Menopause is a physiologic process that affects all women, not a pathologic or disease-based one. The problem is that vasomotor symptoms, such as hot flashes, flushes and night sweats, can have an adverse effect on most women who are perimenopausal (around menopause) or postmenopausal. Approximately 80 percent of women report having these symptoms, with half experiencing moderate to severe symptoms.

Symptoms last, on average, between one and five years, though they may persist longer than a decade. Unfortunately, many women suffer through them without treatment.

According to a recent study, there are also increased cardiovascular risks in women who experience early menopause, occurring before the age of 46. Early menopause increases the risk of heart attacks and strokes twofold. The authors suggest the best way to lower risk may be to follow general preventive measures for reducing the risk of heart disease (Menopause. online June 11, 2012).

Are there viable treatment options to alleviate menopausal symptoms? The answer is yes, and we will look at some of these options including lifestyle modifications, hormone therapy and soy products.

Lifestyle modifications

In the Women’s Health Initiative Dietary Modification Trial, a large, randomized trial, the combination of weight loss and diet played a significant role in reducing or eliminating vasomotor symptoms in 90 percent of menopausal women (Menopause. online July 9, 2012).

When women lost more than 10 percent of their body weight, they were 56 percent more likely to eliminate vasomotor symptoms when compared to women who were in the control group and did not lose weight. This is impressive, but the results get even better. When dietary modifications were combined with greater than 10 percent weight loss, nearly nine out of 10 women saw an elimination of symptoms.

The design of the trial involved a low-fat diet with 20 percent of calories from fat, plus five servings of fruits and vegetables and an increase in fiber from whole grains to six servings daily.

This diet made it more than three times as likely that women would lose weight compared to the control group. The study involved over 17,000 women who were not on hormone therapy for menopausal symptoms. Thus, the results were purely due to weight loss and dietary changes.

Hormone therapy

Hormone therapy has been a hotly debated topic in recent years. The Women’s Health Initiative is one of the trials that prompted this debate, with unexpectedly negative results showing increased risk of stroke, heart attack, deep vein thrombosis and pulmonary embolism. However, there may be more to the story. This has to do with timing, personal history and dosage.

In a consensus statement by 15 medical organizations, short-term hormone therapy is thought to be safe for the treatment of vasomotor symptoms, depending on the woman’s health history, age and when menopause commenced (Menopause. online July 9, 2012).

Of note, the American College of Obstetricians and Gynecologists was not part of this consensus statement. Patients need to make an informed decision with their OB/GYN to determine if the benefits outweigh the risks on an individualized basis. For healthy women younger than 59 or within 10 years of the beginning of moderate-to-severe vasomotor symptoms, low-dose hormone therapy may be appropriate.

In March, the FDA approved a combination low-dose hormone therapy of 0.25 mg progestin and 0.50 mg estrogen called drospirenone/estradiol (www.fda.gov) for the treatment of hot flashes and night sweats. It reduced the frequency by two episodes a day at four weeks and by three episodes a day by 12 weeks. However, there are side effects, and it is contraindicated in several circumstances, the most severe being increased risk of stroke. Do not consider this medication without consulting your OB/GYN first.

Soy effect

Soy may have benefit in terms of brain functioning. In preliminary results, soy and soy isoflavones (nutrients from soy) have shown to potentially improve cognitive function in early menopause, something that hormone therapy is not approved for (Menopause. 2011; 18(7);732-753). This effect is lost on women who are older than 65 when soy is first given. In other words, there is an ideal window for treatment, much like there is with hormone therapy. For more about soy, see my March 8 article.

Soy products have had mixed results in treating vasomotor symptoms. In a recent meta-analysis (a group of 17 studies), soy supplements reduced hot flashes in menopausal women by a modest 21 percent (Menopause. online March 19, 2012). They are thought to have weakly estrogenic effects. When they did occur, hot flashes tended to be milder. The authors suggest that if no results are seen within four weeks, then it is unlikely that soy will affect hot flashes.

The choices are numerous. Lifestyle modifications appear to have the greatest beneficial impact, and the side effects are beneficial for the treatment and prevention of other diseases, as well. Soy may also be of benefit, especially with cognitive aspects. There is really no downside to adopting a nutrient-rich dietary approach.

Hormone therapy is an individual choice that should made in partnership with an OB/GYN. Women should not have to struggle through perimenopausal symptoms negatively impacting their quality of life because they were spooked by past treatment studies.

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Glaucoma is the second-leading cause of blindness in the world, behind cataracts. It is neurodegenerative (deterioration of the optic nerve) with increased intraocular pressure (IOP) — pressure inside the eye — as an indicator that nerve damage is more likely. The most common types of glaucoma are open angle and angle closure, with the majority of cases in the United States being the former.

Glaucoma initially causes peripheral vision loss and then works its way inward to the central vision. If untreated, it can lead to irreversible blindness (Lancet. 2004;363(9422):1711). Fortunately, there are treatments that revolve around reducing eye pressure, such as prostaglandins and beta blockers.
The occurrence of this disease is rising, with a current 2.8 million Americans affected and a predicted level of 3.4 million in the U.S. by 2020.

