Medical Compass

Pedometers can be the first step to helping those with mild COPD. Stock photo
Lifestyle changes can reduce COPD exacerbations

By David Dunaief, M.D.

Dr. David Dunaief

COPD, or chronic obstructive pulmonary disease, is the third leading cause of mortality in the United States (1), although it’s not highlighted much in the layman’s press.

COPD is an umbrella term that includes emphysema, chronic bronchitis of more than three months for two consecutive years and/or chronic obstructive asthma. It is an obstructive lung disease that limits airflow. The three most common symptoms of the disease involve shortness of breath, especially on exertion, production of sputum and cough. This disease affects 6.7 percent of the U.S. population (2).

It tends to be progressive, meaning more frequent and severe exacerbations over time. Since it is a devastating and debilitating chronic disease with no cure, anything that can identify and prevent COPD exacerbations, as well as comorbidities (associated diseases), is critically important.

What are the traditional ways to reduce the risk of and treat COPD exacerbations? The most important step is to stop smoking, since 80 percent of COPD is related to smoking. Supplemental oxygen therapy and medications, such as corticosteroids, bronchodilators (beta-adrenergic agonists and anticholinergics) and antibiotics help to alleviate symptoms (3).

One of the underlying components of COPD may be chronic inflammation (4). Therefore, reducing inflammation may help to stem COPD exacerbations. There are several inflammatory biomarkers that could potentially help predict exacerbations and mortality associated with this disease, such as interleukin-6 (IL-6), C-reactive protein (CRP), leukocyte (white blood cell) count and fibrinogen (a clotting factor of the blood).

How do we reduce inflammation, which may contribute to exacerbations of this disease? Some drugs, such as statins, work partially by reducing inflammation. They may have a role in COPD. Lifestyle changes that include a high-nutrient, anti-inflammatory diet and exercise may also be beneficial. Let’s look at the evidence.

Biomarkers for inflammation

In a recent population-based study with over 60,000 participants, results show that as three biomarkers (CRP, leukocyte count and fibrinogen) were elevated, the risk of COPD exacerbation increased in a linear manner (5). In other words, the risk of frequent exacerbation increased 20, 70 and 270 percent within the first year as the number of elevated biomarkers increased from one to three, compared to patients who did not have biomarker elevations.

As time progressed beyond the first year of follow-up, risk exacerbation continued to stay high. Patients with all three biomarkers elevated for longer periods had a 150 percent increased risk of frequent exacerbations. These predictions were applicable to patients with stable and with mild COPD.

In an observational study, results showed that when the biomarker IL-6 was elevated at the start of the trial in stable COPD patients, the risk of mortality increased almost 2.7-fold (6). Also, after three years, IL-6 increased significantly. Elevated IL-6 was associated with a worsening of six-minute walking distance, a parameter tied to poor physical performance in COPD patients. However, unlike the previous study, CRP did not show correlation with increased COPD exacerbation risk. This was a small trial, only involving 53 patients. Therefore, the results are preliminary.

These biomarker trials are exciting for their potential to shape treatments based on level of exacerbation risk and mortality, creating more individualized therapies. Their results need to be confirmed in a randomized controlled trial (RCT). Many of these biomarkers mentioned in the two trials are identifiable with simple blood tests at major labs.

Statin effect

Statins have been maligned for their side effects, but their efficacy has been their strong suit. An observational trial showed that statins led to at least a 30 percent reduction in the risk of COPD exacerbations, with the effect based on a dose-dependent curve (7). In other words, as the dose increased, so did the benefit.

Interestingly, even those who had taken the statin previously saw a significant reduction in COPD exacerbation risk. The duration of statin use was not important; a short use of statins, whether presently or previously, had substantial benefit. 

However, the greatest benefit was seen in those who had been on a medium to high dose or were on the drug currently. The researchers believe that the mechanism of action for statins in this setting has to do with their anti-inflammatory and immune-modulating effects. This was a retrospective (backward-looking) study with over 14,000 participants. We will need a prospective (forward-looking) study and an RCT to confirm the results.

Exercise

Pedometers can be the first step to helping those with mild COPD. Stock photo

Exercise is beneficial for almost every circumstance, and COPD is no exception. But did you know that a pedometer might improve results? In a three-month study, those with mild COPD were much more successful at achieving exercise goals and reducing exacerbations and symptoms when they used pedometers, compared to the group given advice alone (8). Pedometers gave patients objective feedback on their level of physical activity, which helped motivate them to achieve the goal of walking 9,000 steps daily. This is a relatively easy way to achieve exercise goals and reduce the risk of COPD exacerbations.

When exercising, we are told to vary our exercise routines on a regular basis. One study demonstrates that this may be especially important for COPD patients (9). Results show that nonlinear periodization exercise (NLPE) training is better than traditional routines of endurance and resistance training in severe COPD patients. The goal of NLPE is to alter the time spent working out, the number of sets, the number of repetitions and the intensity of the workout on a regular basis.

This study was randomized, involved 110 patients and was three months in duration. Significantly more severe COPD patients achieved their exercise goals using NLPE rather than the traditional approach. The group that used NLPE also had an improved quality of life response. The researchers believe that compliance with an NLPE-type program is mostly likely going to be greater because patients seem to enjoy it more.

Chronic inflammation may play a central role in COPD exacerbation. Nonspecific inflammatory biomarkers are potentially valuable for providing a more personalized approach to therapy. Drugs that can control inflammation, such as statins, show promise. But don’t forget the importance of lifestyle changes, such as quitting smoking and committing to an exercise regimen that is varied and/or involves the use of a pedometer. And potentially a high-nutrient, anti-inflammatory diet will also contribute positively to reducing the frequency and severity of COPD exacerbations.

References:

(1) Natl Vital Stat Rep. 2011 Dec.;59(10):1-126. (2) cdc.gov. (3) N Engl J Med. 2002;346:988-994. (4) www.goldcopd.org. (5) JAMA. 2013;309:2353-2361. (6) Respiratory Research. 2013;14:24. (7) Am J Med. 2013 Jul;126:598-606. (8) ATS 2013 International Conference: Abstract A1360. (9) Am J Respir Crit Care Med. 2013; online Feb. 28.

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.

In addition to bananas, plenty of other foods are high in potassium. Above are just a few examples. Stock photo
Most Americans don’t consume enough potassium

By David Dunaief M.D.

Dr. David Dunaief

One of the most popular food additives is also one of the most dangerous: salt. We need salt, but not in excess. On the other hand, potassium is beneficial in our diet. However, we have the opposite problem with potassium: It is under-consumed.

More than 90 percent of people consume far too much sodium, with salt being the primary culprit (1). Sodium is found in foods that don’t even taste salty. Bread and rolls are the primary offenders, since we eat so much of them. Other foods with substantial amounts of sodium are cold cuts and cured meats, cheeses, pizza (which has both bread and cheese), fresh and processed poultry, soups, meat dishes, pastas and snack foods. Foods that are processed and those prepared by restaurants are where most of our consumption occurs (2).

By contrast, only about 2 percent of people get enough potassium from their diets (3). According to one study, we would need to consume about eight sweet potatoes or 10 bananas each day to reach appropriate levels. Why is it important to reduce sodium and increase potassium? A high sodium-to-potassium ratio increases the risk of cardiovascular disease by 46 percent, according to the study, which looked at more than 12,000 Americans over almost 15 years (4). In addition, both may have significant impacts on blood pressure and cardiovascular disease.

To improve our overall health, we need to tip the sodium-to-potassium scales, consuming less sodium and more potassium. Let’s look at the evidence.

