Plant Based Diet, Health Benefits for Coronary Artery Disease

by Jeffrey Dach MD

At the recent ICM meeting “Matters of the Heart” in Philadelphia March 6-8, 2019, one of the little known secrets of integrative cardiology was revealed.  The plant based diet can prevent and reverse coronary artery disease.

Case Reports

A few case reports in the medical literature are illustrative:  In 2015, Dr Massera reported on a 60 year old male with typical angina and a positive stress test who declined both drug therapy and invasive treatment.  His symptoms resolved promptly on a plant based diet. (13)

” A 60-year-old man presented with typical angina and had a positive stress test. He declined both drug therapy and invasive testing. Instead, he chose to adopt a whole-food plant-based diet, which consisted primarily of vegetables, fruits, whole grains, potatoes, beans, legumes, and nuts. His symptoms improved rapidly, as well as his weight, blood pressure, and cholesterol levels.” endquote(13)

Here is another 2017 case report from Dr Daniela Massera of a 77 year old female with unstable angina who declined bypass surgery.  Her symptoms resolved on a plant based diet.: (12)

“A 77-year-old hypertensive female with unstable angina was taking atenolol 50 mg and simvastatin 20 mg daily.  She had chest pain (angina) with mild exercise whihc resolved at rest. Coronary angiography showed severe triple vessel disease with normal left ventricular unction (Normal EF).   The patient declined treatment with Cardiac bypass surgery.  Instead she changed her diet from a “healthy western” to a whole-food plant-based diet, (all vegetables, fruits, whole grains, potatoes, beans, legumes and nuts. She avoided all animal products, eggs, dairy, meat.  One month later, symptoms had resolved and the patient could walk on treadmill form 50 minutes without chest pain.”(12)

A third case is a 79 year old male who has an improvement in Left Ventricular function on a plant based diet.(11)  Three more case reports were published by Dr Esselstyn in 2004.(14)

40% Reduction in Mortality from Cardiovascular Disease

According to Dr Kahleova in 2018, Plant Based Diet reduces mortality from Cardiovascular Disease by 40%, the only diet to reverse coronary artery disease, as well as beneficial for weight loss, metabolic syndrome, and type 2 diabetes.(3-4)(9):

“Vegetarian dietary patterns reduce CVD mortality and the risk of coronary heart disease (CHD) by 40%. Plant-based diets are the only dietary pattern to have shown reversal of CHD. Additionally, evidence suggests benefits of vegetarian dietary patterns in both the prevention and the treatment of heart failure and cerebrovascular disease. Plant-based diets are associated with lower blood pressure, lower blood lipids, and reduced platelet aggregation than non-vegetarian diets and are beneficial in weight management, reduce the risk of developing metabolic syndrome, and type 2 diabetes. They have also been shown an effective treatment method in diabetes management.” (3-4)

What is a Plant Based Diet ?

Dr Robert Ostfeld in Geriatric Cardiology 2017 gives us the definition of a Plant Based Diet:  “All minimally processed fruits, vegetables, whole grains, legumes, nuts and seeds, herbs, and spices and excludes all animal products, including red meat, poultry, fish, eggs, and dairy products.”(5)

Benefits for Weight Loss, and Obesity

In 2017 Dr Turner-McGrievy reports that:

“Both clinical trials and observational research indicate advantage of PBDs (Plant Based Diets) for preventing obesity and promoting weight loss.”(6)

A 2017 study in New Zealand showed Plant Based Diet was excellent for weight loss.(7) Another study in 2017 by Dr. Haghighatdoost, showed reduction in CRP for those on plant based diet.(8)

Caldwell B Esselstyn Jr. Advocate of Plant Based Diet

Perhaps Dr Esselstyn is one of the strongest and most dedicated advocates of the Plant Based Diet over many years now.(10)(14)(17-19)(22-23) His many studies and publications extolling the benefits of the plant based diet for preventing and reversing heart disease, and argue for implementing the plant based diet for patients with coronary artery disease as the most logical and rational alternative to invasive procedures.  In spite of Dr Esselstyn’s valiant efforts to convince mainstream cardiologists of the merits of a plant based diet, his message has been largely ignored.  Another advocate of the Plant Bases Diet is Dr Phillip Tuso.(15-16)  He says:

