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Medical Compass

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

By David Dunaief, M.D.

Dr. David Dunaief

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

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

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

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

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

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

The EPIC trial

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

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

Beneficial studies with fruits and vegetables

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

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

Prostate cancer

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

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

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

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

Cruciferous vegetables

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

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

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

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

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

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‘Why’ is as important as ‘how’

By David Dunaief, M.D.

Dr. David Dunaief

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

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

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

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

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

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

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

Low-carbohydrate vs. low-fat diets

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

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

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

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

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

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

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

Diet comparisons

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

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

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

Psyche

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

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

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

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

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

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

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

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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.

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Recent studies suggest that sleep deprivation results in weight gain. Stock photo
Even short-term sleep deprivation can negatively impact health

By David Dunaief, M.D.

Dr. David Dunaief

If you’ve ever felt fatigued, this article is for you. Fatigue is a common patient complaint, and there is a long list of maladies that may be responsible: sleep deprivation, infectious diseases (such as Lyme) and hypothyroidism (low thyroid functioning), to name a few.

In this week’s column, we are going to focus on sleep deprivation, since it may impact our quality of life and influence concerns like weight gain and disorders that involve insulin resistance, kidney function and cognition. Even a short duration of inadequate sleep can have a surprising impact.

How much sleep do we need? Conventional wisdom has always been eight hours (1). However, it varies depending on the individual. About 26 percent of Americans get eight or more hours of sleep per night (2). During the workweek, approximately 30 percent of individuals in the U.S. get fewer than six hours of sleep. When you get down to five hours or less per night, the evidence suggests that most people get into trouble.

Weight gain

In a small, prospective (forward-looking) study, results showed that sleep deprivation results in weight gain. Why is this? You actually burn more calories (about 5 percent more) when you sleep fewer hours, but you consume significantly more calories than you metabolize (3). The individuals who were sleep restricted gained about two pounds. That may not sound like much, but the scary part is it occurred over a short time period — one workweek, or five days.

Study participants were in a controlled setting, with half of them restricted to five hours of sleep and half of them permitted to sleep up to nine hours. Everyone was given access to ample amounts of food. Interestingly, not only did the amount of food consumed by those who were sleep deprived increase, but carbohydrate consumption became dominant. When participants who had been sleep deprived were transitioning toward adequate sleep in the second week, they began to make better food choices and started to lose weight.

In addition, researchers found that natural melatonin levels are altered by sleep deprivation, resulting in a change in our circadian rhythms or biological clocks that make it harder to fall asleep.

In another study, the results were similar (4). This one involved 225 healthy participants. Those who were sleep restricted gained about two pounds of weight over five days. Just like the previous study, participants were in a controlled laboratory where food was provided and their sleep monitored. In both studies, significant late-night eating was common.

In the Nurses’ Health Study, results showed that, for participants who regularly slept five hours or less, there was a 32 percent increased risk of gaining more than 30 pounds (5). This observational study involved approximately 68,000 women and was 16 years in duration.

Effects on aging

In a very small, but well-designed, randomized prospective study, adipocytes (fat cells) in sleep-deprived individuals became resistant or insensitive to ever-higher levels of insulin (6). This may be a precursor to increased risk of weight gain and diabetes. The sleep-deprived participants were allowed four-and-a-half hours of sleep per night over a period of four days compared to the control group, which was allowed eight-and-a-half hours per night. The most surprising effect found was that the fat cells of sleep-deprived individuals aged approximately two decades metabolically, so that participants in their 20s had fat cells that functioned similarly to those of people in their 40s.

Diabetes

In the Millennium Cohort Study, participants with inadequate sleep were at significantly greater risk of developing type 2 diabetes than those with sufficient sleep (7). In fact, participants who had five hours of sleep per night were at a 28 percent increased risk, and those who had fewer than five hours a night had a 52 percent greater risk. Adequate sleep was defined as at least seven hours. This was a prospective (forward-looking) observational study involving over 47,000 military personnel. The researchers brought up a good point: While sleep is on the decline, diabetes has been on the rise over the last three decades.