Risk factors include age — starting at 40, although those over 65 have higher risk and those over 80 have the highest risk — and race, with African-Americans at a three-times higher risk than those of European ancestry. For African-Americans, it is the No. 1 cause of blindness. In the Baltimore Eye Survey, a family history of the disease dramatically increased risk, with siblings having greater probability than offspring of developing the disease (Arch Ophthalmol. 1994;112(1):69). Finally, the higher the IOP, the greater the risk for progression in open-angle glaucoma (Ophthalmology. 2007;114(10):1810).

The effect of increased visual field-testing

In the Advanced Glaucoma Intervention Study, it was found that visual field-testing by an ophthalmologist every six months for patients at higher risk was better at predicting disease progression than annual testing (Arch Ophthalmol. 2011;129(12):1521-1527). The result was that, with more frequent testing, the researchers were 50 percent more likely to detect progression of the disease, if it were to occur.
Interestingly, the U.S. Preventive Services Task Force currently does not recommend screening for open-angle glaucoma, since it feels there is insufficient evidence (Ann Fam Med. 2005;3(2):171). Whether it updates the results based on this study, only time will tell. The American Academy of Ophthalmology recommends screening every three to five years starting at age 40, with increased frequency — every one to two years — starting at age 60. More frequent screening is recommended for those younger than 60 who have more risk factors (AAO Pub 1996).

Prevention steps

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

Diabetes and high blood pressure

In a analysis of two studies, diabetes increased the risk of open-angle glaucoma by greater than 200 percent (Br J Ophthalmol. 2012;96(6):872-876). In the same analysis, however, systemic hypertension (high blood pressure) increased the risk by a meager 7 percent. This yet another reason we need to control or prevent diabetes, aside from diabetic retinopathy (disease of the back of the eye).

Erectile dysfunction association

Those with erectile dysfunction (had an almost threefold increased risk of also having open-angle glaucoma, compared to those without the disorder (Ophthalmology 2012;119:289-293). There may be vascular symptoms associated with open-angle glaucoma as demonstrated by the increased association with ED. The study suggests that the mechanism of action that both disorders have in common is endothelial dysfunction (inner lining of the blood vessels), which involves a decreased level of nitric oxide, a potent vasodilator, which enables the vessels to expand and relax. ED was also associated with high cholesterol and blood pressure, heart disease and diabetes. It is not unusual to find that many diseases have a common underlying pathology. I wrote an article about the impact of ED on Aug. 11, 2011, that gives more detail on the disorder.

Supplements

In an abstract presented at the American Glaucoma Society, supplementation with calcium and iron, looked at separately, increase risk of normal-tension glaucoma (NTG), glaucoma without increased pressure (AGS 2012 abstract 22). The calcium and iron came from a variety of sources, including antacids, multivitamins, prescription and nonprescription supplements.

The results showed that participants who took a composite of 800 mg daily of calcium were at an almost 2.5-times increased risk. Those who took 18 mg of iron on a daily basis were at an even higher risk, 3.8 times, of developing the disease. When taken together, iron and calcium increased risk by a resounding 7.2 fold. The study did not look at dietary sources for iron and calcium.

The good news is that a dose of 300 mg of magnesium citrate in patients with NTG showed a benefit in visual field over one month, compared to those who did not take magnesium (Eur J Ophthalmol. 2010;20(1):131-135). Although this was a randomized-controlled trial, it was also very small with only 30 patients.

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

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Osteoarthritis (or OA) affects half of those over 60, significantly impacting quality of life for 27 million Americans. Historically, the disorder was thought to be solely a wear-and-tear degeneration of the joint(s). However, OA also involves inflammation with the release of cytokines and prostaglandins — inflammatory factors — which cause joint destruction and pain (Rheumatology. 2011;50(12):2157-2165).

The joints most commonly affected include the ankle, knee, hip, spine and hand. OA may affect joints asymmetrically, meaning that it affects a joint on only one side of the body.

One of the mainstays of treatment includes analgesics (painkillers), including acetaminophen and NSAIDs, such as ibuprofen (Advil), naproxen sodium (Aleve) and COX-2 inhibitors (Celebrex). These drugs may also improve joint mobility and NSAIDs have anti-inflammatory effects. There are adverse effects with NSAIDs, including increased gastrointestinal (or GI) bleed and, with long-term use, an increase in cardiovascular events, such as heart attacks, with the elderly being most susceptible. With chronic NSAID use, PPIs (acid-blocking drugs) may be appropriate to avoid GI tract complications (BMC Family Practice 2012;13:23).

Neither medication type, however, structurally modifies the joints. In other words, they may not slow OA’s progression nor rebuild cartilage or the joint space as a whole. Are there therapies that can accomplish these feats and, if so, what are they? We will look at hyaluronic acid, glucosamine and chondroitin, and lifestyle modifications such as exercise and weight loss.

