In my Book, Your Best Health Ever: A Cardiologist’s Surprisingly Simple Guide to What Really Works, I reference numerous books and scientific studies to help explain the importance of lifestyle medicine. For your reference, I have listed these studies with a brief description of them and a link so you can read more if you are interested. I have broken them down into different sections for convenience.

Your Roadmap To Natural Health

2. In fact, a study done on “Biggest Loser” participants showed that almost all of them fared poorly after the show was over. They experienced rapid weight gain with no improvement in their health.

Study Design: 14 participants in the “Biggest Loser” t.v. show had a 6-year follow up measuring weight and resting metabolic rate

Findings: After 6 years, they regained an average 41kg of the originally 58 kg that they lost. In addition, their resting metabolic rate decreased on average by 704 kcal/day.

Strengths and weaknesses: This was a small sample size, but had a good long-term follow up.

Conclusion: Rapid and aggressive weight loss is very difficult to maintain long term, and is associated with a significant decrease in resting metabolic rate. The decreased RMR, in essence fights the body’s attempts at weight loss. This highlights the fact that weight loss is not synonymous with metabolic health and overall health.

3. Scientific studies have shown that technically overweight individuals who meet criteria for being “fit” have similar health benefits as those who are “normal weight.”

Study Design: This was an observational study of 21,000 men who had a baseline body-composition measurement and maximal treadmill exercise test. They were followed for 8-years. The risk of death was correlated with the treadmill and body-comp findings.

Findings: Unfit, lean men had a higher risk of death than did fit, obese men.

Strengths and weaknesses: As an observational trial, this study does not prove cause and effect. It does, however, highlight that there is an association between being fit and a decreased risk of death, even if they individual remains technically obese.

Conclusion: “Fitness” is more important than “fatness.” Of course, it is ideal to be fit and not obese. However, if we had to focus on of the two, fitness appears to be the more important factor for health.

4. In addition, skinny but sedentary people had much worse health outcomes than fit overweight individuals.

A.Study Design: This was an observational study of 3,100 adults who had a maximal exercise treadmill test as well as body fat percentage measurements. They were followed for 6-years for the risk of developing hypertension, metabolic syndrome, and high cholesterol

Findings: Maintaining or improving fitness provided the most protection from developing the adverse health conditions. Increasing body fat provided the highest risk. However, in their combined analysis, they found that maintaining fitness attenuated the increased risk of increasing body fat percentage.

Strengths and weaknesses: As an observational trial, this study does not prove cause and effect. However, it does show the potential protective effect of maintaining a fitness, regardless of body fat.

Conclusion: The best outcomes occurred in those who were fit and reduced their body fat. But if the two, it appears that fitness has a more protective benefit.

B. This is a thorough review article summarizing the studies and highlighting the importance of fitness as a possible protective benefit even in overweight individuals.

Chapter 1: What is Health?

1. Adult obesity increased from 22% in 1994 to 34% by 2012. Adolescent obesity increased from 12% in 2000 to 27% by 2014

This is not a study per se. It is a statistical observation put out by the CDC.

Chapter 2: Using Science to Make Health Decisions

1. Here’s a real-life example. Most primary prevention statin trials show a range of 0.5-1.6% benefit over 5 years. That equates to an NNT as low as 200 (1/.005) and as high as 62 (1/.016)

Summarizing the extensive data on statins is a challenge. I used the website NNT.com as well as the Cochrance review linked above, in addition to reviewing individual trials. These are all discussed in greater detail in the statin section of the Re-examine Your Healthcare chapter.

Chapter 3: Your MIndest is the Key–

1. Dr. Carol Dweck, a psychology professor at Stanford University, wrote the defining book about mindset, appropriately called Mindset: The New Psychology of Success.

This references Carol Dweck’s book Mindset: The New Psychology of Success. This is a must-read for anyone who wants greater detail about the “fixed” vs. “growth” mindset described in my book. Although it is not a research study per se, it is an accumulation of her research summarized in book form. It is an excellent read and thoroughly describes examples of fixed and growth mindsets and the importance of maintaining a growth mindset for success.

1. In His book Blue Zones, Dan Buettner investigated the most common habits in societies where people frequently live into their 90s and 100s.

This book is a collection of observations Mr. Buettner made regrading specific societies with a propensity for longevity. Again, it is not randomized research and does not prove cause and effect. However, it is an excellent collection of observations and is a fascinating read. It highlights many similarities between these cultures and highlights their importance for health and happiness.

Nourish Your BodyReferences #1

Eat Real Food

1. “A shocking study in 2015 showed that Americans get 61% of their calories from moderately or heavily processed foods.”

Study Design: The authors analyzed food buying patterns from over 150,000 households between 2000 and 2012. They gave all the families barcode scanners, and they were instructed to scan everything they bought. They defined processing as “any procedure that alters food from its natural state and includes all processes and technologies that transforms raw food materials and ingredients into consumer food products.”

Aside from raw fruits and veggies, just about every food fits this definition to a degree. To further define this, they subdivided processed foods into 4 categories based on the degree of processing.

• Unprocessed and minimally processed- No or very light modifications that do not change the basic food properties
• Basic processed- These have been processed but remain single foods
• Moderately processed- Flavor additives
• Highly processed- multi ingredient industrially formulated mixtures, no longer recognizable as their original source

Findings: 16% of the purchased food was moderately processed, and a whopping 61% was highly processed. That means only 23% was unprocessed or basic processed.

Strengths and weaknesses: Using the barcode scanner was brilliant. It made the analysis objective rather than using food logs. It is also beneficial that they used the 4 different levels of processing.

Conclusion: This is an eye-opening study about how far we, as a society, have deviated from the concept “Just Eat Real Food.” We have fallen prey to the convenience, taste addiction and marketing that promotes processed foods. We need to acknowledge that food companies do not have our health as their main concern. Their profit margin is what they are after. It will take a shift in culture, in tradition, and in mindset to reverse this trend, and we have to start now.

Eliminate Added Sugars

1. They also contribute to blood sugar related diseases ranging from diabetes to heart disease, dementia, fatty liver and others

A.Study Design: The authors examined data obtained from the NHANES study to determine the association of sugar intake and cardiovascular death

Findings: There was a significant relationship between amount of sugar consumed and increasing risk of cardiovascular death

Strengths and weaknesses: This was an observational trial so it does not prove that sugar caused heart disease. However, it was prospective data from a large cohort of people, which does help its relevance.

Conclusion: People who eat excess sugar are at higher risk of dying from heart disease. This may be due to the sugar itself, or other unhealthy habits these indivduals have.

B. Study Design: Meta analysis of 11 studies that investigated sugar intake and incidence of diabetes

Findings: There was a significant relationship between sugary beverage intake and the risk for diabetes.

Strengths and weaknesses: This was an observational trial so it does not prove that sugar caused diabetes. However, it was prospective data from a large cohort of people, which does help its relevance

Conclusion: People who consume excess sugar are at higher risk of developing diabetes. This may be due to the sugar itself, or other unhealthy habits these individuals have.

C. Study Design: Prospective, observational trial of adults over age 75. They followed them for 7 years and measured glucose levels and clinical signs of dementia.

Findings: Those who developed dementia had a statistically significant higher average glucose levels within the preceding 5 years.

Strengths and weaknesses: This was an observational trial so it does not prove that sugar caused dementia. However, it was prospective data from a large cohort of people, which does help its relevance

Conclusion: Individuals with elevated blood sugar levels are at higher risk of developing dementia. This may be due to the sugar itself, or other unhealthy habits these individuals have.

D. This paper was a literature review that presented the case for fructose consumption as a leading cause of non-alcoholic fatty liver disease.

1. Without the fiber from real foods, your body quickly absorbs the refined sugar and starts a cascade of harmful effects, like quick blood sugar spikes and crashes, and a sustained rise in insulin

Study Design: his study was an extensive review of the increased consumption of dietary sugar and the increased incidence of obesity, diabetes, and cardiovascular risk. They also discuss the mechanisms of how sugar effects the body leading to these diseases

Findings: They concluded that sugar sweetened beverages lead to weight gain due to decreased satiety and increased calories consumption, Both weight gain and the rapidly absorbed sugar predispose to insulin resistance and diabetes, increase inflammatory markers such a CRP, and increase heart disease risk.

Strengths and weaknesses: This was a not a single randomized trial, but rather a summary of existing literature.  The methodologies of the various studies are inconsistent making it difficult to draw cause-and-effect conclusions. But the strength is that it was a fairly exhaustive review of what studies currently exist.

Conclusion: Science backs the theory that sugar consumption produces a cascade of harmful effects in the body.

Everything in moderation

1. A 2015 observational study showed that those who ate with greater diversity and included more foods in moderation had a significantly larger waist than those who ate a fewer variety of foods.

Study Design: This was a review of data from the MESA study involving over 5,00 subjects. They measured the number of different food items eaten more than once per week, a measure of diversity called the Berry index, and the Jaccard distance ( another measure of food diversity)

Findings: Greater food dissimilarity was associated with increased waist circumference, and no change in the risk of diabetes. When restricted to pre-defined “healthy foods” there was no relationship to increased waist size.

Strengths and weaknesses: This was an observational study so it does not prove cause and effects. It does, however, point to an association that deserves more attention. In addition, the study is assuming it has correct measurements of food dissimilarity. I like how they used 3 different measures as opposed to relying upon just one.

Conclusion: The concept of eating everything in moderation may not be the best strategy for most people. We have to strike a balance between realizing there are “good” foods (fresh vegetables, high quality fats) and “bad” foods (processed, refined simple carbs and sugars), while still allowing diversity of food choices. But encouraging moderation of foods that are clearly detrimental to our health is unlikely to be beneficial long-term without greater guidance and clarification of moderation’s definition.

Make your meals vegetable based

1. Vegetable intake has been associated with a decreased risk of cancer, heart disease, diabetes, hypertension, and more.

A. Study Design: This study was a comprehensive literature review regarding fruit and vegetable consumption and a variety of medical conditions.

Findings: They concluded there is convincing evidence that higher fruit and vegetable consumption decreases the risk of hypertension, heart disease and strokes. There is a probable relationship with decreasing risk of cancer, and possible decrease in risk of obesity and other disease.

Strengths and weaknesses: As a review of the literature, the results are dependent upon the quality of the individual studies reviewed.

Conclusion: It is no surprise that the literature suggests numerous health benefits to eating more fruits and veggies. A randomized trial is always best, but the totality of evidence suggests a direct association.

