ATHEROSCLEROSIS & RED MEAT CONSUMPTION

Kristen Dawidiuk, BSDietetic Intern, Andrews University

March 22, 2019

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Composition:

Water, amino acids, fatty acids, vitamins, and minerals

Sources:

• Cow – beef, veal

• Pig – pork

• Deer - venison

• Lamb

• Elk

• Goat

• Bison

RED MEAT

ATHEROSCLEROSIS – WHAT IS IT?

• Arteriosclerosis – hardening of the arteries

• Atherosclerosis – specific type of arteriosclerosis where lipid plaque buildup cause arteries to narrow and harden

• May begin in childhood, as early as 10 years1

References: 1. McMahan CA, et al. Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis. Pediatrics. 2006 Oct;118(4):1447-55.

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ETIOLOGY & PATHOPHYSIOLOGY

Three stages2

1. 2. 3.

5Reference: 2. Crowther MA. Pathogenesis of Atherosclerosis. Hematology Library Website. Accessed at: http://asheducationbook.hematologylibrary.org/content/2005/1/436.full. Published on January 1, 2005.

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RISK FACTORS

• High blood pressure and cholesterol

• Overweight/obesity

• Inactive lifestyle

• Dietary lifestyle

• Family history

• Male gender

• Smoking

• Stress

• Aging7

DIAGNOSIS• Angiogram, blood tests (HDL, LDL, TG), chest x-ray, CT scan,

Duplex scanning, echocardiogram, exercise stress test

TREATMENT

• Dietary and lifestyle modification

• Medication – statins, blood thinners, ACE inhibitors, calcium channel blockers, beta blockers, diuretics

• Surgical procedures – angioplasty and stent placement, endarterectomy, fibrinolytic therapy, bypass surgery

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PREVENTION

AHA recommendations3:

1. Limiting saturated fat intake to ____ % per day

2. Limiting red meat to _____ times per week

3. Limiting cholesterol to _____ per day

4. ___ minutes of moderate-to-vigorous exercise ___ times/week

5. Maintaining healthy weight/BMI

6. Increasing ____________ type foods

7. ______ smoking

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Reference 3: AHA. The American Heart Association's Diet and Lifestyle Recommendations. AHA Website. Accessed at:

http://www.heart.org/HEARTORG/HealthyLiving/HealthyEating/Nutrition/The-American-Heart-Association-Diet-And-Lifestyle-Recommendations_UCM_305855

_Article.jsp?appName=MobileApp. Published August, 2015.

INTESTINAL MICROBIOTA METABOLISM OF L-CARNITINE, A NUTRIENT IN RED MEAT, PROMOTES ATHEROSCLEROSIS.4

4. Koeth RA, Wang Z, Levison BS, et al. Nat Med. 2013 May; 19(5): 576–585.

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ABSORPTION OF L-CARNITINE

L-carnitine – a derivative of the amino acid, lysine, and ammonium compound

• Sources of L-carnitine –red meat, dairy, fish

• Gets metabolized by gut flora to trimethylamine (TMA)4

• TMA oxidized by liver to trimethylamine n-oxide (TMAO) 4

• TMAO -> atherosclerosis

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STUDY ONE - L-CARNITINE IN OMNIVOROUS DIETS INDUCES AN ATHEROGENIC GUT MICROBIAL PATHWAY IN HUMANS.

Koeth RA, Lam-Galvez BR, Kirsop J, Wang Z, et al. J Clin Invest. 2019 Jan 2; 129(1):373-387.

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OBJECTIVE• Study design:

Case control

• Sample: 30 subjects• 20 omnivore, 10

vegan/vegetarian

• Test whether l-carnitine promotes atherogenic gut microbiota

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METHODS

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• Tested all subjects at baseline• Ingested 250 mg of L-carnitine or 250 mg of γ-

butyrobetaine (γBB)• Plasma samples were then drawn at 0, 2, 4, 6, 8, and 24

hours after the challenge• Underwent broad spectrum antibiotics for 7 days• Second challenge of ingestion of either l-carnitine or

γBB for ~2 months

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RESULTS

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FINDINGS

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• TMAO levels increased in omnivores 20 times greater than vegans/vegetarians ingesting l-carnitine (P = 0.001)

• L-carnitine transforms to TMAO in two ways1. Initial rapid generation of γBB2. Transformation of TMA is converted with low-abundance gut flora in omnivores and remarkably lower in vegans/vegetarians

LIMITATIONS

• Small study

• May not apply to other populations

• Antibiotics alter normal metabolism

• Could not rule out dietary influence on flavin monooxygenase–dependent conversions

• Were not able to measure renal excretion

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STUDY TWO - IMPACT OF CHRONIC DIETARY RED MEAT, WHITE MEAT, OR NON-MEAT PROTEIN ON TMAO METABOLISM AND RENAL EXCRETION IN HEALTHY MEN AND WOMEN.

