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A short walk after eating may help lower blood sugar levels
Similar risks found in prediabetes and diabetes

By David Dunaief

Dr. David Dunaief

Let’s start with a quiz:

1. Compared to sitting, which has more benefit on diabetes?

a) Standing for five minutes every half hour

b) Walking for five minutes every half hour

c) Neither had benefit, the activities were too short

d) Both were potentially equal in benefit

2. True or false? Diabetes patients are predominantly obese and overweight.

Diabetes just won’t go away. It seems that every time I write about the disease, the news is doom and gloom about how it has become a pandemic. The prevalence, or the number with the disease, and the incidence, or the growth rate of the disease, always seem to be on the rise, with little end in sight.

Depression and stress

We don’t want to make you depressed or stressed, especially since these conditions combined with diabetes can have dangerous outcomes. In fact, in an observational study, results showed that diabetes patients with stress and/or depression had greater risk of cardiovascular events and death, compared to those with diabetes alone. When diabetes patients had stress or depression, there was a 53 percent increased risk of death from cardiovascular disease (1). And in those diabetes patients who had both stress and depression, there was two times greater risk of death from heart disease than in those without these mental health issues. These results need to be confirmed with more rigorous study.

Something to brighten your day!

However, there is good news. According to the Centers for Disease Control and Prevention, the incidence, or the rate of increase in new cases, has begun to slow for the first time in 25 years (2). There was a 20 percent reduction in the rate of new cases in the six-year period ending in 2014. This should help to brighten your day. However, your optimism should be cautious; it does not mean the disease has stopped growing, it means it has potentially turned a corner in terms of the growth rate, or at least we hope. This may relate in part to the fact that we have reduced our consumption of sugary drinks like soda and orange juice. By the way, the answers to the quiz questions are (1) d and (2) True, although not all patients have a weight issue.

Get up, stand up!

It may be easier than you think to reduce the risk of developing diabetes. This goes along with the answer to the first question: Standing and walking may be equivalent in certain circumstances for diabetes prevention. In a small, randomized control trial, the gold standard of studies, results showed that when sitting, those who either stood or walked for a five-minute duration every 30 minutes, had a substantial reduction in the risk of diabetes, compared to those who sat for long uninterrupted periods (3).

There was a postprandial, or postmeal, reduction in the rise of glucose of 34 percent in those who stood and 28 percent reduction in those who walked, both compared to those who sat for long periods continuously in the first day. The effects remained significant on the second day. A controlled diet was given to the patients. In this study, the difference in results for those who stood and those who walked was not statistically significant.

The participants were overweight, postmenopausal women who had prediabetes, HbA1C between 5.7 and 6.4 percent. The HbA1C gives an average glucose or sugar reading over three months. The researchers hypothesize that this effect of standing or walking may have to do with favorably changing the muscle physiology. So, in other words, a large effect can come from a very small but conscientious effort. This is a preliminary study, but the results are impressive.

Can prediabetes and diabetes have similar complications?

Diabetes is much more significant than prediabetes, or is it? It turns out that both stages of the disease can have substantial complications. In a study of those presenting in the emergency room with acute coronary syndrome (ACS), those who have either prediabetes or diabetes have a much poorer outcome. ACS is defined as a sudden reduction in blood flow to the heart, resulting in potentially severe events, such as heart attack or unstable angina (chest pain).

In the patients with diabetes or prediabetes, there was an increased risk of death with ACS as compared to those with normal sugars. The diabetes patients experienced an increased risk of greater than 100 percent, while those who had prediabetes had an almost 50 percent increased risk of mortality over and above the general population with ACS. Thus, both diabetes and prediabetes need to be taken seriously.

Sadly, most diabetes drugs do not reduce the risk of cardiac events. And bariatric surgery, which may reduce or put diabetes in remission for five years, did not have an impact on increasing survival (4).

What do the prevention guidelines tell us?

The United States Preventive Services Task Force renders recommendations on screening for diseases. On one hand, I commend them for changing their recommendation for diabetes screening. In 2008, the USPSTF did not believe the research provided enough results to screen asymptomatic patients for abnormal sugar levels and diabetes. However, in October 2015, the committee drafted guidelines suggesting that everyone more than 45 years old should be screened, but the final guidelines settled on screening a target population of those between the ages of 40 and 70 who are overweight or obese (5). They recommend that those with abnormal glucose levels pursue intensive lifestyle modification as a first step.

This is a great step forward, as most diabetes patients are overweight or obese; however, 15 to 20 percent of diabetes patients are within the normal range for body mass index (6). So this screening still misses a significant number of people.

Potassium: It’s not just for breakfast anymore

When we think of potassium, the first things that comes to mind is bananas, which do contain a significant amount of potassium, as do other plant-based foods. Those with rich amounts of potassium include dark green, leafy vegetables, almonds, avocado, beans and raisins. We know potassium is critical for blood pressure control, but why is this important to diabetes?

In an observational study, results showed that the greater the excretion of potassium through the kidneys, the lower the risk of cardiovascular disease and kidney dysfunction in those with diabetes (7). There were 623 Japanese participants with normal kidney function at the start of the trial. The duration was substantial, with a mean of 11 years of follow-up. Those who had the highest quartile of urinary potassium excretion were 67 percent less likely to experience a cardiovascular event or kidney event than those in the lowest quartile. The researchers suggested that higher urinary excretion of potassium is associated with higher intake of foods rich in potassium.

Where does this leave us for the prevention of diabetes and its complications? You guessed it: lifestyle modifications, the tried and true! Lifestyle should be the cornerstone, including diet, stress reduction and exercise, or at least mild to moderate physical activity.

References: (1) Diabetes Care, online Nov. 17, 2015. (2) cdc.gov. (3) Diabetes Care. online Dec. 1, 2015. (4) JAMA Surg. online Sept. 16, 2015. (5) Ann Intern Med. 2015;163(11):861-868. (6) JAMA. 2012;308(6):581-590. (7) Clin J Am Soc Nephrol. online Nov. 12, 2015.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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Rheumatoid arthritis typically begins with stiffness in the joints of the hands.
RA medications may increase other risks

By David Dunaief, M.D.

Dr. David Dunaief

We know that inflammation is a critical part of many chronic diseases. Rheumatoid arthritis (RA) is no exception. With RA, inflammation is rampant throughout the body and contributes to painful joints, most commonly concentrating bilaterally in the smaller joints of the body, including the metacarpals and proximal interphalangeal joints of the hand, as well as the wrists and elbows. With time, this disease can greatly diminish our ability to function, interfering with our activities of daily living. The most basic of chores, such as opening a jar, can become a major hindrance.

In addition, RA can cause extra-articular, a fancy way of saying outside the joints, manifestations and complications. These can involve the skin, eyes, lungs, heart, kidneys, nervous system and blood vessels. This is where it gets a bit dicier. With increased complications comes an increased risk of premature mortality (1).

Four out of 10 RA patients will experience complications in at least one organ. Those who have more severe disease in their joints are also at greater risk for these extra-articular manifestations. Thus, those who are markedly seropositive for the disease, showing elevated biomarkers like rheumatoid factor (RF), are at greatest risk (2). They have an increased risk of cardiovascular disease events, such as heart attacks and pulmonary disease. Fatigue is also increased, but the cause is not well understood. We will look more closely at these complications.

Are there treatments that may increase or decrease these complications? It is a very good question because some of the very medications used to treat RA also may increase risk for extra-articular complications, while other drugs may reduce the risks of complications. We will try to sort this out, as well. The drugs used to treat RA are disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate; TNF (tumor necrosis factor) inhibitors, such as Enbrel (etanercept); oral corticosteroids; and NSAIDs (nonsteroidal anti-inflammatory drugs).

It is also important to note that there are modifiable risk factors. We will focus on two of these, weight and sugar. Let’s look at the evidence.