B. Study Design: This was a review of annual surveys sent to random selections of people living in England. They specifically investigated the association between self-reported fruit and vegetable consumption and the risk of death, cancer and heart disease. They tried to statistically control for multiple variables.

Findings: Increased fruit and vegetable consumption was associated with a decreased     risk of death, heart disease and cancer. Vegetables seemed to have a greater benefit than fruit when considered individually.

Strengths and weaknesses: As an observational study, it cannot prove cause-and effect as there are many potential confounding variables.

Conclusion: It is not a surprise that an association exists between fruit and vegetable consumption and decreased risk of death, cancer and heart disease. Although randomized trial are best, the totality of evidence continues to reflect the benefit for fruit and vegetable consumption.

Eat natural monounsaturated fats

1. “The Mediterranean diet, consisting of over 40% fat, primarily from monounsaturated fats, is the only primary nutritional intervention shown to reduce heart attacks and strokes.”

Study Design: The PREDIMED study was a prospective trial that randomized over 7,000 primary prevention subjects to either a low-fat diet that was also low in bakery good and processed foods, a Mediterranean diet with 30g of mixed nuts per day, or a Mediterranean diet with an extra 1-liter of extra-virgin olive oil per week. They followed them for almost 5 years and measured the primary endpoint of combined cardiovascular events (heart attack, stroke, or cardiac death). Both Mediterranean diet group had over 40% of their calories coming from fat.

Findings: Both Mediterranean diets reduced the primary endpoint by 3% (a 30% relative reduction). Sub-analysis of the same data showed reduced incidence of diabetes, as well as lipid inflammation

Strengths and weaknesses: This was a very strong trial as it was prospective, randomized, and it measure hard clinical endpoints. That means it measured heart attacks, strokes and death as opposed to surrogate markers like blood pressure and cholesterol levels.

Conclusion: The Mediterranean diet with added nuts and extra-virgin olive oil reduced the risk of adverse cardiovascular events. This was found in a low risk group (none had previously detected heart disease) and was compared to a diet that was already an improvement over the baseline diet as there was a reduction of processed foods and baked goods.

1. The breakthrough Mediterranean diet study came in 1999 with the Lyon Heart Study.

Study Design: This was a randomized trial of 600 consecutive patients who were admitted to the hospital with a heart attack. They were randomized to a Mediterranean style diet (emphasizing vegetables, fruit, fish, whole grains, and spread fat high in alpha-linolenic acid, with less meat, less processed food, and less sugar) or to a group with no formal nutritional counseling.

Findings: The Mediterranean diet group showed an absolute reduction in risk of death by 1% with a reduction in the composite cardiovascular endpoint of 4% in just 2 years of follow up. The relative reduction was calculated at 70%.

Strengths and weaknesses: As a randomized trial, this is a high level of evidence. There have been numerous concerns about the study given that the control group’s diet was only evaluated at the conclusion of the study, not during the study time. In addition, less than 50% of subjects completed a dietary survey at the conclusion of the study.

Conclusion: Following a Mediterranean style diet instead of a standard diet reduced the risk of heart disease and death after only 2-years. These were groundbreaking results showing the incredible power of food as medicine. In addition, all these results occurred without any significant change in the LDL cholesterol levels.

Avoid manufactured trans fats

1. “Research has shown that these (trans-) fats increase the risk of cancer, cardiovascular disease, and other chronic health conditions.”

A thorough meta-analysis in BMJ showed that saturated fat intake was not associated with overall mortality, cardiac death, strokes, diabetes or heart disease.

Study Design: This was a thorough meta-analysis of the literature evaluating the association between saturated fat and trans-fats and the risk of heart disease, diabetes, strokes and death.

Findings: Saturated fats were not statistically associated with any of the adverse outcomes. Industrial trans fats, on the other hand, were associated with a higher risk of all-cause death, heart related death, and heart disease in general.  Interestingly these same findings did not apply to ruminant trans-fats (those that occur naturally in ruminant animals such as cows, goats etc.

Strengths and weaknesses: Observational studies can evaluate for an association, but cannot prove cause and effects. However, by including multiple studies, they do somewhat improve the quality of the association.

Conclusion: Industrial trans fats appears to be associated with the risk of heart disease, diabetes, strokes and death. The same does not appear to apply to saturated fats and naturally occurring ruminant trans-fats.

1. “Even worse, they increase the oxidation that leads to unstable cholesterol buildup in your arteries and cause greater inflammation throughout your body.”

A.Study Design: Fifty men ate a standard control diet and had blood tests for inflammatory marker such as CRP, fibrinogen, IL-6, and others. They then were switched to diets that included either more dietary cholesterol, trans-fats, oleic acid, or steric acid. Their blood samples were re-measured after 5-weeks on each diet.

Findings: CRP, IL-6 and E-selectin were all higher after consuming the trans-fat diet compared to the other diets.

Strengths and weaknesses: The crossover design lends strength to the study as there was only one intervention. Presumably their lifestyles remained the same. That makes it fairly certain of the causative relationship between the type of fat intake and the change in inflammation.

Conclusion: Trans-fats increase inflammation significantly more than other type of saturated fatty acids.

B.Study Design: The data from the Nurses Health Study was analyzed retrospectively to assess the association between trans-fat intake and inflammatory markers.

Findings: CRP, IL-6, sTNF-2, E-selectin, and sICAM-1 were all significantly higher in those who ate the most trans-fats.

Strengths and weaknesses: As an observational study, this study does not prove cause and effect, it merely identifies an association.

Conclusion: This observational trial supports the prospective cross-over trial referenced earlier that eating trans-fats is related to increased inflammation.

C.Study Design: This was a Medline search meta-analysis examining trans-fat consumption and cardiac risk factors and outcomes.

Findings: Both controlled and observational trials demonstrated increased LDL, decreased HDL, increased inflammatory markers, and worsening endothelial function. They also demonstrated an increased risk of heart attacks and cardiac death.

Strengths and weaknesses: The majority of the evidence is observational and shows an association without causative proof. However, some of the included studies were prospective which does add to the strength.

Conclusion: Eating trans-fats is associated with increased cardiac risk factors, increased inflammation, and increased risk of heart attack and death.

1. “Studies have shown that CLA may actually be beneficial for our health, possibly reducing the risk of cancer and heart disease.”

Study Design: This was a review article on the potential health benefits of CLA

Findings: The review highlights the difficulty with studying CLA as there have been different variants studied. Although the evidence is variable, the trend is toward suggesting health benefits for cardiovascular disease, inflammation and possibly cancer.

Strengths and weaknesses: The evidence is fairly weak as many studies are in lab animals with different compositions of CLA, and the findings are not consistent.

Conclusion: Although the quality of evidence is low, it is very intriguing and deserves further studies to better define the health benefits of CLA.

Eat Mindfully

1. “In fact, science supports the claim that distracted eating leads to unhealthy overeating”

A 2013 meta-analysis published in The American Journal of Clinical Nutrition demonstrated that distracted eating led to a moderate increase in immediate food intake, but more importantly, it led to an even greater increase in food intake later that same day. Mindfulness practices were able to reduce these effects. This shows the important interaction between our food, our sense of feeling satisfied, and our attention to mindfulness. The calories that our body needs may not change, but our brain’s perception of that need can vary to a great extent when we are distracted.

Study Design: This was a meta-analysis of 24 studies that investigated the association between food intake and changes in awareness, distraction or attention.

Findings: The studies concluded that distracted eating led to a moderate immediate increase in food intake, and a and even greater increase in later food intake. The same was true of removing visual information about the food consumed.  Enhancing memory of food intake significantly reduced future eating

Strengths and weaknesses: As a meta-analysis the conclusions are subject to strength of the included trials.

Conclusion: Distracted eating leads to an increase in both immediate food intake, as well as an even greater increase in later food intake. Being present and not distracted while eating is an important tool for controlling portion size and overall calorie intake.

Don’t drink your calories

1. “Human studies have shown that aspartame increases insulin spikes equivalent to those caused by real sugar and can even cause equivalent blood glucose spikes.”

Study Design: 14 men with type 2 DM had their glucose and insulin levels tested after 5 different meals, one of which included aspartame instead of other sugar sources.

Findings: The aspartame meal increased blood glucose and insulin levels similar to the sucrose (real sugar) meal.

Strengths and weaknesses: As a crossover design, the only thing to change was the sugar consumed. Therefore, it is fairly certain that the changed in glucose and insulin were as a result of what they ate.

Conclusion: The synthetic sugar substitute aspartame increases insulin and glucose similarly to real sugar.  It is certainly possible that the brain recognizes the sweet taste and therefore acts the same, regardless of the chemical compound that caused sweet taste.

1. “That’s probably why numerous studies have found links between diet soda intake and ahigher risk of diabetes and obesity.”

A 2009 prospective, observational study in Diabetes Care showed a 36% increased risk of the metabolic syndrome and a 67% increase in Type II diabetes in those who consumed diet soda compared to those who did not.

A.Study Design: This was an observational trial that evaluated frequency of diet soda consumption and the risk for developing metabolic syndrome and diabetes.

Findings: Daily consumption of diet soda was associated with a 36% relative risk of metabolic syndrome, and a 67% relative increased risk of diabetes.

Strengths and weaknesses: As an observational study, it points out an association but doe not establish causative proof.

Conclusion: Drinking diet soda is related to an increased risk of diabetes and metabolic syndrome. When take together with the data showing artificial sweeteners can increase glucose and insulin similar to real sugar, these findings seem to have more validity.

B.This was a review of the biology of artificial sweeteners and a review of the literature that shows an association between diet soda intake and risk of weight gain and increased sugar cravings.

Saturated Fat and Cholesterol

For more on the history of how fat was incorrectly vilified and more detail on Ancel Keys’ Seven Countries Study, I recommend Nina Teicholz’s book The Big Fat Surpriseand Gary Taubes’ book Good Calories, Bad Calories

1. Wenow have evidence showing that the sugar industry systematically paid Harvard scientists to promote fat as the culprit, and to suppress science showing that sugar was a main contributor to heart disease

This was a published investigation of internal documents from the Sugar Research Foundation (SRF). The researchers found that the SRF sponsored trials to promote fat as the cause of heart disease, and specifically paid to suppress data that sugar was related to heart disease. It shows a similar pattern to “big tobacco” using their money and influence to cast doubt on the harms of tobacco. Although SRF did not make up any data, they certainly used their influence to direct the research away from sugar and towards fat.