Wang Z, Bergeron N, Levison BS, et al. Eur Heart J. 2019 Feb 14;40(7):583-594.

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OBJECTIVE

• Study design: Randomized crossover• Sample: 113 subjects - all omnivores• Funded by NHLBI

• To explore the impact of l-carnitine and choline effects and chronic dietary patterns on TMAO levels, metabolism and renal excretion

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METHODS

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METHODS

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• All diets were isocaloric

• Fasting plasma and urine samples were collected on 2 separate days in the last week of each dietary intervention

• Random subset (N= 13) underwent heavy isotope tracer study using oral d6(N,N-dimethyl)-choline and d3(N-methyl)-carnitine challenges during the last week of each experimental diet

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FINDINGS

• A chronic diet enriched in red meat substantially increases plasma and urine trimethylamine N-oxide levels, and may be reversed within 1 month

• Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites

• Isotope tracer studies reveal enhanced microbial production of trimethylamine and trimethylamine N-oxide from carnitine but not choline in subjects following a chronic red meat rich diet

• Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.

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LIMITATIONS

• 2 blood and urine collections

• Blood collection times were also not completely controlled after meals

• Creatinine plasma and urine concentrations were utilized for fractional excretion and varied depending on diet

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STUDY THREE - EFFECTS OF A VERY HIGH SATURATED FAT DIET ON LDL PARTICLES IN ADULTS WITH ATHEROGENIC DYSLIPIDEMIA:A RANDOMIZED CONTROLLED TRIAL

Chiu S, Williams PT, Krauss RM. PLoS One. 2017 Feb 6;12(2): e0170664

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OBJECTIVES

• Study design: Randomized control trial

• Sample: 53 subjects – omnivores

• Both participants and researchers blinded

• Whether the reported effects of saturated fat apply to people with atherogenic dyslipidemia as characterized by small LDL particles (LDL phenotype B)

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METHODS

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• Participants consumed baseline diet for 3 weeks followed by randomization to a low saturated fat (LSF) or high saturated fat (HSF) experimental diet for 3 weeks

• High, low, and non-fat dairy were used as sources of saturated fat.

• All diets were isocaloricallyprepared

FINDINGS

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• HSF diet group had significantly increased plasma TG, and LDL-cholesterol, phenotype B, compared to the LSF group

• No significant changes were found with HDL cholesterol or phenotype A serum levels

• High saturated fat intake was also associated with an increase in total, medium-sized, and small LDL particles

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LIMITATIONS

• Small study

• All participants were LDL phenotype B when enrolled

• Short time frame of dietary patterns measured

• Dairy foods used may not be applicable to other sources of saturated fat

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THE BOTTOM LINE

Further research is needed to conclude these results

CONSIDERATIONS - POSSIBLE SUBSTITUTIONS

• White meat • Fish – mixed results• Non-meat alternatives

• Further research needed

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Reference: Venø SK, Bork CS, Jakobsen MU, et al. Substitution of Fish for Red Meat or Poultry and Risk of Ischemic Stroke. Nutrients. 2018 Nov; 10(11): 1648.

CONSIDERATIONS: MEAT QUALITY

• Close to 95 percent of red meat is factory farmed

• Livestock feed determines quality1,2

• Stress of being in confined spaces

• Hard to identify quality• Antibiotic use

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References : 1. Realini CE, Duckett SK, Windham WR. Effect of vitamin C addition to ground beef from grass-fed or grain-fed sources on color and lipid stability, and prediction of fatty acid composition by near-infrared reflectance analysis. Meat Sci. 2004 Sep;68(1):35-43.2. Calvo L et al. Meat quality, free fatty acid concentration, and oxidative stability of pork from animals fed diets containingdifferent sources of selenium. Food Sci Technol Int. 2017 Dec;23(8):716-728. doi: 10.1177/1082013217718964. Epub 2017 Jul 4.

CONCLUSION & RECOMMENDATIONS

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Reference : Heffron SP, Rockman CB, Adelman MA, Gianos E, Guo Y, Xu JF, Berger JS. Greater Frequency of Fruit and Vegetable Consumption Is Associated With Lower Prevalence of Peripheral Artery Disease. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1234-1240.

• Further research is needed • L-carnitine, TMAO, and saturated fat intake are likely

to be associated with atherosclerosis• Follow AHA recommendations, specifically limiting

red meat to twice a week until more research is concluded

• Eating a variety of nutrient-dense foods, especially plant foods, continue to show evidence for lower risk of atherogenic conditions

“Some people think a whole foods diet is extreme.

Every year, half a million people will have their chests opened up and a vein taken from their leg

and sewn into their coronary artery.

Some people would call that extreme.”

-Dr. Caldwell B. Esselstyn, MD

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