and a Mendelian randomization study even supported the hypothesis that higher iron status may reduce coronary artery disease risk. 

For colorectal cancer the picture is likewise limited. Although haem iron has been proposed to drive carcinogenesis via bacterial N-nitrosation and lipid peroxidation leading to inflammation and DNA damage, human data do not support a straightforward causal link. Comparisons of red versus white meat show similar increases in colonic N-nitrosation, and various large prospective cohorts find little or no association between total, haem, or non-haem iron intakes and colorectal-cancer risk, with results sometimes varying by sex or dietary source. Experimental in vitro and rodent models that demonstrate harmful effects typically employ iron doses far above normal human consumption and diets low in calcium or high in fat; more realistic intakes produce no such effects, and protective dietary factors such as vegetables, olive oil; and calcium can offset potential damage. According to the WCRF, 'the evidence suggesting that the consumption of foods containing haem iron increases the risk of colorectal cancer is limited'.

However, although iron overload is unlikely in most healthy individuals because of tight homeostatic control, it can matter for genetically predisposed people (especially those of Northern-European ancestry). The condition may also affect people that suffer from metabolic disturbances, such as in type-2 diabetic patients due to the suppression of liver hepcidin synthesis, while visceral adiposity contributes to hepcidin-mediated iron deposition and myelin loss with inflammation in the aged brain. In such vulnerable groups, moderating red-meat intake, or using iron chelation and bloodletting when necessary, is advisable.

The idea that Neu5Gc, a signalling molecule in mammalian cells and present in meat and milk, would trigger human antibodies and thereby cause inflammation is speculative. Given that red meat has been a part of human evolutionary diets, such speculation seems highly unlikely.

The conversion of L-carnitine (from meat) or choline (from eggs) into TMAO has been proposed as a mechanism leading to atherosclerosis, but this is likely a red herring. The biological role of TMAO needs to be cautiously considered within a context of complex interactions between diet, gut microbes, and the host. The case becomes more complex when considering the protective effects of fish, which contributes significantly more TMAO than other sources such as meat. Given that both diets rich in fish and whoie grain cereals are known to increase plasma TMAO concentrations, the latter should not be used as a universally valid biomarker of cardiometabolic risk independent of the background diet. Moreover, some studies found no connection between meat and TMAO, especially in a healthy dietary context, while TMAO levels rose in parallel with less healthy plant-based diets. In pigs, a prudent diet with red and processed meat resulted in lower TMAO excretion compared to the same meat-based approach combined with a Western-type background diet. The link between diet, TMAO, and disease is intricate and not as straightforward as it may appear. Factors like cardiometabolic and kidney diseases can elevate TMAO levels, suggesting that observational evidence may be influenced by confounding or reverse causality. 

While the impact of animal source foods on the gut microbiota has been sometimes been portrayed as negative, compared to plant-based diets, this notion has been challenged by an intervention study. Adopting healthy diets lead to a positive shift in gut microbial composition and improved blood lipid profiles, regardless of the inclusion of unprocessed or processed lean red meats. This suggests that the relationship between animal source foods, gut microbiota, and health outcomes is less harmful (if at all) and certainly more complex than often assumed.

The notion that high-protein diets harm kidney and bone health in humans and may promote cancer and type-2 diabetes is not supported by robust evidence in the case of healthy humans. If anything, a generous intake of high-quality protein seems to promote rather than deteriorate health, especially in populations with higher needs, such as older adults. Although animal source foods are rich in certain amino acids like leucine and methionine, which - as such - can theoretically accelerate oxidative stress and aging in excess, there is no clear evidence that this would have harmful effects on cancer risk in healthy humans eating wholesome diets. Moreover, potential negative effects of high-methionine diets can be balanced by higher glycine intake, available through nose-to-tail eating. With respect to type-2 diabetes, there is insufficient evidence for a risk increase with higher intake of animal protein or a risk decrease with plant protein intake, which suggests a lack of effect of protein per se.

Omega-6 fatty acids present in eggs and meats have been (speculatively) linked to inflammation and carcinogenicity. However, the content and types of omega-6 fatty acids, as well as the omega-6/omega-3 ratio, depend on animal feeding methods. Moreover, how all this translates into actual and generalizable health outcomes is uncertain and a topic of debate. Arachidonic acid (AA), an omega-6 fatty acid present in eggs and meats, is sometimes speculatively linked to inflammation and carcinogenicity, although it can also be anti-inflammatory. Consumption of red meat has been associated with circulating AA levels in Chinese adults, which is attributed to pre-formed AA intake rather than its precursor linoleic acid.

Meat processing may create potential carcinogens due to intense smoking or heating (HCA and PAH) or curing (N-nitroso compounds). Yet, evidence on their impact through human diets is mixed. The case against 'processed' meats is less alarming than often stated. It stigmatizes a very heterogenous group of foods, many of which have a long history of consumption in traditional diets, offering valuable nutrition per serving. The 'ultra-processed' variants, however, do require caution. Sodium, often high in processed meats, conflicts with dietary guidelines, but the link between salty foods and health risk is not conclusive for normotensive populations.