Cognition

Sleep deprivation’s impact on cognition may be immediate. In a study, healthy participants were subjected to sleep deprivation that resulted in decreased neurobehavorial functioning, or cognition, when compared to controls (8). Those in the sleep deprivation group were restricted for five days to four hours per night in bed, while those in the control group were allowed 10 hours per night. The sleep-deprived group was then allowed one night of 10 hours of sleep. While they recovered some neurobehavioral functioning, they didn’t reach their previous baseline levels. This study simulated the workweek followed by one day of recovery. The study was an in-laboratory, well-controlled study involving 159 healthy participants.

In the Familial Adult Children Study (FACS), presented at the prestigious 64th Annual American Academy of Neurology Meeting, participants with poor quality sleep were more likely to have high levels of amyloid beta plaques (9). The significance of these plaques is that they may be precursors to Alzheimer’s disease. The researchers discovered that participants who woke five times in each hour of sleep had a substantially greater risk of developing amyloid beta plaques. Thus, those with lesser sleep efficiency were more likely to have preclinical Alzheimer’s disease. None of the patients showed any symptomatic cognitive deficits, only early preclinical signs of Alzheimer’s. This is a very preliminary study that requires further prospective and randomized clinical trials.

At this point, we can agree that sleep deprivation is something to be taken seriously. If you are fatigued, it may not be a bad idea to have your glucose (sugars) checked. Also, getting sufficient sleep may help slow the metabolic aging of your cells — and most of us want to forestall the aging process. As we age, cognition is a central issue. If we can decrease our risk of cognitive decline while aging, this is an ideal scenario. So, make sure you are getting good quality and quantity of sleep that fits your individual needs. If you struggle to sleep, seek professional help. It is not just an inconvenience to be tired, it actually affects your health.

References: (1) Sleep. 1995;18:908. (2) National Sleep Foundation, 2005. (3) Proc Natl Acad Sci USA. 2013;110:5695-5700. (4) Sleep. 2013;36:981-990. (5) Am. J. Epidemiol. 2006;164:947-954. (6) Ann Intern Med. 2012;157:549-557. (7) Diabetes Care Online. July 2013. (8) Sleep. 2010;33:1013-1026. (9) AAN Abstract 703.

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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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.

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The American Academy of Dermatology recommends sunscreen lotion with an SPF of 30 to be used daily by those who spend a lot of time in the sun.
Choose sunscreen and clothing as part of your sun protection regimen
Dr. David Dunaief

This holiday weekend, many headed to the beaches or fired up the outside barbecue for the first weekend of what’s shaping up to be a steamy summer. Long summer days spent outside conjure up pleasant images of friends and family relaxing together.

What could possibly be wrong with this picture? With all these benefits, you need to be cognizant of cutaneous (skin) melanoma. It is small in frequency, compared to basal cell and squamous cell carcinomas, responsible for only about 1 percent of skin cancers; however, it is much more deadly.

Statistics

Unfortunately, melanoma is on the rise. Over the last 40 years from 1970 to 2009, its incidence has increased by 800 percent in young women and by 400 percent in young men (1). These were patients diagnosed for the first time between 18 and 39 years old. Overall, the risk is greater in men, with 1 in 28 lifetime risk. The rate among women is 1 in 44. It is predicted that in 2017, there will have been over 87,000 new diagnoses, with over 11 percent resulting in death (2).

Melanoma risk involves genetic and environmental factors. These include sun exposure that is intense but intermittent, tanning beds, UVA radiation used for the treatment of psoriasis, the number of nevi (moles), Parkinson’s disease, prostate cancer, family history and personal history. Many of these risk factors are modifiable (3).

Presentation

Fortunately, melanoma is mostly preventable. What should you look for to detect melanoma at its earliest stages? In medicine, we use the mnemonic “ABCDE” to recall key factors to look for when examining moles. This stands for asymmetric borders (change in shape); border irregularities; color change; diameter increase (size change); and evolution or enlargement of diameter, color or symptoms, such as inflammation, bleeding and crustiness (4). Asymmetry, color and diameter are most important, according to guidelines developed in England (5).