Chondroitin sulfate beneficial for hand OA

The results with the use of glucosamine and chondroitin have been mixed, depending on the joints affected. In the FACTS trial, a randomized controlled trial, chondroitin sulfate by itself showed significant improvement in pain and function with OA of the hand (Arthritis Rheum. 2011 Nov;63(11):3383-91). The dose of chondroitin used in the study was 800 mg once a day. The patients, all of whom were symptomatic at the trial’s start, also saw the duration of their morning stiffness shorten.

There was also a modest reduction in structural damage of hand joints, compared to placebo. The benefit was seen with prescription chondroitin sulfate, so over-the-counter supplements may not work the same way. Patients were allowed to use acetaminophen, and there was no change in dose or frequency throughout the trial. An effect was seen within three months.

Crystalline glucosamine sulfate

In knee OA, crystalline glucosamine sulfate showed reduction in pain and improvement in functioning in an RCT (Ther Adv Musculoskel Dis. 2012;4(3):167-180). When assessed by radiologic findings, it also slowed the progression of structural damage to the knee joint. In other words, the therapy may have disease-modifying effects over the long term. The glucosamine formulation may work by inhibiting inflammatory factors such as NF-kB. The trial used 1500 mg of prescription crystalline glucosamine sulfate over a three-year period. Again, it’s not clear whether an over-the-counter supplement works the same way.

Glucosamine and/or chondroitin for knee OA

In a meta-analysis (group of 10 studies), glucosamine, chondroitin or the combination did not show beneficial effects — reduced pain or mobility changes — in patients when compared to placebo (BMJ. 2010;341:c4675). It was not clear whether supplemental or prescription-level therapies were used in each trial — or whether that makes a difference. This study was published prior to the crystalline glucosamine sulfate trial of the knee, discussed above, which did show statistical significance.

There is not much downside to using glucosamine and/or chondroitin for OA patients. However, use caution if taking an anticoagulant (blood thinner) like Coumadin, since glucosamine has anticoagulant effects. Also, those with shellfish allergies should not use glucosamine. If there is no effect within three months, it is unlikely that glucosamine and/or chondroitin are beneficial.

Hyaluronic acid

In a meta-analysis (a group of 89 trials), the risks outweighed the benefit of hyaluronic acid, a drug injected into the joint for the treatment of OA (Ann Intern Med. online June 12, 2012). Viscosupplementation involves a combination of hyaluronic acid types that act as a shock absorber and lubricant for the joints. Some of the studies did show a clinical benefit. However, the authors believe that adverse local events, which occurred in 30 to 50 percent of patients, and serious adverse events, with 14 trials showing a 41 percent increased risk, outweigh the benefits. Since there are mixed results with the trials, it is best to discuss this option with your physician.

Impact of weight loss and exercise

No matter where you look, obesity is involved in many chronic diseases. OA is no exception. Obesity treatment with a weight-loss program actually has potential disease-modifying affects (Ann Rheum Dis. 2012;71(1):26-32). It may prevent cartilage loss in the medial aspect of the knee. The good news is that, even with as little as a 7 percent weight loss in the obese patient, these results were still observed. The average weight loss was nine to 10 pounds. It was a dose-response curve — the greater the weight loss, the thicker the knee cartilage.

There was a separate study done with computer modeling showing that obesity reduces quality of life by 12 percent and that OA has a negative impact on the quality of life by about the same amount. Interestingly, the combination decreases the quality of life by 25 percent (Ann Intern Med. 2011; 154(4):217-26). Losing weight would also reduce the number of knee replacements, according to the study.

According to Dr. David Felson, a rheumatologist at Boston University School of Medicine who commented in The New England Journal of Medicine, there is an inverse relationship between the amount of muscle-strengthening exercise, especially of the quadriceps, and the amount of pain experienced in the knee joint. It is very important to do nonimpact exercises such as leg raises, squats, swimming, bicycling and on elliptical machines.

Fortunately, there are a number of options to prevent, treat and potentially modify the effects of OA. With weight loss in the obese patient, quality of life can dramatically increased. Glucosamine and/or chondroitin may be of benefit, depending on the joints affected. The benefits are potential improvements in pain, mobility and structural-modifying effects, which are worth the risk for many patients. When taking glucosamine and/or chondroitin in supplement form, ConsumerLab.com may be a good source for finding a supplement where you get the dose claimed on the box. I would also use formulations in the trials that showed results, even in supplement form.

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, go to www.medicalcompassmd.com and/or consult your personal physician.

Vitamin D is one the most widely publicized and important supplements. We get vitamin D from the sun, food and supplements. Since summer is now in full swing and the beaches are open, I thought it would be appropriate to share some recent findings.

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

The sun

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

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

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

Skin cancer

Vitamin D did not decrease non-melanoma skin cancers (known as NMSCs), such as squamous cell and basal cell carcinoma. It may actually increase them, according to one study done at a single center by an HMO (Arch Dermatol. 2011;147(12):1379-84). The results may be confounded, or blurred, by UV radiation from the sun, so vitamin D is not necessarily the culprit. Most of the surfaces where skin cancer was found were sun exposed, but not all of them.