Reduced sodium

There are two studies that illustrate the benefits of reducing sodium in high blood pressure and normotensive (normal blood pressure) patients, ultimately preventing cardiovascular disease, including heart disease and stroke.

The first study used the prestigious Cochrane review to demonstrate that blood pressure is reduced by a significant mean of −4.18 mm Hg systolic (top number) and −2.06 mm Hg diastolic (bottom number) involving both normotensive and hypertensive participants (5). When looking solely at hypertensive patients, the reduction was even greater, with a systolic blood pressure reduction of −5.39 mm Hg and a diastolic blood pressure reduction of −2.82 mm Hg.

This was a meta-analysis (a group of studies) that evaluated data from randomized clinical trials, the gold standard of studies. There were 34 trials reviewed with more than 3,200 participants. Salt was reduced from 9 to 12 grams per day to 5 to 6 grams per day. These levels were determined using 24-hour urine tests. The researchers believe there is a direct linear effect with salt reduction. In other words, the more we reduce the salt intake, the greater the effect of reducing blood pressure. The authors concluded that these effects on blood pressure will most likely result in a decrease in cardiovascular disease.

In the second study, a meta-analysis of 42 clinical trials, there was a similarly significant reduction in both systolic and diastolic blood pressures (6). This meta-analysis included adults and children. Both demographics saw a reduction in blood pressure, though the effect, not surprisingly, was greater in adults. Interestingly, an increase in sodium caused a 24 percent increased risk of stroke incidence but, more importantly, a 63 percent increased risk of stroke mortality. The risk of mortality from heart disease was increased as well, by 32 percent.

In an epidemiology modeling study, the researchers projected that either a gradual or instantaneous reduction in sodium would save lives (7). For instance, a modest 40 percent reduction over 10 years in sodium consumed could prevent 280,000 premature deaths. These are only projections, but in combination with the above studies may be telling. The bottom line is: decrease sodium intake by almost half and increase potassium intake from foods.

Potassium’s positive effects

When we think of blood pressure, sodium comes to mind, but not enough attention is given to potassium. The typical American diet doesn’t contain enough of this mineral.

In a meta-analysis involving 32 studies, results showed that as the amount of potassium was increased, systolic blood pressure decreased significantly (8). When foods containing 3.5 to 4.7 grams of potassium were consumed, there was an impressive −7.16 mm Hg reduction in systolic blood pressure with high blood pressure patients. Anything more than this amount of potassium did not have any additional benefit. Increased potassium intake also reduced the risk of stroke by 24 percent. This effect was important. If this does not sound like a large reduction, consider that, by comparison, aspirin has been shown to reduce the risk of stroke by 20 percent.

The reduction in blood pressure was greater with increased potassium consumption than with sodium restriction, although there was no head-to-head comparison done. The good news is that potassium is easily attainable in the diet. Foods that are potassium rich include bananas, sweet potatoes, almonds, raisins and green leafy vegetables such as Swiss chard.

Lowering sodium intake may have far-reaching benefits, and it is certainly achievable. We need to reduce our intake and give ourselves a brief period to adapt — it takes about six weeks to retrain our taste buds, once we reduce our sodium intake. We can also improve our odds by increasing our dietary potassium intake, which also has a substantial beneficial effect, striking a better sodium-to-potassium balance.

References:

(1) Am J Clin Nutr. 2012 Sep;96(3):647-657. (2) www.cdc.gov. (3) Am J Clin Nutr. 2012 Sep;96(3):647-657. (4) Arch Intern Med. 2011;171(13):1183-1191. (5) BMJ. 2013 Apr 3;346:f1325. (6) BMJ. 2013 Apr 3;346:f1326. (7) Hypertension. 2013; 61: 564-570. (8) BMJ. 2013; 346:f1378.

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.

Concentrate on lifestyle modifications like going for walks if you want to see potentially disease-modifying effects. Stock photo
Diet and exercise changes may slow progression

By David Dunaief, M.D.

Not surprisingly, osteoarthritis is widespread. The more common joints affected are the knees, hips and hands. There are three types of treatment for this disease: surgery, involving joint replacements of the hips or knees; medications; and nonpharmacologic approaches. The most commonly used first-line medications are acetaminophen and nonsteroidal anti-inflammatory drugs, such as ibuprofen. Unfortunately, medications mostly treat the symptoms of pain and inflammation.

However, the primary objectives in treating osteoarthritis should also include improving quality of life, slowing progression of the disease process and reducing its disabling effects (1).

Dairy and milk

When we think of dairy, specifically milk, there are two distinct camps: One believes in the benefits, and the other thinks it may contribute to the disease. In this case they both may be at least partly correct. In the Osteoarthritis Initiative study, an observational study of over 2,100 patients, results showed that low-fat (1 percent) and nonfat milk may slow the progression of osteoarthritis (2). The researchers looked specifically at joint space narrowing that occurs in those with affected knee joints. Radiographic imaging changes were used at baseline and then to follow the patients for up to 12 to 48 months for changes. Compared to those who did not drink milk, patients who did saw significantly less narrowing of knee joint space.

Was it a dose-dependent response? Not necessarily. Specifically, those who drank less than three glasses/week and those who drank four to six glasses/week both saw slower progression of joint space narrowing of 0.09 mm. Seven to 10 glasses/week resulted in a 0.12 mm preservation. However, those who drank more than 10 glasses/week saw less beneficial effect, 0.06 mm preservation compared to those who did not drink milk. Interestingly, there was no benefit seen in men or with the consumption of cheese or yogurt.

However, there are significant flaws with this study. First, the patients were only asked about their dietary intake of milk at baseline; therefore their consumption could have changed during the study. Second, there was a recall bias; patients were asked to recall their weekly milk consumption for the previous 12 months before the study began. I don’t know about you, but I can’t recall my intake of specific foods for the last week, let alone for the past year. Third, there could have been confounding factors, such as orange consumption.

Oddly, this was not a dose-response curve, since the most milk consumption had less beneficial effect than lower amounts. Also, why were these effects only seen in women? Finally, researchers could not explain why low-fat or nonfat milk had this potential benefit, but cheese was detrimental and yogurt did not show benefit. We are left with more questions than answers.

Would I recommend consuming low-fat or nonfat milk? Not necessarily, but I may not dissuade osteoarthritis patients from drinking it. There are very few approaches that slow the progression of joint space narrowing.

Vitamin D

Over the last five years or so, the medical community has gone from believing that vitamin D was potentially the solution to many diseases to wondering whether, in some cases, low levels were indicative of disease, but repletion was not a change-maker. Well, in a randomized controlled trial (RCT), the gold standard of studies, vitamin D had no beneficial symptom relief nor any disease-modifying effects (3). This two-year study of almost 150 men and women raised blood levels of vitamin D on average to 36 ng/ml, which is considered respectable. Researchers used MRI and X-rays to track their results.

Glucosamine

There is raging debate about whether glucosamine is an effective treatment for osteoarthritis. In the latest installment, there was an RCT, the results of which showed that glucosamine hydrochloride was not effective in treating osteoarthritis (4). In the trial, 201 patients with either mild or moderate knee pain drank diet lemonade with or without 1,500 mg of glucosamine hydrochloride.

There was no difference in cartilage changes in the knee nor in pain relief in those in the placebo or treatment groups over a six-month duration. Bone marrow lesions also did not improve with the glucosamine group. The researchers used 3T MRI scans (an advanced radiologic imaging technique) to follow the patients’ disease progression. This does not mean that glucosamine does not work for some patients. Different formulations, such as glucosamine sulfate, were not used in this study.