It is important to look over your skin completely, not just partially, and have a dermatologist screen for potential melanoma. Screening skin for melanomas has shown a six-times greater chance of detecting them. Skin areas exposed to the sun have the highest probability of developing the disease. Men are more likely to have melanoma tumors on the back, while women are more likely to have melanoma on the lower legs, but they can develop anywhere (6).

In addition, most important to the physician, especially the dermatologist, is the thickness of melanoma. This may determine its probability to metastasize. In a retrospective (backward-looking) study, the results suggest that melanoma of >0.75 mm needs to not only be excised, or removed, but also have the sentinel lymph node (the closest node) biopsied to determine risk of metastases (7).

A positive sentinel node biopsy occurred in 6.23 percent of those with thickness >0.75 mm, which was significantly greater than in those with thinner melanomas. When the sentinel node biopsy is positive, there is a greater than twofold increase in the risk of metastases. On the plus side, having a negative sentinel node helps relieve the stress and anxiety that the melanoma tumor has spread. The two most valuable types of prevention are clothing and sunscreen. Let’s look at these in detail.

Clothing

Clothing can play a key role in reducing melanoma risk. The rating system for clothing protection is the ultraviolet protection factor (UPF). The Skin Cancer Foundation provides a list of which laundry additives, clothing and cosmetics that protect against the sun (8). Clothing that has a UPF rating between 15 and 24 is considered good, 25 and 39 is very good, and 40 and 50 is excellent. The ratings assess tightness of weave, color (the darker the better), type of yarn, finishing, response to moisture, stretch and condition. The most important of these is the weave tightness (9). There are many companies that produce fashionable and lightweight sun protective clothing lines. Gone are the days of needing to wear your jeans into the water while swimming to protect you from the sun.

Sunscreen

We have always known that sunscreen is valuable. But just how effective is it? In an Australian prospective (forward-looking) study, those who were instructed to use sun protective factor (SPF) 16 sunscreen lotion on a daily basis had significantly fewer incidences of melanoma compared to the control group members, who used their own sunscreen and were allowed to apply it at their discretion (10). The number of melanomas in the treatment group was half that of the control group’s over a 10-year period. But even more significant was a 73 percent reduction in the risk of advanced-stage melanoma in the treatment group. Daily application of sunscreen was critical.

The recommendation after this study and others like it is that an SPF of 15 should be used daily by those who are consistently exposed to the sun and/or are at high risk for melanoma according to the American Academy of Dermatology (11). The amount used per application should be about one ounce. However, since people don’t use as much sunscreen as they should, the academy recommends an SPF of 30 or higher.

Note that SPF 30 is not double the protection of SPF 15. The UVB protection of SPFs 15, 30 and 50 are 93, 97 and 98 percent, respectively. The problem is that SPF is a number that registers mostly the blocking of UVB but not so much the blocking of UVA1 or UVA2 rays. However, 95 percent of the sun’s rays that reach sea level are UVA. So what to do?

Sunscreens come in a variety of UV filters, which are either organic filters (chemical sunscreens) or inorganic filters (physical sunscreens). The FDA now requires broad-spectrum sunscreens pass a test showing they block both UVB and UVA radiation. Broad-spectrum sunscreens must be at least SPF 15 to decrease the risk of skin cancer and prevent premature skin aging caused by the sun. Anything over the level of SPF 50 should be referred to as 50+ (3).

The FDA also has done away with the term “waterproof.” Instead, sunscreens can be either water resistant or very water resistant, if they provide 40 and 80 minutes of protection, respectively. This means you should reapply sunscreen if you are out in the sun for more than 80 minutes, even with the most protective sunscreen (3). Look for sunscreens that have zinc oxide, avobenzone or titanium oxide; these are the only ones that provide UVA1 protection, in addition to UVA2 and UVB protection.

In conclusion, to reduce the risk of melanoma, proper clothing with tight weaving and/or sunscreen should be used. The best sunscreens are broad spectrum, as defined by the FDA, and should contain zinc oxide, avobenzone or titanium oxide to make sure the formulation not only blocks UVA2 but also UVA1 rays. It is best to reapply sunscreen every 40 to 80 minutes, depending on its rating. We can reduce the risk of melanoma occurrence significantly with these very simple steps.