1. That’s also likely why low-fat, higher-carbohydrate diets have consistently shown less weight loss than higher-fat, low-carbohydrate diets

Study Design: This was a meta-analysis of randomized controlled trials that investigated the effects of low-carbohydrate diets and weight loss.

Findings: Combining the data from five trials demonstrated that after 6-months, those following a low-carb diet lost 3.3kg more than those on a low-fat diet. Triglycerides and HDL improved more in the low-carb group and LDL improved more in the low-fat group.

Strengths and weaknesses: By combining 5 different studies, they increased their power, but the study sample was still small at only 447. Weight loss is not always the best measure for health, but it is a frequent individual goal.

Conclusion: Low-carbohydrate diets may be better that low-fat for weight loss. We cannot comment on cardiovascular safety. It is certainly encouraging that the HDL and triglycerides improved with a low-carb diet, eventhough the LDL improved with the low-fat diet. They key is understanding what those specific measures mean for long-term outcome measures of heart attack, stroke and death. We certainly need more evidence. But for now, we can rest assured that low-carb diets are effective for weight loss and seem to be a healthy alternative to the traditional low-fat dogma.

1. As an example, a ketogenic diet, which is up to 80% fat and less than 20 grams of carbohydrate per day, is one of the best diets for fat loss.

Study Design: 83 obese men and women had baselines measurements done and then were placed on a ketogenic diet for 24 weeks and their metrics were re-measured.

Findings: While on the ketogenic diet, subjects lost weight, improved their HDL, TG and LDL, and also improved their blood glucose levels, all without any significant side effects or negative changes.

Strengths and weaknesses: There was no control group. Sometimes just being involved in a study result in improvements since people are more aware of what they are eating. A control group would have been important to measure this. Otherwise, it was a well run trial.

Conclusion: A low-carb, higher-fat diet is effective for weight loss. Not surprising, it also benefits HDL, TGs and blood glucose. It was a surprise, however, that LDL also improved. Other high fat trials have shown no change or even an increase in LDL. The type of fat and individual genetic variations could play a role.

1. There is an excellent summary of 23 different studies looking at this exact issue written by Authority nutrition.

They outline 23 different studies, briefly describing the study population, the findings and a brief conclusion. In general, the studies show improved weight loss, less hunger, improved HDL and TG, improved blood glucose and insulin sensitivity, with variable effects on LDL.

1. There are still no randomized controlled trials to support the hypothesis that dietary fat and cholesterol directly increase the risk for heart disease

A.Study Design: This was a meta-analysis of prospective observational trials investigating the association of saturated fats and cardiovascular disease. They combined 21 studies including over 347,000 subjects.

Findings: Intake of saturated fat was not associated with an increased risk of heart disease or stroke. This was true even at the highest quartile of saturated fat intake.

Strengths and weaknesses: As with all observational trials, it is subject to many uncontrolled variables. The main strength is the inclusion of a very large number of participants.

Conclusion: Based on this meta-analysis, it does not appear that saturated fat intake is associated with cardiovascular disease. This is contrary to some other observational trials, but the large number of participants and inclusion of numerous studies makes these findings very compelling.

B. Study Design: This was a review and meta-analysis of studies investigating the association between saturated fat, trans-fats, and risk of death, cardiovascular disease, stroke and diabetes.

Findings: Saturated fat intake was not associated with risk of death, heart disease, stroke, or diabetes. Trans-fats, on the other hand, were associated with risk of death and heart disease, but not with diabetes or stroke. When broken down, this association only held with industrial trans-fats and not with naturally occurring ruminant trans-fats.

Strengths and weaknesses: There were methodological differences in the trials which can make it difficult to combine the results, however, there was again a very large cohort of subjects.

Conclusion: This study also strongly calls into question the assumption that saturated fat intake increases the risk of cardiovascular disease and death. It also helps highlight the differences between natural occurring ruminant trans-fat and the more dangerous industrialized trans-fats.

1. In fact, multiple health studies have shown no correlation between dietary cholesterol intake and cardiovascular risk

Study Design: Meta-analysis of dietary cholesterol and the risk of cardiovascular disease. They included 40 studies and over 361,000 subjects.

Findings: Dietary cholesterol intake was not associated with an increased risk of coronary artery disease or stroke.  It did increase HDL and LDL.

Strengths and weaknesses: As a meta-analysis, it is only as string as the included trials, and there is some variation among the individual trials. However, they included a large number of trials and a large cohort of individuals.

Conclusion: Dietary cholesterol intake does not appear to be associated with an increased risk of heart disease or stroke. This reinforces the fact that cardiovascular disease is a multi-faceted condition that is not simply the result of dietary cholesterol.

1. Compellingly, the American College of Cardiology (ACC) finally reversed their ban on dietary cholesterol in 2014, saying that “There is insufficient evidence to determine whether lowering dietary cholesterol reduces LDL-C”

The guidelines reversed their previous position that dietary cholesterol is dangerous because it raises LDL-C. They still remarked that dietary cholesterol should be limited, but gave no real evidence as to why.

1. In 2015, U.S. federal guidelines followed suit, saying that “Available evidence shows no appreciable relationship between consumption of dietary cholesterol and serum cholesterol.”

Similar to above, they reversed their opinion that dietary cholesterol was dangerous because it raised serum cholesterol. They now admit that there is no such proven association for the majority of the population.

Vegetarianism:

1. Studies on vegetarians have shown a higher likelihood of vitamin and protein deficiencies, as well as higher consumption of grains and simple carbohydrates

Study Design: This was an observational study as part of the European Prospective Investigation into Cancer and Nutrition Oxford cohort study. As part of that study, participants filled out dietary questionaires and were labeled as omnivores, vegetarians, or vegans. They looked back at the blood work to see if there was an association between nutritional habits and risk for vitamin deficiencies.

Findings: B12 deficiency was identified in 52% of vegans, 7% of vegetarians, and less than 1% of omnivores. There was no significant difference in folate deficiency.

Strengths and weaknesses: As an observational trial, this points out an association between dietary habits and B12 deficiency, it does not prove cause and effect.

Conclusion: Veganism and vegetarianism is associated with vitamin B12 deficiency. It makes sense given the restricted animal food choices, which tend to be the best sources of vitamin B12. The same has been shown for iron. Those who choose to eat a vegan or vegetarian diet need to use supplements to counteract their risk for vitamin and nutrient deficiencies.

1. Dr. Ornishhas shown that when people quit smoking, improve their exercise, practice stress management, and follow a vegetarian nutritional pattern, they can halt or reverse the progression of coronary artery disease

Study Design: 48 patients with angiographically established coronary artery disease were randomized to a comprehensive lifestyle program or “usual care” and followed for 5-years. The lifestyle program consisted of  vegetarian diet lass than 10% from fat, regular aerobic exercise, stress management training, smoking cessation, and group psychological support.

Findings: The arterial plaque size (measured as percent diameter stenosis) decreased 3.1% in the lifestyle intervention group at 5-years, whereas it increased by 11.8% in the control group. In addition, there were twice as many cardiac events in the control group than in the intervention group.

Strengths and weaknesses: The main strengths are that this was a randomized trial, and they measured both surrogate endpoints (plaque diameter) and hard clinical end-points (overall cardiac events). The main weakness was the small number of participants

Conclusion: This trial showed that a comprehensive lifestyle management program can reduce cardiac endpoints (need for hospitalizations and angioplasty were the only two that were significantly different), and can reduce plaque diameter stenosis. The main problem I have with this study is that it is frequently used as evidence that a vegetarian, low-fat diet prevents heart disease. But that is not what was studied. The diet was only one part of a comprehensive intervention program. It is impossible to say that the diet was any  more important than the stress reduction, the regular counseling, or the smoking cessation.

1. To be fair, observational studies also show that on average, vegetarians are healthier than meat eaters. Once again, we can’t prove cause and effect as they also tend to make other healthy choiceshttps://www.ncbi.nlm.nih.gov/pubmed/17411462/

Study Design: This was a review of data from the Austrailian Longitudinal Study on Women’s health. Over 9000 women aged 22-27 were labeled as vegetarians, semi-vegetarians, or non-vegetarians. The investigators also collected data on the health habits of the subjects and looked for differences among the groups.

Findings: Vegetarians were more likely to live in urban areas, have a lower BMI, exercise more, have low iron levels, consult alternative health practitioners, and be less likely to take birth control pills.

Strengths and weaknesses: This was an observational trial, so there is no proven cause and effect between nutritional practices and other health habits. However, in a way, that was the purpose of the trial. They showed that vegetarians tend to have other healthy habits compared to non-vegetarians.

Conclusion: Vegetarians tend to have healthier habits than non-vegetarians such as exercising more, having a lower BMI, and consulting alternative health practitioners. These are likely not a result of being vegetarian, but are co-variables that need to be considered. The same holds true for the fact that they were more likely to be iron deficient and have worse menstrual symptoms.

Calorie restriction:

For more details on intermittent fasting and calorie restriction, I recommend Dr. Jason Fung’s book The Complete Guide to Fasting.

1. Intermittent fasting is based on good scientific evidence demonstrating that it helps promote fat loss while maintaining lean body mass, and even has beneficial effects on markers for diabetes.

Study Design: This was a review 6 studies that investigated the effects of intermittent fasting on body weight, blood pressure and insulin levels.

Findings: On average the subjects had an 8.9% weight loss after 6-months. In addition, their blood pressure and insulin levels improved.

Strengths and weaknesses: The strength of the study is improved by combining 6 studies to increase the number of people involved. A more detailed description of the control groups would have been helpful.

Conclusion: Trials consistently show the benefits of intermittent fasting on weight loss as well as blood pressure and insulin levels. This last part is likely the most important. There are many ways to lose weight. The ones that have the greatest health benefits will likely also improve insulin and glucose levels.

Sodium and salt:

1. The DASH trial found that lowering salt below 2300 milligrams reduced blood pressure—but by only 5 points, hardly an earth-shattering result

Study Design: 412 subjects with high normal BP or stage 1 hypertension were randomized to a “typical” American diet or the DASH diet, which emphasizes fruit, vegetables, low-fat dairy, whole grains, poultry, fish and nuts. It limits sweets, sugary drinks, and red meat.

Findings: In the standard American diet, reducing sodium intake from the high to intermediate level reduced SBP by 2.1mmHg. From intermediate to low levels reduced SBP by 4.6mmHg. The differences were even smaller among those following the DASH diet with a maximal reduction of 3mmHg going from high- to low-sodium intake. The largest reduction was changing from a high sodium standard diet to a low sodium DASH diet with a reduction of 7.1mmHg.

