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Exercise

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.

As you become more active, Santa, you’ll find that you have more energy all year round, not just on Christmas Eve.

By David Dunaief, M.D.

Dr. David Dunaief

Dear Santa,

This time of year, people around the world are no doubt sending you lists of things they want through emails, blogs, tweets and old-fashioned letters. In the spirit of giving, I’d like to offer you — and maybe your reindeer — some advice.

Let’s face it: You aren’t exactly the model of good health. Think about the example you’re setting for all those people whose faces light up when they imagine you shimmying down their chimneys. You have what I’d describe as an abnormally high BMI (body mass index). To put it bluntly, you’re not just fat, you’re obese. Since you are a role model to millions, this sends the wrong message.

We already have an epidemic of overweight kids, leading to an ever increasing number of type 2 diabetics at younger and younger ages. According to the Centers for Disease Control and Prevention, as of 2015, more than 100 million U.S. adults are living with diabetes or prediabetes. It complicates the issue that approximately two-thirds of the U.S. population is overweight and/or obese. This is just one of many reasons we need you as a shining beacon of health.

Obesity has a much higher risk of shortening a person’s life span, not to mention quality of life and self-image. The most dangerous type of obesity is an increase in visceral adipose tissue, which means central belly fat. An easy way to tell if someone is too rotund is if a waistline, measured from the navel, is greater than or equal to 40 inches for a man, and is greater than or equal to 35 inches for a woman. The chances of diseases such as pancreatic cancer, breast cancer, liver cancer and heart disease increase dramatically with this increased fat.

Santa, here is a chance for you to lead by example (and, maybe, by summer, to fit into those skinny jeans you hide in the back of your closet). Think of the advantages to you of being slimmer and trimmer. For one thing, Santa, you would be so much more efficient if you were fit. Studies show that with a plant-based diet, focusing on fruits and vegetables, people can reverse atherosclerosis, clogging of the arteries.

The importance of a good diet not only helps you lose weight but avoid strokes, heart attacks, peripheral vascular diseases, etc. But you don’t have to be vegetarian; you just have to increase your fruits, vegetables and whole-grain foods significantly. With a simple change, like eating a handful of raw nuts a day, you can reduce your risk of heart disease by half. Santa, future generations need you. Losing weight will also change your center of gravity, so your belly doesn’t pull you forward. This will make it easier for you to keep your balance on those steep, icy rooftops.

Exercise will help, as well. Maybe for the first continent or so, you might want to consider walking or jogging alongside the sleigh. As you exercise, you’ll start to tighten your abs and slowly see fat disappear from your midsection, reducing risk and practicing preventive medicine. Your fans everywhere leave you cookies and milk when you deliver presents. It’s a tough cycle to break, but break it you must. You — and your fans — need to see a healthier Santa. You might let slip that the modern Santa enjoys fruits, especially berries, and veggies, with an emphasis on cruciferous veggies like broccoli florets dipped in humus, which have substantial antioxidant qualities and can help reverse disease.

As for your loyal fans, you could place fitness videos under the tree. In fact, you and your elves could make workout videos for those of us who need them, and we could follow along as you showed us “12 Days of Workouts with Santa and Friends.” Who knows, you might become a modern version of Jane Fonda or Richard Simmons or even the next Shaun T!

How about giving athletic equipment, such as baseball gloves, footballs and basketballs, instead of video games? You could even give wearable devices that track step counts and bike routes or stuff gift certificates for dance lessons into people’s stockings. These might influence the recipients to be more active.

By doing all this, you might also have the kind of energy that will make it easier for you to steal a base or two in this season’s North Pole Athletic League’s Softball Team. The elves don’t even bother holding you on base anymore, do they?

As you become more active, you’ll find that you have more energy all year round, not just on Christmas Eve. If you start soon, Santa, maybe by next year, you’ll find yourself parking the sleigh farther away and skipping from chimney to chimney.

The benefits of a healthier Santa will ripple across the world. Think about something much closer to home, even. Your reindeer won’t have to work so hard. You might also fit extra presents in your sleigh. And Santa, you will be sending kids and adults the world over the right message about taking control of their health through nutrition and exercise. That’s the best gift you could give!

Wishing you good health in the new year,

David

P.S. I could really use a new baseball bat, if you have a little extra room in your sleigh.

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 recent study found that those who walk with more pace are more likely to decrease their mortality from all causes and increase their longevity.
Look beyond the number of steps you take
Dr. David Dunaief

By David Dunaief, M.D.

For most of us, exercise is not a priority during the winter months, especially during the holiday season. We think that it’s okay to let ourselves go and that a few more pounds will help insulate us from the anticipated cold weather, when we will lock ourselves indoors and hibernate. Of course I am exaggerating, but I am trying to make a point. During the winter, it is even more important to put exercise at the forefront of our consciousness, because we tend to gain the most weight during the Thanksgiving to New Year holiday season (1).

Many times we are told by the medical community to exercise, which of course is sage advice. It seems simple enough; however, the type, intensity level and frequency of exercise may not be well defined. For instance, any type of walking is beneficial, right? Well, as one study that quantifies walking pace notes, some types of walking are better than others, although physical activity is always a good thing compared to being sedentary.

We know exercise is beneficial for prevention and treatment of chronic disease. But another very important aspect of exercise is the impact it has on specific diseases, such as diabetes and osteoarthritis. Also, certain supplements and drugs may decrease the beneficial effects of exercise. They are not necessarily the ones you think. They include resveratrol and nonsteroidal anti-inflammatory drugs (such as ibuprofen). Let’s look at the evidence.

Walking with a spring in your step

While pedometers give a sense of how many steps you take on a daily basis, more than just this number is important. Intensity, rather than quantity or distance, may be the primary indicator of the benefit derived from walking.

In the National Walkers’ Health Study, results showed that those who walk with more pace are more likely to decrease their mortality from all causes and to increase their longevity (2). This is one of the first studies to quantify specific speed and its impact. In the study, there were four groups. The fastest group was almost jogging, walking at a mean pace of less than 13.5 minutes per mile, while the slowest group was walking at a pace of 17 minutes or more per mile.

