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David Dunaief

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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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Men as well as women are at risk

By David Dunaief, M.D.

Dr. David Dunaif

Osteoporosis is a very tricky disease. What do osteoporosis, high blood pressure and high cholesterol have in common? They are all asymptomatic until the later stages. You can’t directly measure the progression or risk of osteoporosis fractures; you can only make an educated guess. The medical community does this mainly by using the Fracture Risk Assessment Tool (FRAX) score (1). FRAX estimates the 10-year risk of fracture in an untreated patient. You can find this tool at www.shef.ac.uk/FRAX.

There are a number of risks including genetics — family history, advanced age and demographics, with Asians being at highest risk — lifestyle, medications such as steroids and chronic diseases. A specific chronic disease that has come into focus relatively recently is heart disease. We will discuss this in more detail. Also, it does not seem that diabetes, neither type 1 nor type 2, contributes to osteoporosis (2).

When we think of osteoporosis, we tend to associate it predominately with postmenopausal women; however, it does affect a significant number of men.

Back pain, caused by changes in the vertebrae, may be the first sign that you have osteoporosis.

Treatments range from lifestyle modifications including diet, exercise and smoking cessation to supplements and medications. The medications that are considered first-line therapy are bisphosphonates, such as Reclast or Zometa (zoledronic acid), Fosamax (alendronate), Actonel (risedronate), Boniva (ibandronate) and Didronel (etidronate).

While all of these drugs have reduced fractures, zoledronic acid has shown disappointing results in reducing fracture risk in the elderly population.

The relatively new medication on the block is Prolia (denosumab), an injectable human monoclonal antibody that works through a different mechanism of action, though the result is the same; it blocks the osteoclastic (breakdown) activity of the bone (3). It has been shown to increase bone mineral density, or thickening of the bone, and reduce fracture risk. Prolia was approved at the end of 2012, so it has not been on the market nearly as long as the bisphosphonates. However, like bisphosphonates, it does have side effects.

As far as supplements go, exciting news is that melatonin may help to increase bone mineral density. Let’s look at the research.

The forgotten sex: men

Rarely are men the forgotten sex when it comes to medical research, but osteoporosis is an exception. Approximately one-third of fractures occur in men, resulting in a 37 percent mortality rate. One in five men over the age of 50 will experience a fracture with osteoporosis as a contributing factor. The predictions are that these rates will climb precipitously and that men need to be treated appropriately (4). Currently, less than 50 percent of men with osteoporosis are receiving treatment (5).

Is bariatric surgery useful?

Though bariatric surgery has been shown to have a number of benefits for many chronic diseases, osteoporosis is not one of them. In the Swedish Obesity Study, results show that women who underwent bariatric surgery were at 50 percent increased risk of fractures as well as long-term osteoporosis (6). The results in men were not statistically significant. The duration of the study was 25 years. The authors hypothesize that malnutrition may play a role in causing this effect. Supplementation may be important to overcome this, as well as frequent follow-ups with blood tests to track micronutrient levels.

Heart disease, really?

When we think of heart disease, we associate it with lots of complications, but osteoporosis is not typically one of them. Well, think again. In the Hertfordshire Cohort Study, results show that there was a significantly increased risk of wrist fracture of the radius in those with heart disease (7). These results were shown overall. However, when the sexes were analyzed separately, this effect held true for men but was not true for women, although the results in women did trend toward significance. This may be an example where men are at greater risk than women. Therefore, it may be important to think about osteoporosis when someone is diagnosed with heart disease, especially since it is not intuitive. Lifestyle factors could be a contributor to this association, as well as estrogen deficiency.

A bisphosphonate that disappointed

Bisphosphonates are the mainstay of treatment for osteoporosis, increasing bone density and decreasing fracture risk. However, zoledronic acid had surprisingly disappointing results in a randomized controlled trial (RCT) (8). Results showed that while zoledronic acid increased bone density over two years, it did not decrease the risk of fracture in elderly women in nursing homes. This does not necessarily have broad implications for other bisphosphonates. There were also weaknesses in this trial, the most serious being that fracture risk was not a primary end point. Additionally, the study may have been too small. However, this still is a very intriguing study.

Melatonin for osteoporosis

What could melatonin possibly have to do with osteoporosis? There are surprisingly positive results with melatonin. In a very small RCT, melatonin in combination with 800 mg/day of vitamin D3 and 800 mg/day of calcium increased bone density significantly in the spine and femoral neck over a one-year period, compared to the control, or placebo, arm containing vitamin D3 and calcium of similar dosage (9).

Interestingly, with melatonin the amount of calcium excreted through the urine in a 24-hour measurement decreased by 12.2 percent. There was a dose-related curve, where melatonin 3 mg/day in combination with vitamin D3 and calcium showed greater results than 1 mg/day of melatonin, which showed significant results over the control arm.