Weight

This could not be an article on osteoarthritis if I did not talk about weight. Do you remember analogies from the SATs? Well here is one for you: Weight loss, weight loss, weight loss is to osteoarthritis as location, location, location is to real estate. In a study involving 112 obese patients, there was not only a reduction of knee symptoms in those who lost weight, but there was also disease modification, with reduction in the loss of cartilage volume around the medial tibia (5).

On the other hand, those who gained weight saw the inverse effect. A reduction of tibial cartilage is potentially associated with the need for knee replacement. The relationship was almost one to one; for every 1 percent of weight lost, there was a 1.2 mm³ preservation of medial tibial cartilage volume, while the exact opposite was true with weight gain.

Exercise and diet

In a study, diet and exercise trumped the effects of diet or exercise alone (6). Patients with osteoarthritis of the knee who lost at least 10 percent of their body weight experienced significant improvements in function and a 50 percent reduction in pain, as well as reduction in inflammation, compared to those who lost 5 to 10 percent and those who lost less than 5 percent. This study was a well-designed, randomized controlled single-blinded study with a duration of 18 months.

Researchers used a biomarker — IL6 — to measure inflammation. The diet and exercise group and the diet-only group lost significantly more weight than the exercise-only group, 23.3 and 19.6 pounds versus 4 pounds. The diet portion consisted of a meal replacement shake for breakfast and lunch and then a vegetable-rich, low-fat dinner. Low-calorie meals replaced the shakes after six months. The exercise regimen included one hour of a combination of weight training and walking with alacrity three times per week.

Therefore, concentrate on lifestyle modifications if you want to see potentially disease-modifying effects. These include both exercise and diet. In terms of low-fat or nonfat milk, while the study had numerous flaws, if you drink milk, you might continue for the sake of osteoarthritis, but stay on the low end of consumption. And remember, the best potential effects shown are with weight loss and with a vegetable-rich diet.

References:

(1) uptodate.com. (2) Arthritis Care Res online. 2014 April 6. (3) JAMA. 2013;309:155-162. (4) Arthritis Rheum online. 2014 March 10. (5) Ann Rheum Dis online. 2014 Feb. 11. (6) 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.

Season allergies are triggered by pollen from trees, grass and weeds. Stock photo

By David Dunaief, M.D.

Dr. David Dunaief

After winter ends, we look forward to mild temperatures. The days get longer, trees and flowers bud and bloom, and grass becomes lush and green. It seems like heaven. But for people who suffer from seasonal allergic rhinitis, hay fever, seasonal allergies or whatever you would like to call it, life can be downright miserable. You probably can rate an allergy season with your own built-in personal barometer, the sneeze factor. How many times are you, your friends or your colleagues sneezing?

Approximately 20 million U.S. adults have had a diagnosis of seasonal allergies within the past year, just a little over 8 percent of the population, and an additional 6.1 million children have this disorder, or about 8.4 percent, according to the Centers for Disease Control and Prevention (1). Sadly, considering the number of people it affects, only a paltry amount of research has been published.

The triggers for seasonal allergies are diverse. They include pollen from leafy trees and shrubs, lush grass and beautiful flowering plants, as well as weeds, with the majority from ragweed (mostly in the fall) and fungus (summer and fall) (2).

What sparks allergies within the body? A chain reaction occurs in seasonal allergy sufferers. When foreign substances such as allergens (pollen, in this case) interact with immunoglobulin E (IgE), antibodies that are part of our immune system, it causes mast cells in the body’s tissues to degrade and release inflammatory mediators. These include histamines, leukotrienes and eosinophils in those who are susceptible. In other words, it is an allergic inflammatory response.

The revved up immune system then responds with sneezing; red, itchy and watery eyes; scratchy throat; congestion; sinus headaches; postnasal drip; runny nose; diminished taste and smell; and even coughing (3). Basically, it emulates a cold, but without the virus. If symptoms last more than 10 days and are recurrent, then it is more than likely you have allergies.

Risk factors for seasonal allergies are tied most strongly to family history and to having other personal allergies, such as eczema or food allergies, but also may include cigarette exposure, being male and, possibly, diet (4). If allergic rhinitis is not properly treated, complications such as ear infections, sinusitis, irritated throat, insomnia, chronic fatigue, headaches and even asthma can result (5).

To treat allergic rhinitis, we have a host of medications from classes including intranasal glucocorticoids (steroids), oral antihistamines, allergy shots, decongestants, antihistamine and decongestant eye drops and leukotriene modifiers (second-line only).

The best way to treat allergy attacks is to prevent them, but this is an arduous process that can mean closing yourself out from the enjoyment of spring by literally closing the windows, using the air-conditioning, and using recycling vents in your car.

The guidelines for treating seasonal allergic rhinitis with medications suggest that intranasal corticosteroids (steroids) should be used when quality of life is affected. If there is itchiness and sneezing, then second-generation oral antihistamines may be appropriate (6). Two well-known inhaled steroids that do not require a prescription are Nasocort (triamcinolone) and Flonase (fluticasone propionate). There does not seem to be a significant difference between them (7). While inhaled steroids are probably most effective in treating and preventing symptoms, they need to be used every day and are not without side effects.

Oral antihistamines, on the other hand, can be taken on an as-needed basis. Second-generation antihistamines include loratadine (Claritin), cetirizine (Zyrtec) and fexofenadine (Allegra), and they have less sleepiness as a side effect than first-generation antihistamines.

Surprisingly good news

Seasonal allergic rhinitis may actually be beneficial for longevity. In a study involving more than 200,000 participants, results showed that those who had allergies had a 25 percent reduction in the risk of heart attacks, a 19 percent reduction in strokes, and a whopping 49 percent reduction in mortality (8). Remember two things: this is an observational trial, which means that it is not the best of trials, and don’t wish allergies on yourself. This effect may be at least partially attributable to the type of white blood cell expressed in the immune system.

In other words, type 2 T helper (Th2) lymphocytes (white blood cells) are elevated with allergies instead of type 1 T helper (Th1) lymphocytes. Why is this important? Th2 is known to decrease cardiovascular disease, while Th1 is known to possibly increase cardiovascular disease. Unfortunately, the same cannot be said about asthma, where cardiovascular events are increased by 36 percent.

Alternative treatments

Butterbur (Petasites hybridus), an herb, may not be just for migraines. There are several small studies that indicate its efficacy in treating hay fever. In fact, in one study, results showed that butterbur was as effective as cetirizine (Zyrtec) in treating this disorder (9). This was a small, randomized, controlled trial involving 131 patients.

In another randomized, controlled trial, results showed that high doses of butterbur — 1 tablet given three times a day — was significantly more effective than placebo (10). The side effects were similar in the placebo group and the butterbur group. The researchers used butterbur Ze339 (carbon dioxide extract from the leaves of Petasites hybridus L., 8 mg petasines per tablet) in the trial. The authors concluded that butterbur would be potentially useful for intermittent allergic rhinitis. The duration of treatment for this study was two weeks.

Still another study, this one a post-marketing study done as a follow-up to the previous study, showed that with butterbur Ze339, symptoms improved in 90 percent of patients with allergic rhinitis (11). Interestingly, anti-allergic medications were co-administered in about half of the patient population, with no additional benefit over butterbur alone. There were 580 patients in this study, and the duration was two weeks. Gastrointestinal upset occurred as the most common side effect in 3.8 percent of the population.

The caveats to the use of butterbur are several. First, the studies were short in duration. Second, the leaf extract used in these studies was free of pyrrolizidine alkaloids (PAs); this is very important since PAs may not be safe. Third, the dose was well-measured, which may not be the case with over-the-counter extracts. Fourth, you need to ask about interactions with your prescription medications.

