Low-Fat Vegan Diets and DiseaseNatalie Mestel NSD 666 Metabolism Fall 2013

Updating a 12-Year Experience With Arrest and Reversal Therapy for Coronary Heart Disease (An Overdue Requiem for Palliative Cardiology) (1985-1999)Caldwell B. Esselstyn, Jr., MD

Medical Surgeries to Treat Heart Disease

• Modern cardiology relies on aggressive interventions [1]

Coronary artery bypass graft: surgery to remove or relieve angina (chest discomfort due to poor blood flow through blood vessels in heart)

Atherectomy: surgically removing atherosclerosis (fat, cholesterol, and other substances build up in walls of arteries and form plaques)

Angioplasty: mechanically widening narrowed or obstructed arteries

Stenting: mesh tube placed in coronary arteries that supply heart to keep arteries open

What Is The Cost of These Procedures?Money• Cost of CVD in 2010: about $444 billion

• CVD treatment accounts for $1 of every $6 spent on health care in U.S [8]

Lives• 1.1% angioplasty, stenting, atherectomy, and 1.3% bypass graft procedures = 240,000

deaths in 1 decade [1]

Author's Argument: • What is being treated are the symptoms, not the disease

• Palliative cardiology: non-treatment of CVD leading to disease extension and fatality [1]

• Total cholesterol levels <150 mg/dl stabilizes and reverses coronary heart disease

• Heart disease rarely seen in cultures that base nutrition on grains, legumes, lentils, vegetables, and fruit

China Study Framingham Heart Study World War II Axis

Epidemiological Basis For StudyThe China Study [4]:• 1983, N=6,500 age 35-64, 65 counties, in 130 villages,

50 adults/village in rural China Rural areas more stable as opposed to cities 90 to 95% born in the county resided at time of survey Consumed locally produced food

• Animal foods tended to increase cholesterol, plant foods decrease cholesterol• Avg. animal pro. intake 0.8% of tot. kcal vs. 11% in

U.S, 64g of protein vs. 91g in U.S, 14.5% tot. kcal fat vs. 34-28% in U.S• No heart disease if total cholesterol below 150

Increased as cholesterol levels went from 150 to 170 Some counties had avg. levels as low as 94 mg/dl Cholesterol good indicator for predicting heart disease

rates• Findings indicate lower percentage of animal-based

foods, greater health benefits, even from 10% to 0% of calories

Epidemiological Basis For Study

• 1940-1945: Axis powers of Germany occupied Norway. Troops took cattle, sheep, goats, pigs, and chickens. Pop. subsisting on plant-based diet

• 1945: War ends, heart disease returns

8 Strom A, Jensen RA. Mortality from circulatory diseases in Norway 1940–1945. Lancet 1951;1:126–129.

Framingham Study [5]: • Purpose: follow development of CVD in large

group w/o CVD symptoms over long-term to identify common contributing factors. Began in 1948

N=5,209 men and women, age 30-62, Massachusetts

Extensive physical exams and lifestyle interviews

1971, Study enrolled second generation of 5,124 of original participants' adult children and spouses

1994, new cohort study to reflect more diverse community

• Results: Participants w/ cholesterol levels between

150-200 mg/dl: 35% of those with coronary disease. Those with cholesterol levels <150 mg/dl, disease is rare

1000 participants at age 50 measured and found to have normal blood pressure. Same group at age 70: 90% have hypertension

World War II [6]:

Initial 5 Year Study to Eliminate CVDStudy Overview• Study 1985-1988

• N=24 age 44-68 (1 woman, 23 men)

Nonsmoking

Non-diabetic

Non-hypertensive

All with severe CVD

• Patients followed plant-based diet <10% calories from fat

No oil, no fish, fowl, meat, or dairy

Encouraged to eat grains, legumes, lentils, vegetables, and fruit

Medications individualized

1985: N=24

18 patients adhered:49

coronary events in 8

years before study

1990: 11 angiographic

analyses

100% disease arrest, 73%

regression, 1 death (not due to

myocardial infarction).

Angina originally reported in 9

eliminated in 2 and improved in 7

1997: 12-year follow up avg. total

cholesterol = 145 mg/dl.

NO CORONARY EVENTS

1997: 12-year follow up 1

patient released

6 patients released

1998: 13 new cardiac events

Goal: to keep total cholesterol <150 mg/dl

Lipid Profiles of 18 Patients At 5 and 12 years

Significance• Results show

nutritional therapy stops rather than slows coronary atherosclerosis

Maintenance 4 Techniques Used

① 60-90 minute interviews with patient and spouse to discuss in-depth objectives upon enrollment

② Bi-weekly visits monitored patients' lipid results for first 5 years. Monthly visits during second 5 year period and quarterly for last 2 years.