The good news is that, for postmenopausal women who have already had an NMSC bout, vitamin D plus calcium appears to reduce its recurrence, according to the Women’s Health Initiative study (J Clin Oncol. 2011 Aug 1;29(22):3078-84). In this high-risk population, the combination of supplements reduced risk by 57 percent. Unlike the previous study, vitamin D did not increase the incidence of NMSC in the general population. NMSC occurs more frequently than breast, prostate, lung and colorectal cancer combined (CA Cancer J Clin. 2009;59(4):225-49).

Cardiovascular mixed results

Several observational studies have shown benefits of vitamin D supplements with cardiovascular disease. For example, the Framingham Offspring Study showed that those patients with deficient levels were at increased risk of cardiovascular disease (Circulation. 2008 Jan 29;117(4):503-11).

However, a recent small randomized controlled trial, the gold standard of studies, calls the cardioprotective effects of vitamin D into question (PLoS One. 2012;7(5):e36617). This study of postmenopausal women, using biomarkers, such as endothelial function, inflammation or vascular stiffness, showed no difference between vitamin D treatment and placebo. The authors concluded there is no reason to give vitamin D for prevention of cardiovascular disease.

The vitamin D dose given to the treatment group was 2500 IUs. Thus, one couldn’t argue that this dose was too low. Some of the weaknesses of the study were a very short duration of four months, its size — 114 participants — and the fact that cardiovascular events or deaths were not used as study endpoints. However, these results do make you think.

Weight benefit

There is good news, but not great news, on the weight front. It appears that vitamin D plays a role in reducing the amount of weight gain in women 65 years and older whose blood levels are more than 30 ng/ml, compared to those below this level, in the Study of Osteoporotic Fractures (J Womens Health (Larchmt). 2012 Jun 25).

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

Mortality decreased

In a recent meta-analyses (a group of eight studies), vitamin D with calcium reduced the mortality rate in the elderly, whereas vitamin D alone did not (J Clin Endocrinol Metabol. online May 17, 2012). The difference between the groups was statistically important, but clinically small: 9 percent reduction with vitamin D plus calcium and 7 percent with vitamin D alone.

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

USPSTF recommendations

The U.S. Preventive Services Task Force recommends against giving “healthy” postmenopausal women the combination of vitamin D 400 IUs plus calcium 1000 mg to prevent fractures (AHRQ Publication No. 12-05163-EF-2). It does not seem to reduce fractures and increases the risk of kidney stones. There is also not enough data to recommend for or against vitamin D with or without calcium for cancer prevention.

Need for clinical trials

We need clinical trials to determine the effectiveness of vitamin D in many chronic diseases, since it may have beneficial effects in preventing or helping to treat them (Endocr Rev. 2012 Jun;33(3):456-92). Right now, there is a lack of large randomized clinical trials. Most are observational, which gives associations, but not links. The VITAL trial is a large RCT looking at the effects of vitamin D and omega 3s on cardiovascular disease and cancer. It is a five-year trial, and the results should be available in 2016.

When to supplement?

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

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, go to www.medicalcompassmd.com and/or consult your personal physician.

Gout is thought of as an inflammatory arthritis. It occurs intermittently, affecting the joints, most commonly the big toe. The symptoms are acute (sudden onset) and include extremely painful, red, swollen and tender joints. Uric acid (or urate) levels are directly related to the risk of gout attacks. As uric acid levels increase, there is a greater chance of urate crystal deposits in the joints.

This disease affects more than three million people in the U.S. (Arthritis Res Ther. 2006;8:Suppl 1:S2). Men between 30 and 50 years old are at much higher risk for their first attack. For women, most gout attacks occur after menopause.

There are a number of potential causes of gout, as well as ways to prevent and treat it. Though heredity plays a role, these risk factors are modifiable. The best way to prevent and treat gout is with medication and lifestyle modifications.

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

Animal versus plant proteins

In a recent case-crossover (epidemiologic forward-looking) study, it was shown that purines from animal sources increase the level of purines far more than those from plant sources (Ann Rheum Dis. online May 30, 2012). The risk of a gout incident was increased approximately 241 percent in the group consuming the highest amount of animal products, whereas the risk of gout was still increased for those consuming plant-rich purine substances, but by substantially less: 39 percent.

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

In another study, meats — including red meat, pork and lamb — increased the risk of gout, as did seafood (NEJM 2004;350:1093-1103). However, purine-rich plant sources did not increase risk of gout. Low-fat dairy actually decreased the risk of gout by 21 percent. The study was a large observational study involving 49,150 men over a duration of 12 years. Therefore, it is unlikely that the patient switching to a nutrient-dense, plant-rich diet increased her risk of gout.

Diuretics (water pills)

My patient was on a diuretic called hydrochlorothiazide for hypertension (high blood pressure). There are several medications thought to increase the risk of gout, including diuretics and chronic use of low-dose aspirin. In the ARIC study, patients who used diuretics to control blood pressure were at a 48 percent greater risk of developing gout than nonusers (Arthritis Rheum. 2012 Jan;64(1):121-9). In fact, nonusers had a 36 percent decreased risk of developing gout. This study involved 5,789 participants and had a fairly long duration of nine years. The longer the patient is treated with a diuretic, the higher the probability they will experience gout. It is likely that my patient’s diuretic contributed to her gout episode.