The slowest walkers had a higher probability of dying, especially from dementia and heart disease. Those in the slowest group stratified even further: Those whose pace equaled 24-minute miles or greater had twice the risk of death compared to those who walked with greater speed. However, the most intriguing aspect of the study was that there were big differences in mortality reduction in the second slowest category compared to the slowest, which might only be separated by a minute-per-mile pace. So don’t fret: You don’t have to be a speed walker in order to get significant benefit.

Mind-body connection

The mind also plays a significant role in exercise. When we exercise, we tend to beat ourselves up mentally because we are disappointed with our results. The results of a new study say that this is not the best approach (3). Researchers created two groups. The first was told to find four positive phrases, chosen by the participants, to motivate them while on a stationary bike and repeat these phrases consistently for the next two weeks while exercising.

Members of the group who repeated these motivating phrases consistently, throughout each workout, were able to increase their stamina for intensive exercise after only two weeks, while the same could not be said for the control group, which did not use reinforcing phrases.

‘Longevity’ supplement may have negative impact

Resveratrol is a substance that is thought to provide increased longevity through proteins called Sirtuin 1. So how could it negate some benefit from exercise? Well, it turns out that we need acute inflammation to achieve some exercise benefits, and resveratrol has anti-inflammatory effects. Acute inflammation is short-term inflammation and is different from chronic inflammation, which is the basis for many diseases.

In a small randomized controlled study, treatment group participants were given 250 mg supplements of resveratrol and saw significantly less benefit from aerobic exercise over an eight-week period, compared to those who were in the control group (4). Participants in the control group had improvements in both cholesterol and blood pressure that were not seen in the treatment group. This was a small study of short duration, although it was well designed.

Impact on diabetes complications

Unfortunately, type 2 diabetes is on the rise, and the majority of these patients suffer from cardiovascular disease. Drugs used to control sugar levels don’t seem to impact the risk for developing cardiovascular disease.

So what can be done? In a recent prospective (forward-looking) observational study, results show that diabetes patients who exercise less frequently, once or twice a week for 30 minutes, are at a higher risk of developing cardiovascular disease and almost a 70 percent greater risk of dying from it than those who exercised at least three times a week for 30 minutes each session. In addition, those who exercised only twice a week had an almost 50 percent increased risk of all-cause mortality (5). The study followed more than 15,000 men and women with a mean age of 60 for five years. The authors stressed the importance of exercise and its role in reducing diabetes complications.

Fitness age

You can now calculate your fitness age without the use of a treadmill, according to the HUNT study [6]. A new online calculator utilizes basic parameters such as age, gender, height, weight, waist circumference and frequency and intensity of exercise, allowing you to judge where you stand with exercise health. This calculator can be found at www.ntnu.edu/cerg/vo2max. The results may surprise you.

Even in winter, you can walk and talk yourself to improved health by increasing your intensity while repeating positive phrases that help you overcome premature exhaustion. Frequency is important as well. Exercise can also have a significant impact on complications of chronic diseases, such as cardiovascular disease and resulting death with diabetes.

When the weather does become colder, take caution when walking outside to avoid black ice or use a treadmill to walk with alacrity. Getting outside during the day may also help you avoid the winter blues.

References: (1) N Engl J Med. 2000;342:861-867. (2) PLoS One. 2013;8:e81098. (3) Med Sci Sports Exerc. 2013 Oct. 10. (4) J Physiol Online. 2013 July 22. (5) Eur J Prev Cardiol Online. 2013 Nov. 13. (6) Med Sci Sports Exerc. 2011;43:2024-2030.

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.

Walking may reduce the need for dialysis. METRO photo
Are activity and exercise the same?

By David Dunaief, M.D.

Dr. David Dunaief

Let’s begin with a pretest. I want to make it clear that a pretest is not to check whether you know the information but that you have an open mind and are willing to learn.

1) Which may have the most detrimental impact on your health?

a.   Smoking

b.   Obesity

c.   Inactivity

d.   A and C

e.   All have the same impact

2) People who exercise are considered active.

a.   True

b.   False

3) Inactivity may increase the risk of what? Select all that apply.

a.   Diabetes

b.   Heart disease

c.   Fibromyalgia

d.   Mortality

e.   Disability

With the recent wave of heat and humidity, who wants to think about exercise? Instead, it’s tempting to lounge by the pool or even inside with air conditioning instead.

First, let me delineate between exercise and inactivity; they are not complete opposites. When we consider exercise, studies tend to focus on moderate to intense activity. However, light activity and being sedentary, or inactive, tend to get clumped together. But there are differences between light activity and inactivity.

Light activity may involve cooking, writing, and strolling (1). Inactivity involves sitting, as in watching TV or in front of a computer screen. Inactivity utilizes between 1 and 1.5 metabolic equivalent units — better known as METS — a way of measuring energy. Light activity, however, requires greater than 1.5 METS. Thus, in order to avoid inactivity, we don’t have to exercise in the dreaded heat. We need to increase our movement.

What are the potential costs of inactivity? According to the World Health Organization, over 3 million people die annually from inactivity. This ranks inactivity in the top five of potential underlying mortality causes (2). The consequences of inactivity are estimated at 1 to 2.6 percent of health care dollars. This sounds small, but it translates into actual dollars spent in the U.S. of between $38 billion and $100 billion (3).

How much time do we spend inactive? Good question. In an observational study of over 7,000 women with a mean age of 71 years old, 9.7 waking hours were spent inactive or sedentary. These women wore an accelerometer to measure movements. Interestingly, as BMI and age increased, the amount of time spent sedentary also increased (4).

Inactivity may increase the risk of mortality and plays a role in increasing risks for diseases such as heart disease, diabetes and fibromyalgia. It can also increase the risk of disability in older adults.

Surprisingly, inactivity may be worse for us than smoking and obesity. For example, there can be a doubling of the risk for diabetes in those who sit for long periods of time, compared to those who sit the least (5).

By the way, the answers to the pretest are 1) e; 2) b; 3) a, b, c, d and e.

Let’s look at the evidence.

Does exercise trump inactivity?