Cardiovascular disease burden

We know that cardiovascular disease is very common in this country for the population at large. However, the risk is even higher for RA patients; these patients are at a 50 percent higher risk of cardiovascular mortality than those without RA (3). The hypothesis is that the inflammation is responsible for the RA-cardiovascular disease connection (4). Thus, oxidative stress, cholesterol levels, endothelial dysfunction and high biomarkers for inflammation, such as ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), play roles in fostering cardiovascular disease in RA patients (5).

The yin and yang of medications

Although drugs such as DMARDs (including methotrexate and TNF inhibitors, Enbrel, Remicade and Humira), NSAIDs (such as celecoxib) and corticosteroids are all used in the treatment of RA, some of these drugs increase cardiovascular events and others decrease them. In meta-analysis (a group of 28 studies), results showed that DMARDs reduced the risk of cardiovascular events by up to 30 percent, while NSAIDs and corticosteroids increased the risk (6).

The oral steroids had the highest risk of heart complications, approximately a 50 percent rise in risk. This may be one reason rheumatologists encourage their RA patients to discontinue oral steroid treatments as quickly as possible.

In an observational study, the results reaffirm that corticosteroids increased the risk of a heart attack in RA patients, this time by 68 percent (7). The study involved over 8,000 patients with a follow-up of nine years. Interestingly, there was a dose-response curve. In other words, the results also showed that for every 5 mg increase in dosage, there was a corresponding 14 percent increase in heart attack risk.

Baffling disease complication

Most complications seem to have a logical connection to the original disease. Well, it was a surprise to researchers when the results of the Nurses’ Health Study showed that those with RA were at increased risk of cardiovascular disease and of respiratory disease (8). In fact, the risk of dying from respiratory disease was 106 percent higher in the women with RA, compared to those without, and the risk was even higher in women who were seropositive (had elevated levels of rheumatoid factor). The authors surmise that seropositive patients have greater risk of death from respiratory disease because they have increased RA severity compared to seronegative patients. The study followed approximately 120,000 women for a 34-year duration.

Why am I so tired?

While we have tactics for treating joint inflammation, we have yet to figure out how to treat the fatigue associated with RA. In a Dutch study, results showed that while the inflammation improved significantly, fatigue only changed minimally (9). The consequences of fatigue can have a negative impact on both the mental and physical qualities of life. There were 626 patients involved in this study for eight years of follow-up data. This study involved two-thirds women, which is significant; women in this and in previous studies tended to score fatigue as more of a problem.

Lifestyles of the painful and more debilitating

We all want a piece of the American dream. To some that means eating like kings of past times. Well, it turns out that body mass index plays a role in the likelihood of developing RA. According to the Nurses’ Health Study, those who are overweight or obese and are ages 55 and younger have an increased risk of RA, 45 percent and 65 percent, respectively (10). There is higher risk with increased weight, because fat has pro-inflammatory factors, such as adipokines, that may contribute to the increased risk. Weight did not influence whether they became seropositive or seronegative RA patients.

With a vegetable-rich, plant-based diet you can reduce inflammation and thus reduce the risk of RA by 61 percent (11). In my clinical practice, I have seen numerous patients able to reduce their seropositive loads to normal or near-normal levels by following this type of diet.

Sugar, sugar!

At this point, we know that sugar is bad for us. But just how bad is it? When it comes to RA, results of the Nurses’ Health Study showed that sugary sodas increased the risk of developing seropositive disease by 63 percent (12). In subset data of those over age 55, the risk was even higher, 164 percent. This study involved over 100,000 women followed for 18 years.

The just plain weird – infection for the better?

Every so often we come across the surprising and the interesting. I would call it a Ripley’s Believe It or Not moment. In one study, those who had urinary tract infections, gastroenteritis or genital infections were less likely to develop RA than those who did not (13). The study did not indicate a time period or potential reasons for this decreased risk. However, I don’t think I want an infection to avoid another disease. When it comes to RA, prevention with diet is your best ally. Barring that, disease-modifying anti-rheumatic medications are important for keeping inflammation and its progression in check. However, oral steroids and NSAIDs should generally be reserved for short-term use. Before considering changing any medications, discuss it with your physician.

References: (1) J Rheumatol 2002;29(1):62. (2) uptodate.com. (3) Ann Rheum Dis 2010;69:325–331. (4) Rheumatology 2014;53(12):2143-2154. (5) Arthritis Res Ther 2011;13:R131. (6) Ann Rheum Dis 2015;74(3):480-489. (7) Rheumatology 2013;52:68-75. (8) ACR 2014: Abstract 818. (9) RMD Open 2015.  (10) Ann Rheum Dis. 2014;73(11):1914-1922. (11) Am J Clin Nutr 1999;70(6),1077–1082. (12) Am J Clin Nutr 2014;100(3):959-967. (13) Ann Rheum Dis 2015;74:904-907.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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People who are considered metabolically healthy may still have a higher risk of developing heart problems if they are obese.
Obesity still increases risks of many chronic diseases

By David Dunaief, M.D.

Have we entered a fourth dimension where it’s possible to be obese and healthy? Hold on to your seats for this wild ride. This would be a big relief, since more than one-third of Americans are obese, another third are overweight and the numbers are on the rise (1). In one analysis referenced by the Centers for Disease Control and Prevention (CDC), the average medical cost for obesity alone is 41.5 percent higher than for those of normal weight, based on 2006 numbers (2). Still, there are several studies that suggest it’s possible to be metabolically healthy and still be obese.

What does metabolically healthy mean? It is defined as having no increased risk of diabetes or cardiovascular disease (heart disease and stroke) because blood pressure, cholesterol levels and inflammatory biomarkers remain within normal limits.

However, read on before thinking that obesity can be equated with health. Though several studies may suggest metabolic health with obesity, there is a caveat: Some of these obese patients will go on to become metabolically unhealthy; but even more importantly, obesity will increase their risk significantly for a number of other chronic diseases. These include osteoarthritis, diverticulitis, rheumatoid arthritis and migraine. There is also a higher rate of premature mortality, or death, associated with obesity. In other words, the short answer is that obesity is NOT healthy.

Metabolically healthy obesity

Several published studies imply that there is such a thing as “metabolically healthy obesity,” or MHO. In the Cork and Kerry Diabetes and Heart Disease Phase 2 Study, results show that approximately one-third of obese patients may fall into the category of metabolically “healthy” (3). This means that they are not at increased risk of cardiovascular disease, based on five metabolic parameters, including LDL “bad” cholesterol, HDL “good” cholesterol, triglycerides, fasting plasma glucose and insulin resistance. The researchers compared three groups: MHO, metabolically unhealthy obese and nonobese participants. Both the MHO participants and the nonobese patients demonstrated these positive results.

There were over 2,000 participants involved in this study, with an equal proportion of men and women ranging in age from 45 to 75. The researchers believe that a beneficial inflammation profile, including a lower C-reactive protein and a lower white blood cell count, may be at the root of these results.

In the North West Adelaide Health Study, a prospective (forward-looking) study, the results show that one-third of obese patients may be metabolically healthy, but it goes further to say that this occurs in mostly younger patients, those less than 40 years old, and those with a lower waist circumference and more fat in the legs (4). The reason for the positive effects may have to do with how fat is transported through the body.

In metabolically unhealthy obese patients, fat is deposited in the organs, such as the liver and heart, potentially leading to cardiovascular disease and type 2 diabetes. A theory is that mitochondria, the cells’ energy source, are disrupted, potentially increasing inflammation.

However, the results also showed that over a 10-year period, one-third of “healthy” obese patients transitioned into the unhealthy category. Over a longer period of time, this number may increase.

Premature mortality

To hammer the nail into the coffin, so to speak, obesity may be associated with premature mortality. In one study, about 20 percent of American patient deaths were associated with being obese or overweight (5). The rates were highest among white men, white women and black women. The researchers found this statistic surprising; previous estimates were far lower. Researchers reviewed a registry of 19 consecutive National Health Interview Surveys, from 1986 to 2004, including more than 500,000 patients with ages ranging from 40 to 84.9 years old.

