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Medical Compass

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Insomnia is frustrating because it does not necessarily have one cause.
Untreated insomnia can have long-term health effects

By David Dunaief, M.D.

Dr. David Dunaief

Insomnia is an all-too-common complaint. Though the statistics vary widely, about 30 percent of Americans are affected, according to the most frequently used estimate, and women tend to be affected more than men (1). Insomnia is thought to have several main components: difficulty falling asleep, difficulty staying asleep, waking up before a full night’s sleep and sleep that is not restorative or restful (2).

Unlike sleep deprivation, patients have plenty of time for sleep. Having one or all of these components is considered insomnia. There is debate about whether or not it is actually a disease, though it certainly has a significant impact on patients’ functioning (3).

Insomnia is frustrating because it does not necessarily have one cause. Causes can include aging; stress; psychiatric disorders; disease states, such as obstructive sleep apnea and thyroid dysfunction; asthma; medication; and it may even be idiopathic (of unknown cause). It can occur on an acute (short term), intermittent or chronic basis. Regardless of the cause, it may have a significant impact on quality of life. Insomnia also may cause comorbidities (diseases), two of which we will investigate further: heart failure and prostate cancer.

Fortunately, there are numerous treatments. These can involve medications, such as benzodiazepines like Ativan and Xanax. The downside of these medications is they may be habit forming. Nonbenzodiazepine hypnotics (therapies) include sleep medications, such as Lunesta (eszopiclone) and Ambien (zolpidem). All of these medications have side effects. We will investigate Ambien further because of its warnings.

There are also natural treatments, involving supplements, cognitive behavioral therapy and lifestyle changes.

Let’s look at the evidence.

Heart failure

Insomnia may perpetuate heart failure, which can be a difficult disease to treat. In the HUNT analysis (Nord-Trøndelag Health Study), an observational study, results showed insomnia patients had a dose-dependent response for increased risk of developing heart failure (4). In other words, the more components of insomnia involved, the higher the risk of developing heart disease.

There were three components: difficulty falling asleep, difficulty maintaining sleep and nonrestorative sleep that is not restful. If one component was involved, there was no increased risk. If two components were involved, there was a 35 percent increased risk, although this is not statistically significant.

However, if all three components were involved, there was a 350 percent increased risk of developing heart failure, even after adjusting for other factors. This was a large study, involving 54,000 Norwegians, with a long duration of 11 years.

Prostate cancer

Prostate cancer has a plethora of possible causes, and insomnia may be a contributor. Having either of two components of insomnia, difficulty falling asleep or staying asleep (sleep disruption), increased the risk of prostate cancer by 1.7 and 2.1 times, respectively, according to an observational study (5).

However, when looking at a subset of data related to advanced or lethal prostate cancer, both components, difficulty falling asleep and sleep disruption, independently increased the risk even further, 2.1 and 3.2 times, respectively.

This suggests that sleep is a powerful factor in prostate cancer, and other studies have shown that it may have an impact on other cancers as well. There were 2,102 men involved in the study with a duration of five years. While there are potentially strong associations, this and other studies have been mostly observational. Further studies are required before any definitive conclusions can be made.

What about potential treatments?

Ambien: While nonbenzodiazepine hypnotics may be beneficial, this may come at a price. In a report by the Drug Abuse Warning Network, part of the Substance Abuse and Mental Health Services Administration (SAMHSA), the number of reported adverse events with Ambien that perpetuated emergency department visits increased by more than twofold over a five-year period from 2005 to 2010 (6). Insomnia patients most susceptible to having significant side effects are women and the elderly. The director of SAMHSA recommends focusing on lifestyle changes for treating insomnia: by making sure the bedroom is sufficiently dark, getting frequent exercise and avoiding caffeine.

In reaction to this data, the FDA required the manufacturer of Ambien to reduce the dose recommended for women by 50 percent (7). Ironically, sleep medication like Ambien may cause drowsiness the next day — the FDA has warned that it is not safe to drive after taking extended-release versions (CR) of these medications the night before.

Magnesium: The elderly population tends to suffer the most from insomnia, as well as nutrient deficiencies. In a double-blinded, randomized controlled trial (RCT), the gold standard of studies, results show that magnesium had resoundingly positive effects on elderly patients suffering from insomnia (8).

Compared to a placebo group, participants given 500 mg of magnesium daily for eight weeks had significant improvements in sleep quality, sleep duration and time to fall asleep, as well as improvement in the body’s levels of melatonin, a hormone that helps control the circadian rhythm.

The strength of the study is that it is an RCT; however, it was small, involving 46 patients over a relatively short duration.