This was a preliminary study involving 81 postmenopausal women divided into three groups. Fracture risk reduction was not an end point. Larger studies with fracture risk as a primary end point are needed. Having said this, these results are exciting. A caveat: If you’re going to use calcium 800 mg/day, it’s best if you split the dose into 400 mg twice a day; the body does not typically absorb more than 500 mg of calcium at one time.

Though medications such as bisphosphonates and a monoclonal antibody may have an important place in the treatment of osteoporosis, not all medications may be equal. It is important to treat with lifestyle modifications including potentially supplements — melatonin, calcium and vitamin D3 — as well as diet, exercise and overall behavior modifications. Heart disease’s unexpected association with osteoporosis is a good reason to treat the whole patient, not just the disease. And don’t forget that men may have this disease too!

References: (1) uptodate.com. (2) Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S493-514. (3) epocrates.com. (4) iofbonehealth.org. (5) J Bone Miner Res. 2014;29:1929-1937. (6) ECO 2015. Abstract T8:OS3.3. (7) Osteoporos Int. 2015;26(7):1893-1901. (8) JAMA Intern Med. Online April 13, 2015. (9) J Pineal Res. Online June 3, 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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A recent study showed that men who ate greater amounts of fish — more than one serving per week — had lower resting heart rates than those who ate fish rarely.
Resting heart rate is a predictor of disease

By David Dunaief, M.D.

Dr. David Dunaief

Everyone has a heart rate, so everyone needs to pay attention. But what does that heart rate, or pulse, tell us beyond the obvious fact that we are alive?

Our “normal” resting heart rate is between 60 to 100 beats per minute (bpm). We know that a resting heart rate (RHR) above 100 bpm is abnormal. It is referred to as tachycardia, or a racing heartbeat, and it has potentially serious consequences. However, even normal RHRs can be stratified to identify risks for diseases. What I mean is that, even in the normal range, as your resting heart rate increases, so do your potential risks. Actually, resting heart rate below approximately 70 bpm may be ideal.

The importance of the resting heart rate should not be underestimated. In fact, it may play a role in longevity, heart disease — including heart failure, arrhythmias, heart attacks and sudden cardiac death — and even chronic kidney disease. The good news is that RHR is modifiable. Methods that may reduce your rate include medications for high blood pressure, such as beta blockers, and lifestyle modifications, including meditation, dietary changes and exercise.

Impact on life span

We all want to live longer and healthier lives. Reducing the RHR may be an important component in achieving this goal. In the Copenhagen Male Study, a prospective (forward-looking) study that followed 2,798 participants for 16 years, results showed that those with higher resting heart rates had a greater risk of death (1). There was a linear relationship between the risk of death and increasing RHR. Those who had a resting heart rate above 90 bpm were at a threefold greater risk of death, compared to those who had a RHR at or below 50 bpm. RHR was inversely related to the amount of physical activity.

Thus, the authors concluded that a “healthy” person with higher RHR may still have a shorter life span, with all other factors being equal, such as physical activity and blood pressure.

In contrast with the previous study, the following one took a “glass is half-full” approach to longevity. The Jerusalem Longitudinal Cohort Study showed that elderly women and men who had a lower RHR lived the longest (2). There were more than 2,000 study participants, ranging from 70 to 90 years old.

Heart disease mortality

In the Nord-Trondelag Health Study, a prospective observational study, those who had a higher RHR at the end of the study than they did at the beginning of the study 10 years prior were more likely to die from heart disease (3). In other words, as the RHR increased from less than 70 bpm to over 85 bpm, there was a 90 percent greater risk of heart disease, compared to those who maintained a RHR of less than 70 throughout the two measurements. This study involved 30,000 participants. However, unlike some other studies, many of us can relate to the population: They were at least 20 years old and were healthy volunteers.

Heart attacks

It is more common for women to have heart attacks with atypical symptoms than men. Therefore, it is very important for women to reduce their heart attack risks. In the Women’s Health Initiative, results showed a 26 percent decrease in the risk of cardiovascular events in those postmenopausal women who had a RHR below 62 bpm, compared to those who had a RHR above 76 bpm (4). Interestingly, these results were even more substantial in the subgroup of women who were newly postmenopausal, ranging in age from 50 to 64.

 Effect on kidney function

I have written many times about chronic kidney disease. I thought an interesting follow-up might be resting heart rate and its impact on kidney function. In the Atherosclerosis Risk in Communities Study, results showed that the most severe form of chronic kidney disease, end-stage renal disease, was 98 percent more likely to occur in those with the highest RHR, compared to those with the lowest (5). There were approximately 13,000 participants in the study, with a 16-year follow-up. The authors hypothesized that this negative effect on the kidney may be due to a loss of homeostasis in the autonomic (involuntary) nervous system, resulting in blood vessel dysfunction, such as increased inflammation and vasoconstriction (narrowing).