Interestingly, obesity seems to have more of an effect on mortality as we age: obesity raised mortality risk 100 percent in those who were 65 and over, compared to a 25 percent increased risk in those who were 45.

Osteoarthritis

It is unlikely that any group of obese patients would be able to avoid pressure on their joints. In an Australian study, those who were obese had a greater than two times increased risk of developing osteoarthritis of the hip and a greater than seven times increased risk of developing osteoarthritis of the knee (6). If this weren’t bad enough, obese patients complained of increased pain and stiffness, as well as decreased functioning, in the hip and knee joints. There were over 1,000 adults involved in this study. Patients who were 39 years or older demonstrated that obesity’s impact on osteoarthritis can affect those who are relatively young.

There is a solution to obesity and its impact on osteoarthritis of the knees and hips. In a randomized controlled trial of 454 patients over 18 months, those who lost just 10 percent of their body weight saw significant improvement in function and knee joint pain, compared to those who lost less than 10 percent of their body weight (7). So, if you are 200 pounds, this would mean you would experience benefits after losing only 20 pounds.

When diet and exercise together were utilized, patients saw the best outcomes, with reduced pain and inflammation and increased mobility, compared to diet or exercise alone. However, diet was superior to exercise in improving knee joint pressure. Also, inflammatory biomarkers were reduced significantly more in the combined diet and exercise group and in the diet alone group, compared to the exercise alone group.

The diet was composed of two shakes and a dinner that was vegetable rich and low in fat. The exercise component involved both walking with alacrity plus resistance training for a modest frequency of three times a week for one hour each time. Thus, if you were considering losing weight and did not want to start both exercise and diet regimens at once, focusing on a vegetable-rich diet may be most productive.

While it is interesting that some obese patients are metabolically healthy, this does not necessarily last, and there are a number of chronic diseases involved with increased weight. Though we should not be prejudiced or judgmental of obese patients, this disease needs to be treated to avoid increased risk of mortality and increased risk of developing other diseases.

References: (1) CDC.gov. (2) Health Aff. September/October 2009;vol. 28 no. 5 w822-w831. (3) J Clin Endocrinol Metab online. 2013 Aug. 26. (4) Diabetes Care. 2013;36:2388-2394. (5) Am J Public Health online. 2013 Aug. 15. (6) BMC Musculoskelet Disord. 2012;13:254. (7) JAMA. 2013;310:1263-1273.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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Stress may increase cold virus severity

By David Dunaief, M.D.

Dr. David Dunaief

September marks the beginning of the academic calendar and noticeably shorter daylight hours. The pace of life tends to become more hectic. Although some stress is valuable to help motivate us and keep our minds sharp, high levels of constant stress can have detrimental effects on the body.

It is very likely that there is a mind-body connection when it comes to stress. In other words, it may start in the mind, but it can lead to acute or chronic disease promotion. Stress can also play a role with your emotions, causing irritability and outbursts of anger and possibly leading to depression and anxiety.

Stress symptoms are hard to distinguish from other disorders, but they can include stiff neck, headaches, stomach upset and difficulty sleeping. Stress may also be associated with cardiovascular disease, with an increased susceptibility to infection from viruses causing the common cold and with cognitive decline and Alzheimer’s (1).

A stress steroid hormone called cortisol is released from the adrenal glands and can have beneficial effects in small bursts. We need cortisol in order to survive. Some of cortisol’s functions include raising glucose (sugar) levels when they are low and helping reduce inflammation and stress levels (2). However, when cortisol gets out of hand, higher chronic levels may cause inflammation, leading to disorders such as cardiovascular disease, as research suggests. Let’s look at the evidence.

Inflammation 

Inflammation may be a significant contributor to more than 80 percent of chronic diseases, so it should be no surprise that it is an important factor with stress. In a meta-analysis (a group of two observational studies), high levels of C-reactive protein (CRP), a biomarker for inflammation, were associated with increased psychological stress (3).

What is the importance of CRP? It may be related to heart disease and heart attacks. This study involved over 73,000 adults who had their CRP levels tested. The research went further to suggest that increased levels of CRP may result in more stress and also depression. With CRP higher than 3.0 there was a greater than twofold increase in depression risk. The researchers suggest that CRP may heighten stress and depression risk by increasing levels of different proinflammatory cytokines, inflammatory communicators among cells (4).

In another study, results suggested that stress may influence and increase the number of hematopoietic stem cells (those that develop all forms of blood cells), resulting specifically in an increase in inflammatory white blood cells (5). The researchers suggest that this may lead to these white blood cells accumulating in atherosclerotic plaques in the arteries, which ultimately could potentially increase the risk of heart attacks and strokes.

Chronic stress overactivates the sympathetic nervous system — our “fight or flight” response — which may alter the bone marrow where the stem cells are found. This research is preliminary and needs well-controlled trials to confirm these results.

Infection

Stress may increase the risk of colds and infection. Cortisol over the short term is important to help suppress the symptoms of colds, such as sneezing, cough and fever. These are visible signs of the immune system’s infection-fighting response.

However, the body may become resistant to the effects of cortisol, similar to how a type 2 diabetes patient becomes resistant to insulin. In one study of 296 healthy individuals, participants who had stressful events and were then exposed to viruses had a higher probability of catching a cold. It turns out that these individuals also had resistance to the effects of cortisol. This is important because those who were resistant to cortisol had more cold symptoms and more proinflammatory cytokines (6).

Diabetes and heart disease

When we measure cortisol levels, we tend to test the saliva or the blood. However, these laboratory findings only give one point in time. Thus, when trying to determine if raised cortisol may increase cardiovascular risk, the results are mixed. However, in a study measuring cortisol levels from scalp hair was far more effective (7). The reason for this is that scalp hair grows slowly, and therefore it may contain three months’ worth of cortisol levels. The study showed that those in the highest quartile of cortisol levels were at a three times increased risk of developing diabetes and/or heart disease compared to those in the lowest quartile. This study involved older patients between the ages of 65 and 85.

Lifestyle changes can reduce effects of stress

Lifestyle plays an important role in stress at the cellular level, specifically at the level of the telomere, which determines cell survival. The telomeres are to cells what the plastic tips are to shoelaces; they prevent them from falling apart. The longer the telomere, the slower the cell ages and the longer it survives. In a study, those women who followed a healthy lifestyle — one standard deviation over the average lifestyle — were able to withstand life stressors better since they had longer telomeres (8).

This healthy lifestyle included regular exercise, a healthy diet and a sufficient amount of sleep. On the other hand, the researchers indicated that those who had poor lifestyle habits lost substantially more telomere length than the healthy lifestyle group. The study followed women 50 to 65 years old over a one-year period.

In another study, chronic stress and poor diet (high sugar and high fat) together increased metabolic risks, such as insulin resistance, oxidative stress and central obesity, more than a low-stress group eating a similar diet (9). The high-stress group members were caregivers, specifically those caring for a spouse or parent with dementia. Thus, it is especially important to eat a healthy diet when under stress.

Interestingly, in terms of sleep, the Evolution of Pathways to Insomnia Cohort (EPIC) study shows that those who deal with stressful events directly are more likely to have good sleep quality. Using medication, alcohol or, most surprisingly, distractors to deal with stress all resulted in insomnia after being followed for one year (10). Cognitive intrusions or repeat thoughts about the stressor also resulted in insomnia.

Psychologists and other health care providers sometimes suggest distraction from a stressful event, such as television watching or other activities, according to the researchers. However, this study suggests that this may not help avert chronic insomnia induced by a stressful event. The most important message from this study is that how a person reacts to and deals with stressors may determine whether they suffer from insomnia.