Diet

While there are no significant studies on diet, there is one review of literature that suggests that a plant-based diet may reduce symptoms of allergies, specifically rhinoconjunctivitis, affecting the nose and eyes, as well as eczema and asthma. This is according to the International Study of Asthma and Allergies in Childhood study in 13- to 14-year-old teens (12). In my clinical practice, I have seen patients who suffer from seasonal allergies improve and even reverse the course of allergies over time with a vegetable-rich, plant-based diet, possibly due to an anti-inflammatory effect.

While allergies can be miserable, there are a significant number of over-the-counter and prescription options to help to reduce symptoms. Diet may play a role in the disease process by reducing inflammation, though there are no formal studies. There does seem to be promise with some herbs, especially butterbur. However, alternative supplements and herbs lack large, randomized clinical trials with long durations. Always consult your doctor before starting any supplements, herbs or over-the-counter medications.

References: (1) CDC.gov. (2) acaai.org/allergies/types/pollen-allergy. (3) Allergy Clin Immunol. 2003;112(6):1021-1031. (4) umm.edu. (5) J Allergy Clin Immunol. 2010;125(1):16-29. (6) Otolaryngol Head Neck Surg. online February 2, 2015. (7) Otolaryngol Head Neck Surg. 2003;129(1):16. (8) AAAAI 2014: Abstract 811. (9) BMJ 2002;324:144. (10) Arch Otolaryngol Head Neck Surg. 2004;130(12):1381-1386. (11) Adv Ther. 2006;23(2):373-384. (12) Eur Respir J. 2001;17(3):436-443.

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.

Symptoms of gallstones include dull or crampy abdominal pain that is exacerbated by meals and lasts one to five hours. Stock photo

By David Dunaief, M.D.

Dr. David Dunaief

Gallstones are a very common gastrointestinal disease; they affect up to 20 million Americans between the ages of 20 and 74, with a more than two-times increased occurrence in women than in men, according to the NHANES III survey (1). There are two types of gallstones, 80 percent of which are cholesterol stones and 20 percent of which are pigment stones.

Common symptoms

Gallstones may be asymptomatic; however, when gallstones block either the cystic or common bile ducts, symptoms occur. Symptoms include dull or crampy abdominal pain that is exacerbated by meals and lasts one to five hours. Jaundice, which includes yellowing of skin and eyes, is another symptom. Others include nausea and vomiting, rapid heart rate, hypotension (low blood pressure) and fever (2).

Tests used for diagnosis

Blood tests include complete blood count, where there may be a rise in white blood cells; liver enzymes; and the pancreatic enzymes lipase and amylase. In general, diagnostic tests that have more accuracy are the endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). However, these are invasive tests. Less accurate but noninvasive tests include abdominal X-ray, ultrasound and CAT scan (CT). The tests used also depend on where the stone may be located. Hepatobiliary (HIDA) scans are accurate if the stone is located in the cystic duct. And magnetic resonance retrograde cholangiopancreatography (MRCP) is used if the stone is thought to be located in the common bile duct (2).

What are the risk factors?

There are a multitude of risk factors. Some of these are modifiable, some others are not. The modifiable ones include obesity, measured by body mass index (BMI); rapid weight loss; fat consumption; hormone replacement therapy (HRT); oral contraceptives; decreased physical activity; Crohn’s disease; and certain drugs. One nonmodifiable risk factor is age; the older we get, the higher the risk, with age 40 being the demarcation line (3). Other risk factors are gender, with females being more predisposed; pregnancy; and family history (4). Let’s look at the evidence.

Obesity risks

Obesity may play an important role. Obesity is not age discriminant; it can impact both adults and children. The reason obesity is implicated is potentially due to bile becoming supersaturated (5). Bile is a substance produced in the liver and stored in the gallbladder. Bile aids in the digestion or breakdown of fats in the small intestines. Crystals may form, creating cholesterol gallstones from the bile.

Body mass index

A body mass index of greater than 30 kg/m² is considered obese. In a meta-analysis of two prospective, forward-looking observational trials, Copenhagen General Population Study and the Copenhagen City Heart Study, those in the highest quintile of BMI were almost three times as likely to experience symptomatic gallstones compared to those who were in the lowest quintile (6). The highest quintile was those who had a mean BMI of 32.5 kg/m² and thus were obese, whereas those in the lowest quintile had a mean BMI of 20.9 kg/m². This is a comparison of ideal to obese BMI. Not surprisingly, since women in general have a higher risk of gallstones, they also have a higher risk when their BMI is in the obese range compared to men, a 3.36-fold increase and 1.51-fold increase, respectively.

Also, the research showed that for every 1 kg/m² increase in BMI, there was a 7 percent increase in the risk of gallstones. Those who had genetic variants that increased their likelihood of an elevated BMI had an even greater increase in gallstone risk —17 percent — per 1 kg/m². In the study population of approximately 77,000, more than 4,000 participants became symptomatic for gallstones.

Gallstones in children

Sadly, obese children are not immune to gallstones, even though they are young. In a prospective observational study based on Kaiser Permanente data from southern California, children who were overweight had a twofold increased risk of gallstones (7). But if that is not enough, girls who were extremely obese had a higher propensity for gallstones, similar to women in the previous study, with a greater-than-sevenfold increase compared to a still very substantial greater-than-threefold increase for obese boys. Hispanic children were affected the most. The age range in this study was between 10 and 19 years old. Obesity is a disease that is blind to age.

Physical activity

We know physical activity is very important to stave off many diseases, but in this case, the lack of physical activity can be detrimental. In the Physicians’ Health Study, a prospective observational trial, those in the lowest quintile of activity between the ages of 40 and 64 had a 72 percent increased risk of gallstone formation, and those 65 and older had a 33 percent increased risk (8). Also, men who were 65 and older and watched television more than six hours a week were at least three times as likely to have gallstones as those who watched fewer hours. There was a substantial increased risk for those under 65, as well, though to a slightly lesser degree.

Diabetes rears its ugly head

Just like with obesity, diabetes is almost always a culprit for complications. In a prospective observational study, those with diabetes were at a significant 2.55-times greater risk of developing gallstones than those without (9). Again, women had a higher propensity than men, but both had significant increases in the risk of gallstone formation, 3.85-times and 2.03-times, respectively. There were almost 700 participants in this study. The researchers believe that an alteration in glucose (sugar) metabolism may create this disease risk.

Hormone replacement therapy

If you needed another reason to be leery of hormone replacement therapy (HRT), then gallstones might be it. In a prospective observational trial, women who used HRT, compared to those who did not, had a 10 percent increased risk in cholecystectomy — removal of the gallbladder — to treat gallstones (10). Though this may not sound like a large increase, oral HRT increased the risk 16 percent, and oral estrogen-only therapy without progestogens increased the risk the most, 38 percent. Transdermal HRT did not have a significantly increased risk.

It is never too early or too late to treat obesity before it causes, in this case, gallstones. With a lack of exercise, obesity is exacerbated and, not surprisingly, so is symptomatic gallstone formation. Diabetes needs to be controlled to prevent complications. HRT, unless menopausal symptoms are unbearable, continues to show why it may not be a good choice. Next week, we will look at the complications of gallstones and how to prevent them.

References: (1) Gastroenterology. 1999;117:632. (2) emedicine.medscape.com. (3) J Hepatol. 1993;18 Suppl 1:S43. (4) uptodate.com. (5) Best Pract Res Clin Gastroenterol. 2014 Aug;28:623-635. (6) Hepatology. 2013 Dec;58:2133-2141. (7) J Pediatr Gastroenterol Nutr. 2012;55:328-333. (8) Ann Intern Med. 1998;128:417. (9) Hepatology. 1997;2:787. (10) CMAJ. 2013;16;185:549-550.

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.