Cognitive behavioral therapy

In a study, just one 2½-hour session of cognitive behavioral therapy delivered to a group of 20 patients suffering from chronic insomnia saw subjective, yet dramatic, improvements in sleep duration from 5 to 6½ hours and decreases in sleep latency from 51 to 22 minutes (9). The patients who were taking medication to treat insomnia experienced a 33 percent reduction in their required medication frequency per week. The topics covered in the session included relaxation techniques, sleep hygiene, sleep restriction, sleep positions and beliefs and obsessions pertaining to sleep. These results are encouraging.

It is important to emphasize the need for sufficient and good-quality sleep to help prevent, as well as not contribute to, chronic diseases, such as cardiovascular disease and prostate cancer. While medications may be necessary in some circumstances, they should be used with the lowest possible dose for the shortest amount of time and with caution, reviewing possible drug-drug and drug-supplement interactions.

Supplementation with magnesium may be a valuable step toward improving insomnia. Lifestyle changes including sleep hygiene and exercise should be sought, regardless of whether or not medications are used.

References: (1) Sleep. 2009;32(8):1027. (2) American Academy of Sleep Medicine, 2nd edition, 2005. (3) Arch Intern Med. 1998;158(10):1099. (4) Eur Heart J. online 2013;Mar 5. (5) Cancer Epidemiol Biomarkers Prev; 2013;22(5):872–879. (6) SAMSHA.gov. (7) FDA.gov. (8) J Res Med Sci. 2012 Dec;17(12):1161-1169. (9) APSS 27th Annual Meeting 2013; Abstract 0555.

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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Foods high in Vitamin D include egg yolks, beef, shiitake mushrooms, cheese, milk and cold-water fatty fish like salmon, above.
In most geographic locations, sun exposure will not correct vitamin D deficiencies

By David Dunaief, M.D.

Dr. David Dunaief

Vitamin D is one the most widely publicized and important supplements. We get vitamin D from the sun, food and supplements. With our days rapidly shortening here in the Northeast, I thought it would be worthwhile to explore what we know about vitamin D supplementation.

Vitamin D has been thought of as an elixir for life, but is it really? There is no question that, if you have low levels of vitamin D, replacing it is important. Previous studies have shown that it may be effective in a wide swath of chronic diseases, both in prevention and as part of the treatment paradigm. However, many questions remain. As more data come along, their meaning for vitamin D becomes murkier. For instance, is the sun the best source of vitamin D?

At the 70th annual American Academy of Dermatology meeting, Dr. Richard Gallo, who was involved with the Institute of Medicine recommendations, spoke about how, in most geographic locations, sun exposure will not correct vitamin D deficiencies. Interestingly, he emphasized getting more vitamin D from nutrition. Dietary sources include cold-water fatty fish, such as salmon, sardines and tuna.

We know its importance for bone health, but as of yet, we only have encouraging — but not yet definitive — data for other diseases. These include cardiovascular and autoimmune diseases and cancer.

There is no consensus on the ideal blood level for vitamin D. The Institute of Medicine recommends more than 20 ng/dl, and The Endocrine Society recommends at least 30 ng/dl. More experts and data lean toward the latter number.

Skin cancer

Vitamin D did not decrease nonmelanoma skin cancers (NMSCs), such as squamous cell and basal cell carcinoma. It may actually increase them, according to one study done at a single center by an HMO (1). The results may be confounded, or blurred, by UV radiation from the sun, so vitamin D is not necessarily the culprit. Most of the surfaces where skin cancer was found were sun exposed, but not all of them.

The good news is that, for postmenopausal women who have already had an NMSC bout, vitamin D plus calcium appears to reduce its recurrence, according to the Women’s Health Initiative study (2). In this high-risk population, the combination of supplements reduced risk by 57 percent. However, unlike the previous study, vitamin D did not increase the incidence of NMSC in the general population. NMSC occurs more frequently than breast, prostate, lung and colorectal cancers combined (3).

Cardiovascular mixed results

Several observational studies have shown benefits of vitamin D supplements with cardiovascular disease. For example, the Framingham Offspring Study showed that those patients with deficient levels were at increased risk of cardiovascular disease (4).

However, a small randomized controlled trial (RCT), the gold standard of studies, calls the cardioprotective effects of vitamin D into question (5). This study of postmenopausal women, using biomarkers such as endothelial function, inflammation or vascular stiffness, showed no difference between vitamin D treatment and placebo. The authors concluded there is no reason to give vitamin D for prevention of cardiovascular disease.

The vitamin D dose given to the treatment group was 2,500 IUs. Thus, one couldn’t argue that this dose was too low. Some of the weaknesses of the study were a very short duration of four months, its size — 114 participants — and the fact that cardiovascular events or deaths were not used as study end points. However, these results do make you think.