Constant stress is something that needs to be recognized. If it’s not addressed, it can lead to suppressed immune response or increased levels of inflammation. CRP is an example of an inflammatory biomarker that may actually increase stress. In order to address chronic stress and lower CRP, it is important to adopt a healthy lifestyle that includes sleep, exercise and diet modifications. Good lifestyle habits may also be protective against the effects of stress on cell aging.

References: (1) Curr Top Behav Neurosci. 2014 Aug. 29. (2) Am J Physiol. 1991;260(6 Part 1):E927-E932. (3) JAMA Psychiatry. 2013;70:176-184. (4) Chest. 2000;118:503-508. (5) Nat Med. 2014;20:754-758. (6) Proc Natl Acad Sci U S A. 2012;109:5995-5999. (7) J Clin Endocrinol Metab. 2013;98:2078-2083. (8) Mol Psychiatry Online. 2014 July 29. (9) Psychoneuroendocrinol Online. 2014 April 12. (10) Sleep. 2014;37:1199-1208.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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The pancreas is about 6 inches long and sits across the back of the abdomen, behind the stomach.
Increasing vegetable intake may improve outcomes
Dr. David Dunaief

By David Dunaief, M.D.

Everyone has heard of pancreatic cancer, but pancreatitis is a significantly more common disease in gastroenterology and seems to be on an upward projection. Ironically, this disease gets almost no coverage in the general press. In the United States, it is among the top reasons for patients to be admitted to the hospital (1).

Now that I have your attention, let’s define pancreatitis. A rudimentary definition is an inflammation of the pancreas. There are both acute and chronic forms. We are going to address the acute — abrupt and of short duration — form. There are three acute types: mild, moderate and severe. Those with the mild type don’t have organ failure, whereas those with moderate acute pancreatitis experience short-term or transient (less than 48 hours) organ failure. Those with the severe type have persistent organ failure. One in five patients present with moderate or severe levels (2).

What are the symptoms?

In order to diagnosis this disease, the American College of Gastroenterology guidelines suggest that two of three symptoms be present. The three symptoms include severe abdominal pain; increased enzymes, amylase or lipase, that are at least three times greater than normal; and radiologic imaging (ultrasound, CT, MRI, abdominal and chest X-rays) that shows characteristic findings for this disease (3). Most of the time, the abdominal pain is in the central upper abdomen near the stomach (epigastric), and it may also present with pain in the right upper quadrant of the abdomen (4). Approximately 90 percent of patients may also experience nausea and vomiting (5). In half of patients, there may also be pain that radiates to the back.

What are the risk factors?

There is a multitude of risk factors for acute pancreatitis. These include gallstones, alcohol, obesity and, to a much lesser degree, drugs. Gallstones and alcohol may cause up to 75 percent of the cases (2). Many of the other cases of acute pancreatitis are considered idiopathic (of unknown causes). Although medications are potentially responsible for between 1.4 and 5.3 percent of cases, making it rare, the number of medications implicated is diverse (6, 7). These include certain classes of diabetes therapies, some antibiotics — Flagyl (metronidazole) and tetracycline — and immunosuppressive drugs used to treat ailments like autoimmune diseases. Even calcium may potentially increase the risk.

Obesity effects

When given a multiple-choice question for risk factors that includes obesity as one of the answers, it’s a safe bet to choose that answer. Pancreatitis is no exception. However, in a recent study, using the Swedish Mammography Cohort and the Cohort of Swedish Men, results showed that central obesity is an important risk factor, not body mass index or obesity overall (8). In other words, it is fat in the belly that is very important, since this may increase risk more than twofold for the occurrence of a first-time acute pancreatitis episode. Those who had a waist circumference of greater than 105 cm (41 inches) experienced this significantly increased risk compared to those who had a waist circumference of 75 to 85 cm (29.5 to 33.5 inches). The association between central obesity and acute pancreatitis occurred in both gallbladder-induced and non-gallbladder-induced disease. There were 68,158 patients involved in the study, which had a median duration of 12 years. Remember that waistline is measured from the navel, not from the hips. This may be a surprising wake-up call for some.

Mortality risks

What makes acute pancreatitis so noteworthy and potentially dangerous is that the rate of organ failure and mortality is surprisingly high. One study found that the risk of mortality was 5 percent overall. This statistic broke out into a smaller percentage for mild acute pancreatitis and a greater percentage for severe acute pancreatitis, 1.5 and 17 percent, respectively (9). This was a prospective (forward-looking) observational trial involving 1,005 patients. However, in another study, when patients were hospitalized for this disease, the mortality rate was even higher, at 10 percent overall (10).

Diabetes risks

The pancreas is a critical organ for balancing glucose (sugar) in the body. In a recent meta-analysis (involving 24 observational trials), results showed that more than one-third of patients diagnosed with acute pancreatitis went on to develop prediabetes or diabetes (11). Within the first year, 15 percent of patients were newly diagnosed with diabetes. After five years, it was even worse; the risk of diabetes increased 2.7-fold. If we can reduce the risk of pancreatitis, we may also help reduce the risk of diabetes.

Surgical treatments

Gallstones and gallbladder sludge are major risk factors, accounting for 35 to 40 percent of acute pancreatitis incidence (12). Gallstones are thought to cause pancreatitis by temporarily blocking the duct shared by the pancreas and gallbladder that leads into the small intestine. When the liver enzyme ALT is elevated threefold (measured through a simple blood test), it has a positive predictive value of 95 percent that it is indeed gallstone-induced pancreatitis (13). If it is gallstone-induced, surgery plays an important role in helping to resolve pancreatitis and prevent recurrence of acute pancreatitis. In a recent study, results showed that surgery to remove the gallbladder was better than medical treatment when comparing hospitalized patients with this disease (14). Surgery trumped medical treatment in terms of outcomes, complication rates, length of stay in the hospital and overall cost for patients with mild acute pancreatitis. This was a retrospective (backward-looking) study with 102 patients.

Can diet have an impact?

The short answer is: Yes. What foods specifically? In a large, prospective observational study, results showed that there was a direct linear relationship between those who consumed vegetables and a decreased risk of nongallstone acute pancreatitis (15). For every two serving of vegetables, there was 17 percent drop in the risk of pancreatitis. Those who consumed the most vegetables — the highest quintile (4.6 servings per day) — had a 44 percent reduction in disease risk, compared to those who were in the lowest quintile (0.8 servings per day). There were 80,000 participants involved in the study with an 11-year follow-up. The authors surmise that the reason for this effect with vegetables may have to do with their antioxidant properties, since acute pancreatitis increases oxidative stress on the pancreas.

References: (1) Gastroenterology. 2012;143:1179-1187. (2) www.uptodate.com. (3) Am J Gastroenterol. 2013;108:1400-1415. (4) JAMA. 2004;291:2865-2868. (5) Am J Gastroenterol. 2006;101:2379-2400. (6) Gut. 1995;37:565-567. (7) Dig Dis Sci. 2010;55:2977-2981. (8) Am J Gastroenterol. 2013;108:133-139. (9) Dig Liver Dis. 2004;36:205-211. (10) Dig Dis Sci. 1985;30:573-574. (11) Gut. 2014;63:818-831. (12) Gastroenterology. 2007;132:2022-2044. (13) Am J Gastroenterol. 1994;89:1863-1866. (14) Am J Surg online. 2014 Sept. 20. (15) Gut. 2013;62:1187-1192.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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A gluten-free diet can significantly improve symptoms in patients with irritable bowel syndrome.
Gluten control may help with IBS

By David Dunaief, M.D.

Dr. David Dunaief

Gluten has been gaining in notoriety over the last several years. When we hear someone mention a gluten-free diet, several things tend to come to mind. One may be that this is a healthy diet. Along the same lines, we may think gluten is bad for us. However, gluten-free is not necessarily synonymous with healthy. There are many beneficial products containing gluten.