“Changing from a Western diet to a plant-based diet may be a simple, low-cost intervention that prevents atherothrombotic CAD…..Physicians should consider recommending a plant-based diet to all their patients, especially those with high blood pressure, diabetes, cardiovascular disease, or obesity.”(15-16)

My previous articles discuss the idea that coronary artery disease is caused by infection, and that atherosclerotic plaque is polymicrobial biofilm caused by endotoxemia arising from “leaky gut” and periodontal disease.(29)   Indeed, the enteric bacteria, E. Coli,  has been found in atherosclerotic plaques.(26)  Metabolic endotoxemia has other pathological effects, one of which we see commonly is low testosterone in males caused by hypothalamic dysfunction.(27-28)

Fatty Meal Causes Endotoxemia – no Animal Fat in Plants

Consumption of animal products, especially animal fat has been associated with postprandial endotoxemia.  Diabetics and the obese seem most sensitive to this.(31-38)  Needless to say, a plant based diet avoids these episodes of excess postprandial endotoxemia, since no animal products or fats are consumed.

Anti-Inflammatory and Antimicrobial Substances in Plants

Another benefit of the plant based diet is the anti-inflammatory and antimicrobial substances in plants.(8)

Conclusion

In conclusion, here is a quote from Dr Esselstyn. He says: (10)

“Despite overwhelming evidence for the safety, simplicity, and efficacy of plant nutrition to halt and prevent coronary artery disease, the cardiovascular medicine community has failed to embrace this option of therapy and persists in palliative treatments associated with high morbidity, mortality, and expense. It is long overdue to question why.”(10)

Jeffrey Dach MD
7450 Griffin Road Suite 180/190
Davie, Florida 33314
954-792-4663

Articles With Related Interest

Books:

Kahn, Joel K. The Plant-based Solution: America’s Healthy Heart Doc’s Plan to Power Your Health. Sounds True, 2018

Above Header  image courtesy of : Prev Cardiol. 2001 Autumn;4(4):171-177. Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.  Esselstyn CB Jr1.  Fig 1 LAD Before (Red) and after (green) Plant based diet for 32 months without cholesterol lowering medication.

.links and references

1)  6 Ways to Kick Off a Plant-Based Diet  by Joel Kahn MD

2)  5 Questions with Dr. Joel Kahn, Leading Cardiologist and Author of The Plant-Based Solution  Max Goldberg February 11, 2018 living max well

The love of animal products raised on grass or grain-fed is a dinosaur that will be soon be considered barbaric and primitive, like 8-track tape players. Slowly the functional medicine world will get it.

2018

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3) Prog Cardiovasc Dis. 2018 May – Jun;61(1):54-61.Vegetarian Dietary Patterns and Cardiovascular Disease. Kahleova H, Levin S1, Barnard ND2.

Cardiovascular (CV) disease (CVD) is the leading global cause of mortality, being responsible for 46% of non-communicable disease deaths. It has been estimated that about 85.6 million Americans are living with some form of CVD, which continues to rise. Healthy lifestyle choices may reduce the risk of myocardial infarction by >80%, with nutrition playing a key role. Vegetarian dietary patterns reduce CVD mortality and the risk of coronary heart disease (CHD) by 40%. Plant-based diets are the only dietary pattern to have shown reversal of CHD. Additionally, evidence suggests benefits of vegetarian dietary patterns in both the prevention and the treatment of heart failure and cerebrovascular disease. Plant-based diets are associated with lower blood pressure, lower blood lipids, and reduced platelet aggregation than non-vegetarian diets and are beneficial in weight management, reduce the risk of developing metabolic syndrome, and type 2 diabetes. They have also been shown an effective treatment method in diabetes management. Well planned vegetarian diets provide benefits in preventing and reversing atherosclerosis and in decreasing CVD risk factors and should be promoted through dietary guidelines and recommendations.

4) Kahleova, Hana, Susan Levin, and Neal Barnard. “Cardio-Metabolic Benefits of Plant-Based Diets.” Nutrients 9.8 (2017).
Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan) diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also reduce the risk of developing metabolic syndrome and type 2 diabetes by about one half. Properly planned vegetarian diets are healthful, effective for weight and glycemic control, and provide metabolic and cardiovascular benefits, including reversing atherosclerosis and decreasing blood lipids and blood pressure. The use of plant-based diets as a means of prevention and treatment of cardio-metabolic disease should be promoted through dietary guidelines and recommendations.