Weight benefit

There is good news, but not great news, on the weight front. It appears that vitamin D plays a role in reducing the amount of weight gain in women 65 years and older whose blood levels are more than 30 ng/dl, compared to those below this level, in the Study of Osteoporotic Fractures (6).

This association held true at baseline and after 4.5 years of observation. If the women dropped below 30 ng/dl in this time period, they were more likely to gain more weight, and they gained less if they kept levels above the target. There were 4,659 participants in the study. Unfortunately, vitamin D did not show statistical significance with weight loss.

Mortality decreased

In a meta-analysis of a group of eight studies, vitamin D with calcium reduced the mortality rate in the elderly, whereas vitamin D alone did not (7). The difference between the groups was statistically important, but clinically small: 9 percent reduction with vitamin D plus calcium and 7 percent with vitamin D alone.

One of the weaknesses of this analysis was that vitamin D in two of the studies was given in large amounts of 300,000 to 500,000 IUs once a year, rather than taken daily. This has different effects.

USPSTF recommendations

The U.S. Preventive Services Task Force recommends against giving “healthy” postmenopausal women the combination of vitamin D 400 IUs plus calcium 1,000 mg to prevent fractures (8). It does not seem to reduce fractures and increases the risk of kidney stones. There is also not enough data to recommend for or against vitamin D with or without calcium for cancer prevention.

Need for clinical trials

We need clinical trials to determine the effectiveness of vitamin D in many chronic diseases, since it may have beneficial effects in preventing or helping to treat them (9). Right now, there is a lack of large randomized clinical trials. Most are observational, which provides associations, but not links. The VITAL study is a large RCT looking at the effects of vitamin D and omega-3s on cardiovascular disease and cancer. It is a five-year trial, and the results should be available in 2018.

When to supplement?

It is important to supplement to optimal levels, especially since most of us living in the Northeast have insufficient to deficient levels. While vitamin D may not be a cure-all, it may play an integral role with many disorders.

References: (1) Arch Dermatol. 2011;147(12):1379-1384. (2) J Clin Oncol. 2011 Aug 1;29(22):3078-3084. (3) CA Cancer J Clin. 2009;59(4):225-249. (4) Circulation. 2008 Jan 29;117(4):503-511. (5) PLoS One. 2012;7(5):e36617. (6) J Women’s Health (Larchmt). 2012 Jun 25. (7) J Clin Endocrinol Metabol. online May 17, 2012. (8) AHRQ Publication No. 12-05163-EF-2. (9) Endocr Rev. 2012 Jun;33(3):456-492.

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

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Lower triglycerides may reduce cardiovascular risk

By David Dunaief, M.D.

Dr. David Dunaief

The lipid, or cholesterol, profile is one of the most common batteries of blood tests. Why? Abnormal cholesterol levels may have an integral role in exacerbating a number of chronic diseases. These diseases are some of the most common, including atherosclerosis (hardening of the arteries), cardiovascular disease (heart disease and stroke) and vascular dementia. It’s even thought to be a component of age-related macular degeneration, the number one cause of vision loss in those who are at least age 60 in industrialized countries (1).

Let’s delve into the components that make up the cholesterol profile. The lipid panel is made up of several components. These include total cholesterol, HDL or “good cholesterol,” LDL or “bad cholesterol” and triglycerides. Many people focus more on total cholesterol, HDL, and LDL and less on triglycerides. We worry about whether the levels are high enough for HDL and are low enough for total cholesterol and LDL. Is this the proper focus? With total cholesterol and LDL, this seems to be appropriate.

However, with HDL it is becoming more complicated; it is less about how high the levels are and more about the functionality of HDL. There are drugs that increase HDL levels, such as niacin and the fibrates, without significantly reducing cardiovascular events. This was demonstrated in the AIM-HIGH trial (2). In this trial, niacin added to a statin drug increased HDL levels and decreased triglyceride levels without a change in the primary end point of cardiovascular outcomes. Thus, they were deemed less than satisfactory and the trial was abruptly ended. However, triglycerides get the short end of the stick. Just look at the lack of coverage in the mainstream media. In this article, we will explore the different components of the lipid panel and the supposed roles they play in our health. Let’s look at the research.

HDL — the good cholesterol that may not be so good

Eating one-and-a-half cups of oatmeal each day can lower your cholesterol by 5 to 8 percent.

For years, when patients were told their total cholesterol and LDL are high, they asked if their HDL levels compensated for this. Of course, we in the medical community are partially to blame for fueling this thinking. More and more studies point to the importance of HDL functionality rather than the level.