③ Calls to each patient after clinic visit to review lipid profile and dietary/medication adjustments.

④ Group meetings several times yearly to review treatment objectives, exchange menus, and socialize. Physician committed to same diet for additional motivation.

Endothelial Cells• Produce Nitric Oxide

Cause Vasodialtion Improves blood flow Prevents platelets adhesion

• Endothelial cell damage due to oxidized LDL ①LDL enters through endothelium②LDL oxidized into pro-inflammatory lipids③Endothelial injured by oxidized LDL ④Monocytes differentiate into macrophages,

consume LDL > now foam cells ⑤Foam cells accumulate, release cytokines >

lead to more plaque formation⑥Endothelial unable to produce NO >

monocytes adhere to endothelial cells, move to sub-endothelium

⑦Endothelial tears lead to propagating blood clot, blocking artery, depriving heart of O2

Nitric Oxide• Nitric Oxide

Causes vasodilation = GOOD! ✓

• Arginine Catalyzes Nitric Oxide Synthase to produce NO = GOOD!

✓

• ADMA: Asymmetric DiMethylArginine Normal byproduct of protein metabolism ADMA competitive inhibitor of nitric oxide synthase =

BAD! ✖• Has a greater affinity to displace arginine• Natural ways to rid ADMA:

Through enzyme DDAH: Dimethyl Arginine, Dimethyl Amino Hydrolase• Hypertension, high triglycerides, insulin resistance,

tobacco smoke, high cholesterol, free radicals lead to oxidative stress will destroy DDAH.

Why Low Fat?Triggers Inflammatory Response

• Diets high in whole grains, plant sterols, soy protein, fiber, low in SFA

and dairy associated lower CRP (C-Reactive Protein) levels

• Ideal ratio of Omega-6 and Omega-3 around 1:1, 2:1, or 3:1 Average in U.S is 10:1, 20:1, or 30:1

• N-3 anti-inflammatory Associated with lower levels of cytokines and IL-6 Due to anti-inflammatory cytokines and series 1 & 3 prostaglandins

• Series 1 and 3 Vasodilation, endurance, oxygen flow, immune system function Pain, cellular proliferation, platelet aggregation

• N-6 pro-inflammatory Thromboxane, peroxide, leukotriene and series 2 prostaglandin

production• Series 2

Vasoconstriction, pain, cellular proliferation, platelet aggregation Endurance, immune system function, oxygen flow

Fiber & Anti-Oxidants Are KeyPlant-based diets

• High in FiberMore bile excreted leads to more LDL-c removed

from blood circulation Viscous fiber interferes with micelle formationFermentation of short chain FA inhibit cholesterol

synthesisFiber lowers insulin spikes which lead to less

active HMG CoA reductase

• High in Anti-Oxidants Flavonoids prevent free radicals (potent oxidizers)

from:• binding to cell receptor to enable NF-KB to make

more cytokines and CAMs

• oxidizing LDL-c within coronary endothelium leading

to plaques

• 50 food products highest in antioxidant concentrations:

13 spices 8 fruits and veggies 5 berries

5 chocolate-based

5 cereals 4 nuts or seeds

[9]

Conclusions About LF Vegan Diets and CVD

• AHA, National Research Council, and National Cholesterol Education Program recommend 30% max for fat calories and total cholesterol <200 mg/dl [1]

CVD develops and progresses within these guidelines!

• Epidemiological evidence based research identifies threshold for coronary artery disease <150 mg/dl

• Threshold can be achieved and maintained with a plant-based diet to reverse and eliminate heart disease.

Lipid-lowering medication used when necessary

Real World Example: My Daddy! Before vegan (0 months):

Total cholesterol = Up to 308 mg/dl

Vegan with oil & processed foods with full dose statins (3 months):

Total cholesterol = 225 mg/dl

No Oil Vegan with half dose statins (6

months):

Total cholesterol = 137 mg/dl

0

50

100

150

200

250

300

350

308

225

137 126

Time (Months)

Total Choles-terol

(mg/dl)

0 3 6 9

Current Status:

COMPLETELY OFF STATINS! (9 months):

Total CHL = 126 mg/dl

Real World Example: My Daddy!