Eating fish

What can be done to reduce the resting heart rate with minimal side effects? Fish consumption has recently been shown to have a positive effect. In a study, European men who ate greater amounts of fish — more than one serving per week — had lower resting heart rates than those who ate fish rarely (6). There was also a direct relationship between the amount of fish consumed and the RHR: the more fish consumed per week, the greater the reduction in RHR. This was a prospective observational study involving about 5,000 men. Some beneficial side effects of eating fish included decreased triglycerides and diastolic (lower number) blood pressure, as well as increased HDL (“good cholesterol”).

Even after controlling for these beneficial side effects, there still was a significant improvement in RHR with fish consumption. Is there a resting heart rate that is too low? Well, it depends on the context. If you are a marathoner or an athlete, then a RHR in the 40s may not be abnormal. For a healthy, physically active individual, it is not uncommon to have a resting heart rate in the 50s. However, if you are on medications that reduce your RHR and/or have a chronic disease, such as heart failure, it is probably not advisable to go much below 60 bpm. Always ask your doctor about the appropriate resting heart rate for your particular situation.

Thus, resting heart rate is an easy and inexpensive biomarker to potentially determine risk stratification for disease manifestation and to increase longevity, even for those in the normal range. We can utilize RHR as a tool for primary prevention of disease. The fact that it is modifiable means it is something that we need to monitor, so that we can achieve the ideal RHR, rather than just the normal.

References: (1) Heart Journal 2013 Jun;99(12):882-887. (2) J Am Geriatr Soc. 2013;61(1):40-45. (3) JAMA 2011; 306:2579-2587. (4) BMJ. 2009 Feb 3;338:b219. (5) J Am Soc Nephrol. 2010 Sept;21(9):1560-1570. (6) Circulation. 2003;108:820-825.

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

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A recent study showed that patients who are very obese could lose almost two decades of healthy living
Quality of life impacts are considerable

By David Dunaief, M.D.,

Dr. David Dunaief

The media is increasingly focused on covering obesity-related issues. With this in mind, let’s start off with a short quiz to test your knowledge of obesity-related issues. The answers and research are provided below. Regardless of your quiz score, it is important to understand the research.

1. Obesity reduces life span by up to:

A) Not at all

B) 4 years

C) 8 years

D) 10 years

2. Obesity shortens healthy years of life by:

A) 8 years

B) 12 years

C) 15 years

D) 20 years

3. Food cravings can be reduced for the short term by:

A) Counting to 20

B) Tapping your finger against your head

C) Watching TV

D) Texting on your cellphone

4. Obesity can lead to the following complication(s):

A) High blood pressure

B) Diabetes

C) Cancer

D) All of the above

Are you eager to find out the answers? I hope so, because there are some very salient points I am trying to make by providing multiple choice questions. The answers are: 1. D; 2. D; 3. B; 4. D. So how did you do? One of the questions was actually similar to a question on a medical website for doctors, so don’t be too hard on yourself if you did not get them all right. Let’s look at the research.

Mortality and effect on life span

Many of you know that obesity could have an impact on development of other chronic diseases and a decrease in quality of life, but to what extent? A 2013 study indicated that almost as many as one in five deaths in the U.S. is associated with obesity (1).

In a computer modeling study, the results showed that those who are obese may lose up to eight years, almost a decade, of their life span (2). But that is only part of the results. The other, more compelling result is that patients who are very obese, defined as a BMI >35 kg/m², could lose almost two decades of healthy living. According to the researchers, this means you may have diseases such as diabetes and cardiovascular disease. However, even those patients who were obese and those who were overweight also could have reductions in life span, up to 6 years and 3 years, respectively.

There were 3,992 adults between the ages of 20 and 79 evaluated in this study. The data was taken from an NHANES database from 2003 to 2010, which looked at participants who went on to develop diabetes and cardiovascular disease. Though this is not a clinical trial, and there is a need for more study, the results are eye-opening, with the youngest and very obese negatively impacted the most.

Cancer impact

Since it is very difficult to “cure” cancer, although hopefully someday soon we will, it is important to reduce modifiable risk factors. Obesity may be one of these contributing factors, although it is hotly debatable how much of an impact obesity has on cancer development.  The American Society of Clinical Oncologists (ASCO), in a position paper, supported the idea that it is important to treat obesity in the fight against cancer (3). The authors indicate obesity may make the prognosis worse, may hinder the delivery of therapies to treat cancer, and may increase the risk of malignancy.

Also, possibly reinforcing ASCO’s stance, a study suggested that upward of a half-million cases of cancer worldwide were related to being overweight or obese, with the overwhelming concentration in North American and Europe (4).