We tend to think that exercise trumps all; if you exercise, you can eat what you want and, by definition, you’re not sedentary. Right? Not exactly. Diet is important, and you can still be sedentary, even if you exercise. In a meta-analysis — a group of 47 studies — results show that there is an increased risk of all-cause mortality with inactivity, even in those who exercised (6). In other words, even if you exercise, you can’t sit for the rest of the day. The risk for all-cause mortality was 24 percent overall.

However, those who exercised saw a blunted effect with all-cause mortality, making it significantly lower than those who were inactive and did very little exercise: 16 percent versus 46 percent increased risk of all-cause mortality. So, it isn’t that exercise is not important, it just may not be enough to reduce the risk of all-cause mortality if you are inactive for a significant part of the rest of the day.

In an earlier published study using the Women’s Health Initiative, results showed that those who were inactive most of the time had greater risk of cardiovascular disease (7). Even those who exercised moderately but sat most of the day were at increased risk of cardiovascular disease. Moderate exercise was defined as 150 minutes of exercise per week. Those at highest risk were women who did not exercise and sat at least 10 hours a day. This group had a 63 percent increased risk of cardiovascular disease (heart disease or stroke).

However, those who sat fewer than five hours a day had a significantly lower risk of cardiovascular events. And those who were in the highest group for regular exercise (walking seven hours/week or jogging/running four to five hours/week) did see more benefit in cardiovascular health, even if they were inactive the rest of the day. Sitting longer did not have a negative impact on the individuals in the high exercise level group.

Worse than obesity?

Obesity is a massive problem in this country; it has been declared a disease, itself, and it also contributes to other chronic diseases. But would you believe that inactivity has more of an impact than even obesity? In an observational study, using data from the EPIC trial, inactivity might be responsible for two times as many premature deaths as obesity (8). This was a study involving 330,000 men and women.

Interestingly, the researchers created an index that combined occupational activity with recreational activity. They found that the greatest reduction in premature deaths (in the range of 16 to 30 percent) was between two groups, the normal weight and moderately inactive group versus the normal weight and completely inactive group. The latter was defined as those having a desk job with no additional physical activity. To go from the completely inactive to moderately inactive, all it took, according to the study, was 20 minutes of brisk walking on a daily basis.

All is not lost!

In another study, which evaluated 56 participants, walking during lunchtime at work immediately improved mood (9). This small study clearly shows that by lunchtime activity changed mood for the better, increasing enthusiasm and reducing stress when compared to morning levels, before participants had walked. Participants had to walk at least 30 minutes three times a week for 10 weeks; pace was not important.

So what have we learned thus far about inactivity? It is all relative. If you are inactive, increasing your activity to be moderately inactive by briskly walking for 20 minutes a day may reduce your risk of premature death significantly. Even if you exercise the recommended 150 minutes a week, but are inactive the rest of the day, you may still be at risk for cardiovascular disease. You can potentially further reduce your risk of cardiovascular disease by increasing your activity with small additions throughout the day.

The underlying message is that we need to consciously move throughout the day, whether at work with a walk during lunch or at home with recreational activity. Those with desk jobs need to be most attuned to opportunities to increase activity. Simply setting a timer and standing or walking every 30 to 45 minutes may increase your activity levels and possibly reduce your risk.

References: (1) Exerc Sport Sci Rev. 2008;36(4):173-178. (2) WHO report: https://bit.ly/1z7TBAF. (3) forbes.com. (4) JAMA. 2013;310(23):2562-2563. (5) Diabetologia 2012; 55:2895-2905. (6) Ann Intern Med. 2015;162:123-132, 146-147. (7) J Am Coll Cardiol. 2013;61(23):2346-2354. (8) Am J Clin Nutr. online Jan. 24, 2015. (9) Scand J Med Sci Sports. Online Jan. 6, 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.

Walking is an easy way to help you lose weight, which will help relieve pain and restore function in your joints. Stock photo
Walking can reduce the risk of functional decline

By David Dunaief, M.D.

Dr. David Dunaief

As the population ages, we see more and more osteoarthritis (OA); and as the population gets heavier, we see more; and as people become more active, we see more; and as the population becomes more sedentary (weakened muscles), we see more. The point is that age, although a strong factor, may not be the only one.

Over 27 million people in the U.S. suffer from OA (1). Osteoarthritis is insidious, developing over a long period of time, and it is chronic by nature. It is a top cause of disability (2). What can we do about it?

It turns out that OA is not just caused by friction or age-related mechanical breakdown but rather by a multitude of factors. These include friction, but also local inflammation, genes and metabolic processes at the cellular level (3). Being a more complicated process means that we may be able to prevent and treat it better than we thought by using exercise, diet, medication, injections and possibly even supplements. Let’s look at some of the research.

How can exercise be beneficial?

In an older study, results showed that even a small 10-pound weight loss could result in an impressive 50 percent reduction of symptomatic knee OA over a 10-year period (4).

One of the exercises that most of us either can tolerate or actually enjoy is walking. We have heard that walking can be dangerous for exacerbating OA symptoms; the pounding can be harsh on our joints, especially our knees. Well, maybe not. Walking may have benefits. And once we figure out what exercise might be useful, in this case walking, how much should we do? In the Multicenter Osteoarthritis Study (MOST), results showed that walking may indeed be useful to prevent functional decline (5). But certainly not in overweight or obese patients and not older patients, right?

Actually, the patients in this study were a mean age of 67 and were obese, with a mean body mass index (BMI) of 31 kg/m2, and either had or were at risk of knee arthritis. In fact, the most interesting part of this study was that the researchers quantified the amount of walking needed to see a positive effect. The least amount of walking to see a benefit was between 3,250 and 3,750 steps per day, measured by an ankle pedometer. The best results were seen in those walking >6,000 steps per day, a relatively modest amount. This was random, unstructured exercise. In addition, for every 1,000 extra steps per day, there was a 16 to 18 percent reduced risk of functional decline two years later.

Walking is an easy way to help you lose weight, which will help relieve pain and restore function in your joints.

Where does vitamin D fit in?

For the last decade or so, we thought vitamin D was the potential elixir for chronic diseases. If it were low, that meant higher risk for disease, and we needed to replete the levels.