A plant-based diet involving lots of vegetables, fruits and some grains may have a similar effect as steroids in reducing inflammation. Stock photo
Steroids reduce inflammation, but it comes at a cost

By David Dunaief, M.D.

Dr. David Dunaief

Steroid use as a performance-enhancing drug was a significant factor in the recent Olympics, with the Russian team banned for their illegal use. However, if we look beyond the flashy headlines to rudimentary use, we see that corticosteroids, or steroids, play an important role in medicine.

This is a commonly prescribed class of medications. In fact, our bodies make corticosteroids, the indigenous form of steroids, in the cortex of the adrenals, glands that sit on top of the kidneys. Here, we are going to concentrate on the exogenous form, meaning from the outside as medication.

Use or benefit

Steroids have an anti-inflammatory effect. This is critical since many acute and chronic diseases are based at least partially on inflammation. Chronic diseases that benefit include allergic, inflammatory and immunological diseases (1). These types of diseases touch on almost every area of the body from osteoarthritis and autoimmune diseases — rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, lupus, psoriasis and eczema — to asthma, COPD (emphysema and chronic bronchitis) and eye disorders. This type of medication is pervasive.

Delivery

Steroids are delivered orally, topically as creams, lotions and eye drops, or via injections, intravenous solutions and inhaled formulations. The most commonly known medication is prednisone, but there is a plethora of others, including prednisolone, methylprednisolone, cortisone, hydrocortisone and dexamethasone. Their benefits can be tremendous, improving functionality and reducing pain or improving breathing. You could say they are lifesaving in some instances, and with rescue inhalers they may just be that.

The bad

However, there is a very big caveat: they come at a price. Steroids have lots of adverse events associated with them. This is where the bad part comes in and keeps on coming. Steroids cause weight gain, increased glucose (sugars), high blood pressure, cardiovascular events, osteoporosis, change in mood (psychoses), cataracts, glaucoma, infection, peptic ulcers, Cushing’s syndrome and the list goes on. Ironically, steroids help with breathing; however, as I’ve seen in my clinical experience, they can cause shortness of breath when weaned from a longer-use high dose too quickly.

The upshot

The good news is that a plant-based diet may have similar beneficial effects in chronic diseases as steroids without all the downsides. Let’s look at the evidence.

The role in pneumonia

Pneumonia is among the top-10 leading causes of death in the world (2). It can be a most painful and debilitating disease. I know, for I experienced it personally while I was in my medical training. Every time I coughed, it felt like there was a fire in my chest.

In a meta-analysis (a group of nine studies), there was no overall effect of corticosteroids in reducing the risk of mortality in community-acquired pneumonia (3). However, don’t fret; when the data was broken into subsets, the findings were different. In subset data of those who had severe pneumonia, there was a statistically significant 74 percent reduction in mortality. And when duration was the main focus in subgroup analysis, those who received prolonged use of steroids reduced their risk of mortality by half.

Unfortunately, with the benefit comes an increased risk of adverse events, and this meta-analysis was no exception. There was a greater than two-times increased risk of abnormally high glucose levels with prolonged use. Thus, when giving steroids, especially for a prolonged use, it may be wise to check glucose levels.

In a more recent randomized controlled trial (RCT), the gold standard of studies, the results reinforced the beneficial effects of steroids on pneumonia. They showed that in those with both severe pneumonia and high inflammation, there was a two-thirds reduction in treatment failures when corticosteroids were added to the regimen (4). There were 120 patients involved in the study. They received antibiotics plus either methylprednisolone or placebo for five days.

Osteoarthritis: surprising results

As we know, osteoarthritis specifically of the knee is very common, especially as the population continues to age. Intra-articular (in the joint) injections directly into the knee are becoming routine treatment. A recent study compared injectable hyaluronic acid to injectable corticosteroid (5). The results showed that over three months, the corticosteroid was superior to hyaluronic acid in terms of reducing pain, 66 percent versus 43.8 percent, respectively. Interestingly, over the longer term, 12 months, hyaluronic acid reduced the pain and maintained its effect significantly longer than the steroid, 33 percent versus a meager 8.2 percent, respectively.

Study groups received five injections of either steroid or of hyaluronic acid directly to the knee over a five-week period. Thus, steroids may not always be the most effective choice when it comes to pain reduction. Hyaluronic acid may have caused this beneficial effect by reducing inflammation, protecting cartilage and preventing cell death, according to the authors.

COPD: length may not matter

It is not unusual to treat COPD patients with oral steroids. But what is the proper duration? The treatment paradigm has been two weeks with 40 mg of corticosteroids daily. However, results in an RCT showed that five days with 40 mg of corticosteroid was noninferior (equivalent) to 14 days of the same dosage and frequency (6). About one-third of patients in each group experienced a COPD exacerbation within the six-month duration of the trial. The hope is that the shorter use of steroids will mean fewer side effects. There were over 600 patients in this trial. We have come a long way; prior to 1999, eight weeks of steroids was a more commonplace approach to treating acute COPD exacerbations.

Topical steroid risk

Even topical creams and lotions are not immune to risk. For example, potent topical creams and lotions placed around the orbit of the eye with prolonged use may negatively affect vision (7). However, the evidence is based mostly on case reporting, which is a low level of evidence.

Dietary effect

One of the great things about steroids is that they reduce inflammation, and we know that the basis of greater than 80 percent of chronic disease is inflammation. A plant-based diet involving lots of vegetables, fruits and some grains may have a similar effect as steroids. The effect of diet on chronic disease may be to modify the immune system and reduce inflammation (8).

The bioactive substances from plants thought to be involved in this process are predominantly the carotenoids and the flavonoids. Thus, those patients who respond even minimally to steroids are likely to respond to a plant-based diet in much the same beneficial way without the downsides of a significant number of side effects. Diet, unlike steroids, can be used for a long duration and a high intake, with a direct relationship to improving disease outcomes.

In conclusion, it is always better to treat with the lowest effective dose for the shortest effective period when it comes to steroids. The complications of these drugs are enumerable and must always be weighed against the benefits. Sometimes, other drugs may have more beneficial effects over the long term, such as hyaluronic acid injections for knee osteoarthritis. A plant-based diet, with anti-inflammatory properties similar to steroids, may be a useful alternative for chronic disease or may be used alongside these drugs, possibly reducing their dosage and duration.

References: (1) uptodate.com.(2) N Engl J Med. 1995;333(24):1618-24. (3) PLoS One. 2012;7(10):e47926. (4) JAMA. 2015;313(7):677-686. (5) Open Access Rheum 2015;7:9-18. (6) JAMA. 2013;309(21):2223-31. (7) Australas J Dermatol. Mar 5, 2015. (8) Int J Vitam Nutr Res. 2008 Dec;78(6):293-8.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management.

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If there were ever a reason needed for obese patients to lose weight, treating atrial fibrillation should be on the top of the list. Stock photo
Medications treat rate or rhythm or prevent strokes

By David Dunaief, M.D

Dr. David Dunaief

Atrial fibrillation is the most common arrhythmia, an abnormal or irregular heartbeat, found in the U.S. Unfortunately, it can be very complicated to treat. Though there are several options, including medications and invasive procedures, it mostly boils down to symptomatic treatment rather than treating or reversing underlying causes.

What is AFib? It is an electrical malfunction that affects the atria, the two upper chambers of the heart, causing them to beat “irregularly irregular.” This means there is no set pattern that affects the rhythm and potentially causes a rapid heart rate. The result of this may be insufficient blood supply throughout the body.

Complications that may occur can be severely debilitating, such as stroke or even death. AFib’s prevalence is expected to more than double by 2030 (1). Risk factors include age (the older we get, the higher the probability), obesity, high blood pressure, premature atrial contractions and diabetes.