Medical conditions

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

Obesity

Obesity, like smoking, seems to have its impact on almost every disease. In the CLUE II study, obesity was shown to not only increase the risk of gout but also accelerate the age of onset (Arthritis Care Res (Hoboken). 2011 Aug;63(8):1108-14). Those who were obese experienced gout three years earlier than those who were not. Even more striking is the fact that those who were obese in early adulthood had an 11-year earlier onset of gout. The study’s duration was 18 years. My patient was obese and had started to lose some weight before the gout occurred.

Vitamin C

Vitamin C may reduce gout risk. In the Physicians Follow-up Study, a 500 mg daily dose of vitamin C decreased levels of uric acid in the blood (J Rheumatol. 2008 Sep;35(9):1853-8).

Prevention

The key to success with gout lies with prevention. Patients who do get gout writhe in pain. Luckily, there are modifications that significantly reduce the risks. They involve very modest changes, such as not using diuretics in patients with a history of gout, losing weight for obese patients and substituting more plant-rich foods for meats and seafood. Although the cause of gout may be apparent to you, always check with your doctor before changing your medications or making significant lifestyle modifications as we have learned from this case study of my patient.

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Most of us, myself included, have a love-hate relationship with exercise. Sometimes it’s difficult to get motivated or carve out the time, however, the feeling afterward can be rejuvenating. For the longest time, with a few exceptions, the belief has been that exercise always has positive effects. However, this may not be the case for everyone, according to a new study’s findings. Let’s look at the potential downsides and upsides of exercise, as well as the optimal workout intensity.

The downsides of exercise

Those with certain diseases, such as heart failure and hypertrophic cardiomyopathy, need to be especially cautious when exercising. However, when heart failure patients do exercise, some trials, like the HF-ACTION trial, show improvements in symptoms, exercise capacity and quality of life (J Am Coll Cardiol. 2011;58:561-569).

A new study suggests that exercise may have negative cardiovascular and diabetes impacts on 10 percent of the population (PLoS One. 2012;7(5):e37887. Epub 2012 May 30). That’s scary. To make matters worse, the effect was random — there was no one cohort or group affected. When you analyze the study, however, there are some potential weaknesses.

The study endpoints included biomarkers, such as HDL “good” cholesterol levels, blood pressure, triglycerides and insulin levels. Many things can affect these endpoints. For example, I had a patient who exercised in the morning, yet his blood glucose (sugar) was worse postexercise. It turned out he was drinking pomegranate juice before exercising, which increased his glucose levels.

Also, as I mentioned in last week’s article, the cholesterol marker, HDL, may not have protective effects nor be directly correlated to cardiovascular disease. Therefore, we really don’t know what it means when HDL levels go down with exercise.

Better endpoints for this study would have been outcomes measurements, such as overall mortality, cardiovascular mortality and morbidity (sickness), and cardiovascular event rates. I worry, as do others, that people may use this study as an excuse not to exercise. I think the message should be: Use caution when exercising, but do exercise. Let’s look at why.

The upsides

We know that exercise has tremendously positive impacts on a multitude of diseases and disorders, such as obesity, heart disease, stroke, diabetes, Alzheimer’s, rheumatoid arthritis, migraines and cancer.

One recent study shows exercise is directly related to improvements in sleep (Am J of Med. 2012;125(5):485-490). In the epidemiologic study, the hours of exercise a week decreased the occurrence of mild and moderate sleep-disordered breathing 24 percent and 33 percent, respectively. The opposite was also true: As the hours of exercise declined in some patients, sleep-disordered breathing worsened.

What about longevity?

There are two recent studies that show exercise helps to improve longevity. In the Copenhagen City Heart Study, the results showed that light jogging at a slow to moderate pace for 1 to 2 1/2 hours a week was ideal. The mean increase in longevity was 6.2 years in men and 5.6 years in women. Even elderly patients saw longevity improvements. There were improvements in insulin levels, bone density and lipid profiles which contributed to the longevity effect. This study was observational, with 20,000 participants over a 35-year duration (EuroPRevent 2012: Abstract). The good news is that you don’t have to be an elite athlete to achieve the increased longevity.

In a second study, those who jogged at a modest pace saw a three-year increase in longevity. Those in the “low volume” activity group, defined as 92 minutes of exercise per week, realized a 14 percent reduction in the risk of death and a three-year increase in life expectancy when compared to the sedentary group (Lancet. 2011 Oct 1;378(9798):1244-53). In other words, 15 minutes of exercise a day has a powerful effect on longevity. This was a very large prospective (forward-looking) observational study.

How best to approach exercise?