We might think that gluten-free diets are a fad, like low-fat or low-carb diets. Still, we keep hearing how more people feel better without gluten. Could this be a placebo effect? What is myth and what is reality in terms of gluten? In this article I will try to distill what we know about gluten and gluten-free diets, who may benefit and who may not.

But first, what is gluten? Most people I ask don’t know the answer, which is okay; it is part of the reason I am writing the article. Gluten is a plant protein found mainly in wheat, rye and barley.

Now to answer the question of whether going gluten-free is a fad. The answer is a resounding “no” since we know that patients who suffer from celiac disease, an autoimmune disease, benefit tremendously when gluten is removed (1). In fact, it is the main treatment.

But what about people who don’t have celiac disease? There seems to be a spectrum of physiological reaction to gluten, from intolerance to gluten (sensitivity) to gluten tolerance (insensitivity). Obviously, celiac disease is the extreme of intolerance, but even these patients may be asymptomatic. Then, there is nonceliac gluten sensitivity (NCGS), referring to those in the middle portion of the spectrum (2). The prevalence of NCGS is half that of celiac disease, according to the NHANES data from 2009-2010 (3). However, many disagree with this assessment, indicating that it is much more prevalent and that its incidence is likely to rise (4). The term was not even coined until 2011.

What is the difference between full-blown celiac disease and gluten sensitivity? They both may present with intestinal symptoms, such as bloating, gas, cramping and diarrhea, as well as extraintestinal (outside the gut) symptoms, including gait ataxia (gait disturbance), malaise, fatigue and attention deficit disorder (5). Surprisingly, they both may have the same results with serological (blood) tests, which may be positive or negative. The first line of testing includes anti-gliadin antibodies and tissue transglutaminase. These measure a reaction to gluten; however, they don’t have to be positive for there to be a reaction to gluten. HLA–DQ phenotype testing is the second line of testing and tends to be more specific for celiac disease.

What is unique to celiac disease is a histological change in the small intestine, with atrophy of the villi (small fingerlike projections) contributing to gut permeability, what might be called “leaky gut.” Biopsy of the small intestine is the most definitive way to diagnose celiac disease. Though the research has mainly focused on celiac disease, there is some evidence that shows NCGS has potential validity, especially in irritable bowel syndrome.

Before we look at the studies, what does it mean when a food says it’s “gluten-free”? Well, the FDA has weighed in by passing regulation that requires all gluten-free foods to have no more than 20 parts per million of gluten (6).

Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a nebulous disease diagnosed through exclusion, and the treatments are not obvious. That is why the results from a randomized controlled trial, the gold standard of studies, showing that a gluten-free diet significantly improved symptoms in IBS patients, is so important (7). Patients were given a muffin and bread on a daily basis.

Of course, one group was given gluten-free products and the other given products with gluten, though the texture and taste were identical. In six weeks, many of those who were gluten-free saw the pain associated with bloating and gas mostly resolve; significant improvement in stool composition, such that they were not suffering from diarrhea; and their fatigue diminished. In fact, in one week, those in the gluten group were in substantially more discomfort than those in the gluten-free group. There were 34 patients involved in this study.

As part of a well-written March 4, 2013 editorial in Medscape by David Johnson, M.D., a professor of gastroenterology at Eastern Virginia Medical School, he questions whether this beneficial effect from the IBS trial was due to gluten withdrawal or to withdrawal of fermentable sugars because of the elimination of some grains, themselves (8). In other words, gluten may be just one part of the picture. He believes that nonceliac gluten sensitivity is a valid concern.

Autism

Autism is a very difficult disease to quantify, diagnose and treat. Some have suggested gluten may play a role. Unfortunately, in a study with children who had autism spectrum disorder and who were undergoing intensive behavioral therapy, removing both gluten and casein, a protein found in dairy, had no positive impact on activity or sleep patterns (9). These results were disappointing. However, this was a very small study involving 22 preschool children. Removing gluten may not be a panacea for all ailments.

Antibiotics

The microbiome in the gut may play a pivotal role as to whether a person develops celiac disease. In an observational study using data from the Swedish Prescribed Drug Register, results indicate that those who were given antibiotics within the last year had a 40 percent greater chance of developing celiac disease and a 90 percent greater risk of developing inflammation in the gut (10). The researchers believe that this has to do with dysbiosis, a misbalance in the microbiota, or flora, of the gastrointestinal tract. It is interesting that celiac disease may be propagated by change in bacteria in the gut from the use of antibiotics.

Not everyone will benefit from a gluten-free diet. In fact, most of us will not. Ultimately, people who may benefit from this type of diet are those patients who have celiac disease and those who have symptomatic gluten sensitivity. Also, patients who have positive serological tests, including tissue transglutaminase or anti-gliadin antibodies are good candidates for gluten-free diets.

There is a downside to a gluten-free diet: potential development of macronutrient and micronutrient deficiencies. Therefore, it would be wise to ask your doctor before starting gluten withdrawal. The research in patients with gluten sensitivity is relatively recent, and most gluten research has to do with celiac disease. Hopefully, we will see intriguing studies in the near future, since the U.S. market for gluten-free packaged products has grown to over $1.5 billion.

References: (1) Am J Gastroenterol. 2013;108:656-676. (2) Gut 2013;62:43–52. (3) Scand J Gastroenterol. (4) Neurogastroenterol Motil. 2013 Nov;25(11):864-871. (5) medscape.com. (6) fda.gov. (7) Am J Gastroenterol. 2011; 106(3):508-514. (8) medscape.com. (9) 9th annual AIM for Autism Research 2010; abstract 140.007. (10) BMC Gastroenterol. 2013:13(109).

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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Studies have shown that eating grapefruit reduces your risk of developing diabetes.
Be wary of ‘no sugar added’ labels

By David Dunaief, M.D.

Dr. David Dunaif

We should all reduce the amount of added sugar we consume because of its negative effects on our health. It is recommended that we get no more than 10 percent of our diet from added sugars (1). However, we are consuming at least 30 percent more added sugar than is recommended (2).

Is all sugar bad for us? The answer is not straightforward. It really depends on the source, and when I mention “source,” my meaning may surprise you.

We know that white, processed sugar is bad. But, I am constantly asked which sugar source is better: honey, agave, raw sugar, brown sugar or maple syrup. None are really good for us; they all raise the level of glucose (a type of sugar) in our blood.

Two-thirds of our sugar intake comes from processed food, while one-third comes from sweetened beverages, according to the most recent report from the Centers for Disease Control and Prevention. (2) Sweetened beverages are defined as sodas, sports drinks, energy drinks and fruit juices. That’s right: Even 100 percent fruit juice can raise glucose levels. Don’t be deceived by “no added sugar” labels.

These sugars increase the risk of, and may exacerbate, chronic diseases, such as diabetes, heart disease, high blood pressure, cancer and obesity. This is such a significant problem that several legislative initiatives have been introduced that would require a warning label on sweetened drinks (3).

However, I did say that sugar’s source impacts its effect. Most fruits have beneficial effects in preventing disease, including diabetes, and do not raise sugar levels, even in patients with diabetes. It is a myth that whole fruit raises your sugar levels. However, dried fruits, fruit juice and fruit juice concentrate do raise your sugar levels. Note that sugar extracted from fruit has an effect similar to that of sugar added to foods and sweetened beverages. Let’s look at the evidence.

Heart disease

When we think of sugar’s effects, heart disease is not usually the first disease that comes to mind. However, results from a 20-year study of 31,000 U.S. adults showed that, when comparing those who consumed the least amount of added sugar (less than 10 percent of calories daily) with those who consumed 10 to 25 percent and those who consumed more than 25 percent of daily calories from sugar, there were significant increases in risk of death from heart disease (4). The added sugar was from foods and sweetened beverages, not from fruit and fruit juices. This was not just an increased risk of heart disease, but an increased risk of cardiovascular death. This is a wake-up call to rein in our sugar consumption.