References: (1) Mayo Clin Proc. 2012; 87(4): 328–334. (2) cancer.org. (3) uptodate.com. (4) JAMA. 2004;292(22):2771. (5) Br J Dermatol. 1994;130(1):48. (6) Langley, RG et al. Clinical characteristics. In: Cutaneous melanoma, Quality Medical, St. Louis, 1998, p. 81. (7) J Clin Oncol. 201;31(35):4385-4386. (8) skincancer.org. (9) Photodermatol Photoimmunol Photomed. 2007;23(6):264. (10) J Clin Oncol. 2011;29(3):257. (11) aad.org.

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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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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Early treatment is crucial

By David Dunaief, M.D.

Dr. David Dunaief

Ah, summer is upon us. Unfortunately, this means that tick season is getting into full swing. Projections for this year’s tick population are ominous, because of seemingly unrelated issues like an increase in last year’s acorn population, which feeds mice that are carriers, and a relatively mild winter (1).

Thus, it is good timing to talk about Borrelia burgdorferi, better known as the bacteria that causes Lyme disease. This bacteria is from the spirochete class and is typically found in the deer tick, also known as the blacklegged tick.

What do deer ticks look like? They are small and can be as tiny as a pencil tip or the size of a period at the end of a sentence. The CDC.gov site is a great resource for tick images and other information related to Lyme disease.

What if you have been bitten by a tick? The first thing you should do is remove it with forceps, tweezers or protected fingers (paper) as close to the skin as possible and pull slow and steady straight up. Do not crush or squeeze the tick, for doing so may spread infectious disease (2). In the study, petroleum jelly, fingernail polish, a hot kitchen match and 70 percent isopropyl alcohol all failed to properly remove a tick. The National Institutes of Health recommend not removing a tick with oil (3).

The deer tick on the right is about half the size of a dog tick,
as seen on the left.

When a tick is removed within 36 to 48 hours, the risk of infection is quite low, according to the Centers for Disease Control and Prevention (4). However, a patient can be given a prophylactic dose of the antibiotic doxycycline, one dose of 200 mg, if the erythema migrans, or bulls-eye rash — a red outer ring and red spot in the center — has not occurred, and it is within 72 hours of tick removal (5). Those who took doxycycline had significantly lower risk of developing the bulls-eye rash and thus Lyme disease; however, treatment with doxycycline did have higher incidence of nausea and vomiting than placebo.

What are the signs and symptoms of Lyme disease? There are three stages of Lyme disease: early stage, where the bacteria are localized; early disseminated disease, where the bacteria have spread throughout the body; and late-stage disseminated disease. Symptoms for early localized stage and early disseminated disease include the bulls-eye rash, which occurs in about 80 percent of patients, with or without systemic symptoms of fatigue (54 percent), muscle pain and joint pain (44 percent), headache (42 percent), neck stiffness (35 percent), swollen glands (23 percent) and fever (16 percent) (6).

Early disseminated disease may cause neurological symptoms such as meningitis, cranial neuropathy (Bell’s palsy) and motor or sensory radiculoneuropathy (nerve roots of spinal cord). Late disseminated disease can cause Lyme arthritis (inflammation in the joints), heart problems, facial paralysis, impaired memory, numbness, pain and decreased concentration (3).

How do we prevent this disease? According to the CDC, we should wear protective clothing, spray ourselves with insect repellent that includes at least 20 percent DEET and treat our yards (4). Always check your skin and hair for ticks after walking through a woody or tall grassy area. Many of us on Long Island have ticks in the yard, so remember to check your pets; even if treated, they can carry ticks into the house. My Golden Retriever, Buddy, whom I loved dearly, died of Lyme complications.

Diagnosis of Lyme disease

Many times Lyme disease can be diagnosed within the clinical setting. When it comes to serologic or blood tests, the CDC recommends an ELISA test followed by a confirmatory Western blot test (4). However, testing immediately after being bitten by a tick is not useful, since the test will tend to be negative, regardless of infection or not (7). It takes about one to two weeks for IgM antibodies to appear and two to six weeks for IgG antibodies (8). These antibodies sometimes remain elevated even after successful treatment with antibiotics.