Possible solutions

A potential counterweight to both the reductions in life quality and life expectancy may be the Mediterranean diet. In a published analysis of the Nurses’ Health Study, results show that the Mediterranean diet helped slow shortening of the telomeres (5). Repeat sequences of DNA found at the end of chromosomes, telomeres, shorten with age; the shorter the telomere, the shorter life expectancy.

Thus, the Mediterranean diet may decrease occurrence of chronic diseases, increase life span and decrease premature mortality — hence, the opposite effect of obesity. In fact, it may help treat obesity, though this was not mentioned in the study. Interestingly, the effects of the Mediterranean diet were on a dose-response curve. The greater the adherence to the diet, rated on a scale of 0 to 9, the better the effect. Those who had an increase in adherence by three points saw a corresponding decrease in telomere aging by 4.5 years. There were 4,676 middle-aged women involved in this analysis. The researchers believe that the anti-inflammatory and antioxidant effects could be responsible for the diet’s effects.

According to an accompanying editorial, no individual component of the diet was identified as having beneficial effects by itself, so it may be the diet as a whole that is important (6).

Short-term solutions

There are easy-to-use distraction tactics that involve physical and mental techniques to reduce food cravings. These include tapping your foot on the floor, staring at a blank wall and, yes, alternating tapping your index finger against your forehead and your ear (7). The forehead and ear tapping was most effective, although probably most embarrassing in public. Among mental techniques, seeing pictures of foods that were unhealthy and focusing on their long-term detriments to health had the most impact (8). All of these short-term distractors were done for 30 seconds at a time. The results showed that in obese patients they indeed decreased food cravings.

Exercise impact

I have written about exercise and that it does not lead to fat percentage loss in adults. Well, before you write off exercise for fat loss, it seems that adolescents may benefit from exercise. In a randomized controlled trial, the gold standard of studies, results show that those in the resistance training group alone and those in a combined resistance and aerobic training group had significantly greater percentages of fat loss compared to a control group (9).

However, the aerobic group alone did not show a significant change in fat percent versus the control. There were 304 study participants, ages 14 to 18, followed for a six-month duration, and results were measured with MRI. The reason that resistance training was effective in reducing fat percentage may have to do with an increase in muscle mass rather than a decrease in actual fat. Still, exercise is important. It doesn’t matter if it decreases the fat percentage; it is still getting you to the goal.

Obesity can have devastating effects, from potentially inducing cancer or worsening it, to shortening life expectancy and substantially decreasing quality of life. Fortunately, there may be ways to help treat obesity with specific lifestyle modifications. The Mediterranean diet as a whole may be an effective step toward decreasing the burden of obesity and reducing its complications. Kids, teenagers specifically, should be encouraged to “Play 60,” as the NFL has encouraged, but also to do some resistance training. As we mentioned, there are simple techniques that may help reduce short-term food cravings.

References: (1) Am J Public Health. 2013;103:1895-1901. (2) The Lancet Diabetes & Endocrinology, online Dec. 5, 2014. (3) J Clin Oncol. 2014;32(31):3568-3574. (4) The Lancet Oncology. online Nov. 26, 2014. (5) BMJ. online Dec. 2, 2014. (6) BMJ 2014;349:g6843. (7) Obesity Week 2014 abstract T-2658-P. (8) Obesity Week 2014 abstract T-3023-OR. (9) JAMA Pediatr. 2014;168(11):1006-1014.

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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Hypertension risk factors include poor diet, lack of exercise, age and depression.
Complications are highest during sleeping hours

By David Dunaief, M.D.

Dr. David Dunaief

Hypertension (high blood pressure) deserves a substantial amount of attention. There are currently about 76 million people with high blood pressure in the U.S. Put another way, one in three adults have this disorder (1). If that isn’t scary enough, the Centers for Disease Control and Prevention reports that the number of people dying from complications of hypertension increased by 23 percent from 2000 to 2013 (2).

And talk about scary, it turns out that fear of the boogie man should take a back seat to high blood pressure during nighttime sleeping hours. This is when the probability of complications, such as cardiovascular events and mortality, may have their highest incidence.

Unfortunately, as adults, it does not matter what age or what sex you are; we are all at increased risk of complications from high blood pressure, even isolated systolic (top number) blood pressure, which means without having the diastolic (bottom number) elevated as well. Fortunately, hypertension is highly modifiable in terms of reducing the risk of cardiovascular disease and mortality (3). At least some of the risk factors are probably familiar to you. These include being significantly overweight and obese (BMI >27.5 kg/m²), smoking, poor diet, lack of exercise, family history, age, increased sodium, depression, low vitamin D, diabetes and too much alcohol (4).

Of course, antihypertensive (blood pressure) medications treat this disorder. In addition, there are nonpharmacological approaches that have benefits. These include lifestyle modifications with diet, exercise and potentially supplements. An item on the game show “Jeopardy” read: “You can treat it with diet and lifestyle changes as well as drugs: HBP.” The corresponding answer was, “What is high blood pressure?” We made the big time!