Strengths and weaknesses: The main weakness was that the outcomes were “surrogate” end points. Blood pressure was measured, but it is unclear if the changes were significant enough to reduce the risk of strokes and heart attacks (the results we really care about). Also, the study was overly complicated with high, intermediate, and low sodium levels of both the standard and DASH diets.  When comparing the standard to the dash diets, we don’t know for sure that it was the sodium that made the difference. Was it the sugar? The processed food? This is unclear.

Conclusion: Reducing sodium made a very small difference in blood pressure. It is very dubious that it would be enough to reduce heart attacks and strokes. In addition, any change away from excess sugar and processed foods is likely going to improve blood pressure regardless of the amount of sodium consumed.

1. Two separate meta analysisstudies concluded that salt intake was linked to a U-shaped outcome.

A.Study Design: Since no randomized controlled trials were found, they did a meta-analysis of 23 observational cohort studies that looked at sodium intake and risk of death or heart disease.

• : Risk of death or heart attacks was decreased in the usual sodium group (2.5-5mg/day) when compared to the low sodium group (<2.5mg/day). There was less of an association with increased events in the high sodium group (>5mg/day) when compared to the usual sodium group.

Strengths and weaknesses: Since it was a meta-analysis of observational trials, it does not prove cause and effect. But since it included 23 studies it helps draw a consistent and strong association.

• : Low and very high daily sodium intake may increase the risk of cardiovascular events or even death. Although it is not causative proof, it certainly calls in to question the recommendations to limit sodium intake in the general population.

B. Study Design: This was a pooled analysis from four large trials including 133,000 subjects, half with hypertension and half without. They measured 24-hour urine sodium excretion as a marker for sodium intake and correlated that with risk of death and cardiac disease over 4 years.

Findings: For those with hypertension, both a very high and very low sodium excretion was associated with an increased risk of death and heart disease. For those who were not hypertensive, only low sodium excretion was associated with an increased risk. High sodium excretion had no such correlation.

Strengths and weaknesses: This was a very large trial. They used sodium excretion as a very accurate measure of sodium intake (not dependent on food estimates). However, this makes it unclear what level of sodium intake is considered high or low. Lastly, it was not a randomized trial, so the findings suggest a correlation but do not prove cause and effect.

Conclusion: For those who already have hypertension, it makes sense to keep sodium intake in the “average” range. That means avoiding excessively high or excessively low intake of sodium. For those who are not hypertensive, there appears to be no reason to regulate sodium intake.

Best way to eat

1. Subsequent investigations published as the now-famous Lyon Heart Study and the PREDIMED study demonstrated that a Mediterranean-style diet reduced the risk of early death, cardiovascular diseases, diabetes, and lowered the oxidation of plaque-causing cholesterol

Study Design: The PREDIMED study was a prospective trial that randomized over 7,000 primary prevention subjects to either a low-fat diet that was also low in bakery good and processed foods, a Mediterranean diet with 30g of mixed nuts per day, or a Mediterranean diet with an extra 1-liter of extra-virgin olive oil per week. They followed  them for almost 5 years and measured the primary endpoint of combined cardiovascular events (heart attack, stroke, or cardiac death).

• Both Mediterranean diets reduced the primary endpoint by 3% (a 30% relative reduction). Sub-analysis of the same data showed reduced incidence of diabetes, as well as lipid inflammation

Strengths and weaknesses: This was a very strong trial as it was prospective, randomized, and it measure hard clinical endpoints. That means it measured heart attacks, strokes and death as opposed to surrogate markers like blood pressure and cholesterol levels.

• : The Mediterranean diet with added nuts and extra-virgin olive oil reduced the risk of adverse cardiovascular events. This was found in a low risk group (none had previously detected heart disease) and was compared to a diet that was already an improvement over the baseline diet as there was a reduction of processed foods and baked goods.

Forget old school diets

1. A study of commercial weight loss programs in 2015 found that only Weight Watchers and Jenny Craig had any significant success at helping participants maintain weight loss for more than one year

Study Design: This was a meta-anaylsis of 39 randomized studies that compared a commercial weight loss program with basic nutritional education for at least 12 months.

Findings: Jenny Craig participants lost 4.9% more weight than controls, and Weight Watchers lost 2.6% more than controls. Other programs either did not have data going out 12 months or did not show sustained significant weight loss.

Strengths and weaknesses: May of the trials were not 12 months long. That made it difficult to accurately compare the trials. In addition, there was a high drop put rate in the included studies.

Conclusion: Only 2 commercial weight loss programs have data to show that they provide sustained weight loss at 12-months. Even then, the weight loss was moderate at best at only 2.6-4.9%.

Food Quality Matters

1. Studies have clearly shown higher nutrient content and lower toxin content in grass-fed rather than grain-fed meat, wild as opposed to farmedfish, pasture-raised instead of pen-raised chicken and hens

A. Study Design: This was a review of studies that have investigated the difference between grass-fed and grain-fed meat.

• s: Grass-fed cattle have increased levels of conjugated linoleic acid (CLA) and omega-3 fatty acids The amount of saturated fat was generally the same, but there was a higher proportion of stearic acid and less myristic and palmitic acid (felt to be more worrisome for health). Grass-fed beef was also higher in vitamin A and E

Strengths and weaknesses: They did an extensive review of the literature, including a large number of studies and going into great detail of the science of fatty acids.

• : Grass-fed meat has a significantly more favorable nutrition profile than grain-fed meat.

B. Study Design: This study specifically measured Dioxin contamination in farmed Atlantic salmon compared to wild pacific Alaskan salmon.

• The farmed salmon had significantly higher levels of PCBs, toxaphene, dioxins and other contaminants

Strengths and weaknesses: They directly measured the dioxin concentration from over 2 metric tons of salmon. The large sample size lends great validity to the study.

• : Farmed salmon has significantly higher toxin levels when compared to wild salmon.

C. Study Design: This was a prospective, controlled study of the nutrient variation in eggs from hens allowed to graze on natural grasses (pasture raised) vs. those fed commercial hen feed. They used sister hens as their subjects

Findings: Pastured hen’s eggs had twice as much vitamin E and omega-3 fatty acids, 38% higher concentration of vitamin A.

Strengths and weaknesses: This was a well-designed, randomized, prospective study using genetically related hens. They also used a crossover method to measure the effects of feed on each hen.

Conclusion: Pasture raised, naturally grazing hens fed grass significantly improved the nutritional quality of the eggs with increased vitamin E, omega-3 fatty acids, and vitamin A concentration.

“Move With A Purpose”

1. “A 2015 study of about 600,000 middle-aged adults found that the highest risk of death was in those who did not exercise at all.”

Study Design: Large meta-analysis that pooled 6 different studies that were prospective, observational studies.

Findings: They found that individuals who performed any activity, but less than the official recommendations, had a 20% lower risk of death compared to those who do not exercise at all. Those who met the recommendations of 150 minutes per week had a 31% lower death risk, with a maximal 39% lower death risk in those who exercised 3-5 times the recommended limit.

Strengths and Weaknesses:  As with many observational studies, it suggests a correlation but does not prove causation. In its favor, it was a very large study, which can somewhat offset the observational aspect, albeit not completely.

Conclusions: A big take home from this study is that the maximal benefit (from 0 to 20% mortality reduction) was seen between those who were sedentary and those who did some, albeit less than the recommended amount of physical activity. More activity beyond that still added benefit, but the “biggest bang for your buck” is to just get moving. Start doing something physical and you have already succeeded. Don’t be intimidated by guidelines that may seem out of your reach. Just get started and you have already succeeded.

1. “Another study, The Copenhagen Heart Study also found that “light” exercise—running, in this case—even just once per week lowered the risk of early death.”

Study Design: This was a study over 1000 joggers and almost 4,000 non-joggers, followed prospectively over 12 years.

Findings: Those who jogged 1-2.4 hours per week had the lowest risk of death. Interestingly, those who jogged the most, or at the highest intensity, did not see a mortality difference.

Strengths and weaknesses: Again, since this was an observational study, it is difficult to draw conclusive evidence. It can be suggestive of benefit without clear proof. One of its strengths is that it confirms the findings of other similar studies suggesting minimal activity is beneficial.

Conclusions: Mild activity, even “light jogging” for less than 2.4 hours per week seemed to reduce the risk of death. That’s pretty powerful for an easy-to-do intervention! Again, the focus should be on getting started and being active. We all have time to improve and build up our activity levels. But we all need to start now!

1. “The catchy headlines about a 2014 study declared that “As Little As 5 Minutes of Daily Running Saves Lives.” Was it true?”

Study Design: This study followed over 55,000 adults for over 15 years. They correlated their risk of dying with a questionnaire of how much they run.

Findings: They found that any amount of running, even at slow speed, was correlated with up to 30% a lower risk of death.

Strengths and weaknesses: As with most observational studies, this did not prove that the running directly caused the lower death rate. It did, however, point to the importance of being active to any degree, and the potential for significant health benefits.

Conclusions: The catchy conclusion that 5-minutes of running saves lives may have been overstated, but it doesn’t change the fact that there continues to be an association with being active and being healthier.

1. “How about 1 minute of intense exercise?”

Study Design:  This study randomized 25 sedentary adults to either a control group that did no activity, a sprint interval training group (SIT), or a medium-intensity cardio training group (MICT).  They followed them for 12-weeks and measured various markers of cardiorespiratory fitness. The SIT group exercised for a total of 9 minutes, with only 1 minute of maximum intensity. The started bywarming up for two minutes. Then they cycled as hard as they could, at maximum intensity, for three sets of 20 seconds each. Between each set, they recovered by cycling for two minutes at a low intensity. Then they cooled down for two minutes. The MICT group cycled for 45 minutes at moderate intensity, defined as 70% of their maximum predicted heart rate.

Findings: The SIT and MICT groups had equal decreases in body fat and improved their oxygen uptake by almost 20%, an important fitness indicator. The SIT participants also improved their insulin sensitivity, although the MICT group did not.

Strengths and weaknesses: This was a prospective, randomized trial, the strongest level of scientific evidence. There was one difference between the groups- the manner in which they exercised. Therefore it is clear that the changes that occurred were a direct result of the exercise. The weakness is that the trial was too short and too small to measure hard endpoints such as heart attacks or deaths.

Conclusion: sprint interval training is an incredibly valuable form of exercise. It requires less time and can still yield similar cardiorespiratory results as longer exercise, and can even improve insulin sensitivity. Given that lack of time is the number one excuse for why people don’t get regular physical activity, this study is a welcome addition It is a vital part of a balanced and varied exercise plan.