Well, a randomized controlled trial (RCT), the gold standard of studies, has shown that low vitamin D levels may indeed contribute to knee osteoarthritis (6). However, repleting levels of vitamin D did not seem to stem disease progression. In fact, it had no effect on the disease, to the bewilderment of the researchers. There was no change in joint space, knee pain, mobility or cartilage loss slowing. Hmm. The patients were supplemented with vitamin D 2,000 IU for two years.

There were 146 patients involved in the study. Blood levels of vitamin D were raised by 16.1 ng/ml in the treatment group to >36 ng/ml, which was significantly greater than the 2.1 ng/ml increase in the placebo group. Since the reasons for the results are unclear, work to maintain normal levels of vitamin D to possibly prevent OA, rather than wait to treat it later.

Acetaminophen may not live up to its popularity

Acetaminophen (e.g., Tylenol) is a popular initial go-to drug for the treatment of osteoarthritis, but what does the research say about its effectiveness? The answer might surprise you. Although acetaminophen doesn’t have anti-inflammatory properties, it does have analgesic properties. However, in a meta-analysis (involving 137 studies), acetaminophen did not reduce the pain for OA patients (7).

In this study, all other oral treatments were significantly better than acetaminophen including diclofenac, naproxen and ibuprofen as well as intra-articular (in the joint) injectables, such as hyaluronic acid and corticosteroids, except for an oral Cox-2 inhibitor, celecoxib, which was only marginally better.

What about NSAIDs?

NSAIDs (nonsteroidal anti-inflammatory drugs) by definition help to reduce inflammation. However, they have side effects that may include gastrointestinal bleed, and they have a black box warning for heart attacks. Risk tends to escalate with a rise in dose. But there is a twist: the FDA has approved a newer formulation of an NSAID, diclofenac (Zorvolex) (8). This formulation uses submicron particles, which are roughly 20 times smaller than the older version; since they provide a greater surface area, which helps the drug to dissolve faster, they require less dosage.

The approved dosage for OA treatment is 35 mg, three times a day. In a 602-patient, one-year duration, open-label randomized controlled trial, the newer formulation of diclofenac demonstrated improvement in pain, functionality and quality of life (9). The adverse effects, or side effects, were similar to the placebo. The only caveat is that there was a high dropout rate in the treatment group; only 40 percent completed the trial when they were dosed three times daily.

Don’t forget about glucosamine and chondroitin

Study results for this supplement combination or its individual components for the treatment of OA have been mixed. In a double-blind RCT, the combination supplement improved joint space, narrowing and reducing the pain of knee OA over two years. However, pain was reduced no more than was seen in the placebo group (10). In a Cochrane meta-analysis review study (involving 43 RCTs) results showed that chondroitin, with or without glucosamine, reduced the symptom of pain modestly compared to placebo in short-term studies (11). However, the researchers stipulate that most of the studies were of low quality.

So, think twice before reaching for the Tylenol. If you are having symptomatic OA pain, NSAIDs such as diclofenac may be a better choice, especially with SoluMatrix fine-particle technology that uses a lower dose and thus means fewer side effects, hopefully. Even though results are mixed, there is no significant downside to giving glucosamine-chondroitin supplements a chance.

However, if it does not work after 12 weeks, it is unlikely to have a significant effect. Also, try increasing your walking step count gradually; this could improve your risk of functional decline. And above all else, if you need to lose weight and do, you will reduce your risk of OA significantly.

References: (1) Arthritis Rheum. 2008;58:26-35. (2) Popul Health Metr. 2006;4:11. (3) Lancet. 1997;350(9076):503. (4) Ann Intern Med.1992;116:535-539. (5) Arthritis Care Res (Hoboken). 2014;66(9):1328-1336. (6) JAMA. 2013;309:155-162. (7) Ann Intern Med. 2015;162:46-54. (8) FDA.gov. (9) ACR 2014 Annual Meeting: Abstract 249. (10) Ann Rheum Dis. Online Jan 6, 2014. (11) Cochrane Database Syst Rev. 2015 Jan 28;1:CD005614.

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.

Exercise may be a step toward reversing the metabolic clock.
Obscenely short intervals of exercise can still generate significant benefit
Dr. David Dunaief

By David Dunaief, M.D.

What better way to start an article than with a pretest?

1) What minimum amount of exercise will reduce cardiovascular disease risk?

a. 5 to 10 minutes per day b. 30 minutes most days c. 60 minutes most days d. I don’t care — I don’t like pretests

2) How does inactivity affect menopausal symptoms?

a. Increases hot flashes b. Worsens risk of anxiety and depressive moods c. Decreases memory and concentration d. B and C

3) Exercise may have an impact on the following: a. Changing gene expression b. Metabolic aging c. Weight management d. All of the above

With all that’s been written about exercise in the past few years, I’ll bet you did well. The answers to the quiz are: 1) a, 2) d, 3) d. Before we go further, let’s differentiate between physical activity and exercise. Physical activity involves skeletal muscle contraction. It’s an umbrella term that includes exercise, but it also includes housework, yard work, movement on the job, etc. Exercise involves repetitive movements, structure and goal orientation such as walking, running, resistance training or playing sports (1). While you want to be physically active, exercise has more benefit.

We have long-held paradigms in medicine that may or may not be accurate. Medicine is always changing with the evolution of evidence-based research. We know that exercise has benefits for helping to prevent and possibly reverse some chronic diseases, but it also may have benefit for menopausal symptoms, slowing the metabolic aging process and even changing our genes, or at least gene expression.

The Fountain of Youth

Ponce de León sought a physical fountain of youth. While we tend to chuckle at that thought, metaphorically there may be at least some truth to the mythical fountain. Exercise may be a step toward reversing the metabolic clock. Until recently, we thought that when we hit 40 years old, we should expect a decline in physical abilities, with each passing year raising the probability of greater muscle atrophy. This may not actually be the case. Just because a paradigm has been around a long time does not make it correct.

In a small observational study, results showed that the participants, spanning ages 55 to 79, were unable to be differentiated based on age for the majority of tests (2). In other words, those who were in their 70s performed similarly to those in their 50s for many, but not all, parameters. It would be impossible to tell who was what age based purely on the data.