Risk factors matter, but not equally

In a study, results showed that those with poor diets had 2.19 times increased risk of developing high blood pressure. This was the greatest contributor to developing this disorder (5). Another risk factor with a significant impact was being at least modestly overweight (BMI >27.5 kg/m²) at 1.87 times increased risk. This surprisingly, albeit slightly, trumped cigarette smoking at 1.83 times increased risk. Interestingly, weekly binge drinking at 1.87 times increased risk was equivalent to being overweight. This study was observational and involved 2,763 participants. The moral is that a freewheeling lifestyle can have a detrimental impact on blood pressure and cause at least stage 1 hypertension (systolic between 140 and 159 mmHg and/or diastolic between 90 and 99 mmHg).

High blood pressure doesn’t discriminate

One of the most feared complications of hypertension is cardiovascular disease, because it can result in death. In a study, isolated systolic hypertension was shown to increase the risk of cardiovascular disease and death in both young and middle-aged men and women between 18 and 49 years old, compared to those who had optimal blood pressure (6). The effect was greatest in women, with a 55 percent increased risk in cardiovascular disease and 112 percent increased risk in heart disease death. High blood pressure has complications associated with it, regardless of onset age. Though this study was observational, which is not the best, it was very large and had a 31-year duration.

Nightmares that may be real

Measuring blood pressure in the clinic can be useful. However, in a meta-analysis (involving nine studies from Europe, South America and Asia), the results showed that high blood pressure measured at nighttime was potentially a better predictor of myocardial infarctions (heart attacks) and strokes, compared to daytime and clinic readings (7).

For every 10 mmHg rise in nighttime systolic blood pressure, there was a corresponding 25 percent increase in cardiovascular events. This was a large meta-analysis that utilized studies that were at least one year in duration. Does this mean that nighttime readings are superior in predicting risk? Not necessarily, but the results are interesting. The nighttime readings were made using 24-hour ambulatory blood pressure measurements (ABPM).

There is something referred to as masked uncontrolled hypertension (MUCH) that may increase the risk of cardiovascular events in the nighttime. MUCH occurs in those who are well-controlled during clinic readings for blood pressure; however, their nocturnal blood pressure is uncontrolled. In the Spanish Society of Hypertension ABPM Registry, MUCH was most commonly seen during nocturnal hours (8). Thus, the authors suggest that ABPM may be a better way to monitor those who have higher risk factors for MUCH, such as those whose pressure is borderline in the clinic and those who are smokers, obese or have diabetes.

Previously, a study suggested that taking at least one antihypertensive medication at night may be more effective than taking them all in the morning (9). Those who took one or more blood pressure medications at night saw a two-thirds reduction in cardiovascular event risk. Now we can potentially see why. These were patients who had chronic kidney disease (CKD). Generally, 85 to 95 percent of those with CKD have hypertension.

Dietary tidbits

Diet plays a role in controlling high blood pressure. In a study, blueberry powder (22 grams) in a daily equivalent to one cup of fresh blueberries reduced systolic blood pressure by a respectable 7 mmHg and diastolic blood pressure by 5 mmHg over 2 months (10). This is not bad, especially since the patients were prehypertensive, not hypertensive, at baseline, with a mean systolic blood pressure of 138 mmHg.

This is a modest amount of fruit with a significant impact, demonstrating exciting results in a small, preliminary, double-blind, placebo-controlled randomized trial. Blueberries increase a substance called nitric oxide, which helps blood vessels relax, reducing blood pressure.

The results of another study showed that girls who consumed higher levels of potassium-rich foods had a significant reduction in both systolic and diastolic blood pressure (11). The highest group consumed at least 2,400 mg of potassium daily, whereas the lowest group consumed less than 1,800 mg. The girls were 9 and 10 years old and were followed for a 10-year duration. Though the absolute change was not large, the baseline blood pressure was already optimal for both groups, so it is impressive to see a significant change.

In conclusion, nighttime can be scary for high blood pressure and its cardiovascular complications, but lifestyle modifications, such as taking antihypertensive medications at night and making dietary changes, can have a big impact in altering these serious risks.

References: (1) Health Stat Report 2011. (2) CDC.gov. (3) Diabetes Care 2011;34 Suppl 2:S308-312. (4) uptodate.com. (5) BMC Fam Pract 2015;16(26). (6) J Am Coll Cardiol 2015;65(4):327-335. (7) J Am Coll Cardiol 2015;65(4):327-335. (8) Eur Heart J 2015;35(46):3304-3312. (9) J Am Soc Nephrol 2011 Dec;22(12):2313-2321. (10) J Acad Nutr Diet 2015;115(3):369-377. (11) JAMA Pediatr online April 27, 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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Mediterranean Diet
Can we overcome our genes?

By David Dunaief, M.D.