Plant-based diets are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease [6].Plant-based diets are characterized by a reduction or elimination of animal product consumption. They are typically based on the consumption of grains, legumes, vegetables, fruits, and nuts. Vegan diets contain only plant foods, while lacto-ovo-vegetarian diets include dairy and/or egg products.

Plant-based diets have been shown to be a particularly effective dietary approach for weight loss [29,30]. A recent study showed a mean BMI reduction of 4.4 kg/m2 with a 6-month, whole-food, plant-based diet with no energy restrictions, compared with usual care (0.4 kg/m2), in overweight or obese subjects [31].
Plant-based diets appear to reduce the risk of developing metabolic syndrome by about one half [33].
Vegetarian diets have been shown to be helpful not only in prevention but also in the treatment of type 2 diabetes in several clinical trials.
A recent meta-analysis of six randomized controlled trials showed that consumption of vegetarian diets was associated with a significant reduction in HbA1c by 0.4 absolute percentage points, compared with conventional diets in patients with type 2 diabetes [41].
In randomized controlled trials, vegetarian diets decreased both systolic and diastolic blood pressure by 4.8 and 2.2 mm Hg, respectively [78].

2017

Definition of a plant-based diet

5) Ostfeld, Robert J. “Definition of a plant-based diet and overview of this special issue.” Journal of geriatric cardiology: JGC 14.5 (2017): 315.
1. Definition of a plant-based diet: A plant-based diet consists of all minimally processed fruits, vegetables, whole grains, legumes, nuts and seeds, herbs, and spices and excludes all animal products, including red meat, poultry, fish, eggs, and dairy products.

6) Turner-McGrievy, Gabrielle, Trisha Mandes, and Anthony Crimarco. “A plant-based diet for overweight and obesity prevention and treatment.” Journal of geriatric cardiology: JGC 14.5 (2017): 369.
The goal of this paper is to review the evidence related to the effect of plant-based dietary patterns on obesity and weight loss, including both observational and intervention trials. Literature from plant-based diets (PBDs) epidemiological and clinical trial research was used to inform this review. In addition, data on dietary quality, adherence, and acceptability were evaluated and are presented. Both clinical trials and observational research indicate an advantage to adoption of PBDs for preventing overweight and obesity and promoting weight loss. PBDs may also confer higher levels of diet quality than are observed with other therapeutic diet approaches, with similar levels of adherence and acceptability. Future studies should utilize health behavior theory to inform intervention development and delivery of PBDs studies and new technologies to bring interventions to scale for greater public health impact. Research examining PBDs and weight loss is also needed with more diverse populations, including older adults. Based on the available evidence, PBDs should be considered a viable option for the treatment and prevention of overweight and obesity.

7) Wright, N., et al. “The BROAD study: A randomised controlled trial using a whole food plant-based diet in the community for obesity, ischaemic heart disease or diabetes.” Nutrition & Diabetes 7.3 (2017): e256.

PBD – Lower CRP Levels

8) Haghighatdoost, Fahimeh, et al. “Association of vegetarian diet with inflammatory biomarkers: a systematic review and meta-analysis of observational studies.” Public health nutrition 20.15 (2017): 2713-2721.

Objective:  Vegetarian diets contain various anti-inflammatory components. We aimed to investigate the effects of vegetarianism on inflammatory biomarkers when compared with omnivores.

Literature search was conducted in Science Direct, Proquest, MEDLINE and Google Scholar up to June 2016. Summary estimates and corresponding 95 % CI were derived via the DerSimonian and Laird method using random effects, subgroup analyses were run to find the source of heterogeneity and a fixed-effect model examined between-subgroup heterogeneity.
Subjects  Studies were included if they evaluated effects of any type of vegetarianism compared with omnivores on circulating levels of inflammatory biomarkers. No restriction was made in terms of language or the date of study publications.
Results  Eighteen articles were included. Pooled effect size showed no difference in high-sensitivity C-reactive protein (hs-CRP) levels in vegetarians v. omnivores (Hedges’ g=−0·15; 95 % CI −0·35, 0·05), with high heterogeneity (I 2=75·6 %, P<0·01). A subgroup analysis by minimum duration of vegetarianism showed that a minimum duration of 2 years vegetarianism was associated with lower hs-CRP levels v. omnivores (Hedges’ g=−0·29; 95 % CI −0·59, 0·01), with moderate heterogeneity (I 2=68·9 %, P<0·01). No significant effect was found in studies using a minimum duration of 6 months of vegetarianism, with low heterogeneity. Vegetarianism was associated with increased IL-6 concentrations (0·21 pg/ml; 95 % CI 0·18, 0·25), with no heterogeneity (I 2=0·0 %, P=0·60).
Conclusions  The meta-analysis provides evidence that vegetarianism is associated with lower serum concentrations of hs-CRP when individuals follow a vegetarian diet for at least 2 years. Further research is necessary to draw appropriate conclusions regarding potential associations between vegetarianism and IL-6 levels. A vegetarian diet might be a useful approach to manage inflammaging in the long term.