Obesity and weight gain

Does soda increase obesity risk? An assessment published in PLoS One, a highly respected, peer-reviewed journal, showed that it depends on whether studies were funded by the beverage industry or had no ties to any lobbying groups (5). Study results were mirror images of each other: Studies not affiliated with the industry show that soda may increase obesity risk, while studies funded by the beverage industry show there may not be any association.

In studies without beverage industry funding, greater than 80 percent (10 of 12) showed associations between sugary drinks and increased weight or obesity, whereas with the beverage industry-funded studies, greater than 80 percent of them did not show this result (5 of 6). The moral of the story is that patients must be diligent in understanding how studies are funded; and if the results sound odd, they probably are. If this is the case, make sure to ask your doctor about the studies’ findings. Not all studies are equally well designed.

Diabetes and the benefits of fruit

Diabetes requires the patient to limit or avoid fruit altogether. Correct? This may not be true. Several studies may help change the long-standing, commonly held paradigm that fruit should be restricted in patients with diabetes and to prevent development of diabetes.

One study found that whole fruit may reduce the risk of diabetes by reducing inflammation and reducing insulin resistance (6). Specifically, results demonstrated a reduction in the inflammatory biomarker hsCRP. Ultimately, this may result in better glucose control. A potential reason for these impressive results may be the high levels of flavonoids, specifically anthocyanins and flavones.

Flavonoids, as a class, are phytochemicals (plant nutrients) that provide pigment to fruits and vegetables and may have substantial antioxidant activities. Substances that are high in these two flavonoids include red grapes, berries, tea and wine.

Another study, a meta-analysis that looked at three large studies, including the Nurses’ Health Study, NHS II, and the Health Professionals Follow-up Study, showed that those who consumed the highest amount of anthocyanins were likely to experience a 15 percent reduction in the development of type 2 diabetes (7). Researchers compared those in the highest quintile of anthocyanin consumption with those in the lowest quintile.

Specifically, at least two servings of blueberries per week were shown to reduce the risk of diabetes by 23 percent, and at least five servings of apples and pears per week were also shown to reduce the risk by 23 percent. These were compared to those who consumed less than one serving per month. This is a small amount of fruit for a significant reduction.

From the same three studies, it was also shown that grapes, bananas and grapefruit reduce the risk of diabetes, while fruit juice and cantaloupe may increase risk (8).

In still another diabetes study, involving those who were newly diagnosed with type 2 diabetes, the risk of increasing glucose levels was no greater in those who consumed more than two servings of fruit per day, when compared to those who consumed fewer than two servings per day (9).

The properties of flavonoids, which are found in whole fruit, may also result in anticancer and anticardiovascular disease properties, the opposite effect of added sugars (10).

Chronic disease incidence and complications from these diseases have skyrocketed in the last several decades. Therefore, any modifiable risk factor should be utilized to decrease our risk. By keeping added sugar to a minimum in our diets, we could make great strides in the fight to maintain our quality of life as we age.

We don’t have to avoid sugar completely; we still can satiate a sweet tooth by eating ripe fruits. Our access to fruit, even off-season, has expanded considerably. The most amazing thing is that fruit may actually reduce the risk of diabetes, something we thought for years might exacerbate it.

References: (1) health.gov: Dietary Guidelines for Americans 2015-2020, eighth edition. (2) cdc.gov. (3) reuters.com. (4) JAMA Intern Med. online Feb 3, 2014. (5) PLoS Med. 2013 Dec;10(12):e1001578. (6) J Nutr. 2014 Feb;144(2):202-208. (7) Am J Clin Nutr. 2012 Apr;95(4):925-933. (8) BMJ. online Aug 29, 2013. (9) Nutr J. published online March 5, 2013. (10) Plant Foods Hum Nutr. 2004 Summer;59(3):113-122.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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Coffee may decrease levothyroxine absorption

By David Dunaief, M.D.

Dr. David Dunaief

It seems like everyone has heard of hypothyroidism. But do we really know what it is and why it is important? The thyroid is a butterfly-shaped organ responsible for maintaining our metabolism. It sits at the base of the neck, just below the laryngeal prominence, or Adam’s apple. The prefix “hypo,” derived from Greek, means “under” (1). Therefore, hypothyroidism indicates an underactive thyroid and results in slowing of the metabolism.

Many people get hypo- and hyperthyroidism confused, but they are really complete opposites. Blood tests determine if a person has hypothyroidism. Items that are tested include thyroid stimulating hormone (TSH), which is usually increased, thyroxine (free T4) and triiodothyronine (free T3 or T3 uptake). Both of these last two may be suppressed (2).

The thyroid sits at the base of the neck, just below the Adam’s apple and is responsible for maintaining metabolism.

There are two types of primary hypothyroidism: subclinical and overt. In the overt (more obvious) type, classic symptoms include weight gain, fatigue, thinning hair, cold intolerance, dry skin and depression, as well as the changes in all three thyroid hormones on blood tests mentioned above. In the subclinical, there may be less obvious or vague symptoms and only changes in the TSH. The subclinical can progress to the overt stage rapidly in some cases (3). Subclinical is substantially more common than overt; its prevalence may be as high as 10 percent of the U.S. population (4).

What are potential causes or risk factors for hypothyroidism? There are numerous factors, such as medications, including lithium; autoimmune diseases, whether personal or in the family history; pregnancy, though it tends to be transient; and treatments for hyperthyroidism (overactive thyroid), including surgery and radiation.

The most common type of hypothyroidism is Hashimoto’s thyroiditis (5). This is where antibodies attack thyroid gland tissues. Several blood tests are useful to determine if a patient has Hashimoto’s: thyroid peroxidase (TPO) antibodies and antithyroglobulin antibodies.

Myths versus realities

I would like to separate the myths from the realities with hypothyroidism. Does treating hypothyroidism help with weight loss? Not necessarily. Is soy potentially bad for the thyroid? Yes. Does coffee affect thyroid medication? Maybe. And finally, do vegetables, specifically cruciferous vegetables, negatively impact the thyroid? Probably not. Let’s look at the evidence.

Treatments: medications and supplements

When it comes to hypothyroidism, there are two main medications: levothyroxine and Armour Thyroid. The difference is that Armour Thyroid converts T4 into T3, while levothyroxine does not. Therefore, one medication may be more appropriate than the other, depending on the circumstance. However, T3 can be given with levothyroxine, which is similar to using Armour Thyroid.

What about supplements?

A recent study tested 10 different thyroid support supplements; the results were downright disappointing, if not a bit scary (6). Of the supplements tested, 90 percent contained actual medication, some to levels higher than what are found in prescription medications. This means that the supplements could cause toxic effects on the thyroid, called thyrotoxicosis. Supplements are not FDA-regulated, therefore, they are not held to the same standards as medications. There is a narrow therapeutic window when it comes to the appropriate medication dosage for treating hypothyroidism, and it is sensitive. Therefore, if you are going to consider using supplements, check with your doctor and tread very lightly.

Soy impact

What role does soy play with the thyroid? In a randomized controlled trial, the gold standard of studies, the treatment group that received higher amounts of soy supplementation had a threefold greater risk of conversion from subclinical hypothyroidism to overt hypothyroidism than those who received considerably less supplementation (7). Thus, it seems that in this small, yet well-designed, study, soy has a negative impact on the thyroid. Therefore, those with hypothyroidism may want to minimize or avoid soy. Interestingly, those who received more soy supplementation did see improvements in blood pressure and inflammation and a reduction in insulin resistance, but, ultimately, a negative impact on the thyroid.

The reason that soy may have this negative impact was illustrated in a study involving rat thyrocytes (thyroid cells) (8). Researchers found that soy isoflavones, especially genistein, which are usually beneficial, may contribute to autoimmune thyroid disease, such as Hashimoto’s thyroiditis. They also found that soy may inhibit the absorption of iodide in the thyroid.