The cardiac impact

What are some of the complications of Lyme disease? Lyme carditis is a rare complication affecting 1.1 percent of those with disseminated disease, but it can result in sudden cardiac death due to second- or third-degree atrioventricular (AV) node conduction (electrical) block. Among the 1.1 percent who had Lyme carditis, there were five sudden deaths (9). If there are symptoms of chest pain, palpitations, light-headedness, shortness of breath or fainting, then clinicians should suspect Lyme carditis.

Does chronic Lyme disease exist?

There has been a debate about whether there is something called “chronic Lyme” disease. The research, unfortunately, has not shown consistent results that indicate that it exists. In the most recent report, chronic Lyme is refuted (10). In the analysis, the authors comment that the definition of chronic Lyme disease is obfuscated and that extended durations of antibiotics do not prevent or alleviate post-Lyme syndromes, according to several prospective trials. The authors do admit that there are prolonged neurologic symptoms in a subset population that may be debilitating even after the treatment of Lyme disease. These authors also suggest that there may be post-Lyme disease syndromes with joint pain, muscle pain, neck and back pain, fatigue and cognitive impairment.

A previous analysis suggested that chronic Lyme may indeed exist and that post-Lyme disease syndrome is a nebulous term (11). The authors point to several randomized controlled trials (RCT) to help validate their point (12). They believe that the bacteria may be able to evade shorter courses of antibiotics.

Ultimately, it comes down to the IDSA (Infectious Diseases Society of America) arguing against chronic Lyme but in favor of post-Lyme disease syndromes, while the ILADS (International Lyme and Associated Diseases Society) believes chronic Lyme exists.

Regardless, the lingering effects of Lyme can be debilitating. This may be as a result of systemic inflammation (13). Systemic inflammation and its symptoms can be improved significantly with dietary and other lifestyle modifications.

But to throw one more wrench in the mix, the CDC recommends that physicians look beyond Lyme for other possible diagnoses before diagnosing someone with chronic Lyme disease (14).

So what have we learned? Prevention is key to helping stem Lyme disease. If this is not possible, treating prophylactically when pulling off a tick is an important step. Contact your physician as soon as you notice a tick. If you have a bulls-eye rash and it is early, then treatment for two to three weeks needs to be started right away. If it is prolonged and disseminated, then treatment should be for approximately three to four weeks with antibiotics. If it has affected the central nervous system, then IV antibiotics could be needed. Post-Lyme syndrome vs. chronic Lyme disease needs to be discussed with your physician. Symptoms attributed to chronic Lyme could have another cause.

References: (1) npr.org online March 6, 2017. (2) Pediatrics. 1985;75(6):997. (3) nlm.nih.gov. (4) cdc.gov. (5) N Engl J Med. 2001;345(2):79. (6) N Engl J Med. 2003;348(24):2472. (7) Clin Infect Dis. 2008;47(2):188. (8) uptodate.com. (9) MMWR. 2014;63(43):982-983. (10) Expert Rev Anti Infect Ther. 2011;9(7):787-797. (11) Future Microbiol. 2008;3(6):621-624. (12) Neurology 70,992-1003 (2008). (13) J Infect Dis. 2009;199(9:1379-1388). (14) JAMA Intern Med. online Nov. 3, 2014.

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

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Studies show that wine may have heart benefits in well-controlled patients with type 2 diabetes.
Wine — yes, wine — may have benefits

By David Dunaief, M.D.

Dr. David Dunaif

Soda has a lot of sugar, with 39 grams per 12-ounce can. Not surprisingly, soda is associated with increased risk of diabetes. However, the drink with the lowest amount of sugar is wine, red or white. Even more surprising, it may have benefits in reducing complications associated with diabetes. Wine has about 1.2 grams of sugar in five ounces. I know what you’re thinking: These different drinks are based on different quantities; however, per ounce, soda has the most and wine has the least.

Why is this important? Well, it wouldn’t be if diabetes were going the way of the dodo bird. Instead, the prevalence of diabetes has continued to climb over three decades in the United States at an alarmingly rapid rate to its current level of 12 to 14 percent (1). The even scarier news is that more than one-third don’t know they have diabetes. The number of patients with prediabetes (HbA1C of 5.7-6.4 percent) is greater than one in three in this country.