1. “Studies have shown that overweight individuals who met criteria for being “fit” had similar health benefits as those who were “normal” weight.

A. The first article reviewed the evidence of the so-called “Obesity paradox,” whereby overweight individuals seemed to have a better survival than leaner counterparts. After an extensive review of the literature, the authors concluded that this paradox was seen only when overweight subjects were compared to leaner but less fit individuals. This suggests that fitness may be more important than weight in predicting cardiovascular disease risk.

B. The second study published in JACC in 2012 followed over 3,000 subjects, measuring their cardiorespiratory fitness and their body fat percentage over 6-years. They monitored the subjects for development of hypertension, high cholesterol, and metabolic syndrome. They found that improving fitness was the best predictor of not developing these health conditions, whereas gaining fat was associated with an increased risk. That was not much of a surprise. The big conclusion, however, was that the increased risk that accompanied an increase in body fat was at least partially mitigated by also improving fitness. This was a strong indication that those who are overweight can still see significant health benefits from improving their fitness, even in the absence of fat loss.

Manage Your Stress and Sleep:

Stress:

1. studies have shown that stress increases cortisol and adrenaline levels in our bodies, and harms our health over time.

These are two review articles of the effects stress has on our long-term health. While short-term stress can have some physical benefits, long-term stress raises catecholamines, suppresses the immune system, increases blood glucose levels, changes stomach acid content, and other physiological effects. It also has significant effect on psychological health.

1. Here’s the shocker, though: these studies also discovered that the effect of stress on your health is under your control.

This was a series of 3 studies that first validated a tool for measuring an individual’s assessment of the beneficial or detrimental effects of stress. The second demonstrated that one’s mindset toward stress can be altered by external influences, in this case short videos that presented factual information about stress in either a positive or negative manner. Lastly, they demonstrated how an altered perception of stress effects the body’s physiological response to stress with improved cortisol reactivity and an outward expression of wanting more feedback (deemed to be a positive reaction toward stress).

1. “Studies have shown that practicing mindful meditation, instead of judgement, can improve your immune function,reduce overly emotional reactions, and improve your overall wellbeing”

Study Design: Twenty-five subjects underwent an 8-week mindfulness meditation training course, and sixteen subjects served as controls. They had brain electrical stimulation measured at baseline, 8 weeks later, and 4-months later. In addition, everyone received the influenza vaccine at the 8^th week.

Findings: There was a significant increase in the left-anterior activation in the meditation group compared to the controls. In addition, vaccine titers were higher in the meditation group.

Strengths and weaknesses: This was a small study, but it was a well-run, prospective, controlled study this making the findings very reliable.

Conclusion: Mindful meditation can change the areas of brain function and can boost an individual’s immune response.

B. The second article is a review article summarizing the evidence supporting that meditation improves subjective well-being, reduces symptoms of depression and anxiety, and improves overall health.

1. Many people are shocked when they first hear that mindfulness can even change the physical structure of your brain

Study Design: Sixteen subjects underwent an 8-week mindfulness meditation course, and were compared to seventeen control subjects. They all had baseline brain MRIs which were repeated after 8-weeks.

Findings: Those in the mindfulness program had greater increases in the size of certain parts of their brains, specifically the left hippocampus, posterior cingulate cortex, the tempero-parital junction, and the cerebellum. These areas are most involved with learning, emotional regulation, and the internalization of external stimuli.

Strengths and weaknesses: The study sample was small, but it was helped by being a single intervention, prospective, controlled trial.

Conclusion: An 8-week mindfulness meditation program can change the anatomic structure of the brain. Pretty amazing stuff!

Sleep:

1. A fascinating 2003 study in the journal Sleep showed that people who got no more than six hours of daily sleep for 10 consecutive days suffered almost the same cognitive and physical declines as people who were completely deprived of sleep for two whole days.https://www.ncbi.nlm.nih.gov/pubmed/12683469

Study Design: 48 healthy subjects underwent sleep deprivation being allowed either 8, 6, or 4 hours of sleep per night for 14 consecutive days, or they were not allowed to sleep at all for 3 consecutive days. All subjects underwent identical cognitive performance tests as well as reporting subjective levels of sleepiness.

Findings: Subjective sleep rating declined immediately once sleep deprivation began, but did not continue to fall over the remainder of the 2 weeks. However, the cognitive function tests continued to decline linearly with increasing duration of sleep deprivation. It did not appear that there was a significant difference between the 4- and 6-hour sleep groups.

Strengths and weaknesses: The measurements were complicated, but overall it was a string study involving well controlled study groups and consistent data measuring.

Conclusion: Sleeping 6-hours per night or less produces significant decline in cognitive function. The individual tends to realize this at first, but then they feel as if they do not worsen as the sleep deprivation continues, even though test scores continue to decline. In addition, the declines are similar to those who were completely sleep deprived for 2-days. This shows the danger of sleep deprivation, as people underestimate their degree of psychological impairment.

1. Yet another incredible study examined the sleep patterns of traditional hunter-gatherer tribes

Study Design: Three geographically distinct pre-industrial societies were studied using a watch-like device that tracks sleep patterns.  They were also observed during the day tracking light exposure.

Findings: Sleep-wake cycles were very consistent, and followed ambient temperature changes. All three group began sleep an average of 3 hours after sunset when temperature began falling. They woke before sunrise when the temperature began rising again. Their time in bed averaged 7.5 hrs. with actual sleep time 7 hours.

Strengths and weaknesses: This was an observational study so cannot prove that the sleep habits were the cause of the lack of sleep problems in their societies. However, what is fascinating is that all 3 societies had very similar patterns, even though they were not connected and were geographically diverse.

Conclusion: Consistent wake and sleep patterns based on natural temperature changes appears to be the “natural” sleep wake cycle for humans. Adhering to this pattern, and spending 8 hours in bed, with ample morning light exposure, could be an effective first line treatment for sleep disorders.

1. Poor sleep causes spikes in ghrelin, and suppresses leptin

Study Design: 1024 volunteers underwent sleep studies and filled out questionnaires about their sleep duration. Their also had the BMI calculated and had blood tests for leptin, ghrelin, and other measurements.

Findings: For those who slept less than 8-hours, BMI increased linearly with decreasing sleep time. In addition, those who slept 5-hours had 15% reduction in leptin and 15% increase in ghrelin compared to those who slept 8-hours.

Strengths and weaknesses: As an observational study, it cannot prove cause and effect.

Conclusion: It is certainly possible that there is a relationship between poor sleep habits, altered leptin and ghrelin, and resulting weight gain.

1. The blue light from laptops, smartphones and tablets disrupts our natural 24-hour physical, mental and behavior cycles, the “circadian rhythm” of our bodies. It also disrupts melatonin and other sleep hormones

This was a review article summarize the literature dating back all the way to 1958 up to the present. They describe the various studies demonstrating how the circadian rhythm works, and how blue light disrupts that rhythm and serves as an activating light.

1. In one study, people who practiced mindfulness had better sleep, less depression and less fatigue than those who simply received general sleep hygiene education. Even 10 minutes of mindfulness meditation achieves proven results.

Study Design: This was a randomized trial of 49 subjects with moderate sleep disturbance. Half underwent a 6-week mindful awareness practices, and half had sleep hygiene education. They were followed with a standardized measurement of sleep quality (PSQI), as well as with questionnaires regrading daytime impairment, depression, fatigue and other measures.

Findings: The mindful group showed a greater improvement in sleep quality, reducing their PSQI score from 10 to 7, whereas the sleep hygiene group reduced theirs from 10 to 9. IN addition, they had lower ratings for insomnia, depression and fatigue compared to the sleep hygiene group.

Strengths and weaknesses: This was a strong, randomized trial with a variety of data. Some of the data is subjective, and the sample size was small. However, it still is an excellent introductory study for mindfulness.

Conclusion: Mindfulness is superior to sleep hygiene education for sleep quality as well as depression and fatigue symptoms. It seems natural to use both sleep hygiene and mindfulness to treat sleep disorders.

Build Your Support Community:

1. The leading research in this field began in 1938 and is still underway over 75 yearslater!

This is an article in Forbes describing the study. They researchers followed Harvard college men, and compared them to similar aged men who were uneducated and lived in the poor area of Boston. They were followed and their happiness scale was measured. The study since evolved to involve subsequent generations as well. Although the study is not described in exact detail, the researchers report that the main relationship they found was the association between happiness and the number and strength of social connections.

1. Hundreds of other studies have reached similar conclusions, and have shown that people who maintain close social relationships are happier, less depressed, and feel a greater sense of purpose.

This is a review article summarizing the literature supporting the connection between social relationships and happiness. The science supports that this is the strongest contributor to happiness, certainly more so than material gains or possessions.

Re-examine Your Healthcare

Statins:

1. The 2013 American College of Cardiology and American Heart Association cholesterol treatment guidelines dramatically altered mainstream medicine’s use of statins.

            This was not a study, but rather a combined guideline from the American Heart Association and the American College of Cardiology. There were many implications of the recommendations beyond the scope of this post. The main point for here is that they recommended getting more aggressive with statin therapy for individuals who do not have heart disease, so called primary prevention, recommending it for anyone with c10-year calculated risk of 7.5% or greater, and to consider it even down to 5% or greater. This was a significant change from the prior guidelines which were closer to 10-20% 10-year risk. Were there new trials that dramatically changed their opinion?

Cholesterol- not the real enemy

1. Multiple studies- not all, but more than just a few- have suggested that individuals over age 75 are more likely to die if they have low cholesterol than if they have high cholesterol, Some of the  references are HereHere and Herehttp://onlinelibrary.wiley.com/doi/10.1111/j.1365-2753.2011.01767.x/abstract?hc_location=ufi

Study Design: All three of these trials looked back at data collected from specific studies and correlated cholesterol concentrations and risk of death.

Findings: All three studies showed a correlation between higher cholesterol levels and lower risk of death, and conversely, lower cholesterol concentration and a higher risk of death.

Strengths and weaknesses: As with all retrospective studies, this does not prove cause and effect. It does, however, raise a very interesting association and deserves further research.

Conclusion: These trials lend more evidence to the concept that cholesterol, including LDL, serves a vital role in our bodies and it cannot be labeled as “bad.” Reducing cholesterol, especially in the elderly, comes with a substantial risk and therefore any potential benefit needs to be significantly greater than that risk. At present, it is unclear to me that such a benefit exists in elderly primary prevention subjects given the apparent risks.