Weight loss

Since being overweight and obese is a growing epidemic, wouldn’t it be nice if the silver lining of hypothyroidism is that, with medication to treat the disease, we were guaranteed to lose weight? In a recent retrospective (looking in the past) study, results showed that only about half of those treated with medication for hypothyroidism lost weight (9). This has to be disappointing to patients. However, this was a small study, and we need a large randomized controlled trial to test it further.

WARNING: The FDA has a black box warning on thyroid medications — they should never be used as weight loss drugs (10). They could put a patient in a hyperthyroid state or worse, having potentially catastrophic results.

Coffee

I am not allowed to take away my wife’s coffee; she draws the line here with lifestyle modifications. So I don’t even attempt to with my patients, since coffee may have some beneficial effects. But when it comes to hypothyroidism, taking levothyroxine and coffee together may decrease the absorption of levothyroxine significantly, according to one study (11). It did not seem to matter whether they were taken together or an hour apart. This was a very small study involving only eight patients. Still, I recommend avoiding coffee for several hours after taking the medication. This should be okay, since the medication must be taken on an empty stomach.

Vegetables

There is a theory that vegetables, specifically cruciferous ones such as cauliflower, cabbage and broccoli, may exacerbate hypothyroidism. In one animal study, results suggested that very high intake of these vegetables reduces thyroid functioning (12). This study was done over 30 years ago, and it has not been replicated.

Importantly, this may not be the case in humans. In the recently published Adventist Health Study-2, results showed that those who had a vegan-based diet were less likely to develop hypothyroidism than those who ate an omnivore diet (13). And those who added lactose and eggs to the vegan diet also had a small increased risk of developing hypothyroidism. However, this trial did not focus on raw cruciferous vegetables, where additional study is much needed.

There are two take-home points, if you have hypothyroid issues: Try to avoid soy products, and don’t think supplements that claim to be thyroid support and good for you are harmless because they are over the counter and “natural.” In my clinical experience, an anti-inflammatory, vegetable-rich diet helps improve quality of life issues, especially fatigue and weight gain, for those with Hashimoto’s thyroiditis.

References: (1) dictionary.com. (2) nlm.nih.gov. (3) Endocr Pract. 2005;11:115-119. (4) Arch Intern Med. 2000;160:526-534. (5) mayoclinic.org. (6) Thyroid. 2013;23:1233-1237. (7) J Clin Endocrinol Metab. 2011 May;96:1442-1449. (8) Exp Biol Med (Maywood). 2013;238:623-630. (9) American Thyroid Association. 2013;Abstract 185. (10) FDA.gov. (11) Thyroid. 2008;18:293-301. (12) Crit Rev Food Sci Nutr. 1983;18:123-201. (13) Nutrients. 2013 Nov. 20;5:4642-4652.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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Adding cruciferous vegetables to your diet significantly decreases the risk of developing multiple cancers. Stock photo
Small studies show diet may affect gene expression

By David Dunaief, M.D.

Dr. David Dunaief

Cancer, a word that for decades was whispered as taboo, has become front and center in the medical community. Cancer is the number one killer of Americans, at least those less than 85 years old, even ahead of cardiovascular disease (1). We have thought that diet may be an important component in preventing cancer. Is diet a plausible approach?

An April 24, 2014, article published in the New York Times, entitled “An Apple a Day and Other Myths,” questioned the validity of diet in the prevention of cancer. This article covered cancer in general, which is a huge and daunting topic.

The article’s author referenced a comment by Walter Willet, M.D., a professor at the Harvard School of Public Health’s Epidemiology and Nutrition Department, as indicating that the research is inconsistent when it comes to fruits and vegetables. The article went on to state that even fiber and fats may not play significant roles in cancer.

I don’t necessarily disagree with this assessment. However, I would like to emphasize that Willet also commented that there are no large, well-controlled diet studies. This leaves the door open for the possibility that diet does have an impact on cancer prevention. I would like to respond.

As Willet hinted, the problem with answering this question may lie with the studies themselves. The problem with diet studies in cancer, in particular, is that they rely mainly on either retrospective (backward-looking) or prospective (forward-looking) observational studies.

Observational studies have many weaknesses. Among them is recall bias, or the ability of subjects to remember what they did. Durability is also a problem; the studies are not long enough, especially with cancer, which may take decades to develop. Confounding factors and patient adherence are other challenges, as are the designs and end points of the studies (2). Plus, randomized controlled trials are very difficult and expensive to do since it’s difficult and much less effective to reduce the thousands of compounds in food into a focus on one nutrient. Let’s look at the evidence.

The EPIC trial

Considered the largest of the nutrition studies is the European Prospective Investigation into Cancer and Nutrition (EPIC). It is part of what the author was using to demonstrate his point that fruits and vegetables may not be effective, at least in breast cancer. This portion of the study involved almost 300,000 women from eight different European nations (3). Results showed that there was no significant difference in breast cancer occurrence between the highest quintile of fruit and vegetable consumption group compared to the lowest. The median duration was 5.4 years.

Does this study place doubt in the dietary approach to cancer? Possibly, but read on. The most significant strength was its size. However, there were also many weaknesses. The researchers were trying to minimize confounding factors, but there were eight countries involved, with many different cultures, making it almost impossible to control. It is not clear if participants were asked what they were eating more often than at the study’s start. Risk stratification was also not clear; which women, for example, might have had a family history of the disease?

Beneficial studies with fruits and vegetables

Also, using the same EPIC study, results showed that fruit may have a statistically significant impact on lung cancer (4). Results showed that there was a 40 percent decrease in the risk of developing lung cancer in those that were in the highest quintile of fruit consumption, compared to those in the lowest quintile. However, vegetables did not have an impact. The results were most pronounced in the northern European region. I did say the answer was complex.

Ironically, it seems that some other studies, mostly smaller studies, show potentially beneficial effects from fruits and vegetables. This may be because it is very difficult to run an intensive, well-controlled, large study.

Prostate cancer

Dean Ornish, M.D., a professor of medicine at UC San Francisco Medical School, has done several well-designed pilot studies with prostate cancer. His research has a focus on how lifestyle affects genes. In one of the studies, results of lifestyle modifications showed a significant increase in telomere length over a five-year period (5).

Telomeres are found on the end of our chromosomes; they help prevent the cell from aging, becoming unstable and dying. Shorter telomeres may have an association with diseases, such as cancer and aging and morbidity (sickness). Interestingly, the better patients adhered to the lifestyle modifications, the more telomere growth they experienced. However, in the control group, telomeres decreased in size over time. There were 10 patients in the lifestyle (treatment) group and 25 patients in the control group — those who followed an active surveillance-only approach.

In an earlier study with 30 patients, there were over 500 changes in gene expression in the treatment group. Of these, 453 genes were down-regulated, or turned off, and 48 genes were up-regulated, or turned on (6). The most interesting part is that these changes occurred over just a three-month period with lifestyle modifications.

In both studies, the patients had prostate cancer that was deemed at low risk of progressing into advanced or malignant prostate cancer. These patients had refused immediate conventional therapy including hormones, radiation and surgery. In both studies, the results were determined by prostate biopsy. These studies involved intensive lifestyle modifications that included a low-fat, plant-based, vegetable-rich diet. But as the researchers pointed out, there is a need for larger randomized controlled trials to confirm these results.

Cruciferous vegetables

A meta-analysis involving a group of 24 case-control studies and 11 observational studies, both types of observational trials, showed a significant reduction in colorectal cancer (7). This meta-analysis looked at the effects of cruciferous vegetables, also sometimes referred to as dark-green, leafy vegetables.

