On my tiktok channel (@drterrysimpson or terrysimpson309) putting up a review of red meat the comments are reflective of the polarization that makes politics look like gentle disagreements.

Nutrition is nuanced - meaning, it is rare that something is good or bad for us, except for Death Cap Mushrooms, they will kill you, although I hear they are delicious. The same is true for red meat. What we have are rarely the types of nutrition studies where we feed people precise amounts of food and see the results (the DASH diet studies were great with this -ref 1 ). Instead we rely on what people tell us, which can be accurate, or not - and we look at markers for disease instead of the disease itself (looking at end points of heart disease we look at LDL, cholesterol, C-reactive protein, and rather non-specific markers.

Red Meat and Glycemic Control and Inflammation

In this study (ref 2) they examined the premise that red meat's has an effect on inflammatory markers and glycemic control. So the study  was a meta analysis of randomized control of glycemic control and inflammatory markers.

Adults that were studied were given various quantities of red meats and then checked for glycemic control and inflammation. The end result "Total red meat consumption, for up to 16 weeks, does not affect changes in biomarkers of glycemic control or inflammation for adults free of, but at risk for, cardiometabolic disease. "

Does this put this to bed - not really, but the proposed ill effect of red meat is not something that is seen in these studies.  Here are the markers they studied: glucose, insulin levels, HOMA-R, Hemoglobin A1c, C-reactive protein, IL-6, and TNF-alpha.

This was a group of studies that went to about 16 weeks (four months) so any longer term issues with red or even red processed meats, were not seen. But there were clearly no indication found in these studies.

What about other markers for heart disease?

So the next question is the effect of red meat on lipids, lipoproteins and blood pressure(ref 3)? It turned out that increasing red meat did not affect those variables for heart disease.

What if you check not just red meat, but "red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets."- from ref 4.  They found that changing red meat for plant protein had a minimal effect, and yet other studies (ref 2) found that plant protein had no significant difference at all.

Those short term studies, which are clear changes with specific amounts over a short period of time, appear to contrast with the studies of various groups where they look at the risk of type 2 diabetes and red meat consumption. Take reference 5, where they looked at the increase of diabetes in different groups based on self-reporting of red meat intake. These studies are not as powerful as the controlled trials above, and they are confounded by other variables - people who eat more red meat have higher caloric intake and more obesity, they also tend to drink more and to smoke more. It is not easy to isolate, statistically, those variables out and this is always the issue with large cohort studies.

Take the many studies of the Seventh Day Adventist group, who are considered America's Blue Zone in Loma Linda, California. They don't eat meat, they live longer -- but there is more, that group tends to exercise more, they do not smoke, they do not drink, and they have a strong sense of community. When studied (reference 6) it appears to have an increased in all cause mortality with an increase in red meat and processed meat. But again, a cohort study where it is difficult to refine the variables is not as strong as a study where you feed people precise amounts and look for surrogate markers of disease.

The other issue with following cohort groups is what else they consume. Red meat eaters who increase vegetables have lower long term risk of colo-rectal cancer or as we say - the risk of colon cancer is mitigated by increased vegetable and fibrous foods.  While looking at cohorts of meat eaters they tend not to eat much in the way of this food, in some studies they can account for this, in some studies they cannot and it becomes all the more confusing (ref 7).

When looking at red meat and heart disease, researchers have wondered why poultry doesn't seem to cause an increase in heart disease as red meat. One thought is that it is the increased iron with red meat, or the heme protein. While this has never been proven, and there are no good animal models for this, one unique theory is the reason people who exercise more have less issue with red meat is not only being in shape, but that exercise causes a faster turnover of blood cells allowing less build up of iron and thus less issues with heart disease (reference 8). I know, it is a long way around for a hypothesis that seems interesting and novel but doesn't quite make it out of any laboratory model. But from so many studies in medicine and science, while we can make a perfectly good logical argument, biology often is more elegant than our sense of logic.

Another novel idea is that red meat is as a source of glycation end products which can lead to inflammation.  So stick with me here - " Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis." - from ref 9. These are thought to be a marker, or even one of the terminal pathways for atherosclerosis and perhaps even neuropathy from diabetes. And while it again, makes a logical argument to decrease red meat and inflammation, the studies do not show that a decrease in red meat will actually do this. Again, logic doesn't make biology.