In a study investigating a specific gene variant, or mutation, those who had very high levels of HDL, a mean of 106 mg/dL, and two copies of a P376L mutation, had an increased risk of heart disease (3). In a population of 300 participants with this very high level of HDL, only one had this mutation.

When the investigators broadened the number to 1,282 participants, the results were the same. Results were consistent when they looked at a meta-analysis of 300,000 participants with high HDL.

Carriers of the gene mutation, meaning they had one copy instead of two, were at a 79 percent increased risk of heart disease. Those who had this gene mutation were mostly Ashkenazi Jews of European descent. The good news is that this gene mutation is rare. However, it does show that in certain circumstances, HDL is not always good.

Lest you become too relaxed about this study, since the occurrence was uncommon, another study’s results showed that there is a U-shaped curve when it comes to HDL levels (4). In other words, those on the lowest and the highest ends of HDL levels had higher risk of death from both cardiovascular and noncardiovascular death. There were associations among HDL and other factors, like vegetable and fruit consumption, high blood pressure, diabetes, age and sex. Thus, HDL may not by itself be an indicator of heart disease death risk as suggested by the investigators in the trial. This was a large population-based study with over 600,000 participants.

In a third study, results showed that functionality is more important than HDL level (5). What is called the cholesterol-efflux capacity may be central to HDL functionality. This technique calibrates the reverse transport of cholesterol. Cholesterol is removed from a type of white blood cell in the wall of the artery, put back into the bloodstream and removed by the liver. The importance of the functionality is that a higher cholesterol-efflux capacity results in a lower risk of cardiovascular disease. In other words, you may not be able to rely on HDL levels to determine cardioprotective effects.

Triglycerides should get their due

Triglycerides need their 15 minutes of fame, just like the rest of the cholesterol profile. Triglycerides may be an independent risk factor for cardiovascular disease. In a study, results showed that triglycerides are an independent risk factor for all-cause mortality in those with heart disease (6). But even more interesting is that those with high normal levels, those between 100 and 150 mg/dL, have a significantly increased risk of cardiovascular death. In other words, those who are still within normal limits, but at the upper end, should consider reducing their levels.

The results also showed a dose-dependent curve; the higher the levels of triglycerides, the higher the risk of death from cardiovascular disease. Measurements used included borderline high of 150-199 mg/dL, moderately high of 200-499 mg/dL and very high of >500 mg/dL. This was a secondary prevention trial, meaning the patients already had heart disease. Unfortunately, a disproportionate number of patients were men, 81 percent. However, this study had a strong duration of 22 years with data based on 15,000 patients. The weakness of this trial was its inability to control for confounders such as sickness, treatments and cause of death. Still, this signifies that triglycerides have an important role in our health.

Triglycerides are affected by diet. The elements in the diet that raise levels include sugars, grains — for some even whole grains — and starchy vegetables as well as saturated fats and trans fats.

What about whole eggs? Good, bad or neutral?

Today, the debates in the medical community over eggs’ merits, detriments or neutrality continue. In an observational trial from Finland, results show that one egg a day did not increase the risk of heart disease (7). Whew, now we can put that debate behind us and eat eggs, right? NOT SO FAST!

While the strength of the trial was its very impressive duration of 21 years, the weaknesses of the trial were huge. First, participants were asked for a four-day dietary history at the start of the trial and then never again. It was assumed that they were eating the same foods over this long time period. Second, there were no blood tests taken specifically for the study. In other words, there are no cholesterol levels for the trial. So we don’t know if one egg a day — and remember we’re making a gigantic assumption that they did eat one egg a day — had any negative impact on cholesterol levels. Third, this study population did not include women. There were 1,032 men involved. Having said all this, you could try an egg a day. However, I would highly recommend a physician’s supervision.

In my practice, I had several patients eat two eggs a day, and their total cholesterol levels went up by approximately 100 mg/dL in one month. But this is anecdotal data from my clinical experience.

In conclusion, don’t think you’re safe if you have a high HDL level. It is best to lower your triglycerides to below 100 mg/dL, and an effective way to do this is by reducing sugars, grains, starchy vegetables and saturated fat in your diet. However, there is subset data suggesting that the fibrate class of drugs may have benefit in those who have triglycerides of at least 500 mg/dL (6).

References: (1) www.nlm.nih.gov. (2) N Engl J Med 2011; 365:2255-2267. (3) Science 2016; 351:1166-1171. (4) AHA 2015 Scientific Sessions; Nov. 10, 2015. (5) N Engl J Med. 2014;371(25):2383-2393. (6) Circ Cardiovasc Qual Outcomes 2016;9:100-108. (7) Am J Clin Nutr. 2016;103(3):895-901.

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 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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