So where do we stand? Only recently did the United States Preventive Services Task Force (USPSTF) and the American Diabetes Association (ADA) converge on screening guidelines. However, originally, the USPSTF recommended that asymptomatic patients not be screened for diabetes since the evidence is inconclusive and screening may not improve mortality. Now they give the evidence a grade of B, which means there is a moderate amount of evidence, not even a grade of A. ADA guidelines suggest testing those who are overweight and who have one or more risk factors for diabetes and all of those who are over 45 (2, 3).

It turns out that, for those with diabetes, cardiovascular risk and severity may not be equal between the sexes. In two trials, women had greater risk than men. In one study, women with diabetes were hospitalized due to heart attacks at a more significant rate than men, though both had substantial increases in risk, 162 percent and 96 percent, respectively (4). This was a retrospective (backward-looking) study. The same result was found in a second study (5). In this meta-analysis (a group of 19 studies), there was a 38 percent greater increased risk of cardiovascular events in women than men. The latter was presented as a poster, not fully published data.

What may reduce risks of disease and/or complications? Fortunately, we are not without options. Several factors may help. These include timing of blood pressure medications, lifestyle modifications (diet and exercise) and wine.

Diet trumps popular drug for prevention

All too often in the medical community, we are guilty of reaching for drugs and either overlooking lifestyle modifications or expecting that patients will fail with them. This is not only disappointing, but it is a disservice; lifestyle changes may be more effective in preventing this disease. In a head-to-head comparison study (Diabetes Prevention Program), diet plus exercise bests metformin for diabetes prevention (7). This study was performed over 15 years of duration in 2,776 participants who were at high risk for diabetes because they were overweight or obese and had elevated sugars.

There were three groups in the study: those receiving a low-fat, low-calorie diet with 15 minutes of moderate cardiovascular exercise; those taking metformin 875 mg twice a day; and a placebo group. Diet and exercise reduced the risk of diabetes by 27 percent, while metformin reduced it by 18 percent over the placebo, both reaching statistical significance. While these are impressive results that speak to the use of lifestyle modification and to metformin, this is not the optimal diabetes diet.

Wine is beneficial, really?

Alcohol in general has mixed results. Wine is no exception. However, the CASCADE trial, a randomized controlled trial, considered the gold standard of studies, shows wine may have heart benefits in well-controlled patients with type 2 diabetes by altering the lipid (cholesterol) profile (6).

Patients were randomized into three groups, each receiving a drink with dinner nightly; one group received five ounces of red wine, another five ounces of white wine, and the control group drank five ounces of water. Those who drank the red wine saw a significant increase in their “good cholesterol” HDL levels, an increase in apolipoprotein A1 (the primary component in HDL) and a decrease in the ratio of total cholesterol-to-HDL levels compared to the water drinking control arm. In other words, there were significant beneficial cardiometabolic changes.

White wine also had beneficial cardiometabolic effects, but not as great as red wine. However, white wine did improve glycemic (sugar) control significantly compared to water, whereas red wine did not. Also, slow metabolizers of alcohol in a combined red and white wine group analysis had better glycemic control than those who drank water. This study had a two-year duration and involved 224 patients. All participants were instructed on how to follow a Mediterranean-type diet.

Does this mean diabetes patients should start drinking wine? Not necessarily, because this is a small, though well-designed, study. Wine does have calories, and these were also well-controlled type 2 diabetes patients who generally were nondrinkers.

Drugs — not diabetes drugs — show good results

In the May 11, 2017 column I wrote that taking blood pressure medications at night may control blood pressure better than only taking these medications in the morning. Well, it turns out this study also shows that taking blood pressure medications has another benefit, lowering the risk of diabetes (8). There was a 57 percent reduction in the risk of developing diabetes in those who took blood pressure medications at night rather than in the morning.

It seems that controlling sleep-time blood pressure is more predictive of risk for diabetes than morning or 48-hour ambulatory blood pressure monitoring. This study had a long duration of almost six years with about 2,000 participants.