Is it Good or is it Bad?

Isn't that what we all want to know? When the Annals of Internal Medicine published five papers looking at red meat it caused quite a stir, because many were thinking red meat was bad.

The first one (ref 10) looked at 61 articles with 55 cohorts and they found: "Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes." So giving up a bit of meat doesn't have a lot of evidence that it makes a large difference.

What about Cancer?

No one wants cancer, so what about red meat and cancer? Well this brings us to reference 11.  To quote: "Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose-response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer." So we think, with a lot of uncertainty, that reducing intake of meat or processed meat may have a small decrease in mortality from cancer. Is it worth that decrease in risk - we are not certain.

Are you willing to give up red meat?

I mean, it is delicious, but let's look at the data in reference 12. If we cannot say for certain that meat will cause you a problem then most people are not willing to give it up - to quote: "Low-certainty evidence suggests that omnivores are attached to meat and are unwilling to change this behavior when faced with potentially undesirable health effects." So for all the preaching that vegans might do to give up meat, it turns out that meat lovers are not going to change behavior especially given the evidence is pretty weak.

Cancer and Heart Disease and Death

The final of the great five papers was looking at the effect of lower vs higher intake of meat have little or no impact on mortality from heart disease or cancer. To quote "Of 12 eligible trials, a single trial enrolling 48 835 women provided the most credible, though still low-certainty, evidence that diets lower in red meat may have little or no effect on all-cause mortality (hazard ratio [HR], 0.99 [95% CI, 0.95 to 1.03]), cardiovascular mortality (HR, 0.98 [CI, 0.91 to 1.06]), and cardiovascular disease (HR, 0.99 [CI, 0.94 to 1.05]). That trial also provided low- to very-low-certainty evidence that diets lower in red meat may have little or no effect on total cancer mortality (HR, 0.95 [CI, 0.89 to 1.01]) and the incidence of cancer, including colorectal cancer (HR, 1.04 [CI, 0.90 to 1.20]) and breast cancer (HR, 0.97 [0.90 to 1.04])." This is reference 13.

So can I enjoy the steak?

In conclusion you can. The difficulty with red meat is that everyone looks at cigarettes and thinks we have that kind of association, but we don't. You can cherry pick data, but when you look at all the data it is small. Look at the relative risk of eating red meat - it doesn't get to 2, where as the relative risk of cancer from smoking is 20 - and this is a log scale.

This is not the end, we still need real studies with more variables that are able to be controlled in a tight environment, or statistically removed.

If you are obese, don't exercise, and don't otherwise eat well it is different

One thing is clear from a number of studies - if you are overweight, if you don't exercise, if you don't eat a lot of vegetables, legumes, whole grains, and fruits, then eating red meat is not the best choice. Not only is it filled with saturated fat and calorie dense, so it will increase all risk factors - the other variables in your life probably need to change, as they all have their own mortality and morbidity associated with them.

Hey - hit me up on tiktok for comments - join the fray - and listen to the podcast

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Fork U is part of the Your Doctors Orders network of podcasts and is hosted by noted physician and surgeon Dr. Terry Simpson.

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REFERENCES

(1).  Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001 Jan 4;344(1):3-10. doi: 10.1056/NEJM200101043440101. PMID: 11136953.

(2).  O'Connor LE, Kim JE, Clark CM, Zhu W, Campbell WW. Effects of Total Red Meat Intake on Glycemic Control and Inflammatory Biomarkers: A Meta-Analysis of Randomized Controlled Trials. Adv Nutr. 2021 Feb 1;12(1):115-127. doi: 10.1093/advances/nmaa096. PMID: 32910818; PMCID: PMC7850054.

(3).  O'Connor LE, Kim JE, Campbell WW. Total red meat intake of ≥0.5 servings/d does not negatively influence cardiovascular disease risk factors: a systemically searched meta-analysis of randomized controlled trials. Am J Clin Nutr. 2017 Jan;105(1):57-69. doi: 10.3945/ajcn.116.142521. Epub 2016 Nov 23. PMID: 27881394; PMCID: PMC5183733.