1. Moreover, more than 50% of people with heart attacks have “normal” cholesterol levels and people taking statins still have heart attacks. 

Study Design: They retrospectively investigated 136,905 hospital admission for coronary artery disease from 2000-2006 and looked specifically for lipid levels measured within 24-hours of admission.

Findings: Of those admitted specifically for heart disease, the mean LDL was 104, essentially a “normal” value. In fact, 17% had an “ideal” level less than 70. Only 46% had an HDL greater than 40.

Strengths and weaknesses: This was a very large sample, and was specific for heart disease admissions. It was retrospective, so the same caveats apply as do other retrospective studies.

Conclusion: Amazingly, the authors concluded that this was evidence that the “LDL goal” should be even lower. I would conclude that LDL is not the main predictor of heart disease. Almost half of all admissions for heart disease had normal LDL levels. It seems to me that there are more important factors that have nothing to do with LDL.

1. In some of the best statin trials, such as the PROVE-ITtrial, 20% of those taking statins had a heart attack within only two years.

Study Design: This was a prospective, randomized trial of 4162 patients who had a recent heart attack. They were prescribed either 10mg of pravastatin or 80mg of atorvastatin, both lipid lowering medications. They wanted to see if more intensive therapy had a more beneficial effect.

Findings: They declared the study a success for the higher dose statin as the primary endpoint was reduced by 4% over two years. However, at only 2-years, there were still 22-26% of patients who had a cardiac event.

Strengths and weaknesses: This was a strong study since it was a randomized prospective trial.

Conclusion: Higher dose statin therapy did have a small benefit in reducing cardiovascular events. But clearly statin therapy is not all powerful as over 20% of the patients had a cardiac event despite very aggressive statin therapy. Reducing the cardiac event rate from 26 to 22% in two years does not seem like a dramatic improvement we should be proud of. It tells me that the study is missing a big part of the puzzle that has nothing to do with LDL cholesterol and statin drugs.

1. In fact, studies have shown that after starting a statin people exercise less, eat more, and gain more weight

Study Design: The NHANES study involved over 27,000 subjects where hordes of data was collected. In this particular study, they retrospectively looked at caloric intake and BMI and compared the between statin users and nonusers.

Findings: In the beginning of the study, statin users ate fewer calories than non-users. But as time went on, the statin users increased their caloric intake and fat consumption far more than the non-users. In addition, statin users increased their BMI more than non-users.

Strengths and weaknesses: This was a retrospective observational study, so it can show a correlation but cannot prove causation. The information was gathered in a prospective manner, and the study cohort was very large, thus making it a higher quality observational trial.

Conclusion: Statin users increased their caloric intake and their BMI faster than non-statin users. It is not causative proof, but is certainly plausible, that once someone starts a statin, they feel like they are “cured” and therefore can eat as much as they want. This is all part of the general philosophy that drugs are a quick fix, when in reality, they usually mask symptoms without “curing” anything.

The Science

1. The scientific literature generally shows that statins provide approximately a 30% reduction in heart attacks in high-risk patients, defined as those who have had heart attacks before. Remember, however, that a 30% reduction is the relative risk reduction, and not the absolute risk reduction. In reality, these studies show a 2-3% absolute reduction in heart attacks over a five-year period. There is an even smaller reduction of the risk of death in men, and there is no consistent death benefit seen in women.

The NNT website summarizes available literature as an absolute risk reduction and as a number needed to treat. This avoids the confusion that can occur with quoting only the relative risk, which is generally substantially higher than the absolute risk and less clinically relevant.

1. In people who have not had previous heart attacks (called primary prevention in the medical literature), the benefits are only a 0.5%-1.6% reduction in heart attacks over two to five years. It’s statistically significant, but far from earth shattering. And there is no benefit on risk of death.

A.The NNT website summarizes available literature as an absolute risk reduction and as a number needed to treat. This avoids the confusion that can occur with quoting only the relative risk, which is generally substantially higher than the absolute risk and less clinically relevant.

B.Study Design: This was a meta-analysis of 11 prospective, randomized statin trials (including over 65,000 subjects) that included participants without prior heart attacks (primary preventions) and reported the incidence of all-cause death.

Findings: The use of statins did not reduce the risk of death by a statistically significant amount.

Strengths and weaknesses: As a meta-analysis, the study strength is dependent of the included studies. However, the large sampling of over 65,000 subjects helps lend credibility to the findings.

Conclusions: In a primary prevention setting, statin therapy does not provide a statistically significant protection against death. There are some studies that suggest otherwise, but given the conflicting evidence, if such a benefit does exist, it is clearly very small.

1. Will statins make you feel better, more energetic, or stronger? Quite the opposite. Statins have been shown to decrease exercise activity, worsen sleep patterns, and increase daily aches and painshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463373/

A.Study Design: Review of the literature and summary of muscle effects of statins

Findings: Damage to the mitochondria (the energy center of the cell) is the most likely cause of statin side effects. They hypothesize that the same mechanism can cause memory loss, neuropathy and liver disease.

Strengths and weaknesses: This wasn’t an actual study. It was a summary report of prior studies and raised a hypothesis of the mechanism of statin adverse effects. But it did nicely highlight the numerous potential negative effects of statins and the effect of peoples lives and wellbeing.

Conclusion: Statins are actually toxic to the energy center of our cells, the mitochondria. That causes the muscle associated adverse effects and may play a role in numerous other potential side effects.

B. This is an extensive review article demonstrating the incidence of muscle weakness and resulting reduction in strength and aerobic performance in those taking statins, although the data is sparse and somewhat conflicting. It was consistent that stain related muscle complaints are made worse with exercise. They hypothesize that the decrease in muscular CoQ10 and altered mitochondrial function play a role in the etiology of statin-induced muscle complaints.

Cholesterol…or inflammation?

1. The widely-known JUPITER trialstudied the role of statins in primary prevention—preventing heart attacks in people who had never had one

Study Design: This was a prospective, randomized trial of over 17,000 individuals without prior cardiac disease, LDL levels less than 130, and elevated CRP levels above 2.0. They were treated with either rosouvastatin 20 or placebo and followed for a combined cardiovascular outcome (heart attack, stroke, angioplasty/stent, hospitalization for angina, or heart-related death)

Findings: The trial was stopped early, after only 2-years, because of a significant benefit to rosuvastatin. It reduced LDL by 50%, CRP by 37%, and had an absolute reduction of the primary endpoint of 0.59%. The risk of death was reduced by 0.25%, heart attack by 0.2%.

Strengths and weaknesses: This is the highest-level evidence as it is a randomized, placebo controlled study. Any time a study is stopped early, it brings into question the longer-term validity of the findings. But the main weakness of the study is that, although the findings are statistically significant, the absolute numbers are very small. It would have been better to see longer term results to see if they continued to increase, or if they stayed at the small absolute reductions.

Conclusion: This is another statin trial showing a very small, but statistically significant, benefit to taking the drug. What sets this trial apart from the others is that it selected a population with increased inflammation as measured by CRP. Since statins are known to reduce inflammation as well as LDL, forces the question of which on had the greater benefit?

1. It turns out that in addition to reducing cholesterol, statins also reduce inflammationhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394171/

This was a review of the literature that exists demonstrating the anti-inflammatory properties of statins. In addition to blocking an enzyme crucial for ldl production, statins also reduce CRP and other pro-inflammatory cytokines, and limit the effects of potentially harmful vascular reactive oxygen species.

1. In fact, analysis of the study’s data suggests that the beneficial effect of statins was only seen in those who had a reduction in their hs-CRP inflammation marker

In this paper, the authors showed evidence that whne evaluating the results from the JUPITER study, the association between statin therapy and reduced cardiovascular outcomes was only present if there was a reduction in CRP. Those who took statin and did not have a reduction in CRP did not see a significant protective benefit.

1. Oxidized and inflamed plaques appear to more likely to cause heart attacks compared to less inflamed plaques

This is an extensive NEJM review article highlighting the evidence suggesting that plaque inflammation is the main risk factor for acute plaque rupture and heart attacks.

1. After all, smoking cessation, regular exercise, stress reduction and proper nutrition have all been shown to reduce inflammation and to reduce heart attacks

A.This is a review article highlighting the association between healthy lifestyle habits and reduced markers of inflammation.

B.Study Design: Dr. Ornish’s trial randomized 20 patients with coronary disease either to an intensive lifestyle modification program (including smoking cessation, regular aerobic exercise, stress management classes, group support, and a vegetarian diet) or to a control group and followed them for 5-years.

Findings: At the end of 5-years, the lifestyle intervention group had greater reduction in coronary artery plaque volume, and also had a lower risk of cardiac events.

Strengths and weaknesses: This was a very small trial, thus limiting the statistical conclusion that can be made. However, it was a randomized trial of an extensive lifestyle program and showed significant findings despite the very small sample size.

Conclusion: An intensive lifestyle program reduced coronary plaque volume and reduces the risk for cardiac events.

What will statins do for you?

1. Well, guess what? Both the standard American diet, as well as the low-fat high-carb diet, have been shown to increase inflammation and promote oxidation

Study Design: This was a review article summarizing the evidence on nutrition and inflammation.

Findings: The evidence suggests that refined diets high in starches, sugars, and industrialized trans-fatty acids and low in fruits, vegetables, omega-3 fatty acids, and whole grains increased the production on inflammatory cells and suppresses the production of anti-inflammatory cells.

Strengths and weaknesses: This was a not a dietary intervention study, but rather a summary of other diet studies. It is only as strong as the studies reviewed. Given the various studies all had different interventions and data collection, it is difficult to say with certainty if the conclusions are accurate or causative. However, there was fairly good consistency among the studies included, so it does lend credence to the conclusions.

Conclusion: Sugar and refined carbs likely increase inflammation and fruits, vegetables, and omega 3 fats decrease inflammation. This is supportive evidence for studies like the PREDIMED Lyon studies which show reduced cardiovascular events despite no change in LDL cholesterol levels. Perhaps the beneficial effects have much more to do with healthy eating and decreased inflammation.

1. In fact, a 2016 study in NEJM showed that lifestyle interventions can reduce the risk of heart disease in those at highest genetic risk by almost 50%. And guess what? These benefits were accomplished with minimal if any change in the LDL.

Study Design: This study was a compilation of data from four separate studies that evaluated DNA sequences stratifying subjects according to their genetic risk for heart attacks, and investigated how healthy lifestyle choices (regular physical activity, healthy diet, not smoking and not being obese) impacted that risk. They included 55,000 individuals.