Participants were also compared to standards related to typical aging in each group, such as comparing 70-year-old cyclists versus inactive 70-year-olds. The ones who were cyclists were metabolically much younger. Thus, the researchers concluded that activity, rather than chronological age, may play a more important role in the aging process. The cyclists were not professional athletes, though they were required to pass a cycling endurance test prior to being accepted into the study. To at least some degree, we are more in control of our aging than we had thought. This is good news; we would all like to turn back the physical clock.

Can we really change our genes?

One of the greatest achievements of modern medicine has been mapping the human genome. However, gene therapy mostly has lagged. Well, there is a field called epigenetics. This word literally means “above” or “on” the gene. Epigenetics explores how to alter which of our genes get expressed and how. How can we do this? Methyl groups, one of the most basic groups of atoms in organic chemistry, latch on to genes and help to turn on and off their expression. Lifestyle modifications, like exercise, influence methylation groups to affect genes.

In a small study, results showed greater than 5,000 alterations in the genes of muscle cells such that there were different patterns of methyl groups that occurred in exercised legs compared to inactive legs (3). The genes that were affected are known to be involved in insulin sensitivity and inflammation. Let me explain further.

The researchers had 23 healthy volunteers use a stationary bike for 40 minutes, four times a day, for three months. Here is the catch: Participants only used one leg and did not exercise the other leg, limiting confounding variables. In the same participant, the leg that was exercised had dramatic changes in gene expression, whereas the other leg did not.

How can exercise elongate cell life?

In another study, exercise appeared to prevent or reduce the risk of shortened telomeres. Telomeres are important for protecting the DNA and, ultimately, the cell (4). There were four different categories of exercises surveyed. If respondents said yes to each category, there was an exponentially greater chance that they would not have very short telomeres.

The categories included walking, running, walking/riding a bike to work or school and weight lifting. When a participant was involved in one category in the previous month, there was a 3 percent reduced risk of shorter telomeres, whereas participants who were involved in all four categories had a 59 percent reduced risk of having very short telomeres. This greatest impact was seen in adults between ages 40 and 65.

Menopause symptoms

Although menopause is a rite of passage for women, not a disorder, there are symptoms that may negatively impact quality of life. Exercise may help alleviate menopausal symptoms. In a study, women who exercised regularly (resistance training twice weekly, plus either 150 minutes weekly of moderate activity, like walking, or 75 minutes weekly of intense exercise, like jogging or running) had a better overall sense of well-being and fewer symptoms during menopause compared to their less active counterparts (5). Those who were less active were more likely to be in depressed/anxious moods, have “brain fog,” difficulties with memory and concentration and experience increased vasomotor symptoms. Interestingly though, there was no change in hot flashes between the two groups.

I don’t have time to exercise!

There have been several studies that have shown that you can have obscenely short intervals of exercise and still get significant benefit. In one study, a one-minute intensive interval was broken into 20-second intervals within 10 minutes of exercise three times a week (6). Overweight participants had improved blood pressure and endurance capacity, as well as beneficial gains among other parameters.

In another study, as little as five to 10 minutes of running a day reduced the risk of dying from any cause by 30 percent and dying from heart disease by 45 percent (7). The best part of the results was that there was a significant difference between runners and nonrunners, but not between those who ran at a less-than-six-minute-mile pace and those who ran at a slower-than-10-minute-mile pace.

References: (1) uptodate.com. (2) J Physiol. online Jan. 6, 2015. (3) Epigenetics. Dec. 7, 2014. (4) Med Sci Sports Exerc. 2015;47(11):2347-2352. (5) Maturitas. 2015 Jan;80(1):69-74. (6) PLoS One. 2014;9(11):e111489. (7) J Am Coll Cardiol. 2014;64(5):472-481.

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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What keeps us young? Well, certainly eating healthy foods, exercising and sleeping are all on that list.

But there’s something else that works, too. If you can, try hanging out with a group of younger people at a party, even if the music is loud and incomprehensible.

At a recent party, I wasn’t sure what my daughter was saying, as I watched her sing every word with her eyes wide open and her hands fluttering at her sides like a butterfly’s wings.

It’s as if both of my children have sped up the needle so fast on their speech that I suspect that what’s coming out of their mouths probably started out as distinct words at some point. I’m hoping that the message they are repeating isn’t something offensive or objectionable, like, “Environmental regulation is bad, so let’s put the fox in charge of the hens at the Environmental Protection Agency. Go fox, Go fox, Go fox.” No, wait, this isn’t about politics.

A room full of children at the party, held by a family friend, made me think a bright scientist may one day figure out how to harness that energy, store it and release it at just the right time, either when someone needed to warm a house or a heart.

The next generation seems to follow a simple formula: Why walk when you can run, skip or flip, why talk when you can shout and why stay on the ground when you can challenge gravity to hold you down?

I recognize that loud parties filled with perplexing music may not be everyone’s cup of tea. The decibel level may damage hearing aids, destabilize pacemakers, or rattle fillings or dentures.

You don’t need to attend a kids party, especially if you weren’t invited to one, to share the exuberance of youth. Have you stopped your car on the way back along familiar routes to watch a T-ball baseball game, to listen to a chorus singing music you might know, or to watch a marching band trying to master John Philip Sousa while figuring out what yard line they’re supposed to be on when they reach the high notes?

All that energy begets energy. I’ve heard people talk about how their children keep them young. Imagine multiplying that, even for a day or a few hours, by however many kids are celebrating the moment in a way that doesn’t get bogged down in blinking Blackberries, a pending deadline or a need to disappear into the immobile ether of the television.

And if you’re fortunate enough, you can engage with some of the next generation in questions they raise about the world. Many of us think we are pretty knowledgeable. That may be the case, until a child asks us a question we can’t answer. Of course, we could rush to the internet to find an answer we might soon forget, or we could try to inch our way to an answer or even revisit a question we hadn’t pondered in years.

I’m sure teachers feel the same kinds of highs and lows that appear in so many other jobs. They have to discuss the Magna Carta year after year, or explain how the change in Y over the change in X represents the slope of a line.

But, then, every once in a while, a student may ask a new question that brings the material to life and gives the teacher an opportunity to learn from the student. The best answers inevitably lead to the next best questions.

Energy, insight, curiosity and joy don’t exist solely in the world of youth, but they are often easier to spot among a group of children whose joie de vivre lifts off at a party.

