The Pro-oxidative Risks of a Red Meat Diet

Sahil A. Desai, Mercer University College of Pharmacy

Consuming red meat has been shown to cause a higher risk of premature death [1] and the intake of processed red meat may be more likely to cause coronary heart disease, stroke, and/or diabetes. [2] Meats are stated to be rich in the pro-oxidants heme iron, nitrates, and nitrites which can cause oxidative damage and inflammation in different organs. [3] According to the American Cancer Society (ACS) [4] and American Heart Association (AHA) [5], both unprocessed and processed red meat can increase the risks of cancer and heart disease, respectively. It was recommended that substituting white meat and fish for red meat can reduce the risks of disease development. 

Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study [6]
Design Population-based, prospective cohort; N= 536,969
Objective To determine the correlation of various types of meat intake and their associated compounds with overall and cause specific mortality
Study Groups Divided into 5 groups based on average total red meat intake, g/1000 kcal:

  1. 9.3 (n= 107,393)
  2. 21.3 (n= 107,394)
  3. 31.4 (n= 107,394)
  4. 43.0 (n= 107,394)
  5. 67.5 (n= 107,394)
Methods National Cancer Institute Diet History Questionnaires (DHQ) were sent out to American Association of Retired Persons (AARP) members aged 50-71 from six states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and two metro areas (Atlanta, Georgia; and Detroit, Michigan). These questionnaires collected information on participant’s usual consumption of foods and drinks and portion sizes over the previous 12 months. Exclusion criteria included individuals who moved out of the study areas before returning the questionnaire; members with prevalent cancer, heart disease, stroke, or diabetes before study entry; and those who had 10 or more recording errors on questionnaire.

The meats were differentiated into four categories of unprocessed red meat that included beef, pork, hamburger, and steaks. Processed red meats were defined as bacon, ham, beef cold cuts, hot dogs, and sausages. Unprocessed white meat included unprocessed chicken, turkey, fish, and canned tuna. The final group was processed white chicken which was cold deli poultry, low-fat sausage, and low-fat hot dogs made out of poultry. Meat-associated compound calculations were based on frequency of meat consumption and using established database measurements from published studies and reports.

Follow ups were conducted by confirming the survival status of the patient via Social Security Administration agency statistics and a centralized database used to view causes of death.

Duration 16 year follow up from return of baseline questionnaire
Primary Outcome Measure Mortality from any cause during follow ups
Secondary Outcome Measure Mortality mediation analysis based on heme iron, nitrate, and nitrite
Baseline Characteristics  

Group 1 Group 2 Group 3 Group 4 Group 5
Male, n (%) 48,818 (45.5) 55,869 (52.0) 63,012 (58.7) 70,343 (65.5) 78,463 (73.1)
Mean age, years 62.5 62.5 62.3 62.0 61.5
Race, n (%)
Non-Hispanic White 93,733 (87.3) 97,623 (90.9) 99,051 (92.2) 100,151 (93.3) 100,229 (93.3)
Non-Hispanic Black 6,454 (6.0) 4,641 (4.3) 3,770 (3.5) 3,049 (2.8) 2,606 (2.4)
Mean body mass index 25.8 26.7 27.2 27.6 28.3
Mean energy intake, kcal/day 1,696 1,755 1,827 1,892 1,989
Mean red meat, g/1000 kcal 9.3 21.3 31.4 43.0 67.5
Processed red meat, g/1000 kcal 2.3 5.2 7.9 11.1 17.2
Unprocessed red meat, g/1000 kcal 6.9 16.1 23.5 31.9 50.3
Mean white meat, g/1000 kcal 37.0 33.8 32.5 32.0 32.1
Processed white meat, g/1000 kcal 2.8 2.9 2.9 2.8 2.7
Unprocessed white meat, g/1000 kcal 34.1 30.9 29.6 29.3 29.5
Mean fruit intake, g/1000 kcal 2.4 1.9 1.6 1.4 1.2
Meat-associated compound intake
Mean heme iron, μg/1000 kcal 70.2 121.8 170.3 231.0 372.5
Mean processed meat nitrate, mg/1000 kcal 0.18 0.36 0.53 0.72 1.11
Mean processed meat nitrite, mg/1000 kcal 0.02 0.05 0.08 0.11 0.17

 