Findings: Those with the highest genetic risk for heart attacks had a 91% increased risk compared to the lowest risk. Adhering to even one healthy lifestyle reduced the risk of heart attacks. Those who were at the highest genetic risk for a heart attack and followed all four healthy lifestyles had a 46% lower risk of actually having a heart attacks. In absolute terms, the difference ranged between 2.6% and 5.6% over ten years. The LDL difference between the favorable and unfavorable lifestyle groups was minimally different.

Strengths and weaknesses: This was an observational trial, so it does not prove cause and effects. But by combining multiple studies and involving 55,000 subjects, it is a strong marker for the benefits of healthy lifestyles, even in those at highest genetic risk.

Conclusion: Healthy lifestyle habits reduces the risk of heart attacks by almost 50% in those at the highest genetic risk for the disease. Even 1 healthy habit reduced the risk, with an additive response for each additional habit. And these benefits came with minima, if any, reduction in LDL cholesterol.

1. Remember the PREDIMED study that showed the Mediterranean diet reduces cardiovascular events? It also showed a significant benefit with no meaningful reduction in LDL.

Study Design: The PREDIMED study was a prospective trial that randomized over 7,000 primary prevention subjects to either a low-fat diet that was also low in bakery good and processed foods, a Mediterranean diet with 30g of mixed nuts per day, or a Mediterranean diet with an extra 1-liter of extra-virgin olive oil per week. They followed them for almost 5 years and measured the primary endpoint of combined cardiovascular events (heart attack, stroke, or cardiac death). Both Mediterranean diet group had over 40% of their calories coming from fat.

Findings: Both Mediterranean diets reduced the primary endpoint by 3% (a 30% relative               reduction). Sub-analysis of the same data showed reduced incidence of diabetes, as well as lipid inflammation. There was no significant reduction in LDL in the Med diet group compared to controls.

Strengths and weaknesses: This was a very strong trial as it was prospective, randomized, and it measure hard clinical endpoints. That means it measured heart attacks, strokes and death as opposed to surrogate markers like blood pressure and cholesterol levels.

Conclusion: The Mediterranean diet with added nuts and extra-virgin olive oil reduced the risk of adverse cardiovascular events. This was found in a low risk group (none had previously detected heart disease) and was compared to a diet that was already an improvement over the baseline diet as there was a reduction of processed foods and baked goods. And all these beneficial effects were seen without a reduction in LDL. This suggests that changes in LDL concentration is not the best marker for health outcomes. That is why studies with hard end-points (heart attacks, strokes, death, etc.) are much stronger trials than those that use surrogate endpoints (LDL, weight, blood pressure etc.).

Adverse effects of statins

1. Significant statin-induced muscle aches or weakness have been reported in at least 10% of users. Anecdotal “real-world” reports are as high as 50% in some settings, especially in active individuals.

Study Design: A survey was sent to 7900 patients in France who were taking statin therapy.

Findings: Muscle symptoms were reports by 10% of patients. 38% reported that the pain prevented moderate exertion during every day activity.

Strengths and weaknesses: This study should have had a control group not on statins to improve its strength.

Conclusion: Statin side effects are far greater than the 1-2% generally reported in industry-sponsored statin trials.

1. In fact, statin users tend to decrease their exercise after starting the medication

This was a review article describing the effects statins have on muscles from both a clinical and physiological perspective.  They demonstrated decreased muscle strength, and a decrease in exercise after starting statin therapy.

1. Biopsy studies, however, do suggest muscle cell damage even in the absence of abnormal lab results

Study Design: This study involved four patients who reported statin muscle symptoms, had normal muscle enzyme blood tests, and had resolution of their symptoms when changed to a placebo.

Findings: Muscle biopsies showed mitochondrial dysfunction and alterations in muscle fiber appearance and function.

Strengths and weaknesses: This was a very small study and would have benefitted from a control group.

Conclusion: Statins can cause damage to muscle fibers and mitochondria even in the absence of abnormal muscle enzyme blood tests.

1. Studies showed that treating between 166 individuals and 250 individuals with a statin for two years would result in one new case of diabetes

A. This was the JUPITER study referenced earlier. There was a 0.6% increased risk of diabetes over the 2-year study. The NNH=1/ARR=1/0.006=166.

B. Study Design: This was a meta-analysis of randomized controlled trials that included statin therapy and measurement of risk of developing diabetes. They included 5 trials comprising over 32,000 subjects.

Findings: There was a 0.4% increased risk of diabetes. NNH=1/ARR=1/0.004=250

Strengths and weaknesses: This was a large meta analysis with over 32,000 subjects, and the only trials included were randomized prospective studies. That makes this a very strong study.

Conclusion: The number needed to harm by causing diabetes needs to be considered against the lower, although some what similar, number need to treat to provide benefit with statins (60-140 people).

1. It should be no surprise, therefore, that reducing it puts our brains at risk for dementia

Study Design: This was a retrospective reviews of 482,000 statin users, a “matched” group of 482,000 controls who did not use lipid lowering drugs, and 26,000 who used non-statin lipid lowering drugs (i.e. zetia, niacin, fibrates etc.). They identified 68,000 subjects who suffered from cognitive decline and memory loss, and then looked to see if there was an association with taking lipid lowering drugs.

Findings: There was a significant association between starting a lipid lowering drug and the risk of cognitive decline as early as 30-days after starting the medication. It did not appear to matter if it was a statin or other lipid lowering medication, both had a correlation with cognitive decline.

Strengths and weaknesses: Any case-control study such as this can identify a potential association but cannot prove cause and effect. There could be other explanations, such as the presence of higher cholesterol was the risk factor (although that does not explain the risk of memory decline within 30-days of starting a lipid lowering drug).

Conclusion: This study raises the possibility that lipid lowering can cause memory difficulty and cognitive decline. There is a plausible explanation given the importance of cholesterol for neuronal function, but the study does not prove causation. It certainly warrants further study and significant consideration when starting statin therapy.

What if a statin is recommended?

1. A trial published in the Journal of the American College of Cardiology looked at that exact question

Study Design: This study looked back at data from the MESA trial that evaluated 4,700 subjects between ages 45-75 and followed them for 10 years. They calculated their 10-year risk for heart disease. They the included the results of their coronary calcium score and re-calculated their risk. They compared these risks scores to the actual data of who experienced heart disease within the ten years.

Findings: Based on the guidelines, 50% of all participants would have been candidates for moderate-to-high-intensity statin therapy. Of these subjects, 44% had a calcium score of zero and a very low event rate of 0.04%.

Strengths and weaknesses: This was an analysis of data that was obtained in a prospective trial. It was not randomized, but the data is still very compelling. There was no intervention to change the outcomes, it was merely observational.

Conclusion: Calcium score can reclassify almost 50% of people to no longer meet criteria for statin therapy. Given the potential side effects associated with statins, coronary calcium scores could be considered for all statin-eligible patients to see if they truly would benefit from drug therapy.

Don’t forget about HDL

1. In fact, some trials showed a potential harm from their use with an increased risk of death!

Study Design: This study included 15,000 individuals and randomized them to either torcetrapib (a CETP inhibitor) plus atorvastatin, or a placebo plus atorvastatin. They were followed for 12-months.

Findings: At 12-months, the tocetrapib group had a 71% increase in HDL, 25% decrease in LDL, but also had a small yet significant increased risk of heart attacks and death.

Strengths and weaknesses: This was a well conducted trial that was randomized and blinded with a placebo control. This is the strongest level of evidence.

Conclusion: There is far more to cardiovascular health than measurements of LDL and HDL. Altering HDL with drugs does not provide any clinical benefit, and may even cause harm. This is in direct contrast to the changes in HDL that result from healthy lifestyle habits. It is likely that the HDL itself may not be a marker of increased health. An increased HDL may simply reflect the healthy habits, and it is those habits that confer the health protection benefits.

1. In fact, a 2016 publication questioned the benefits of HDL, but likely missed the most important point

Study Design: This was a retrospective review of observational data from the CANHEART study of 630,000 presumably healthy individuals in Ontario Canada. Subjects had to have a cholesterol panel done at entry. They followed the subjects over 5 years. Of those who died, they looked back at their HDL levels to see if there was a correlation between HDL levels and cause of death.

Findings: Low HDL levels were correlated with risk of death from both cardiac and non-cardiac causes, where as high HDL levels (>70 in men, >90 in women) was associated with increased risk of non-cardiac death but not cardiac-related death. Importantly, they also noted that low HDL was associated with unhealthy lifestyles, high triglyceride levels, and other medical comorbidities.

Strengths and weaknesses: This is a pure observational study. It does not prove that HDL had anything to do with the causes of death. It merely looks statistically to see if there is any correlation.

Conclusion: HDL is a marker of healthy lifestyles. Exercise increases HDL. A high monounsaturated fat, nutrient rich, real foods diet increases HDL. There may or may not be anything magical about the HDL level itself. This study does nothing to prove or disprove that. But it is clear that HDL is a marker of health lifestyles, and that is why low HDL levels are correlated with all-cause mortality risk. As for higher HDL levels, that may represent a genetic mutation that places individuals at higher risk of non-cardiac death but that is purely hypothetical.

1. Regular exercise, including resistance training, can naturally raise HDL

A. Study Design: This study had 12 physically fit women had their blood tested before, an at multiple time points after a standardized treadmill workout.

Findings: HDL significantly increased 48 hours after exercise

Strengths and weaknesses: This was a good study for acute changes in HDL. It would have been more powerful with a longer term follow up and with a control group for comparison.

Conclusion: Aerobic exercise increases HDL in women. This adds to the accepted data that It does the same in men.

B. This was a review article of 13 studies investigating the relationship between exercise and HDL. They found that regular physical training significantly increases HDL, and there was a particular association with resistance training.

1. In addition, a high-fat nutrient-dense diet can naturally raise HDL

A. Study Design: 63 obese men and women were randomized to a high fat, low carb diet (HFLC) or a low fat, high carb (LFHC) diet. They were followed for 1-year.

Findings: HFLC subjects increased their HDL by 11% at 1-year whereas the LFHC group improved only 1.6%. There was no significant change in LDL in the HFLC group, and a 3% decreases in the LFHC group.

Strengths and weaknesses: This was a strong, randomized trial with good execution and follow up.

Conclusion: A high fat, low carb diet naturally increases HDL cholesterol. In this trial there was no significant change in LDL.

B. Study Design: Individuals with a diagnosis of high cholesterol were randomly assigned to a high fat, low car ketogenic diet or a low-fat, reduced calorie diet for 24-weeks.