Studies show that even moderate exercise can significantly lower mortality risk when compared with no physical activity at all.

Reducing inflammation is part of this process.

By David Dunaief, M.D.

Dr. David Dunaief

When asked what was more important, longevity or healthy aging (quality of life), more people choose the latter. Why would you want to live a long life but be miserable? Well, it turns out the two components are not mutually exclusive. I would like you to ponder the possibility of a third choice, “all of the above.” Would you change your answer and, instead of making a difficult choice between the first two, choose the third?

I frequently use the example of Jack LaLanne, a man best known for popularizing fitness. He followed and preached a healthy lifestyle, which included diet and exercise. He was quite a motivator for many and ahead of his time. He died at the ripe old age of 96.

This brings me to my next point, which is that the number of 90-year-olds is growing by leaps and bounds. According to the National Institutes of Health, those who were more than 90 years old increased by 2.5 times over a 30-year period from 1980 to 2010 (1). This group is among what researchers refer to as the “oldest-old,” which includes those aged 85 and older.

What do these people have in common? According to one study, they tend to have fewer chronic morbidities or diseases. Thus, they tend to have a better quality of life with a greater physical functioning and mental acuity (2).

In a study of centenarians, genetics played a significant role. Characteristics of this group were that they tended to be healthy and then die rapidly, without prolonged suffering (3). Another benchmark is the amount of health care dollars spent in their last few years. Statistics show that the amount spent for those who were in their 60s and 70s was significantly higher, three times as much, as for centenarians in their last two years (4).

Factors that predict one’s ability to reach this exclusive club may involve both genetics and lifestyle choices. One group of people in the U.S. that lives longer lives on average than most is Seventh-day Adventists. We will explore why this might be the case and what lifestyle factors could increase our potential to maximize our healthy longevity. Exercise and diet may be key components of this answer. Now that we have set the tone, let’s look at the research.

Exercise

For all those who don’t have time to exercise or don’t want to spend the time, this next study is for you. We are told time and time again to exercise. But how much do we need, and how can we get the best quality? In a 2014 study, the results showed that 5 to 10 minutes of daily running, regardless of the pace, can have a significant impact on life span by decreasing cardiovascular mortality and all-cause mortality (5).

Amazingly, even if participants ran fewer than six miles per week at a pace slower than 10-minute miles, and even if they ran only one to two days a week, there was still a decrease in mortality compared to nonrunners. Here is the kicker: Those who ran for this very short amount of time potentially added three years to their life span. There were 55,137 participants ranging in age from 18 to 100 years old.

An accompanying editorial to this study noted that more than 50 percent of people in the United States do not meet the current recommendation of at least 30 minutes of moderate exercise per day (6). Thus, this recent study suggests an easier target that may still provide significant benefits.

Diet

A long-standing paradigm is that we need to eat sufficient animal protein. However, there have been cracks developing in this façade of late, especially as it relates to longevity. In an observational study using NHANES III data, results show that those who ate a high-protein diet (greater than 20 percent from protein) had a twofold increased risk of all-cause mortality, a four times increased risk of cancer mortality and a four times increased risk of dying from diabetes (7). This was over a considerable duration of 18 years and involved almost 7,000 participants ranging in age at the start of the study from 50 to 65.

However, this did not hold true if the protein source was from plants. In fact, a high-protein plant diet may reduce the risks, not increase them. The reason for this effect, according to the authors, is that animal protein may increase insulin growth factor-1 and growth hormones that have detrimental effects on the body.

Interestingly, those who are over the age of 65 may benefit from more animal protein in reducing the risk of cancer. However, there was a significantly increased risk of diabetes mortality across all age groups eating a high animal protein diet. The researchers therefore concluded that lower animal protein may be wise at least during middle age.

The Adventists Health Study 2 trial reinforced this data. It looked at Seventh-day Adventists, a group whose emphasis is on a plant-based diet, and found that those who ate animal protein up to once a week had a significantly reduced risk of dying over the next six years compared to those who were more frequent meat eaters (8). This was an observational trial with over 73,000 participants and a median age of 57 years old.

Inflammation

You may have heard the phrase that inflammation is the basis for more than 80 percent of chronic disease. But how can we quantify this into something tangible?

In the Whitehall II study, a specific marker for inflammation was measured, interleukin-6. The study showed that higher levels did not bode well for participants’ longevity (9). In fact, if participants had elevated IL-6 (>2.0 ng/L) at both baseline and at the end of the 10-year follow-up period, their probability of healthy aging decreased by almost half.

The takeaway from this study is that IL-6 is a relatively common biomarker for inflammation that can be measured with a simple blood test offered by most major laboratories. This study involved 3,044 participants over the age of 35 who did not have a stroke, heart attack or cancer at the beginning of the study.

The bottom line is that, although genetics are important for longevity, so too are lifestyle choices. A small amount of exercise, specifically running, can lead to a substantial increase in healthy life span. While calories are not equal, protein from plants may trump protein from animal sources in reducing the risk of mortality from all causes, from diabetes and from heart disease. This does not necessarily mean that one needs to be a vegetarian to see the benefits. IL-6 may be a useful marker for inflammation, which could help predict healthy or unhealthy outcomes. Therefore, why not have a discussion with your doctor about testing to see if you have an elevated IL-6? Lifestyle modifications may be able to reduce these levels.

References: (1) nia.nih.gov. (2) J Am Geriatr Soc. 2009;57:432-440. (3) Future of Genomic Medicine (FoGM) VII. Presented March 7, 2014. (4) CDC.gov. (5) J Am Coll Cardiol. 2014;64:472-481. (6) J Am Coll Cardiol. 2014;64:482-484. (7) Cell Metab. 2014;19:407-417. (8) JAMA Intern Med. 2013;173:1230-1238. (9) CMAJ. 2013;185:E763-E770.

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.

Exercise is important in reducing the risk of fractures. Stock photo

By David Dunaief, MD

Osteoporosis is a complex disease. For one thing, it progresses with no symptoms, until the more severe stage of fractures that cause potential disability and increase mortality. For another, the only symptoms are from the treatment with medications, better known as side effects. Third, lifestyle modifications and supplements, while important, require adherence to a regimen.