Results  

Group 2 Group 3 Group 4 Group 5 (p value)*
Total deaths, n 23,765 25,532 27,321 29,831
Hazard ratios for all red meat intake and mortality (95% confidence interval)*
Overall 1.06 (1.04, 1.08) 1.12 (1.10, 1.14) 1.18 (1.16, 1.20) 1.26 (1.23, 1.29) p< 0.0001
Cancer 1.02 (0.99, 1.05) 1.08 (1.05, 1.12) 1.14 (1.10, 1.18) 1.18 (1.14, 1.23) p< 0.0001
Heart disease 1.07 (1.03, 1.11) 1.12 (1.08, 1.16) 1.18 (1.13, 1.22) 1.27 (1.22, 1.33) p< 0.0001
Respiratory disease 1.25 (1.16, 1.34) 1.47 (1.36, 1.57) 1.54 (1.43, 1.66) 1.83 (1.68, 2.00) p< 0.0001
Stroke 1.04 (0.95, 1.13) 1.11 (1.02, 1.21) 1.21 (1.11, 1.33) 1.17 (1.05, 1.30) p< 0.0001
Diabetes 1.11 (0.98, 1.25) 1.22 (1.08, 1.37) 1.35 (1.19, 1.52) 1.44 (1.26, 1.64) p< 0.0001
Infections 1.06 (0.93, 1.21) 1.08 (0.94, 1.23) 1.23 (1.08, 1.42) 1.24 (1.06, 1.45) p< 0.005
Alzheimer’s disease 0.86 (0.76, 0.98) 0.87 (0.76, 1.00) 0.85 (0.73, 0.99) 0.98 (0.82, 1.16) p= 0.80
Chronic kidney disease 1.06 (0.90, 1.24) 1.23 (1.05, 1.44) 1.29 (1.09, 1.52) 1.47 (1.22, 1.77) p< 0.0001
Chronic liver disease 1.08 (0.86, 1.34) 1.53 (1.23, 1.90) 1.63 (1.30, 2.05) 2.30 (1.78, 2.99) p< 0.0001
Other causes 1.06 (1.01, 1.11) 1.07 (1.02, 1.12) 1.12 (1.07, 1.18) 1.21 (1.14, 1.28) p< 0.0001

*compares the Group 5 hazard ratio vs. Group 1 hazard ratio

Median proportion, % (95% CI) p-value
Heme Iron:
Overall 21.3 (16.5 to 27.1) <0.0001
Cancer 22.8 (13.7 to 35.3) <0.0001
Cardiovascular disease 24.1 (14.4 to 37.4) <0.0001
Respiratory disease 20.9 (13.7 to 30.4) <0.0001
Processed meat nitrate:
Overall 50.1 (36.1 to 64.1) <0.0001
Cancer 37.0 (14.8 to 66.4) <0.005
Cardiovascular disease 72.0 (34.5 to 92.7) <0.0001
Respiratory disease 55.8 (32.4 to 76.8) <0.001
Processed meat nitrite:
Overall None
Cancer None
Cardiovascular disease None
Respiratory disease 14.9 (3.9 to 43.3) 0.10

 

Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Mortality risks from all causes were elevated as consumption of both processed and unprocessed red meats increased. Heme iron, nitrate, and nitrite and other lifestyle choices were suggested for these increased rates. Supplemental data with hazard ratios showed a lower risk of mortality when substituting white meat, more specifically unprocessed white meat.

 

Of concern from this study was the higher proportion of mediation caused by nitrates, substantiating the claim that pro-oxidative compounds other than heme iron play a role in poor health outcomes. Social history, lack of physical activity and reduced fruit and vegetable intake may contribute to certain diseases and death but family history of cancer and use of hormone replacement therapy were not accounted for within the results. Although correlation exists between red meat consumption and increased mortality, baseline characteristics were based on participant response. This is a cause of concern to the analyzed data as this data is more sensitive to bias and less accurate than objective measures.

 

References

[1] Kmietowicz Z. Red meat consumption is linked to higher risk of death from most major causes. BMJ. 2017;357:j2241.

[2] Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation 2010;121:2271-83.

[3] Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: an overview. Meth Enzymol. 1990;186:1-85.

[4] Diet and activity factors that affect risks for certain cancers. American Cancer Society. https://www.cancer.org/healthy/eat-healthy-get-active/acs-guidelines-nutrition-physical-activity-cancer-prevention/diet-and-activity.html. Published February 5, 2017. Accessed May 18, 2017.

[5] Understanding Blood Pressure Readings. American Heart Association.http://www.heart.org/HEARTORG/HealthyLiving/HealthyEating/Nutrition/The-American-Heart-Associations-Diet-and-Lifestyle-Recommendations_UCM_305855_Article.jsp#.WSIVWesrLIW. Published August 2015. Accessed May 18, 2017.

[6] Etemadi A, Sinha R, Ward MH, et al. Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study. BMJ. 2017;357:j1957.

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