The blood pressure medications used in the trial were ACE inhibitors, angiotensin receptor blockers and beta blockers. The first two medications have their effect on the renin-angiotensin-aldosterone system (RAAS) of the kidneys. According to the researchers, the drugs that blocked RAAS in the kidneys had the most powerful effect on preventing diabetes. Furthermore, when sleep systolic (top number) blood pressure was elevated one standard deviation above the mean, there was a 30 percent increased risk of type 2 diabetes. Interestingly, the RAAS blocking drugs are the same drugs that protect kidney function when patients have diabetes.

We need to reverse the trend toward higher diabetes prevalence. Diet and exercise are the first line for prevention. Even a nonideal diet, in comparison to medication, had better results, though medication such as metformin could be used in high-risk patients that were having trouble following the diet. A modest amount of wine, especially red, may have effects that reduce cardiovascular risk. Blood pressure medications taken at night, especially those that block RAAS in the kidneys, may help significantly to prevent diabetes.

References: (1) JAMA 2015;314(10):1021-1029. (2) uspreventiveservicestaskforce.org. (3) Diabetes Care 2015;38(Suppl. 1): S1–S94. (4) Journal of Diabetes and Its Complications 2015;29(5):713-717. (5) EASD 2015; Poster #269. (6) Ann Intern Med. 2015;163(8):569-579. (7) Lancet Diabetes Endocrinol. Online Sept. 11, 2015. (8) Diabetologia. Online Sept. 23, 2015.

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

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Treatment options vary wildly

By David Dunaief, M.D.

Dr. David Dunaief

With summer almost here and — believe it or not — beach weather around the corner, millions of Americans will expose their toes. Some will be more self-conscious about it than others because of a disease called onychomycosis, better known as nail fungus.

Nail fungus usually affects toenails but can also affect fingernails. It turns the nails yellow, makes them potentially brittle, creates growth underneath the nail (thickening of the nails) and may cause pain.

Many patients are bothered by this disorder. Most patients consider getting treatment for cosmetic reasons, but there are also medical reasons to treat, including the chronic or acute pain caused by nail cutting or pressure from bedsheets and footwear. There is an increased potential risk for infections, such as cellulitis, in those with compromised immune systems (1).

Onychomycosis is not easy to treat and can be quite uncomfortable. Onychomycosis affects approximately 8 percent of the population (2). The risk factors are unclear but may be relate to family history, tinea pedis (athlete’s foot), older age, swimming, diabetes, psoriasis, suppression of the immune system and/or living with someone affected by it (3).

There are many organisms that can affect the nail. The most common class is dermatophytes, but others are yeast (Candida) and nondermatophytes. A test commonly used to differentiate the organisms is a KOH (potassium hydroxide) preparation, which is a simple microscopic exam of skin and nail shavings. This is important since some medications work better on one type than another. Also, yellow nails alone may not be caused by onychomycosis; they can be a sign of the autoimmune disease psoriasis.

There are a plethora of therapies available for treatment. These range from over-the-counter alternative therapies to prescription topical medications to systemic, or oral, prescription therapies to laser therapies and, finally, surgery. I am regularly asked which treatment works best.

With all of these options, how is one to choose? Well, there are several important criteria, including effectiveness, length of treatment and potential adverse effects. The bad news is that none of the treatments are foolproof, and the highest “cure” rate is around two-thirds. Oral medications tend to be the most efficacious, but they also have the most side effects. The treatments can take from around three months to one year. So there is no overnight success. Unfortunately, the recurrence rate of fungal infection is thought to be approximately 20 to 50 percent with patients who have experienced “cure” (4).

Fortunately, most cases of nail fungus are benign, with only a fraction leading to infections. Infection is most common in those with diabetic neuropathy, where the patient loses feeling in their feet. Let’s look at the evidence.

Oral antifungals

There are several options for oral antifungals, including terbinafine (Lamisil), fluconazole (Diflucan) and itraconazole. These medications tend to have the greatest success rate, but the disadvantages are their side effects.

