Part one of this series outlined that due to the high probability of confounding factors and the low relative risks that are consistently reported in epidemiological studies, it should be considered an embellishment to say that red meat causes cancer or heart disease.
 
When epidemiological evidence indicates that factor A might cause B, research begins to identify mechanistic supporting it.  Even though there is only weak epidemiological evidence against meat, there are several causative mechanistic hypotheses.  This article will review five common mechanistic hypotheses used against red meat. 
 
Saturated Fat

Due to poorly designed studies and several other factors, the idea that saturated fat is bad for us was ingrained into North American society and medical practice for a long time.  Thankfully, recent high-quality research shows that saturated fat is not bad for us and this information is becoming more mainstream.  You are probably already aware of this, so I will move on.
 
Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines (HA) are considered carcinogenic and we are exposed to them in a variety of ways not limited to air pollution, smoking, cooked food, and drinking water.  The main dietary source of HA is cooked meat and the main sources of PAH are cereals, bread, and vegetables.  To be clear, we are exposed to these things from multiple dietary sources, not just meat. 
 
Many factors determine if HA in cooked meat is bad for our health.  First, total exposure to these chemicals, not just from food, is important because our body’s antioxidant system can neutralize a certain amount of them.  Think of the antioxidant system like a funnel and PAH/HA like the water.  If we pour water too fast the funnel will overflow before draining out the bottom.  Chronic overflow is problematic.  Consequently, if you are not over-exposed to these chemicals elsewhere, the amount of HA from eating red meat is likely not a problem.
 
Second, the quality of our diet and lifestyle are important.  Proper antioxidant system function is dependent on multiple nutrients, exercise, sleep, and stress levels.  Along with vitamins and minerals from nutrient-dense whole foods, there are also phytochemicals in plants that support our antioxidant system.  Using the funnel example, if we don’t eat necessary nutrients, our funnel shrinks and cannot hold as much water.  Therefore, choosing nutrient-dense whole foods like vegetables, fruits, nuts, seeds, and quality meat/fish along with exercising, sleeping, and managing stress will help your antioxidant system function properly.
 
Third, well done, charred, and fried meat contain more of these compounds than low temperature baking, braising, boiling, and steaming.  Additionally, because of the antioxidant content in vegetables, meats cooked with rubs, crusts, marinades, and broths containing herbs and spices also reduce HA levels.
 
Not only that, PAH/HA are found in similar amounts in cooked non-red meats which are not linked to cancer and disease in the scientific literature.
 
TMAO

In humans, TMAO is formed from TMA which we get directly from food or through the metabolism of choline, betaine, and carnitine by gut bacteria.  Contrary to what you may have heard, the argument that TMAO causes cardiovascular disease falls short. 
 
Elevated TMAO may be a by-product of cardiovascular disease, meaning that the disease may cause elevated TMAO not the other way around.  Subjects in many of these studies had reduced kidney function, and since TMAO is excreted through the kidneys, reduced kidney function is known to cause elevated TMAO.           
 
Additionally, studies looking at how our diet impacts TMAO levels are inconclusive.  While meat and eggs are the highest sources of carnitine, they do not always raise serum TMAO levels.  Furthermore, fish is the highest source of TMAO/TMA and has been consistently shown to raise serum TMAO levels, yet fish intake is known to reduce cardiovascular disease risk. 
 
Finally, much of the TMAO evidence comes from rodent studies in which the dosages of TMAO provided far exceeds anything that would be possible in a real live human being.   
 
Mammalian Target of Rapamycin (mTOR)

Proper mTOR activity is essential for health but too little mTOR activity will kill us and too much mTOR activity causes chronic diseases including cancer, diabetes, and neurodegeneration.
 
mTOR regulates cell metabolism, growth, division, and survival.  It senses the cellular environment and initiates growth and survival when conditions are right.  It is an important pathway for many things including muscle and structural tissue growth, new cell generation, neuroplasticity/neuron generation/cognitive health, and cellular metabolism.
 
Some say excess meat causes cancer because it contains amino acids which are a key requirement for mTOR activation; however, human studies do not show a connection between dietary amino acid intake and cancer.
 
mTOR responds to multiple factors in the cellular environment, not just amino acids.  mTOR is also activated by growth factors (Insulin and IGF-1), energy status, and inflammation.  Evidence shows that amino acids cannot activate mTOR efficiently without the presence of insulin or IGF-1.  This means that for excessive activation of mTOR, excess amino acids and growth factors must both be present in addition to a possible contribution from inflammation.   
 
To wrap this up, protein is necessary for mTOR activity but cannot do it alone.  Insulin, IGF-1, and inflammation also activate mTOR in the presence of amino acids.  Protein is essential for muscle, bone, hormonal, and neurological health, which are important health factors as we age.  Therefore, due to its importance for health, protein does not appear to be the major problem with mTOR, high insulin, IGF-1, and chronic inflammation are better candidates.  The type of diet that raises insulin, IGF-1, and inflammation is one that causes obesity, metabolic syndrome, and diabetes; high sugar, high refined/nutrient-poor foods, and excessive calories.  Therefore, dietary factors preventing metabolic syndrome are more important than worrying about meat intake.
 
Heme iron

Iron is essential for our health.  It is involved in the transport and storage of oxygen and too many other functions to list.  However, excessive iron can cause inflammation and oxidative stress and is linked to multiple chronic diseases such as cancer, diabetes, and cardiovascular disease.
 
There are 2 types of dietary iron, heme and non-heme.  Our body absorbs more heme than non-iron which we get mainly from red meat.  Therefore, some say red meat is bad for us because it causes excess iron in our bodies.  While there is a small portion of people with a genetic predisposition to iron overload/hemochromatosis they are not representative of the general public.
 
There is evidence from petri dish and animal studies that excess heme iron may contribute to cancer.  However, there is criticism of whether these findings apply to humans due to flaws in study design.   Most animal studies use isolated forms of heme which do not accurately represent the chemical make-up of heme iron found in red meat.  Furthermore, researchers in most studies fed animals the equivalent of 9 to 225 times the amount of heme that is contained in the average human diet.  Therefore, findings from such studies cannot reasonably be applied to humans.
 
Additionally, diets used in rodent models are purified which helps researchers control the intake of nutrients.  However, this creates problems when assuming the findings apply to humans whose diet contains many vitamins, minerals, and phytochemicals that protect against possible damaging effects of excess heme intake.  
 
It`s also well known that beneficial gut bacteria play a role in protecting our gut lining from cancerous substances such as heme iron.  Since the human and rodent gut microbiota differs significantly it’s hard to apply animal study findings to humans.    
 
Probably the most recent review study on this topic concluded that there is insufficient evidence to indicate that heme contributes to an increased risk of colon cancer in the context of a normal diet.
 
So, there you have it, neither the epidemiological nor mechanistic evidence available to date shows that red meat is bad for our health in the context of a healthy human diet.  As I always say, the most important focus should be eating nutrient-dense whole foods (vegetables, meat/fish, nuts/seeds, and fruits) while avoiding refined, ultra-processed, nutrient-poor foods.