In a study presented at the American College of Sports Medicine, there was a 19 percent reduction in the risk of mortality for those who “ran” at a modest pace — defined as 5.5 to 6 miles per hour, or a 10- to 11-minute mile — compared to those who did not run, those who ran more than 20 miles per week, and those who ran faster than 7 mph (although the last two groups were less common). This benefit was seen as long as participants ran between 1 and 20 miles per week. Therefore, a modest distance at a modest pace resulted in the most benefit. This study was part of the Aerobics Center Longitudinal Study at the Cooper Institute in Dallas, Texas.

Thus, it appears that the benefits of exercise far outweigh the risks, even in patients who have heart failure. The most beneficial levels of exercise seem to be in the modest zone for both duration and intensity. This does not mean you can’t exercise with more intensity, with your doctor’s permission. However, it does imply that inactivity is far more dangerous than exercise: There are several studies showing that inactivity reduces longevity and increases cardiovascular events.

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Diabetes is always on the medical radar screen. As incidence of the disease continues to grow, there is a constant stream of new research on the topic. One thing you can say definitively about diabetes:  it never gets dull. The American Diabetes Association meeting in June did not disappoint, revealing both good and bad news.

Fortunately, the good news is abundant. Most importantly, mortality decreased 23 percent overall in diabetes patients and 40 percent in diabetics with cardiovascular disease when comparing 2006 and 1997 results, according to a Centers for Disease Control  survey (Diabetes Care June 2012 vol. 35 no. 6 1252-1257). The author of the study warns, however, that diabetics are still at increased risk for severe complications.

Breakfast’s impact

Mothers always struggle to get their children to eat breakfast. In this case, Mom may be onto something. In a study of almost 4,000 participants, ages 27 to 35 years old, those who ate breakfast were less likely to develop type 2 diabetes (ADA June 2012, abstract 1364-P). For each breakfast consumed during the week, there was a 5 percent reduction in risk. When the researchers compared those who ate breakfast at least five times a week to those who ate it three or fewer times a week, the risk of developing type 2 diabetes fell 31 percent among the frequent breakfast eaters. Those who ate breakfast more frequently did not gain as much weight, 0.5 kg/m2. BMI played a role in this effect. This is an easy way to help ward off diabetes, as well as get you charged for the day.

Insulin and cancer

There have been concerns that insulin increases the risk of cancer. However, in three very large epidemiologic studies presented at the ADA meeting, there was no significant association between the use of glargine insulin and an increased risk of cancer, when compared to other insulins (ADA June 2012, abstract CT-SY13).

However, there are caveats to these studies. For instance, why they compared glargine to other insulins and not to oral drugs seems to weaken the study’s conclusions. There were also slight, but non-significant, increases in breast cancer, 12 percent, and prostate cancer, 11 percent, in one of the studies. The studies’ durations were not very long when you consider the length of time it takes to develop cancer. They ranged from 1.2 years to 3.1 years with glargine and 1.1 years to 3.5 years with other insulins. Hence, I think it is important to interpret the results with a bit of skepticism, though they do point in the right direction.

Metformin and B12 deficiency 

Yet another study presented at the ADA found that those diabetes patients who are taking metformin and have B12 deficiencies have a much higher risk of developing peripheral neuropathies (tingling, numbness and pain in the extremities) that may lead to permanent nerve damage (ADA June 2012, abstract 954-P). Chronic metformin use may be a contributing factor to the B12 deficiency. Before attributing the symptoms to diabetic neuropathy, it is important to test patients’ B12 and methylmalonic acid levels. As age increased, not surprisingly, the likelihood of B12 deficiency also increased. For more information on the appropriate levels of B12, please see my May 1, 2012 article.

Fruit and vegetable effect

Those patients who consumed the most fruits and vegetables saw a 21 percent reduction in risk of diabetes, compared to those who consumed the least, according to the EPIC study (Diabetes Care 2012;35(6):1293-1300). Quantity was important with vegetables, showing a 24 percent lower risk in those who ate the most, but quantity did not play a role in fruits. More important to fruit was the variety, with a 30 percent reduction in those with the most diversity in fruit intake. Combining varied fruits and vegetables resulted in the greatest reduction, 39 percent.

Omega-3 Fatty acids

In a recent randomized controlled trial omega-3 (fish oil) supplements showed disappointing results (NEJM online June 11, 2012). Supplementation with 900 mg of omega-3s did not reduce the incidence of stroke, heart disease or death from cardiovascular disease in pre-diabetes or diabetes patients. This dose may be too low, but still it is unlikely that taking omega-3s will reduce the risk of strokes or heart attacks in diabetes patients. I wrote a two-article series, starting on May 22, 2012, that showed omega-3s were effective in some diseases, but not in others. Therefore, there are more efficient ways to treat diabetes than with fish oil.

Thus, the moral of the story is that lifestyle modifications are an important ingredient in preventing and treating diabetes. If you are taking insulin, you can breathe a sigh of relief that it may not increase your risk of cancer. Make sure to test B12 levels, especially if you are taking metformin, and don’t rely on fish oil to prevent complications from diabetes or pre-diabetes. And as my mom always says, eat your breakfast.