Usefulness of Vegetarian and Vegan Diets for Treating Type 2 Diabetes (2010)Caroline B. Trapp Neal D. Barnard

Low Fat Vegan Diets and Diabetes:Two Adventist Cohort Studies [2] (Snowdon DA, Phillips RL) (onstad S, Butler T, Yan R, Fraser GE)

• N=25,698, and N=22,434 men and 38,469 women

• 1.6-2 times diabetes among non-vegetarians compared with vegetarians and vegans As consumption of animal products , corresponding

prevalence of Type 2 Diabetes

Harvard's Women's Health Study, Nurses' Health Study, Health Professionals' Follow-Up Study [2] (Aune D, Ursin G, Veierod MB)

• Men and women who ate most meat, risk for Type 2 Diabetes Red meat and processed meat associated 21% and 41% risk Progressive worsening renal function associated with animal

protein intake in individuals with some degree renal impairment

Low Fat Vegan Diets and Diabetes22 Week Randomized Trial [2] (Barnard ND, Cohen J, Jenkins DJ et al)

• N=99 with type 2 diabetes Two groups: low- fat vegan diet (n = 49), or portion-controlled omnivorous

diet (n = 50) following 2003 ADA guidelines

• Results: Hemoglobin A1c: Vegan group 1.23 points, ADA group 0.38

points (P=0.01) Body weight: Vegan group 14.3 lb, ADA group 6.8 lb (P =

0.001) LDL cholesterol: Vegan group 22.6 mg/dL (21.2%), ADA group

10.7 mg/dL (9.3%) (P=0.02) Medications: 43% (21/49) of vegan group diabetes medications,

26% (13/50) of ADA group Glycemia & Plasma Lipid: After 74 weeks, same patients showed

better concentrations in vegan study group Urinary Albumin: Vegan group by −15.9 mg per 24 hours, ADA

group by −10.9 mg per 24 hours (P = 0.013)

22

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Low Fat Vegan Diets and DiabetesWeek Pilot Trial [2] (Barnard ND, Cohen J, Jenkins DJ et al)

• 2-week inpatient program included low-fat vegan diet and 30-minute walk per day

• Results: 17 of 21 participants have pain free legs, remaining 4 partial improvement

22 Week Randomized Control Trial [2] (Turner-McGrievy et al.)

• Effect of low vegan diet on overall nutrition

• 3-day dietary records evaluated using Alternative Healthy Eating Index (AHEI) AHEI shown to be reliable predictor of risk of CVD and other major chronic diseases [2]

• Results: Vegan diet led to significant improvements in energy, total fat, trans fat, and cholesterol,

fiber intake, vitamins and minerals, and improved AHEI score ADA group saw no improvement in AHEI score If followed long term, a low-fat vegan diet may reduce risk of major chronic diseases

Con

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HE

I Sco

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• Scores diets based on servings per day of vegetables, fruit, nuts, and soy protein; ratio in grams of white to red meat; grams of cereal fiber; percent of energy from trans fat; ratio in grams of polyunsaturated to saturated fatty acids

Conclusions About LF Vegan Diets and Diabetes

• In observational studies, diabetes prevalence lower in vegans and vegetarians compared with omnivores, with increased prevalence as consumption of animal products increases

• Low-fat vegan diets promote weight loss via improved glycemic control

Associated with hemoglobin A1c reduction

• Plant sources of protein meet daily requirements. Carefully planned low-fat vegan diets are nutritionally adequate and may have a higher diet quality

<10% of energy fat, 10% to 15% protein, 75%-80% carbohydrate [2]

May have additional advantages in terms of promoting satiety through increased fiber

Improved clinical outcomes are achieved without carbohydrate calculations or portion size control, making approach easier patients [2]

Effects of a Very Low-Fat, Vegan Diet in Subjects With Rheumatoid Arthritis (2002)John McDougall, M.D Bonnie Bruce Dr.pH Gene Spiller, Ph.D John Westerdahl, M.P.H., R.D., C.N.S., Mary McDougall

Low Fat Vegan Diets and ArthritisStudy Overview• Purpose: To demonstrate effects of very low-fat vegan diet on patients with RA [3]

• N=24 with moderate (41%) to severe (58%) disease 56+- 11 years old. Women 92% of group None could follow vegan or dairy-free diet 4 weeks before study or have other diseases

• Pre and post tests conducted on degree of pain, limitation in function, morning stiffness due to RA by unbiased rheumatologist

• 4 Week single-blind dietary intervention

• Patients followed plant-based diet No animals products or added oil of any kind Foods to include: beans, breads, corn, pastas, potatoes, sweet potatoes, rice, fruits, vegetables Allowed to eat ad libitum (no calorie restriction) Four weekly meetings held to teach diet

Low Fat Vegan Diets and ArthritisMethods and Results

• Statistical Package for Social Sciences (SPSS) used for statistical analysis. Paired t-test (two-tailed) from baseline to 4 weeks was computed Diet records analyzed by Nutritionist IV program by RD

• Results: Energy intake: +-447 kcal to +-317 kcal daily (p<0.001), % kcal from carbs: 49% (+- 7) to 76% (+- 7)