Dr. David Dunaief

We have made great strides in the fight against heart disease, yet it remains the number one cause of death in the United States. Approximately one-third of Americans over the age of 35 will die of heart disease (1). I hope this statistic has captured your attention, because it should. What is causing or contributing to such high numbers of heart disease deaths: genetics, environment or both? Many of us have the propensity toward heart disease. Can we alter this course, or is it our destiny?

A 2013 study, involving the Paleo-type diet and other ancient diets, suggests that there is a significant genetic component to cardiovascular disease, while another study looking at the Mediterranean-type diet implies that we may be able to reduce risk factors greatly. Most of the risk factors for heart disease, such as high blood pressure, high cholesterol, sedentary lifestyle, diabetes, smoking and obesity are modifiable (2). Let’s look at the evidence.

Genetic components

In a study published online in The Lancet, researchers used computed tomography scans to look at 137 mummies from ancient times across the world, including Egypt, Peru, the Aleutian Islands and Southwestern America (3). The cultures were diverse, including hunter-gatherers (consumers of a Paleo-type diet), farmer-gatherers and solely farmers. Their diets were not vegetarian but rather involved significant amounts of animal protein: fish and/or cattle.

Researchers found that one-third of these mummies had atherosclerosis (plaques in the arteries), which is a precursor to heart disease. The ratio should sound familiar. It seems to coordinate with modern times.

Interestingly, but not surprisingly, the average age of death was 43. The authors concluded that atherosclerosis could be part of the aging process in humans. In other words, it may be a result of our genes. Being human, we all have a genetic propensity toward atherosclerosis and heart disease — some more than others — but many of us can reduce our risk factors significantly.

I am not saying that the Paleo-type diet specifically is not beneficial compared to the standard American diet. Rather, that we do not know it based on this study, which was not meant to provide the validity of the Paleo-type diet, but whether atherosclerosis is part of the normal aging process. However, other studies demonstrate that we can reduce our chances of getting heart disease with lifestyle changes, potentially by following a Mediterranean-type diet with an emphasis on a plant-rich approach.

Mediterranean-type diet

A study about the Mediterranean-type diet and its potential positive impact on cardiovascular disease risk was published in the New England Journal of Medicine (4). Here, two variations on the Mediterranean-type diet were compared to a low-fat diet. People were randomly assigned to three different groups. The two Mediterranean-type diet groups both showed about a 30 percent reduction in the risk of cardiovascular disease, with end points including heart attacks, strokes and mortality, compared to the low-fat diet. This improvement in risk profile occurred even though there was no significant weight loss.

The Mediterranean-type diets both consisted of significant amounts of fruits, vegetables, nuts, beans, fish, olive oil and potentially wine. I call them “the Mediterranean diet with opulence,” because both groups consuming this diet had either significant amount of nuts or olive oil and/or wine. If the participants in the Mediterranean diet groups drank wine, they were encouraged to drink at least one glass a day.

The study included three groups: a Mediterranean diet supplemented with mixed nuts (almonds, hazelnuts or walnuts), a Mediterranean diet supplemented with extra virgin olive oil (at least four tablespoons a day) and a low-fat control diet. The patient population included over 7,000 participants in Spain at high risk for cardiovascular disease. The high-risk population included those with high blood pressure (80 percent of the population), diabetes and those who were overweight and/or were smokers.

The strength of this study, beyond its high-risk population and its large size, was that it was a randomized clinical trial, the gold standard of trials. However, there was a significant flaw, and the results need to be tempered. The group assigned to the low-fat diet was not, in fact, able to maintain this diet throughout the study. Therefore, it really became a comparison between variations on the Mediterranean diet and the standard American diet.

What do the leaders in the field of cardiovascular disease and integrative medicine think of the Mediterranean diet study? Interestingly there are two diametrically opposed opinions, split by field. You may be surprised by which group liked it and which did not. Cardiologists hailed the study as a great achievement. They included Henry Black, M.D., who specializes in high blood pressure, and Eric Topol, M.D. They emphasized that now there is a large RCT measuring clinical outcomes, such as heart attacks, stroke and death.

On the other hand, the integrative medicine physicians, Caldwell Esselstyn, M.D., and Dean Ornish, M.D., both of whom stress a plant-rich diet that may be significantly more nutrient dense than the Mediterranean diet in the study, expressed disappointment with the results. They feel that heart disease and its risk factors can be reversed, not just reduced. Both clinicians have published small, well-designed studies showing significant benefits from plant-based diets (5, 6). Ornish actually showed a reversal of atherosclerosis in one of his studies (7).

So which group of physicians is correct about the Mediterranean diet? Each opinion has its merits. The cardiologists’ enthusiasm is warranted, because a Mediterranean diet, even one of “opulence,” will appeal to more participants, who will then realize the benefits. However, those who follow a more strict diet, with greater amounts of nutrient-dense foods, will potentially see a reversal in heart disease, minimizing risk — and not just reducing it.