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Last week, I shared the depressing news that omega-3 fatty acids from fish and/or fish oil may not have any positive effects in some diseases, such as heart disease, cancer and multiple sclerosis — a surprise to the medical community. However, omega-3s from these sources may be beneficial in other diseases and disorders, including age-related macular degeneration, dry eye, Alzheimer’s, rheumatoid arthritis, diabetes, anxiety and, ironically, depression. So don’t avoid fish or fish oil yet. Talk to your doctor first. Let’s review some of the studies.

AMD effect

In the Women’s Health Study, there was a significant reduction in risk of developing AMD for those women who ate fish on a regular basis (Arch Ophthalmol. 2011;129(7):921-929). AMD is the leading cause of central vision loss or blindness in patients over 55. The great news is that you don’t have to eat a substantial amount of fish — just one serving per week results in a 42 percent reduction in risk. The fish that had most impact included salmon, mackerel, tuna, bluefish, swordfish and sardines.

I would recommend sardines and salmon, which are lower in mercury than the others and higher in omega-3s. In those who were taking fish oil supplements containing docosahexaenoic acid and eicosapentaenoic acid there were significant, though slightly less robust, reductions in the risk of AMD, 38 percent and 34 percent respectively.

This was a large observational study with 39,000 participants and a mean 10 year follow-up duration. The researchers believe that the mechanism of action may have to do with an anti-inflammatory process, since AMD has underlying inflammation.

AREDS 2 is an ongoing five-year randomized controlled trial, the gold standard of studies, that includes fish oil (clinicaltrials.gov). It will be interesting to see if it reinforces these results.

Alzheimer’s disease
Alzheimer’s disease is neurodegenerative disease. There are no medications yet to reverse or slow its progression, only to treat its symptoms. Thus, it is crucial to find lifestyle modifications that may prevent and treat its effects. In a recent study, consumption of omega-3s from fish showed a significant reduction in beta-amyloid protein, a nonspecific marker of Alzheimer’s disease, as measured in the blood (Neurology online May 2).

In another study, consumption of fish at least one time a week showed preservation of brain volume, tested using MRI scans, in the hippocampus and frontal lobe. These areas are responsible for memory and cognitive function.

Both studies are encouraging for Alzheimer’s disease prevention (RSNA Abstract SST11-04). In yet another study, fish oil seemed to reduce the progression of cognitive impairment in patients with very mild Alzheimer’s disease (Arch Neurol. 2006;63:1402-1408).

Rheumatoid arthritis

In the May 24 article, I wrote about a meta-analysis that showed reduction in joint pain and morning stiffness in those who consumed fish oil (Pain. 2007 May;129(1-2):210-23).
These are two of the most common complaints of patients with rheumatoid arthritis.

Diabetes

Omega-3 fatty acids seem to play a role in prevention of type 2 diabetes. In the Cardiovascular Disease Study, there was a 36 percent reduction in the risk of developing diabetes for those who consumed the most omega-3s (Am J Clin Nutr. 2011;94(2):527-33).
The study was unique in that it tested the levels of DHA and EPA in the blood, a quantitative approach, and determined that participants with the highest levels of these omega-3s were least likely to develop the disease.

This was an observational study with 3,000 participants over a 10-year period. These are encouraging results and may indicate another way to reduce diabetes risk.

Dry eye syndrome

The prevalence of dry eye syndrome increases with age and is a common problem, with a higher prevalence among women (Am J Ophthalmol. 2003;136(2):318-26). In the Women’s Health Study, omega-3 fatty acids reduced the risk of dry eye by 17 percent (Am J Clin Nutr. 2005; 82(4):887-93). The omega-3s may work by blocking pro-inflammatory factors in the eye. The best results were found with tuna: one serving per week reduced risk by 19 percent, while two servings reduced risk by a whopping 68 percent. Interestingly, a high omega-6 (pro-inflammatory) to omega-3 ratio increased the risk of dry eye 2.5 times. The typical American diet is low in omega-3s but very high in omega-6s. Included in this latter category are processed foods; meats — especially red meat; dairy such as cheese, whole milk and butter; and certain processed oils. These are foods that are high in fat, but not good fats.
Omega-3s play a potentially significant role in many diseases, but not in all. There is greater upside for omega-3 fatty acids than downside, except as it relates to prostate cancer risk. However, just as with other substances, it may be better to obtain omega-3s from fish than to rely on fish oil. One thing is sure: We get too many omega-6s and not enough omega-3s in our diet and thus may have a higher propensity toward inflammation, which promotes chronic diseases.

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Omega-3 fatty acids are found in many substances, such as fish, supplements and even an approved drug. Fish oil is one of the most frequently used supplements, and we eat fish in the hope that it will prevent chronic diseases. We believed that the effects of omega-3s are beneficial, since they have anti-inflammatory properties and reduce triglycerides (Brit J. Pharmcol. 2008:153:S200-215; Am J Clin Nutr. 2003:77;300-307). But does the research into clinical outcomes confirm this, or is it conjecture?