(p< 0.001), % from fat: 32% (+-6) to 10% (+-5) (p<0.001), % from protein: from 17% (+- 3) to 13% (+- 3) (p<0.001), body weight: from 150 lb (+-42) to 143 lb (+-39.7) (p<0.001)

ESR: Unchanged 50 mm/hr (+-30) to 50 mm/hr (+-28) (p<0.05) C-reactive protein: Non-significant in 2.08 mg/dl (+-1.8) to 1.74 mg/dl (+_1.7) (p> 0.05) Rheumatoid factor: Non-significant 371.5 IU/mL (+-573) to 333.3 IU/mL (+-504) (p> 0.05) Degree of pain: from 49 (+-20) to 34 (+-20) (p<0.004) Limitation in function: from a score of 47 (+-25) to 29 (+-22) (p<0.001) Joint tenderness: score from 24 (+-12) to 17 (+-16) (p<0.01), Joint swelling: from 27 (+-9) to 22 (+-8) (p<

0.02) Morning stiffness: 49 (+-21) to 36 (+-27) (p<0.004)

Mechanisms for Inflammation• High CHL, animal proteins negative effect on

intestine Increased "leaky gut" permeability allows antigens to

enter body More free radicals and large molecules can pass into

blood Food proteins are recognized as foreign

• Triggers antibodies and inflammatory response

• Molecular mimicry

Antibodies directed to foreign protein antigens find similar antigen sites in joint tissues, attacking these tissues, leads to autoimmune diseases

Molecular mimicry in rheumatoid arthritis has been identified with cow’s milk [10]

• Amino acid residues of bovine albumin identified as same as amino acids found in human collagen in joints

• Antibodies synthesized to attack foreign cow’s milk proteins, attack joint tissues because of shared sequences of amino acids

Conclusions About LF Vegan Diets and Arthritis

• Results of study found patients experience dramatic improvement in arthritis symptoms, some with complete remission

• Complete avoidance of food by a water-only fast is most complete method of avoiding exposure to foreign proteins [3]

Fasting with limited amounts vegetable and fruit juices shown to decrease intestinal permeability and avoids dairy proteins found to worsen symptoms [3]

• Problem: Fasting can only be sustained for limited time

• Solution: Low-fat plant-based diets eliminate foods most likely to cause immune reactions

In ConclusionLow-Fat Vegan Diets:• Can help prevent or reverse effects of chronic disease

• Long-term, controlled studies needed

• Evidence of present epidemiological research makes strong case for use of diet in MNT

References• [1] Esselstyn Jr., Caldwell B. M.D., (1999). Updating a 12-Year Experience With

Arrest and Reversal Therapy for Coronary Heart Disease (An Overdue Requiem for Palliative Cardiology). The American Journal of Cardiology. 84: 339-341.

• [2] Trapp, Caroline B., Barnard, Neal D. (2010). Usefulness of Vegetarian and Vegan Diets for Treating Type 2 Diabetes. Current Diabetes Reports. 10: 152-158.

• [3] McDougall, John, M.D., Bruce, Bonnie, PhD., Spiller, Gene, PhD., Westerdahl, John, M.P.H., R.D., C.N.S., McDougall, Mary. (2002).

• {4} Chen J, Campbell TC, Li J, et al. Diet, life-style and mortality in China. A study of the characteristics of 65 Chinese counties. Oxford, UK; Ithaca, NY; Beijing, PRC: Oxford University Press; Cornell University Press; People's Medical Publishing House, 1990.

• [5] (http://www.framinghamheartstudy.org/about/history.html)

• [6] Certificate in Plant-Based Nutrition Course Two: Diseases of Affluence: Heart Disease.(2012). Lecture by Caldwell B. Esselstyn Jr, 1-26

• [7] http://www.sabiosciences.com/pathway.php?sn=LDL_Oxidation_in_Atherogenesis

• [8] (http://www.webmd.com/healthy-aging/features/heart-disease-medical-costs)

• [9] Carlsen, Monica H., Halvorsen, Bente L., Holte, Kari, Bohn, Siv K., Dragland, Steiner, Sampson, Laura, Willey, Carol, Senoo, Haruki, Umezono Yuko, Sanada Chiho, Barikmo, Ingrid, Berhe, Nega, Willett, Walter C., Phillips, Katherine M., Jacobs Jr, David R., Blomhoff, Rune. (2010). The Total Antioxidant Content of More Than 3100 Foods, Beverages, Spices, Herbs, and Supplements Used Worldwide. Nutrition Journal. 9:3

• [10] Perez-Maceda B et al. Antibodies to Dietary Antigens in Rheumatoid Arthritis—Possible Molecular Mimicry Mechanism. Clin Chim Acta 1991;203:153-65.