I am not a big advocate of medication, as I am sure you have gathered from my previous articles; however, medication does have its place. There are studies that show benefit from the two main classes for osteoporosis, bisphosphonates such as alendronate (Fosamax, though it is now generic) and the newer class that involves monoclonal antibodies such as denosumab (Prolia). And, of course, I am a big advocate of lifestyle modifications including diet, exercise, smoking cessation and even some supplements. The side effects of these modifications are better health outcomes for chronic diseases and disorders in general. What I can’t advocate for, as a physician sworn to help people, is the new emerging cohort that I refer to as the “do-nothing group.”

Recently, a New York Times article on June 1, 2016, entitled, “Fearing Drugs’ Rare Side Effects, Millions Take Their Chances With Osteoporosis,” reported that prescriptions for medications to treat the disease have fallen by more than 50 percent from 2008 to 2012 because of the fear of the side effect profile that include rare instances of atypical fractures and jawbone necrosis (1).

In the article, one doctor mentions that patients prefer diet and exercise, but that it does not work. Well, he may be partially correct. Diet and exercise may not work if they’re not implemented. However, if people actually make lifestyle modifications, there could be substantial benefit. Just to give up on the medications for osteoporosis or to refuse to take them is not going to improve your chances or reduce your risk of getting fractures in the spine, hip, wrist or other locations. In other words, the “do-nothing” approach won’t help and may significantly increase your risk of fracture and other complications, such as death.

At the top of the list of risk factors for osteoporosis is nontraumatic fractures — in other words, breaking of bone with low-impact events. In this case, once you have had a fracture, the probability of having a recurrent or subsequent fracture increases more than three times in the first year, according to a recent Icelandic study (2). Lest you think that you are in the clear after a year since your first fracture: After 10 years, the risk of subsequent fracture still remains high, with a twofold increased risk.

Osteoporosis involves bone loss. We typically measure this through the bone mineral density (BMD) biomarker using a DXA scan. However, another component is bone quality. Sarcopenia, or loss of lean muscle mass, may play a role in bone quality. There are vitamins, such as vitamin K2, that can have beneficial effects on bone based on bone quality as well. No, this is not the same as the more well-known vitamin K1 used in clotting, which may also have a smaller benefit in preserving bone.

Let’s look at the evidence.

Avoiding sacropenia

Sarcopenia is a fancy word for a depressing phenomenon that occurs as we age and become more and more sedentary; it is the loss of lean skeletal muscle mass at the rate of 3 to 8 percent each consecutive decade after 30 and also loss of strength (3). It may have significant effects on about one-third of those over age 60 and half of those over 80. Unless, of course, you are physically active on a regular basis. In the Study for Osteoporotic Fractures in Men, results show that sarcopenia plus osteoporosis, taken together, increases the risk of fracture more than three times in older men (4).

The researchers assessed muscle wasting by using the European Working Group on Sarcopenia in Older Patients (EWGSOP), which takes into account weakness (grip strength <20 kg for men), slowness (walking=0.8 m/s) and low lean muscle mass (< 20 percent). This involved over 5,000 men with a mean age of about 74. The group with sarcopenia had significantly lower grip strength and was less physically active. In another study, those who were healthy 65-year-old adults who had sarcopenia or low lean muscle mass were at a greater than two times risk of experiencing a low-trauma fracture within three years (5). This was according to the EWGSOP1 cutoff criteria for sarcopenia.

Preventing sarcopenia

Well, beyond the obvious of physical activity and formal exercise, there is a medication that has potentially shown positive results. This is the bisphosphonate alendronate (Fosamax). In a study, results showed that alendronate increased muscle mass significantly over a one-year period (6). In the appendicular (locomotive) skeletal muscle, there was a 2.5 times increase in muscle mass, while in lower limb muscle mass there was a greater than four times increase. This was a retrospective (backward-looking), case-control study involving about 400 participants. While these results are encouraging, we need a prospective (forward-looking), randomized controlled trial. For those who don’t want to or can’t for some reason exercise, then medication may help with muscle mass.

Exercise! Exercise! Exercise!

In a meta-analysis (a group of 10 trials), results showed there was a significant 51 percent reduction in the risk of overall fracture in postmenopausal women who exercised (7). This study involve over 1,400 participants. Does exercise intensity matter? Fortunately, the answer is no. If you like jogging or running, that’s great, but walking was also beneficial. This is important, since you want to do the type of activity that is more enjoyable to you, especially since the benefit of exercise dissipates when you stop doing it regularly (8).

The importance of K2

In a recent study, vitamin K2 was shown to reduce the risk of hip fracture by 60 percent, vertebral fracture by 77 percent and nonvertebral fractures by a whopping 81 percent (9). According to the authors, this benefit may be derived from bone strength (BMC, or bone mineral content) rather than from bone mineral density (BMD). There were 325 postmenopausal women in this study. It was a randomized controlled trial with one group receiving vitamin K2 (MK-4, menatetrenone) supplementation of 45 mg/day and the other a placebo group.

Don’t forget fruits and vegetables

In the Singapore Chinese Health Study, a prospective population-based study, results showed that there was a 34 percent reduction in the risk of hip fracture in the highest quintile of vegetable-fruit-soy (VFS) intake, compared to the lowest quintile (10). This study involved over 63,000 men, premenopausal and postmenopausal women with an age range from 45 to 74 years old. The results showed a dose-dependent curve, meaning the more VFS, the higher the reduction in hip fracture risk. Interestingly, there was no difference in risk of fracture when meat in the form of meat dim-sum was used instead of plant-based protein. The researchers concluded that an Asian plant-based diet may help reduce the risk of hip fracture. I’m not saying to take medications for osteoporosis, but you need to do something — either medications, lifestyle modifications, supplements or all three — especially if you have a history of low-trauma fractures, because your risks of disability, complications and death increase significantly with subsequent fractures. But, do not be part of the growing “do-nothing” group.