AFib is not always symptomatic; however, when it is, symptoms include shortness of breath, chest discomfort, light-headedness, fatigue and confusion. This arrhythmia can be diagnosed by electrocardiogram, but more likely with a 24-hour Holter monitor. The difficulty in diagnosing AFib sometimes is that it can be intermittent.

There may be a better way to diagnose AFib. In a study, the Zio patch, worn for 14 days, was more likely to show arrhythmia than a 24-hour Holter monitor (2). The Zio patch is a waterproof adhesive patch on the chest, worn like a Band-Aid, with one ECG lead. While 50 percent of patients found the Holter monitor to be unobtrusive, almost all patients found the Zio patch comfortable.

There are two main types of AFib, paroxysmal and persistent. Paroxysmal is acute, or sudden, and lasts for less than seven days, usually less than 24 hours. It tends to occur with greater frequency over time, but comes and goes. Persistent AFib is when it continues past seven days (3). AFib is a progressive disease, meaning it only gets worse, especially without treatment.

Medications are meant to treat either the rate or rhythm or prevent strokes from occurring. Those that treat rate include beta blockers, like metoprolol, and calcium channel blockers, such as diltiazem (Cardizem). Examples of medications that treat rhythm are amiodarone and sotalol. Then there are anticoagulants that are meant to prevent stroke, such as warfarin and some newer medications, dabigatran (Pradaxa), rivaroxaban (Xarelto) and apixaban (Eliquis). The newer anticoagulants are easier to administer but may have higher bleeding risks, in some circumstances with no antidote.

There is also ablation, an invasive procedure that requires threading a catheter through an artery, usually the femoral artery located in the groin, to reach the heart. In one type of ablation, the inappropriate nodes firing in the walls of the atria are ablated, or destroyed, using radiofrequency. This procedure causes scarring of atrial tissue. When successful, patients may no longer need medication.

Premature atrial contractions

Premature atrial contractions, abnormal extra beats that occur in the atrium, may be a predictor of atrial fibrillation. In a study, PACs alone, when compared to the Framingham Heart Study AFib risk algorithm (a conglomeration of risk factors that excludes PACs) resulted in higher risk of AFib (4). When there were more than 32 abnormal beats/hour, there was a significantly greater risk of AFib after 15 years of PACs. When taken together, PACs and the Framingham model were able to predict AFib risk better at 10 years out as well. Also, when the number of PACs doubled overall in patients, there was a 17 percent increased risk of AFib.

The role of obesity

There is good news and bad news with obesity in regards to AFib. Let’s first talk about the bad news. In studies, those who are obese are at significantly increased risk. In the Framingham Heart Study, the risk of developing AFib was 52 percent greater in men who were obese and 46 percent greater in women who were obese when compared to those of normal weight (5). Obesity is defined as a body mass index >30 kg/m², and normal weight as a BMI <25 kg/m². There were over 5,000 participants in this study with a follow-up of 13 years. The Danish Diet, Cancer and Health Study reinforces these results by showing that obese men were at a greater than twofold increased risk of developing AFib, and obese women were at a twofold increased risk (6).

Now the good news: Weight loss may help reduce the frequency of AFib episodes. That’s right; weight loss could be a simple treatment for this very dangerous arrhythmia. In a randomized controlled trial, the gold standard of studies, those in the intervention group lost significantly more weight, 14 kg (32 pounds) versus 3.6 kg (eight pounds), and saw a significant reduction in atrial fibrillation severity score compared to those in the control group (7). There were 150 patients involved in the study.

An AFSS includes duration, severity and frequency of atrial fibrillation. All three components in the AFSS were reduced in the intervention group compared to the control group. There was a 692-minute decrease in the time spent in AFib over 12 months in the intervention arm, whereas there was a 419-minute increase in the time in AFib in the control group. These results are potentially very powerful; this is the first study to demonstrate that managing risk factors may actually help manage the disease.

Caffeine

According to a meta-analysis (a group of six population-based studies) done in China, caffeine does not increase, and may even decrease, the risk of AFib (8). The study did not reach statistical significance. The authors surmised that drinking coffee on a regular basis may be beneficial because caffeine has antifibrosis properties. Fibrosis is the occurrence of excess fibrous tissue, in this case, in the atria, which most likely will have deleterious effects. Atrial fibrosis could be a preliminary contributing step to AFib. Since these were population-based studies, only an association can be made with this discovery, rather than a hard and fast link. Still, this is a surprising result.

However, in those who already have AFib, it seems that caffeine may exacerbate the frequency of symptomatic occurrences, at least anecdotally. With my patients, when we reduce or discontinue substances that have caffeine, such as coffee, tea and chocolate, the number of episodes of AFib seems to decline. I have also heard similar stories from my colleagues and their patients. So, think twice before running out and getting a cup of coffee if you have AFib. What we really need are randomized controlled studies done in patients with AFib, comparing people who consume caffeine regularly to those who have decreased or discontinued the substance.

The bottom line is this: If there were ever a reason needed for obese patients to lose weight, treating atrial fibrillation should be on the top of the list, especially since it is such a dangerous disease with potentially severe complications.

References:

(1) Am J Cardiol. 2013 Oct. 15;112:1142-1147. (2) Am J Med. 2014 Jan.;127:95.e11-7. (3) Uptodate.com. (4) Ann Intern Med. 2013;159:721-728. (5) JAMA. 2004;292:2471-2477. (6) Am J Med. 2005;118:489-495. (7) JAMA. 2013;310:2050-2060. (8) Canadian J Cardiol online. 2014 Jan. 6.

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.

A 2013 study found that when taken together, iron and calcium supplements increase the risk of developing glaucoma. Stock photo
Some supplements may increase risk
Dr. David Dunaief

By David Dunaief, M.D.

Glaucoma is the second-leading cause of blindness in the world, behind cataracts. It is neurodegenerative (deterioration of the optic nerve) with increased intraocular pressure (IOP) — pressure inside the eye — as an indicator that nerve damage is more likely. The most common types of glaucoma are open angle and angle closure. Open-angle glaucoma represents about 90 percent of U.S. cases and is caused by clogging of the eye’s drainage canals over time (1). Because it develops slowly and over time, its symptoms are not always obvious.

Glaucoma initially causes peripheral vision loss and then works its way inward to the central vision. If untreated, it can lead to irreversible blindness (2). The occurrence of this disease is rising, with an estimated three million Americans affected and a predicted level of roughly 3.4 million in the U.S. by 2020.

Fortunately, there are treatments. Some revolve around reducing fluid production in the eye, such as beta blockers and carbonic anhydrase inhibitors. Others work to increase fluid drainage, such as cholinergics and prostaglandin analogs. Still others do both (1). None of these treatments reverse lost vision or damage. They only slow or halt its progression to preserve your remaining sight. Therefore, prevention and early detection are crucial.

Glaucoma risk factors include age — starting at 40, although those over 65 have higher risk and those over 80 have the highest risk —and race, with African-Americans at a five-times higher risk than those of European ancestry. In the Baltimore Eye Survey, a family history of the disease dramatically increased risk, with siblings having greater probability than offspring of developing the disease (3). Other risk factors include steroid use, including asthma inhalers, eye injury, nearsightedness and hypertension. Finally, the higher the IOP, the greater the risk for progression in open-angle glaucoma (4).

Effect of increased visual field testing

In the Advanced Glaucoma Intervention Study, it was found that visual field testing by an ophthalmologist every six months for patients at higher risk was better at predicting disease progression than annual testing (5). The result was that, with more frequent testing, the researchers were 50 percent more likely to detect progression of the disease, if it were to occur.