In another study that involved a case-control observational design, cruciferous vegetables were shown to significantly decrease the risk of developing multiple cancers, including esophageal, oral cavity/pharynx, breast, kidney and colorectal cancers (8). There was also a trend that did not reach statistical significance for preventing endometrial, prostate, liver, ovarian and pancreatic cancers. The most interesting part is that the comparison was modest, contrasting consumption of at least one cruciferous vegetable a week with none or less than one a month. However, we need large, randomized trials using cruciferous vegetables to confirm these results.

In conclusion, it would appear that the data are mixed in terms of the effectiveness of fruits and vegetables in preventing cancer or its progression. The large studies have flaws, and pilot studies require larger studies to validate them. However, imperfect as they are, there are results that indicate that diet modification may be effective in preventing cancer. I don’t think we should throw out the baby with the bath water. There is no reason not to consume significant amounts of fruits and vegetables in the hopes that it will have positive effects on preventing cancer and its progression. There is no downside, especially if the small studies are correct.

References: (1) CA Cancer J Clin. 2011;61(4):212. (2) Nat Rev Cancer. 2008;8(9):694. (3) JAMA. 2005;293(2):183-193. (4) Int J Cancer. 2004 Jan 10;108(2):269-276. (5) Lancet Oncol. 2013 Oct;14(11):1112-1120. (6) Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8369-8374. (7) Ann Oncol. 2013 Apr;24(4):1079-1087. (8) Ann Oncol. 2012 Aug;23(8):2198-2203.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com.

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‘Why’ is as important as ‘how’

By David Dunaief, M.D.

Dr. David Dunaief

Weight loss should be a rather simple concept. It should be solely dependent on energy balance: the energy (kilocalories) we take in minus the energy (kilocalories) we burn should result in weight loss, if we burn more calories than we consume. However, it is much more complicated. Frankly, there are numerous factors that contribute to whether people who want or need to lose weight can.

The factors that contribute to weight loss may depend on stress levels. High stress levels can contribute to metabolic risk factors such as central obesity with the release of cortisol, the stress hormone (1). Therefore, hormones contribute to weight gain.

Another factor in losing weight may have to do with our motivators. We will investigate this further. And we need successful weight management, especially when approximately 70 percent of the American population is overweight or obese and more than one-third is obese (2).

Focus on improving your health by making lifestyle modifications like walking your dog.

Obesity, in and of itself, was proclaimed a disease by the American Medical Association. Even if you don’t agree with this statement, excess weight has consequences, including chronic diseases such as cardiovascular disease, diabetes, osteoarthritis, autoimmune diseases and a host of others. Weight has an impact on all-cause mortality and longevity.

It is hotly debated as to which approach is best for weight loss. Is it lifestyle change with diet and exercise, medical management with weight loss drugs, surgical procedures or even supplements? The data show that, while medication and surgery may have their places, they are not replacements for lifestyle modifications; these modifications are needed no matter what route is followed.

But the debate continues as to which diet is best. We would hope patients would not only achieve weight loss but also overall health. Let’s look at the evidence.

Low-carbohydrate vs. low-fat diets

Is a low-carbohydrate, high-fat diet a fad? It may depend on diet composition. In the publication of a randomized controlled trial (RCT), the gold standard of studies, results showed that a low-carbohydrate diet was significantly better at reducing weight than low-fat diet, by a mean difference of 3.5 kg lost (7.7 lb), even though calories were similar and exercise did not change (3).

The authors also note that the low-carbohydrate diet reduced cardiovascular disease risk factors in the lipid (cholesterol) profile, such as decreasing triglycerides (mean difference 14.1 mg/dl) and increasing HDL (good cholesterol). Patients lost 1.5 percent more body fat on the low-carbohydrate diet, and there was a significant reduction in an inflammation biomarker, C-reactive protein (CRP). There was also a reduction in the 10-year Framingham risk score. However, there was no change in LDL (bad cholesterol) levels or in truncal obesity in either group.

This study was 12 months in duration with 148 participants, predominantly women with a mean age of 47, none of whom had cardiovascular disease or diabetes, but all of whom were obese or morbidly obese (BMI 30-45 kg/m²). Although there were changes in biomarkers, there was a dearth of cardiovascular disease clinical end points. This begs the question: Does a low-carbohydrate diet really reduce the risk of developing cardiovascular disease (CVD) or its subsequent complications? The authors indicated this was a weakness since it was not investigated.

Digging deeper into the diets used, it’s interesting to note that the low-fat diet was remarkably similar to the standard American diet; it allowed 30 percent fat, only 5 percent less than the 35 percent baseline for the same group. In addition, it replaced the fat with mostly refined carbohydrates, including only 15 to 16 g/day of fiber.

The low-carbohydrate diet participants took in an average of 100 fewer calories per day than participants on the low-fat diet, so it’s no surprise that they lost a few more pounds over a year’s time. Patients in both groups were encouraged to eat mostly unsaturated fats, such as fish, nuts, avocado and olive oil.

As David Katz, M.D., founding director of Yale University’s Prevention Research Center, noted, this study was more of a comparison of low-carbohydrate diet to a high-carbohydrate diet than a comparison of a low-carbohydrate diet to a low-fat diet (4).

Another study actually showed that a Mediterranean diet, higher in fats with nuts or olive oil, when compared to a low-fat diet, showed a significant reduction in cardiovascular events — clinical end points not just biomarkers (5). However, both of these studies suffer from the same deficiency: comparing a low-carbohydrate diet to a low-fat diet that’s not really low fat.

Diet comparisons

Interestingly, in a meta-analysis (a group of 48 RCTs), the results showed that whether a low-carbohydrate diet (including the Atkins diet) or a low-fat diet (including the Ornish plant-based diet) was followed, there was a similar amount of weight loss compared to no intervention at all (6). Both diet types resulted in about 8 kg (17.6 lb) of weight loss at six months versus no change in diet. However, this meta-analysis did not make it clear whether results included body composition changes or weight loss alone.

In an accompanying editorial discussing the above meta-analysis, the author points out that it is unclear whether a low-carbohydrate/high-animal protein diet might result in adverse effects on the kidneys, loss of calcium from the bones, or other potential deleterious health risks. The author goes on to say that, for overall health and longevity and not just weight loss, micronutrients may be the most important factor, which are in nutrient-dense foods.

A Seventh-Day Adventist trial would attest to this emphasis on a micronutrient-rich, plant-based diet with limited animal protein. It resulted in significantly greater longevity compared to a macronutrient-rich animal protein diet (7).

Psyche

Finally, the type of motivator is important, whatever our endeavors. Weight loss goals are no exception. Let me elaborate.

A published study followed West Point cadets from school to many years after graduation and noted who reached their goals (8). The researchers found that internal motivators and instrumental (external) motivators were very important.

The soldiers who had an internal motivator, such as wanting to be a good soldier, were more successful than those who focused on instrumental motivators, such as wanting to become a general. Those who had both internal and instrumental motivators were not as successful as those with internal motivators alone. In other words, having internal motivators led to an instrumental consequence of advancing their careers.

When it comes to health, an instrumental motivator, such weight loss, may be far less effective than focusing on an internal motivator, such as increasing energy or decreasing pain, which ultimately could lead to an instrumental consequence of weight loss.

There is no question that dietary changes are most important to achieving sustained weight loss. However, we need to get our psyches in line for change. Hopefully, when we choose to improve our health, we don’t just focus on weight as a measure of success. Weight loss goals by themselves tend to lead us astray and to disappoint, for they are external motivators. Focus on improving your health by making lifestyle modifications. This tends to result in a successful instrumental consequence.

References: (1) Psychoneuroendocrinol. online 2014 April 12. (2) JAMA 2012;307:491-497. (3) Ann Intern Med. 2014;161(5):309-318. (4) Huffington Post. Sept 2, 2014. (5) N Engl J Med. 2014 Feb 27;370(9):886. (6) JAMA. 2014;312(9):923-933. (7) JAMA Intern Med. 2013;173:1230-1238. (8) Proc Natl Acad Sci U S A. 2014;111(30):10990-10995.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com.

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