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9) Harland, J., and L. Garton. “An update of the evidence relating to plant‐based diets and cardiovascular disease, type 2 diabetes and overweight.” Nutrition bulletin 41.4 (2016): 323-338.

Recent findings from meta‐analyses, European cohorts and randomised controlled trials (RCTs) evaluating the relationship between plant‐based dietary regimes (i.e. those with an emphasis on plant foods, such as vegetarian, vegan, Mediterranean or combination diets), and the incidence of, or risk factors for, cardiovascular disease (CVD), type 2 diabetes (T2D) and obesity are considered in this review. Evidence from meta‐analyses of epidemiological studies indicates that those following plant‐based dietary regimes have around 20–25% lower risk of developing CVD and a similar reduced risk of developing T2D. Evidence from RCTs indicates that those following plant‐based dietary regimes have lower total cholesterol, low‐density lipoprotein‐cholesterol and blood pressure, and modest reductions in inflammatory and endothelial markers. Higher intake of plant foods has been associated with lower incidence of obesity, lower BMI and smaller waist circumference. For weight loss, it seems that following a plant‐based dietary regime results in weight loss comparable to that achieved on conventional reduced calorie diets, but with better overall weight management. The totality of evidence indicates there are benefits for cardiovascular health, risk of developing T2D and weight management from following a plant‐based dietary regime. From a nutritional perspective, plant‐based diets tend to be lower in saturated fatty acids, higher in unsaturated fatty acids and fibre, and lower in energy density than typical ‘Western’ diets. These qualities may be at the core of the health benefits reported and/or it may be simply a greater proportion of plant foods in the diet that is beneficial in its own right.

Esselstyn

10) Esselstyn Jr, Caldwell B. “Defining an Overdue Requiem for Palliative Cardiovascular Medicine.” American journal of lifestyle medicine 10.5 (2016): 313-317.

During the past 40 years, we have witnessed significant advances in the pharmaceutical and interventional treatment of cardiovascular disease (CVD), which have helped achieve a decrease in morbidity and mortality for this illness. Nevertheless, CVD remains the number 1 killer of women and men in Western civilizations. This fact is in stark contrast to the scenario in multiple whole food, plant-based nutrition (WFPBN) cultures, where CVD is virtually nonexistent. The utility of plant-based nutrition to halt and prevent CVD has been demonstrated epidemiologically, during wartime deprivation, in large cohort and population transitioning studies, and through prospective randomized and nonrandomized investigations. A basic scientific study confirms that omnivores have intestinal bacteria capable of converting animal food to trimethylamine oxide (TMAO), which injures blood vessels, whereas those eating plants only do not have intestinal bacteria capable of producing TMAO. Despite this overwhelming evidence for the safety, simplicity, and efficacy of plant nutrition to halt and prevent coronary artery disease, the cardiovascular medicine community has failed to embrace this option of therapy and persists in palliative treatments associated with high morbidity, mortality, and expense. It is long overdue to question why.

2017 case report

11) Choi, Evan Y., et al. “A plant-based diet and heart failure: case report and literature review.” Journal of geriatric cardiology: JGC 14.5 (2017): 375.

2016

12) Massera, Daniele, et al. “Angina rapidly improved with a plant-based diet and returned after resuming a Western diet.” Journal of geriatric cardiology: JGC 13.4 (2016): 364.
In summary, a whole-food plant-based diet was associated with reversing angina symptoms in our patient with severe coronary atherosclerotic disease Her angina returned when she resumed consuming a ‘healthy’ Western diet.