Interestingly, the U.S. Preventive Services Task Force currently does not recommend screening for open-angle glaucoma, since it feels there is insufficient evidence (6). The American Academy of Ophthalmology recommends screening every two to four years starting at age 40, with increased frequency of every one to three years starting at age 55 and every one to two years for those 65 and older. More frequent screening is recommended for those who have more risk factors (7).

Preventative steps

There are several steps that may be valuable, including reducing chronic diseases associated with glaucoma such as type 2 diabetes, Alzheimer’s and erectile dysfunction. If we reduce their incidence, there may also be a reciprocal decline in glaucoma. In addition, avoiding or reducing supplementation with iron and calcium, while potentially increasing magnesium, may decrease incidence of the disease.

Diabetes and high blood pressure

In an analysis of two studies, diabetes increased the risk of open-angle glaucoma by greater than 200 percent (8). In the same analysis, however, systemic hypertension (high blood pressure) increased the risk by a meager 7 percent. This is yet another reason we need to control or prevent diabetes to preserve eye health, aside from diabetic retinopathy (disease of the back of the eye).

Erectile dysfunction association

Those with erectile dysfunction (ED) had an almost threefold increased risk of also having open-angle glaucoma, compared to those without the disorder (9). There may be vascular symptoms associated with open-angle glaucoma as demonstrated by the increased association with ED. The study suggests that the mechanism of action that both disorders have in common is endothelial dysfunction (inner lining of the blood vessels), which involves a decreased level of nitric oxide, a potent vasodilator, which enables the vessels to expand and relax. ED was also associated with high cholesterol and blood pressure, heart disease and diabetes. It is not unusual to find that many diseases have a common underlying pathology.

Supplements

A 2013 study found that supplementation with calcium and iron, looked at separately, increases risk of normal-tension glaucoma (NTG), glaucoma without increased pressure (10). The calcium and iron came from a variety of sources, including antacids, multivitamins and prescription and nonprescription supplements. Roughly one-third of glaucoma patients have NTG (11). Among Japanese patients, a study found that this number increases to two-thirds (12).

The supplementation study results showed that participants who took a composite of 800 mg daily of calcium were at an almost 2.5-times increased risk. Those who took 18 mg of iron on a daily basis were at an even higher risk, 3.8 times, of developing the disease. When taken together, iron and calcium increased risk by a resounding 7.2-fold. Interestingly, dietary sources of iron and calcium were associated with lower odds of glaucoma.

The good news is that a dose of 300 mg of magnesium citrate in patients with NTG showed a benefit in visual field over one month, compared to those who did not take magnesium (13). Although this was a randomized-controlled trial, it was also very small with only 30 patients.

While there are risk factors — such as family history, age and ethnicity — that can’t be changed, there are a number of modifiable factors as well. Glaucoma may be brought on by factors that are related to those causing systemic diseases. Therefore, it’s important to maintain good health overall to reduce the risk for glaucoma and its effects.

References:

(1) glaucoma.org. (2) Lancet. 2004;363(9422):1711. (3) Arch Ophthalmol. 1994;112(1):69. (4) Ophthalmology. 2007;114(10):1810. (5) Arch Ophthalmol. 2011;129(12):1521-1527. (6) Ann Fam Med. 2005;3(2):171. (7) AAO.org. (8) Br J Ophthalmol. 2012;96(6):872-876. (9) Ophthalmology 2012;119:289-293. (10) Curr Eye Res. 2013 Oct;38(10):1049-1056. (11) Ophthalmology. 1992;99(10):1499–1504. (12) Jpn J Ophthalmol. 1991;35(2):133–155. (13) Eur J Ophthalmol. 2010;20(1):131-135.

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.

A retrospective study showed that one of out every 370 patients who took bisphosphonates to prevent and treat osteoporosis were afflicted with scleritis.
Common medications may affect vision

By David Dunaief, M.D.

Dr. David Dunaief

When we refer to adverse events with medications, we usually focus on systemic consequences. However, we rarely address the fact that eyes can be adversely affected by medications. There have been several studies that illustrate this very important point.

It is vital that we recognize the symptoms of eye distress. Some of these may indicate ophthalmic emergencies. The medications studied include common therapeutics, such as bisphosphonates, aspirin, a class of antibiotics called fluoroquinolones and a migraine therapy. I will explain the symptoms to be cognizant of with each.

The impact of bisphosphonates

The class of drugs known as bisphosphonates is a mainstay for the prevention and treatment of osteoporosis. Adverse news about bisphosphonates typically focuses on atypical femur fractures and osteonecrosis (death of part of the jawbone), not on an ocular effect. However, in a large retrospective study (looking at past data), oral bisphosphonates were shown to increase the risk of uveitis and scleritis, both inflammatory eye diseases, by 45 and 51 percent, respectively (1). One out of every 1,100 patients treated with the drugs suffered from uveitis, and one out of every 370 patients treated suffered from scleritis.

Why is this important? The consequences of not treating uveitis can lead to complications, such as glaucoma and cataracts. The symptoms of uveitis typically include eye redness, pain, light sensitivity, decreased vision and floaters (2).

For scleritis, the symptoms are severe pain that radiates to the face and around the orbit, with worsening in the evening and morning and with eye movements (3). Uveitis affects the iris and ciliary body (fluid inside the eye and muscles that help the eye focus), while scleritis affects the sclera, or white part of the eye.

These adverse eye events occurred only in first-time users. The authors believe the mechanism of action may involve the release of inflammatory factors by the bisphosphonates.

Aspirin yet again, maybe not?

It seems aspirin can never get a break. It has been implicated in gastrointestinal bleeds and hemorrhagic (bleeding) strokes. The European Eye Study also suggests that aspirin increases the risk of age-related macular degeneration (4). The primary effect is seen, unfortunately, with wet AMD, which is the form that leads to central vision loss. The risk of wet AMD is directly related to the frequency of aspirin use. When aspirin is used at least once a week, but not daily, the risk is increased by 30 percent.

But, this is not the complete story. The researchers found that there was no increase in wet AMD in patients over 85 years old. They also found that the potential for angina (chest pain) and cardiovascular deaths was not eliminated.

This study was large and retrospective in design, and it included fundoscopic (retinal) pictures, making the results more reliable. The authors recommend that AMD patients not use aspirin for primary prevention, meaning without current cardiovascular disease. However, aspirin use for secondary prevention — for those with heart disease or a previous stroke — the benefits of the medication outweigh the risks.

In fact, the Physician Health Study, a randomized controlled study published in 2001, found that aspirin may even reduce the risk of AMD (5). In yet another study, the Age Related Eye Disease Study (AREDS), aspirin seemed to have a protective effect when it came to AMD (6). Therefore, please do not stop taking aspirin if you have cardiovascular disease since the results, at best, are mixed when it comes to AMD.

However, what is more relevant is that aspirin has been shown to reduce the risk of vascular mortality by 15 percent, stroke by 25 percent and overall mortality by 10 percent (7). While the jury is still out on the effect of aspirin on AMD, there is the ASPREE-AMD study that was started in 2017 to help answer the question of low-dose aspirin’s, 100 mg daily, impact on AMD risk.

The role of antibiotics: fluoroquinolones in retinal detachment

Fluoroquinolones may have toxic effects on the synthesis of collagen and on connective tissue, potentially resulting in retinal detachments and Achilles tendon rupture. This is a common class of antibiotics used to treat acute diseases, such as urinary tract infections and upper respiratory infections.

In an epidemiologic study, these drugs were shown to increase the risk of retinal detachment by 4.5 times (8). Common fluoroquinolones include ciprofloxacin (Cipro), levofloxacin (Levaquin) and gatifloxacin (Tequin). Although it sounds like an impressive number, it’s not a common occurrence. It takes the treatment of 2,500 patients before one patient is harmed. Also, this was only noticed in current users, not in recent or past users. However, it is a serious condition.