In a small but randomized controlled trial (RCT), terbinafine was shown to work better in a head-to-head trial than fluconazole (5). Of those treated, 67 percent of patients experienced a clearing of the fungus in their toenails with terbinafine, whereas 21 and 32 percent experienced these benefits with fluconazole, depending on the duration. The patients in the terbinafine group were treated with 250 mg of the drug for 12 weeks. Those in the fluconazole group were treated with 150 mg of the drug for either 12 or 24 weeks, with those in the 24-week group experiencing the better results.

Thus, this would imply that terbinafine is the more effective drug. This is a small trial, but the results are intriguing. The disadvantage of terbinafine is the risk of potential hepatic (liver) damage and failure, though it’s an uncommon occurrence. Liver enzymes need to be checked while using terbinafine. Its advantages are the efficacy and the duration.

Another approach to reducing side effects is to give oral antifungals in a pulsed fashion. In a RCT, fluconazole 150 or 300 mg was shown to have significant benefit compared to the control arm when given on a weekly basis (6). However, the efficacy was not as great as with terbinafine or itraconazole (7).

Topical medication

A commonly used topical medication is ciclopirox (Penlac). The advantage of this lacquer is that there are minor potential side effects. However, the disadvantages are that it takes approximately a year of daily use, and its efficacy is not as great as the oral antifungals. In two randomized controlled trials, the use of ciclopirox showed a 7 percent “cure” rate in patients, compared to 0.4 percent in the placebo groups (8). There is also a significant rate of fungus recurrence. In one trial, ciclopirox had to be applied daily for 48 weeks. These results were in patients with mild to moderate levels of fungus in the surface area of the infected nails.

Laser therapy

Of the treatments, laser therapy would seem to be the least innocuous. However, there are very few trials showing significant benefit with this approach. A study with one type of laser treatment (Nd:YAG 1064-nm laser) did not show a significant difference after five sessions (9). This was only one type of laser treatment, but it does not bode well. To make matters worse, many laser treatments are not covered by insurance, and they can be expensive. Another research paper that reviewed the current literature concluded that laser therapies are lacking in randomized clinical trials (10).The advantage of laser treatment is the mild side effects. The disadvantages are the questionable efficacy and the cost. We need more research to determine if they are effective.

Alternative therapy

The success of using this product is largely due to its ingredients, which includes menthol, camphor and eucalyptus oil.

Vicks VapoRub may have a place in the treatment of onychomycosis. In a very small pilot trial with 18 patients, 27.8 percent or 5 of the patients experienced complete “cure” of their nail fungus (11). Additionally, partial improvement occurred in the toenails of 10 patients. But what is more interesting is that all 18 patients rated the results as either “satisfying” or “very satisfying.” The gel was applied daily for 48 weeks. The advantages are low risk of side effects and low cost. The disadvantages are a lack of larger studies for efficacy, the duration of use and a lower efficacy when compared to oral antifungals.

So when it comes to onychomycosis, what should one do? None of the treatments are perfect. Oral medications tend to be the most efficacious but also have the most side effects. If treatment is for medical reasons, then oral may be the way to go. If you have diabetes, then treatment may be of the utmost importance.

If you decide on this approach, discuss it with your doctor; there are appropriate precautionary tests, such as liver enzyme monitoring with terbinafine (Lamisil), that need to be done on a regular basis. However, if treatment is for cosmetic reasons, then topical medications or alternative approaches may be the better initial choice. No matter what you and your physician agree upon as the appropriate treatment, have patience. The process may take a while; nails, especially in toes, grow very slowly.

References: (1) J Am Acad Dermatol. 1999 Aug.;41:189–196; Dermatology. 2004;209:301–307. (2) J Am Acad Dermatol. 2000;43:244–248. (3) J Eur Acad Dermatol Venereol. 2004;18:48–51. (4) Dermatology. 1998;197:162–166; uptodate.com. (5) Pharmacoeconomics. 2002;20:319–324. (6) J Am Acad Dermatol. 1998;38:S77. (7) Br J Dermatol. 2000;142:97–102; Pharmacoeconomics. 1998;13:243–256. (8) J Am Acad Dermatol. 2000;43(4 Suppl.):S70-S80. (9) J Am Acad Dermatol. 2013 Oct.;69:578–582. (10) Dermatol Online J. 2013 Sept. 14;19:19611. (11) J Am Board Fam Med. 2011;24:69–74.

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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