Thus, even with a genetic proclivity toward cardiovascular disease, we can very much alter our destinies. The degree depends on the willingness of the participants. Potentially, we can have an impact that ranges from reduction to reversal.

References: (1) Circulation. 2008;117(4):e25. (2) www.uptodate.com. (3) The Lancet. 2013;Mar 11. (4) N Engl J Med. Online 2013;Feb 25. (5) J Fam Pract. 1995;41(6):560-568. (6) Am J Cardiol. 2011;108:498-507. (7) JAMA. 1998 Dec 16;280(23):2001-2007.

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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Implications for thyroid removal are lifelong

By David Dunaief, M.D.

Dr. David Dunaief

It is very interesting that the amount of coverage by the lay press concerning thyroid nodules does not reflect the number of people who actually have them. More than 50 percent of people have thyroid nodules detectable by high-resolution ultrasound (1); however, news coverage for general, nonphysician audiences is infrequent.

You can understand how coverage should be more in the forefront. Fortunately, most nodules are benign. A small percent, 4 to 6.5 percent, are malignant, and the number varies depending on the study (2). Thyroid nodules are being diagnosed more often incidentally on radiologic exams, such as CT scans of the chest, MRI scans, PET scans and ultrasounds of the carotid arteries in the neck (3).

There is a conundrum of what to do with a thyroid nodule, especially when it is found incidentally. It depends on the size. If it is over 1 centimeter, usually it is biopsied by fine needle aspiration (FNA) (4). This is the cutoff point for thyroid nodules found with a radiologic exam. Most are asymptomatic. However, if there are symptoms, these might include difficulty swallowing, difficulty breathing, hoarseness, pain in the lower portion of the neck and a goiter (5).

FNA biopsy is becoming more common. In a study evaluating several databases, there was a greater than 100 percent increase in thyroid FNAs performed over a five-year period from 2006 to 2011 (6). This resulted in a 31 percent increase in thyroidectomies, surgeries to remove the thyroid partially or completely.

However, the number of thyroid cancers diagnosed with the surgery did not rise in this same period. To make matters even more confusing, from 2001 to 2013, the number of thyroid cancers increased by 200 percent. In the study authors call for more detailed guidelines, which are lacking for thyroid nodules. Though the number of cancers diagnosed has increased, the mortality rate has remained relatively stable over several decades at about 1,500 patients per year (7). Thyroid nodules in this study were least likely to be cancerous when the initial diagnosis was by incidental radiologic exam.

Treating borderline results

As much as 25 percent of FNA biopsies are indeterminate. We are going to look at two modalities to differentiate between benign and malignant thyroid nodules when FNA results are equivocal: a PET scan and a molecular genetics test. A meta-analysis (a group of six studies) of PET scan results showed that it was least effective in resolving an unclear FNA biopsy. The PET scan was able to rule out patients who did not have malignancies significantly but did not do a good job of identifying those who did have cancer (8).

On the other hand, a molecular-based test was able to potentially determine whether an indeterminate thyroid nodule by FNA was malignant or benign (9). This test was a combination of microRNA gene expression classifier with the genetic mutation panel. I know the test combination sounds confusing, but the important takeaway is that it was more effective than previous molecular tests in clarifying whether a patient had a benign or cancerous nodule.

Unlike in the PET scan study above, the researchers were able to not only rule out the majority of malignancies but also to rule them in. It was not perfect, but the percent of negative predictive value (ruled out) was 94 percent, and the positive predictive value (ruled in) was 74 percent. The combination test improved the predictive results of previous molecular tests by 65 to 69 percent. This is important to help decide whether or not the patient needs surgery to remove at least part of the thyroid. The trial used hospital-based patients, but follow-up studies need to include community-based practices.

Is a negative FNA definitive?

We know that FNA is the gold standard for determining whether patients have malignant or benign thyroid nodules. However, a negative result on FNA is not always definitive for a benign thyroid nodule. When this occurs, it is referred to as a false negative result. In a retrospective (looking back at events) study, from the Longitudinal Health Insurance Database in Taiwan, 62 percent of thyroid nodules that were cancerous were diagnosed with one biopsy, and 82 percent were found within the year after that biopsy (10). However, about 17 percent of patients needed more than two FNA biopsies, and 19 percent were diagnosed after one year with cancerous thyroid nodules.

Significance of calcification on ultrasound

Microcalcifications in the nodule can be detected on ultrasound. The significance of this may be that patients with microcalcifications are more likely to have malignant thyroid nodules than those without them, according to a small prospective study involving 170 patients (11). This does not mean necessarily that a patient has malignancy with calcifications, but there is a higher risk. The results demonstrated that more than half of the malignant thyroid nodules, 61 percent, had microcalcifications.