Findings: Those in the ketogenic diet lost more weight, had greater improvements in HDL and greater decreases in triglycerides. LDL was unchanged in both groups.

Strengths and Weaknesses: At 6-months, the follow up was shorter than some other trials, but otherwise was a strong randomized trial.

Conclusion: This adds to the consistent findings that a higher fat diet naturally improves HDL and triglyceride levels more than a low-fat diet.

There is a good summary of 23 low-carb studies here

https://authoritynutrition.com/23-studies-on-low-carb-and-low-fat-diets

Consider advanced lipid testing

1. For instance, the degree of oxidation and inflammation of LDL particles increases the risk of cardiovascular events

A. Study Design: This was an observational where the investigators measured blood tests for oxidized LDL in 333 subjects with heart disease and 1700 subjects without heart disease. 

Findings: Those with heart disease had a significantly higher level of oxidized LDL particles. This appeared to be independent of any other measured lipid parameters.

Strengths and weaknesses: As an observational study, this cannot prove cause and effect. It does point to an association between oxidized LDL and risk for heart disease.

Conclusion: This study lends support to the theory that oxidation of LDL increases the risk of clinically significant heart disease.

B.This is a review article summarizing the data implicating the increased risk of cardiovascular disease with increasing LDL oxidation.

1. For instance, small LDL particles may be a better predictor for cardiovascular disease than the total amount of cholesterol in your blood

Study Design: This was an observational study of 11,000 men and women who had blood samples of LDL size and density at baseline and then were followed for their risk pf developing heart disease. They were followed for 11 years.

Findings: Small, dense LDL (sdLDL) was an independent risk factor for developing heart disease. Most importantly, sdLDL was a strong predictor of heart disease even in those who were characterized as low risk based on overall LDL levels.

Strengths and weaknesses: As an observational study, this cannot prove cause and effect. It does point to sdLDL as being a strong predictor of heart disease, even when LDL is normal.

Conclusion: Overall LDL concentration is an imperfect marker for heart disease risk. The size and density of the LDL particles may be a more important factor.

Check your coronary calcium score

1. Those with a calcium score of zero have less than 1% risk of a cardiac event over 5-years

This is a review article that summarizes the data on coronary calcium score and the subsequent risk of heart attacks. There appears to be a clear gradation of risk start at 0, then 1-300, and >300.

Proton Pump Inhibitors-

1. In fact, reducing stomach acid has been linked to a higher risk of infections like pneumonia and the potentially deadly intestinal infection, clostridium difficile, as well asvitamin deficiencies, dementia and kidney disease.

Study Design: This was a retrospective review of 12 observational trials encompassing 2,948 subjects

Findings: They found that the risk of having a clostridium difficile infection increased significantly in those who took PPIs (OR 1.96) as well as H2 blockers (OR 1.4). The same held true for other intestinal infections as well such as Salmonella and Campylobacter.

Strengths and weaknesses: This was a review of observational studies. Therefore, it cannot prove causation. However, it the findings were consistent among the trials and there is a plausible physiologic explanation.

Conclusion: Taking PPI and H2 blockers medications is associated with an increased risk of intestinal infections. There is a very plausible explanation since stomach acid is felt to be protective against infections. The possibility remains that it is something else related to needing to take and anti-secretory drug

1. A study in Germany followed over 73,000 people 75 years old or older and found that those who took PPIs had a 44% increased risk of dementia compared with those who were not taking PPIs

Study Design: This was a prospective observational study of over 73,000 patients over age 75 from a Health insurance company in Germany. The used statistical calculations to analyze the association between the development of dementia and the use of PPIs

Findings: There was a significant increased likelihood that those taking PPIs developed dementia compared to those who were not taking PPIs.

Strengths and weaknesses: This was an observational study. Therefore, it cannot prove causation. But it did include a very large number of patients and followed them prospectively, which makes it a higher quality observational study.

Conclusion: The authors point to animal models that PPIs increase amyloid deposits in mice, so this lends more evidence that PPIs cause dementia. That is a stretch, as this study does not prove causation. But it seems clear that there is either something about having GERD, taking a PPI, or the lifestyle factors that predispose to GERD, or some other related cause that does increase the risk of dementia.

1. Another, earlier, study showed increased risk of kidney disease in PPI users compared to non-users

Study Design: This was an observational study that investigated over 10,000 patients with normal kidney function. They followed them from 1996 to 2011 and looked back at the data to see if there was a correlation between PPI use and developing kidney disease.

Findings: PPI use was statistically correlated with an increased risk of kidney disease. This held true for all the different statistical variations they investigated.

Strengths and weaknesses: This was an observational study. Therefore, it cannot prove causation.

Conclusion: There is an association between PPI use and the increased risk of kidney disease. As in the above trials, it could be directly related to the drug, or it could be the underlying condition that led to the drug being prescribed in the first place. Only a randomized controlled trial could answer the question with scientific certainty.

Type 2 Diabetes

1. In fact, studies have shown that a lower carbohydrate diet can improve diabetes control and lower the need for medication

Study Design: 31 obese individuals were randomized to a diet with 20% carbohydrates or 55% carbohydrates. They were followed initially over 6-months. This study reports the 44-month results.

Findings: In the low carbohydrate group at 44-months body weight had decreased from 100kg to 93kg. HbA1C decreased from 8.0 to 6.8%

Strengths and weaknesses: This was a randomized, prospective trial and thus was a high level of evidence.

Conclusion: Low carbohydrate dies are very effective at controlling diabetes.

Depression

1. For Instance, plant-based, Mediterranean-style eating can significantly improvedepression symptoms

A.Study Design: 3500 subjects without depression were followed for over 7- years and monitored for onset of depression. That risk was then correlated with nutrition surveys regarding their adherence to a Mediterranean-style diet.

Findings: Those who followed the Med diet the best had a 98% lower risk of developing depression compared to those who followed the diet the least.

Strengths and weaknesses: As an observational study this does not prove cause and effects.

Conclusion: This study lends support to the concept that nutritional choices can effects our mood and symptoms of depression.

B.Study Design: 10,000 Spanish subjects without depressions were followed for 4.4 years. They were monitored for onset of depression and this was correlated with their compliance with a Mediterranean-style diet.

Findings: There was a clear association between degree of adherence to a Mediterranean diet and an increased risk of depression. The risk increased with decreasing diet compliance.

Strengths and weaknesses: As an observational study this does not prove cause and effects.

Conclusion: This study confirms the previous findings that there is a clear association between healthy eating habits and the onset of depression symptoms. It is not known if it is cause and effect, but it certainly supports using nutrition as a potential treatment option in mild-moderate depression.

1. Regular exercise is also as effective as prescription medications for the control of mild to moderate depression

Both these studies were review articles exploring the research that exercise improves depression symptoms and should be part of any treatment module for depression, and may even be the only treatment needed for mild-moderate depression.

Omega 3

Supplements:

1. They reduce the risk of death following a heart attack and reduce cardiac arrhythmias

Study Design: Over 11,000 patients who suffered a heart attack were randomized to either 1gm of omega 3 fatty acid supplement, 300mg vitamin E, both vitamin E and omega 3, or the control group with neither supplement. They were followed for 3.5 years.

Findings:

Strengths and weaknesses: As a randomized, controlled trial, this represents the highest level of scientific evidence.

Conclusion: Omega 3 supplements spear to reduce the risk for cardiac death and overall death in people who have had a recent heart attack.

1. They’ve also been shown to reduce inflammation, to inhibit platelet inhibition, lower triglycerides, improve endothelial blood vessel health, and stabilize plaque

This is a thorough review article on the multiple beneficial effects of omega-3 fatty acids. They highlight that there is controversy regarding their effect on cardiovascular disease outcomes due to variations in trial design and results. However, for most people not eating adequate amounts of high quality fish, omega-3 supplements remain a beneficial addition.

1. Observational evidence suggests that replacement of anti-inflammatory omega-3s with pro-inflammatory omega-6s may be related to growth in chronic inflammatory diseases such as heart disease, diabetes, cancer and auto-immune diseases

This is a review article summarizing the changes in industrialized diets to include much more omega-6 fatty acids, and the corresponding increase in chronic inflammatory diseases. This does not prove cause and effect. It was not a randomized trial to answer this question. But it does effectively raise the question. Until we have randomized trials to address this with certainty, it makes sense to pay attention to it. By focusing on vegetable based, real food nutrition with appropriate proportions of high quality animal sources, we will naturally increase omega 3 and decrease omega 6.

1. have shown that their typical diet’s omega-6 to omega-3 ratio is more in line with hunter-gatherer societies

Study Design: This was a review of the nutritional trends in Japan, analyzing their food intake and the percentage of omega 3 and omega 6.

Findings: They found that the O6:O3 raio is 4:1, much lower than the 15 or 20:1 seen in most industrialized countries.

Strengths and weaknesses: This was a review of food intake. It was not designed to make any health claims regarding the ration.

Conclusion: Once again, this study does not prove that the lower omega 3: omega 6 directly reduced inflammatory conditions. But it does present a reasonable explanation.

Vitamin D

1. However, despite their multiple portental benefits, it is estimated that over 50% of Americans are deficient in vitamin D

This is an extensive review article in NEJM that summarizes the current stat of vitamin D deficiency. It provides reasons for why this is, and the potential health risks.

Vitamin K2

1. Clinical trials have shown that the MK-4 version, reduces the risk of fractures, which is the best metric for bone health

Study Design: This was a meta-analysis of thirteen trials investigating the effects vitamin K2 (menaquinone-4) and its effects of bone fractures and risk of bone loss.

Findings: There was a 60% relative risk reduction in fractures with the MK-$ version of vitamin K2.

Strengths and weaknesses: The trials were all conducted in Japanese subjects, so the applicability to all ethnicities is not proven.

Conclusion: Vitamin K2 reduced the risk of bone fractures in Japanese subjects. MK-7 was not tested, so it makes sense to focus on the MK-4 type of vitamin K2 until similar evidence becomes available for MK-7.

1. Importantly, Vitamin K2 and Vitamin D3 work synergistically to promote bone health, and potentially to reduce cardiovascular risk

This is also a review article. So, it is important to point out that Vitamin K2 has not been extensively studied in rigorous randomized trials. There is good reason to believe that it has beneficial effects, but the trial data is not there yet. This is certainly something to look for in the future.

A good friend of mine, Dr. John Neustadt, has written articles and given many excellent talks on this subject.