2015 CASE REPORT !!!!!!!!!!

13)  Case Rep Cardiol. 2015;2015:978906.   A Whole-Food Plant-Based Diet Reversed Angina without Medications or Procedures. Massera D1, Zaman T2, Farren GE3, Ostfeld RJ1.

A 60-year-old man presented with typical angina and had a positive stress test. He declined both drug therapy and invasive testing. Instead, he chose to adopt a whole-food plant-based diet, which consisted primarily of vegetables, fruits, whole grains, potatoes, beans, legumes, and nuts. His symptoms improved rapidly, as well as his weight, blood pressure, and cholesterol levels. Plant-based diets have been associated with improved plasma lipids, diabetes control, coronary artery disease and with a reduction in mortality. Adoption of this form of lifestyle therapy should be among the first recommendations for patients with atherosclerosis.

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14) Esselstyn, Caldwell, and Mladen Golubic. “The Nutritional Reversal of Cardiovascular Disease “Fact or Fiction? Three Case Reports.” (2014). Nutritional Reversal of Cardiovascular Disease Fact or Fiction Esselstyn Three Case Reports 2014

15) Tuso, Phillip, Scott R. Stoll, and William W. Li. “A plant-based diet, atherogenesis, and coronary artery disease prevention.” The Permanente Journal 19.1 (2015): 62.

A plant-based diet is increasingly becoming recognized as a healthier alternative to a diet laden with meat. Atherosclerosis associated with high dietary intake of meat, fat, and carbohydrates remains the leading cause of mortality in the US. This condition results from progressive damage to the endothelial cells lining the vascular system, including the heart, leading to endothelial dysfunction. In addition to genetic factors associated with endothelial dysfunction, many dietary and other lifestyle factors, such as tobacco use, high meat and fat intake, and oxidative stress, are implicated in atherogenesis. Polyphenols derived from dietary plant intake have protective effects on vascular endothelial cells, possibly as antioxidants that prevent the oxidation of low-density lipoprotein. Recently, metabolites of L-carnitine, such as trimethylamine-N-oxide, that result from ingestion of red meat have been identified as a potential predictive marker of coronary artery disease (CAD). Metabolism of L-carnitine by the intestinal microbiome is associated with atherosclerosis in omnivores but not in vegetarians, supporting CAD benefits of a plant-based diet. Trimethylamine-N-oxide may cause atherosclerosis via macrophage activation. We suggest that a shift toward a plant-based diet may confer protective effects against atherosclerotic CAD by increasing endothelial protective factors in the circulation while reducing factors that are injurious to endothelial cells. The relative ratio of protective factors to injurious endothelial exposure may be a novel approach to assessing an objective dietary benefit from a plant-based diet. This review provides a mechanistic perspective of the evidence for protection by a plant-based diet against atherosclerotic CAD.

changing from a Western diet to a plant-based diet may be a simple, low-cost intervention that prevents atherothrombotic CAD.

16) Tuso, Philip J., et al. “Nutritional update for physicians: plant-based diets.” The Permanente Journal 17.2 (2013): 61.

We present a case study as an example of the potential health benefits of such a diet. Research shows that plant-based diets are cost-effective, low-risk interventions that may lower body mass index, blood pressure, HbA1C, and cholesterol levels. They may also reduce the number of medications needed to treat chronic diseases and lower ischemic heart disease mortality rates. Physicians should consider recommending a plant-based diet to all their patients, especially those with high blood pressure, diabetes, cardiovascular disease, or obesity.

2014

Nice images !!!!!

17) J Fam Pract. 2014 Jul;63(7):356-364b.  A way to reverse CAD? Esselstyn CB Jr1, Gendy G, Doyle J, Golubic M, Roizen MF.

Plant-based nutrition achieved coronary artery disease (CAD) arrest and reversal in a small study. However, there was skepticism that this approach could succeed in a larger group of patients. The purpose of our follow-up study was to define the degree of adherence and outcomes of 198 consecutive patient volunteers who received counseling to convert from a usual diet to plant-based nutrition.
METHODS:  We followed 198 consecutive patients counseled in plant-based nutrition. These patients with established cardiovascular disease (CVD) were interested in transitioning to plant-based nutrition as an adjunct to usual cardiovascular care. We considered participants adherent if they eliminated dairy, fish, and meat, and added oil.
RESULTS:Of the 198 patients with CVD, 177 (89%) were adherent. Major cardiac events judged to be recurrent disease totaled one stroke in the adherent cardiovascular participants—a recurrent event rate of .6%, significantly less than reported by other studies of plant-based nutrition therapy. Thirteen of 21 (62%) nonadherent participants experienced adverse events.
CONCLUSION:Most of the volunteer patients with CVD responded to intensive counseling, and those who sustained plant-based nutrition for a mean of 3.7 years experienced a low rate of subsequent cardiac events. This dietary approach to treatment deserves a wider test to see if adherence can be sustained in broader populations. Plant-based nutrition has the potential for a large effect on the CVD epidemic.