References:

(1) J Bone Miner Res. 2015;30(12):2179-2187. (2) World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases 2016. Abstract 0C35. (3) Curr Opin Clin Nutr Metab Care. 2009; 12(1):86–90. (4) American Society of Bone and Mineral Research 2013. Abstract 1026. (5) Age Ageing.2010;39:412-423. (6) Osteoporos Sarcopenia. 2015;1(1):53-58. (7) Osteoporos Int. 2013;24(7):1937. (8) Ann Intern Med. 1988;108(6):824. (9) Osteoporos Int. 2007;18(7):963-972. (10) J Nutr. 2014;144(4):511-518.

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.

Iron is important for exercise motivation and may play a role in peak mental functioning. Stock photo

I believe the most salient teaching point in medical school and beyond was when a professor explained, as it relates to the patient diagnosis, when you hear hooves think horses not zebras. What this means is think of the more common or more likely diseases or disorders in a differential diagnosis rather than the more esoteric or rare diseases. And when a patient presents with fatigue, one of the more common reasons is iron deficiency.

Major causes of low iron are anemia of chronic disease, iron deficiency anemia, sideroblastic anemia and thalassemia. Of these, iron deficiency anemia is the most common. However, there is a much less known, but not uncommon, form of low iron. This is called iron deficiency without anemia. Unlike iron deficiency anemia, the straightforward CBC (complete blood count) that is usually drawn cannot detect this occurrence since the typical indicators, hemoglobin and hematocrit, are not yet affected.

So how do we detect iron deficiency without anemia? Not to despair, since there is a blood test done by major labs called ferritin. What is ferritin? Ferritin is a protein that is involved in iron storage. When ferritin is less than 10 to 15 ng/ml, the diagnosis of iron deficiency is most likely indicated. Even healthy people with ferritin slightly higher than this level may also have iron deficiency (1). The normal range of ferritin is 40-200 ng/ml.

At this point, you should be asking who does low ferritin affect and what are the symptoms? Women and athletes are affected primarily, and low ferritin levels may cause symptoms of fatigue. It is also seen with some chronic diseases such as restless leg syndrome (RLS) and attention deficit hyperactivity disorder (ADHD) in children.

Effect on women

In a prospective (forward-looking) study done in 1993 looking at primary care practices, it was determined that 75 percent of patients complaining of fatigue were women (2). Interestingly, less than 10 percent of these women had abnormal lab results when routine labs were drawn, most probably without a ferritin level. Many of them had experienced these symptoms for at least three months.

There was a randomized controlled trial (RCT), the gold standard of studies, that showed women who were suffering from fatigue and low or low-normal ferritin levels (less than 50 ng/ml), but who did not have anemia, benefited from iron supplementation (3). When comparing women with these ferritin levels, many of those who were given 80 mg of oral prolonged release ferrous (iron) sulfate supplements daily saw a significant improvement in their fatigue symptoms when compared to those women who were not given iron. Almost half the women taking iron supplements had a significant improvement in fatigue symptoms. The results were seen in a very short 12-week period. This is nothing to sneeze at, since fatigue is one of main reasons people go to the doctor. Also, although this was a small study, there were 198 women involved, ranging from 18 to 53 years old.

There are caveats to these study results. There was no improvement in depression or anxiety symptoms, nor in overall quality of life. Even though it was blinded, stool changes occur when a patient takes iron. Therefore, the women taking supplements may have known. Nonetheless, the study results imply that physicians should check ferritin level, not only a CBC, when a premenopausal woman complains of fatigue. Note that all of the women in the study were premenopausal. This is important to delineate, since postmenopausal women are at much higher risk of iron overload, rather than deficiency. They are no longer menstruating and therefore do not rid themselves of significant amounts of iron.

Athletes

According to an article in The American Journal of Lifestyle Medicine, athletes’ endurance may be affected by iron deficiency without anemia (4). Low ferritin levels are implicated, as in the previous study. Iron is important for exercise motivation and may play a role in peak mental functioning, as reported in “Iron: Nutritional and Physiological Significance.” In animal studies, iron deficiency without anemia is associated with reduction in endurance because of a decrease in oxygen-based enzymatic activity within the cells.

However, this has not been shown definitively in human athletes and remains an interesting, but yet to be proven, hypothesis. Interestingly, female endurance athletes are more likely to be affected by iron deficiency without anemia, which occurs in about 25 percent of this population, according to studies (5). Low ferritin is not seen as much in male athletes. This difference in gender may be due to the fact that women not only menstruate, losing iron on a regular basis, but also their intake of dietary iron seems to be lower (6).

However, male athletes are not immune. At the end of the season for high school runners, 17 percent had iron deficiency without anemia (7). Do not take iron supplements without knowing your levels of hemoglobin and ferritin and without consulting a doctor. Studies are mixed on the benefits of iron supplementation without anemia for athletes.

Impact on restless leg syndrome

Iron deficiency with a ferritin level lower than 50 ng/ml affects approximately 20 percent of patients who suffer from restless leg syndrome (8). Restless leg syndrome, classified as a neurologic movement disorder, causes patients to feel like they need to move their legs, most commonly about a half-hour after going to bed. In a very small study, patients with restless leg syndrome who had ferritin levels lower than 45 ng/ml saw significant improvement in symptoms within eight days with iron supplementation (9).

Before you get too excited, the caveat is that 75 percent of restless leg patients have high ferritin levels. It is impressive in terms of being an easy fix for those who have low ferritin levels. And, it may be that high ferritin levels in RLS has the same symptoms as low ferritin for this is the case when it comes to iodine levels in hypothyroid patients. Iron is a trace mineral, meaning we only need small amounts to maintain proper levels.

Ferritin levels — both high and low — may play a role in a number of diseases and symptoms. If you are suffering from fatigue, a CBC test may not be enough to detect iron deficiency. You may want to suggest checking your ferritin level. Though iron supplementation may help those with symptomatic iron deficiency without anemia, it is very important not to take iron supplements without the direct supervision of your physician.

References: (1) Br J Haematol. 1993;85(4):787-798. (2) BMJ 1993;307:103. (3) CMAJ. 2012;184(11):1247-1254. (4) Am J Lifestyle Med. 2012;6(4):319-327. (5) J Am Diet Assoc. 2005;105:975–978. (6) J Pediatr. 1989;114:657–663. (7) J Adolesc Health Care. 1987;8:322–326. (8) Am Fam Physician. 2000;62(4):736. (9) Sleep Med. 2012;13(6):732-735. 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.