(4).  Guasch-Ferré M, Satija A, Blondin SA, Janiszewski M, Emlen E, O'Connor LE, Campbell WW, Hu FB, Willett WC, Stampfer MJ. Meta-Analysis of Randomized Controlled Trials of Red Meat Consumption in Comparison With Various Comparison Diets on Cardiovascular Risk Factors. Circulation. 2019 Apr 9;139(15):1828-1845. doi: 10.1161/CIRCULATIONAHA.118.035225. PMID: 30958719.

(5).  Pan A, Sun Q, Bernstein AM, Manson JE, Willett WC, Hu FB. Changes in red meat consumption and subsequent risk of type 2 diabetes mellitus: three cohorts of US men and women. JAMA Intern Med. 2013 Jul 22;173(14):1328-35. doi: 10.1001/jamainternmed.2013.6633. PMID: 23779232; PMCID: PMC3847817.

(6). Alshahrani SM, Fraser GE, Sabaté J, Knutsen R, Shavlik D, Mashchak A, Lloren JI, Orlich MJ. Red and Processed Meat and Mortality in a Low Meat Intake Population. Nutrients. 2019 Mar 14;11(3):622. doi: 10.3390/nu11030622. PMID: 30875776; PMCID: PMC6470727.

(7) Turner ND, Lloyd SK. Association between red meat consumption and colon cancer: A systematic review of experimental results. Exp Biol Med (Maywood). 2017 Apr;242(8):813-839. doi: 10.1177/1535370217693117. Epub 2017 Jan 1. PMID: 28205448; PMCID: PMC5407540.

(8).  Qi L, van Dam RM, Rexrode K, Hu FB. Heme iron from diet as a risk factor for coronary heart disease in women with type 2 diabetes. Diabetes Care. 2007 Jan;30(1):101-6. doi: 10.2337/dc06-1686. PMID: 17192341.

(9).  Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006 Aug 8;114(6):597-605. doi: 10.1161/CIRCULATIONAHA.106.621854. PMID: 16894049.

(10). Zeraatkar D, Han MA, Guyatt GH, Vernooij RWM, El Dib R, Cheung K, Milio K, Zworth M, Bartoszko JJ, Valli C, Rabassa M, Lee Y, Zajac J, Prokop-Dorner A, Lo C, Bala MM, Alonso-Coello P, Hanna SE, Johnston BC. Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies. Ann Intern Med. 2019 Nov 19;171(10):703-710. doi: 10.7326/M19-0655. Epub 2019 Oct 1. PMID: 31569213.

(11).  Han MA, Zeraatkar D, Guyatt GH, Vernooij RWM, El Dib R, Zhang Y, Algarni A, Leung G, Storman D, Valli C, Rabassa M, Rehman N, Parvizian MK, Zworth M, Bartoszko JJ, Lopes LC, Sit D, Bala MM, Alonso-Coello P, Johnston BC. Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies. Ann Intern Med. 2019 Nov 19;171(10):711-720. doi: 10.7326/M19-0699. Epub 2019 Oct 1. PMID: 31569214.

(12).  Valli C, Rabassa M, Johnston BC, Kuijpers R, Prokop-Dorner A, Zajac J, Storman D, Storman M, Bala MM, Solà I, Zeraatkar D, Han MA, Vernooij RWM, Guyatt GH, Alonso-Coello P; NutriRECS Working Group. Health-Related Values and Preferences Regarding Meat Consumption: A Mixed-Methods Systematic Review. Ann Intern Med. 2019 Nov 19;171(10):742-755. doi: 10.7326/M19-1326. Epub 2019 Oct 1. PMID: 31569219.

(13). Zeraatkar D, Johnston BC, Bartoszko J, Cheung K, Bala MM, Valli C, Rabassa M, Sit D, Milio K, Sadeghirad B, Agarwal A, Zea AM, Lee Y, Han MA, Vernooij RWM, Alonso-Coello P, Guyatt GH, El Dib R. Effect of Lower Versus Higher Red Meat Intake on Cardiometabolic and Cancer Outcomes: A Systematic Review of Randomized Trials. Ann Intern Med. 2019 Nov 19;171(10):721-731. doi: 10.7326/M19-0622. Epub 2019 Oct 1. PMID: 31569236.