18) Prev Cardiol. 2001 Autumn;4(4):171-177. Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.  Esselstyn CB Jr1.
The world’s advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world’s poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to

19) Esselstyn Jr, Caldwell B. “Is the Present Therapy for Coronary Artery Disease the Radical Mastectomy of the Twenty-First Century?.” Curr Surg 60 (2003): 329-337. Present Therapy for Coronary Artery Disease the Radical Mastectomy of the Twenty First Century Caldwell B Esselstyn

20) JAMA. 1998 Dec 16;280(23):2001-7. Intensive lifestyle changes for reversal of coronary heart disease.  Ornish D1, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, Brand RJ.JAMA 1999 Apr 21;281(15):1380.

The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year.
OBJECTIVES:  To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease.
DESIGN:  Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design.
PATIENTS:  Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography.
SETTING: Two tertiary care university medical centers.
INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years.
MAIN OUTCOME MEASURES:  Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events.
RESULTS:  Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]).
CONCLUSIONS:  More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.

21) Circulation. 1999 Feb 16;99(6):779-85.Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.
de Lorgeril M1, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N.

The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence.
METHODS AND RESULTS:

Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95 events versus 180, P=0. 0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9×10(9)/L), female sex (adjusted risk ratios, 0.27 to 0. 46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence.
CONCLUSIONS:  The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted.

22) Dr. Esselstyn’s landmark heart disease reversal program. Success Stories

23) Esselstyn Jr, Caldwell B. “The Hoffman Centre for Integrative Medicine.” Patient Handout 2011
http://www.hoffmancentre.com/wp-content/uploads/2016/12/coronary_artery_disease_present_therapy_patient_handout.pdf

24)  Kahn, Joel K. The Plant-based Solution: America’s Healthy Heart Doc’s Plan to Power Your Health. Sounds True, 2018.

Probiotic Reduces Endotoxemia

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25) Sabico, Shaun, et al. “Effects of a 6-month multi-strain probiotics supplementation in endotoxemic, inflammatory and cardiometabolic status of T2DM patients: A randomized, double-blind, placebo-controlled trial.” Clinical Nutrition (2018).

Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-a (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (-3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers.
Conclusion: Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy.

The probiotics group was allocated with sachets [2 g freeze-dried powder of the probiotic mixture Ecologic®Barrier (Winclove probiotics, the Netherlands) (2.5 × 109 cfu/g)] which contains the following strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 and L. lactis W58. This probiotic combination has been previously investigated for its ability to improve endothelial barrier and its potency to inhibit mast cell activation, inhibit pro-inflammatory cytokines decrease endotoxin load [20].

Finding LPS from E Coli in Atherosclerotic Plaque

26) Carnevale, Roberto, et al. “Localization of lipopolysaccharide from Escherichia Coli into human atherosclerotic plaque.” Scientific reports 8.1 (2018): 3598.

Experimental studies showed that gut-derived lipopolysaccharide (LPS) is pro-atherogenic, however, its relationship with human atherosclerosis is still to be defined. We investigate if gut-derived LPS from Escherichia Coli localizes in human carotid plaque and its potential role as pro-inflammatory molecule in the atherosclerotic lesion. LPS from Escherichia Coli and Toll-like receptor 4 (TLR4) were studied in specimens from carotid and thyroid arteries of 10 patients undergoing endarterectomy and 15 controls matched for demographic and clinical characteristics. Blood LPS were significantly higher in patients compared to controls. Immunochemistry analysis revealed positivity for antibodies against LPS and TLR4 coincidentally with positivity for CD68 only in the atherosclerotic plaque of carotid arteries but not in thyroid arteries; the positivity for LPS and TLR4 was greater in the area with activated macrophages. LPS concentration similar to that detected in atherosclerotic plaque resulted in a dose-dependent TLR4-mediated Nox2 up-regulation by human monocytes. These data provide the first evidence that LPS from Escherichia Coli localizes in human plaque and may contribute to atherosclerotic damage via TLR4-mediated oxidative stress.