Retinal detachment is an ophthalmic emergency, and patients need to be evaluated by an ophthalmologist urgently to avoid irreparable damage and vision loss. Retinal detachments are treatable with surgery. Best results are seen within 24 hours of symptoms, which include many floaters, bright flashes of light in the periphery and a curtain over the visual field (9). Fortunately, retinal detachments usually only affect one eye.

Migraine medication

Topiramate (Topomax) is a drug used to treat and prevent migraines. In a case-control (with disease vs. without disease) study, topiramate increased the risk of glaucoma in current users by 23 percent. The risk more than doubled to 54 percent in first-time users (10). The mechanism of action may be related to the fact that topiramate increases the risk of intraocular pressure.

It is important to be aware that medications not only have systemic side effects, but ocular ones as well. Many of these medications cause adverse effects that require consultation with an ophthalmologist, especially with aspirin, since the cardiovascular benefits seem to outweigh any negative impacts on AMD with people who have cardiovascular disease. If you have ocular symptoms related to medications, contact your physician immediately.

References:

(1) CMAJ. 2012 May 15;184(8):E431-434. (2) www.mayoclinic.org. (3) www.uptodate.com. (4) Ophthalmology. 2012;119:112-118. (5) Arch Ophthalmol. 2001;119:143-149. (6) Medscape.com. (7) Lancet. 2009;373:1849-1860. (8) JAMA. 2012;307:1414-1419. (9) www.ncbi.nlm.nih.gov. (10) Am J Ophthalmol. 2012 May;153(5):827-830.

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.

One simple lifestyle change is to make certain that those susceptible to gout attacks remain hydrated and consume plenty of fluids. Stock photo
Most risk factors are modifiable

By David Dunaief, M.D.

Dr. David Dunaief

Gout is thought of as an inflammatory arthritis. It occurs intermittently, affecting the joints, most commonly the big toe. The symptoms are acute (sudden onset) and include extremely painful, red, swollen and tender joints. In terms of symptoms, if you have ever had kidney stones, gouty arthritis is just as painful.

Uric acid (or urate) levels are directly related to the risk of gout attacks. As uric acid levels increase, there is a greater chance of urate crystal deposits in the joints. Although, and unfortunately, some patients can still experience gout attacks without high levels of uric acid.

This disease affects approximately 8.3 million people in the United States (1). This number has doubled since the 1960s. Men between 30 and 50 years old are at much higher risk for their first attack (2). For women, most gout attacks occur after menopause.

There are a number of potential causes of gout, as well as ways to prevent and treat it. The most common contributors include drugs, such as diuretic use; alcohol intake; uncontrolled hypertension (high blood pressure); obesity; and sweetened beverage and fructose intakes (3). Though heredity plays a role, these risk factors are modifiable.

The best way to prevent and treat gout is by modifying medications and lifestyle. One simple lifestyle change is to make certain, just like with kidney stone prevention, that those susceptible to gout attacks remain hydrated and consume plenty of fluids.

Just like there are medications that may cause gout, there are also medications that can treat and help prevent gout. If you do get a gout attack, NSAIDs such as indomethacin or steroids such as a Medrol pack help treat the symptoms. In terms of prevention, allopurinol helps to reduce the risk of a gout attack.

I thought we might look at gout by using a case study. I had a patient who had started a nutrient-dense, plant-based diet. Within two weeks, she had a gout episode. Initially, it was thought that her change in diet with increased plant purines might have been an exacerbating factor. Purines are substances that raise the level of uric acid. So, it is not surprising that foods with containing purines might substantiate a gout attack. However, not all purines equally raise uric acid levels.

Animal versus plant proteins

In a case-crossover (epidemiologic forward-looking) study, it was shown that purines from animal sources increase our levels of purines far more than those from plant sources (4). The risk of a gout incident was increased approximately 241 percent in the group consuming the highest amount of animal products, whereas the risk of gout was still increased for those consuming plant-rich purine substances, but by substantially less: 39 percent.

The authors believe that decreasing the use of purine-rich foods, especially from animal sources, may decrease the risk of incidences and recurrent episodes of gout. Plant-rich diets are the preferred method of consuming proteins for patients who suffer gout attacks, especially since nuts and beans are excellent sources of protein and many other nutrients.

In another study, meats — including red meat, pork and lamb — increased the risk of gout, as did seafood (5). However, purine-rich plant sources did not increase risk of gout. Low-fat dairy actually decreased the risk of gout by 21 percent. The study was a large observational study involving 49,150 men over a duration of 12 years.

There are several more studies indicating and reaffirming that plant foods do not increase the risk of gout attacks. The Mayo Clinic also suggests that plants do not increase the risk of gout. When considering my patient’s circumstances, it was unlikely that her switch to a nutrient-dense, plant-rich diet had increased her risk of gout.

Diuretics (water pills)

My patient was on a diuretic called hydrochlorothiazide for hypertension (high blood pressure). There are several medications thought to increase the risk of gout, including diuretics and chronic use of low-dose aspirin. In the ARIC study, patients who used diuretics to control blood pressure were at a 48 percent greater risk of developing gout than nonusers (6). In fact, nonusers had a 36 percent decreased risk of developing gout. This study involved 5,789 participants and had a fairly long duration of nine years. The longer the patient is treated with a diuretic, the higher the probability they will experience gout. It is likely that my patient’s diuretic contributed to her gout episode.

Vitamin C

Vitamin C may reduce gout risk. In the Physicians Follow-up Study, a 500-mg daily dose of vitamin C decreased levels of uric acid in the blood (9). However, be careful with vitamin C supplementation because it can increase the risk of kidney stones.

Medical conditions

There are a number of medical conditions that may impact the risk of gout. These include uncontrolled high blood pressure, diabetes and high cholesterol (7). My patient’s high blood pressure was under control, but she also had diabetes and high cholesterol. These disorders may have also contributed.

Obesity

Obesity, like smoking, seems to have its impact on almost every disease. In the CLUE II study, obesity was shown to not only increase the risk of gout but also to accelerate the age of onset (8). Those who were obese experienced gout three years earlier than those who were not. Even more striking is the fact that those who were obese in early adulthood had an 11-year earlier onset of gout. The study’s duration was 18 years. My patient was obese and had just started to lose some weight before the gout occurred.

Prevention

The key to success with gout lies with prevention. Patients who do get gout writhe in pain. Luckily, there are modifications that significantly reduce the risks. They involve very modest changes, such as not using medications called diuretics in patients with a history of gout; losing weight for obese patients; and substituting more plant-rich foods for meats and seafood. Increasing levels of uric acid may be a useful biomarker for indicating an increased risk of gouty arthritis attacks. However, gout attacks do occur without a rise in uric acid levels, so it is not a perfect. Although the cause of gout may be apparent to you, always check with your doctor before changing your medications or making significant lifestyle modifications, as we have learned from this case study of my patient.

References:

(1) Arthritis Rheum. 2011 Oct;63(10):3136-3141. (2) Arthritis Res Ther. 2006;8:Suppl 1:S2. (3) Am Fam Physician. 2014 Dec 15;90(12):831-836. (4) Ann Rheum Dis. online May 30, 2012. (5) NEJM 2004;350:1093-1103. (6) Arthritis Rheum. 2012 Jan;64(1):121-129. (7) www.mayoclinic.com. (8) Arthritis Care Res (Hoboken). 2011 Aug;63(8):1108-1114. (9) J Rheumatol. 2008 Sep;35(9):1853-1858.

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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