Good news

As I mentioned above, most thyroid nodules are benign. The results of one study go even further, showing that most asymptomatic benign nodules do not progress in size significantly after five years (12). This was a prospective (forward-looking) study involving 992 patients with between one and four benign thyroid nodules diagnosed cytologically (by looking at the cells) or by ultrasound. The factors that did contribute to growth of about 11 percent of the nodules were age (<45 years old had more growth than >60 years old), multiple nodules, greater nodule volume at baseline and being male.

The authors’ suggestion is that the current paradigm might be altered and that after the follow-up scan, the next ultrasound scan might be five years later instead of three years. However, they did discover thyroid cancer in 0.3 percent after five years.

Thyroid function may contribute to risk

In considering risk factors, it’s important to note that those who had a normal thyroid stimulating hormone (TSH) were less likely to have a malignant thyroid nodule than those who had a high TSH, implying hypothyroidism. There was an almost 30 percent prevalence of cancer in the nodule if the TSH was greater than >5.5 mU/L (13).

The bottom line is that there is an urgent need for new guidelines regarding thyroid nodules. Fortunately, most nodules are benign and asymptomatic, but the number of cancerous nodules found is growing. We are getting better at diagnosing nodules. Why the death rate remains the same year over year for decades may have to do with the slow rate at which most thyroid cancers progress, especially two of the most common forms, follicular and papillary.

References: (1) AACE 2013 Abstract 1048. (2) Thyroid. 2005;15(7):708. (3) uptodate.com. (4) AACE 2013 Abstract 1048. (5) thyroid.org. (6) AAES 2013 Annual Meeting. Abstract 36. (7) AACE 2013 Abstract 1048. (8) Cancer. 2011;117(20):4582-4594. (9) J Clin Endocrinol Metab. Online May 12, 2015. (10) PLoS One. 2015;10(5):e0127354. (11) Head Neck. 2008 Sep;30(9):1206-1210. (12) JAMA. 2015;313(9):926-935. (13) J Clin Endocrinol Metab. 2006;91(11):4295.

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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0 1157

The best way to get some people motivated is to tell them what they can’t do. I learned that many years ago.

Back in junior high school, I was trying out for the basketball team.

With about a thousand other people — okay, maybe it was 50, but it felt like a thousand — hoping to make the team, I appeared at the gym after school. I remember enjoying basketball from the time I could barely throw the ball high enough to clear the basket.

As I got older, I shot up quickly in height. I was never a particularly great shooter. My five-foot, seven-inch frame, which puts me below the eye level of many of my teenage children’s friends today, seemed taller back then.

I could and did grab rebounds, fight for loose balls and play aggressive defense. At the time, we had three days of cuts. The first day, my name appeared on the “come-back-tomorrow” list, which meant that I was still one of the chosen few.

The second day, after an intense and physical tryout, I knew I’d made the list, because the coach nodded several times when I blocked shots and seemed pleased that I raced up the floor to poke the ball away from someone who thought he had a breakaway layup.

It was during lunch on the third day, before the final cut, that I lost my mojo. I was sitting with one of my friends, whom we’ll call John. Through the bits of a peanut butter and jelly sandwich that were sticking to his braces, he told me he heard some other kids talking about me on the way to school.

“Oh yeah, what did they say?” I asked.

“They said you were still on the list of players who might make the basketball team,” John said.

I beamed. The final cut would only eliminate two or three more players, which meant that I just had to keep doing what I was doing earlier in the week and I’d make it.

“They also said you travel every time you shoot a layup,” he offered.

“What?” I asked, suddenly feeling as if he punched me in the gut.

“They said you didn’t belong on the team.”

Throughout the afternoon, in my head, I heard the echo of the words “didn’t belong.” When I stepped on the court that day, my feet barely moved and I didn’t even attempt a shot. Not surprising, I didn’t make the team.

Would I be in the NBA if John hadn’t planted the “you-can’t-do-it” bug in my ear? Not a chance. Would I have made the team? Well, maybe!

About 15 years later, I got a job at Bloomberg News. At the time, it was a growing news service and a securities trading device that refused to accept second place in anything. The facilities were magnificent, complete with fish tanks on every floor and free food for employees and guests, which included select company like Tom Hanks and Ed Koch, who came to the “Charlie Rose” show.

When I got the job, I overheard some of my former colleagues discussing how I didn’t belong at Bloomberg. This time, rather than slink away, I was determined to prove them wrong. While it was a challenging job, I enjoyed the opportunity not only to provide Bloomberg with relevant stories but also to compete against some of the best journalists in New York City. Early in my tenure at Bloomberg, I won a deadline writing award.

I’m not suggesting people pour cold water on each other’s aspirations through some misdirected tough love approach. I would, however, urge people not to listen to the nattering nabobs of negativism, a term coined by William Safire and shared by former Vice President Spiro Agnew.

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