Endotoxemia and HPA Dysfunction

27) Tremellen, Kelton, Natalie McPhee, and Karma Pearce. “Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men.” Basic and clinical andrology 27.1 (2017): 5.

28) Tremellen, Kelton. “Gut Endotoxin Leading to a Decline IN Gonadal function (GELDING)-a novel theory for the development of late onset hypogonadism in obese men.” Basic and Clinical Andrology 26.1 (2016): 7.

Gut LPS Increased Risk of CV Event

29) Pastori, Daniele, et al. “Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet.” Journal of the American Heart Association 6.6 (2017): e005784.

Postprandial Endotoxemia

30) Vors, Cécile, et al. “Postprandial endotoxemia linked with chylomicrons and lipopolysaccharides handling in obese versus lean men: a lipid dose-effect trial.” The Journal of Clinical Endocrinology & Metabolism 100.9 (2015): 3427-3435.

 

High Fat Meal and Endotoxemia

Hi Fat Intake CAuses Endotoxemia

31) Lyte, Joshua M., Nicholas K. Gabler, and James H. Hollis. “Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study.” Lipids in health and disease 15.1 (2016): 186.

32) Harte, Alison L., et al. “High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects.” Diabetes care 35.2 (2012): 375-382.

These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.

33) Erridge, Clett, et al. “A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation.” The American journal of clinical nutrition 86.5 (2007): 1286-1292.

34) Clemente-Postigo, Mercedes, et al. “Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients.” Journal of lipid research 53.5 (2012): 973-978.

35) Michalski, Marie-Caroline, et al. “Dietary lipid emulsions and endotoxemia.” OCL 23.3 (2016): D306.

36) Piya, Milan K., Alison L. Harte, and Philip G. McTernan. “Metabolic endotoxaemia: is it more than just a gut feeling?.” Current opinion in lipidology 24.1 (2013): 78-85.

37)  Hamilton, M. Kristina, et al. “Changes in intestinal barrier function and gut microbiota in high-fat diet fed rats are dynamic and region-dependent.” American Journal of Physiology-Heart and Circulatory Physiology (2015).

38) Neves, Ana Luísa, et al. “Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk.” Journal of molecular endocrinology 51.2 (2013): R51-R64.

39) Mani, Venkatesh, James H. Hollis, and Nicholas K. Gabler. “Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia.” (2013).

Intestinal derived endotoxin and the subsequent endotoxemia can be considered major predisposing factors for diseases such as atherosclerosis, sepsis, obesity and diabetes. Dietary fat has been shown to increase postprandial endotoxemia. Therefore, the aim of this study was to assess the effects of different dietary oils on intestinal endotoxin transport and postprandial endotoxemia using swine as a model. We hypothesized that oils rich in saturated fatty acids (SFA) would augment, while oils rich in n-3 polyunsaturated fatty acids (PUFA) would attenuate intestinal endotoxin transport and circulating concentrations.
Methods    Postprandial endotoxemia was measured in twenty four pigs following a porridge meal made with either water (Control), fish oil (FO), vegetable oil (VO) or coconut oil (CO). Blood was collected at 0, 1, 2, 3 and 5?hours postprandial and measured for endotoxin. Furthermore, ex vivo ileum endotoxin transport was assessed using modified Ussing chambers and intestines were treated with either no oil or 12.5% (v/v) VO, FO, cod liver oil (CLO), CO or olive oil (OO). Ex vivo mucosal to serosal endotoxin transport permeability (Papp) was then measured by the addition of fluorescent labeled-lipopolysaccharide.
Results    Postprandial serum endotoxin concentrations were increased after a meal rich in saturated fatty acids and decreased with higher n-3 PUFA intake. Compared to the no oil control, fish oil and CLO which are rich in n-3 fatty acids reduced ex vivo endotoxin Papp by 50% (P?
Conclusion

Overall, these results indicate that saturated and n-3 PUFA differentially regulate intestinal epithelial endotoxin transport. This may be associated with fatty acid regulation of intestinal membrane lipid raft mediated permeability.

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Published on April 5th, 2019 by
Jeffrey Dach MD

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