The answer is complicated, since the effects seem to be disease dependent. On the one hand, omega-3 FAs are beneficial for Alzheimer’s, age-related macular degeneration, dry-eye syndrome, depression, anxiety and rheumatoid arthritis. On the other, omega-3s have no effect in cardiovascular disease, multiple sclerosis or cancer prevention, and may even increase the risk of prostate cancer. Let’s look at the studies.

Cardiovascular disease

The prevailing thought has always been that omega-3s, especially from fish oil, reduce the risk of stroke and heart disease. Unfortunately, one recent study did not show a beneficial outcome for secondary (second event) prevention of cardiovascular disease with supplemental fish oil.

These results were surprising to many in the medical community and went counter to the treatment paradigm. In the Korean Meta-analysis Study Group (a group of 14 randomized clinical trials, the gold standard of studies), the results did not show a reduction in heart attacks, all-cause mortality, sudden cardiac death, transient ischemic attacks or strokes (Arch Intern Med. online April 9, 2012).

In a commentary by a respected researcher at Harvard Medical School, Dr. Frank Hu, these results should be taken in stride — trials for fish oils have shown mixed results in cardiovascular disease. There were also flaws in the Korean meta-analysis: Many of the studies may have been too small, too short in duration and the primary endpoints were not focused on cardiovascular disease.

It will be interesting to see the effects in the VITAL trial, an ongoing primary prevention trial in cardiovascular disease using fish oil plus vitamin D (Contemp Clin Trials. 2012;33(1):159-171).

Right now, the evidence is inconclusive to recommend fish oil for cardiovascular disease. However, fish has benefits that go beyond omega-3s. It is a good source of protein and of astaxanthin, a member of the carotenoid family of phytochemicals (Arch Intern Med. online April 9, 2012).

Effect on cancer

In the SU.FOL.OM3 study, patients who had cardiovascular disease were given fish oil and vitamin B (B6, folate and B12) to reduce the risk of cancer and cancer deaths. The results were disappointing. In fact, with women, the fish oil increased the risk of cancer, though the number of cases was extremely small. It did not matter whether the fish oil was given alone or in combination with B vitamins — the results fell short of expectations (Arch Intern Med. 2012 Apr 9;172(7):540-7).

In a shocker, the Prostate Cancer Prevention Trial, fish consumption actually increased the risk of aggressive prostate cancer by 2.5 times when high levels of DHA (docosahexaenoic acid), an omega-3 FA, were found in the blood. This trial was observational and involved 3,461 men (Am J Epidemiol. 2011 Jun 15;173(12):1429-39). Before jumping to conclusions, know that other studies have shown that omega-3s either had no effect or potentially beneficial effects with prostate cancer (Am J Clin Nutr 2010;92(5):1223-1233).

Regardless, I would not recommend omega-3s to reduce the risk of cancer risk — especially prostate cancer. Those with a family history of high-grade prostate cancer should consult their physician about the risk-benefit ratio of consuming omega-3s in the form of fish and fish oil. This does not have any impact on omega-3s from other sources, such as from nuts and seeds, since these are low in DHA.

Multiple sclerosis
Since omega-3s have supposed anti-inflammatory effects and autoimmune diseases are based on inflammation, it would make sense to assume that multiple sclerosis patients would benefit from fish oil. However, in an RCT, there were no differences in either objective or subjective measures including MRI findings, frequency of relapse, quality of life and fatigue between the groups that took fish oil and not (Arch Neurol. online April 16, 2012).
Researchers even added the standard-of-care medication, interferon beta-1a, to both groups after six months. The only effects seen were from the drug therapy. This was the first RCT in MS with fish oil supplementation, and the size of the trial was small with only 92 patients.
Fish oil supplementation must be undertaken with caution. Does this mean we should avoid fatty fish and fish oils? Not at all. Even in trials with negative results, there are others to counterbalance them.

Next week, I will write about the positive contributions of omega-3s to disease prevention and treatment.

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Last week, I wrote about the positive effects of medications and the complexities that chronic diseases add to the risk profile of stroke. In this article I will focus on the confusion around aspirin’s use in combination with another antiplatelet drug and its ideal preventive dose. Then, I will suggest lifestyle modifications that can help lower stroke risk.

Medication combination: negative impact

There are two antiplatelet medications that are sometimes given together in the hopes of reducing stroke recurrence — aspirin and Plavix (clopidogrel). The assumption was that these medications together would work better than either alone. However, in a randomized controlled trial, the gold standard of studies, this combination not only didn’t demonstrate efficacy improvement, but significantly increased the risk of major bleed and death (ISC 2012; Abstract LB 9-4504; www.clinicaltrials.gov NCT00059306).

Major bleeding risk was 2.1 percent with the combination versus 1.1 percent with aspirin alone, an almost twofold increase. In addition, there was a 50 percent increased risk of all-cause death with the combination, compared to aspirin alone. Patients were given 325 mg of aspirin and either a placebo or 75 mg of Plavix. The study was halted due to these deleterious effects. The American Heart Association recommends monotherapy for the prevention of recurrent stroke. If you are on the combination of drugs, please consult your physician.

Aspirin: low dose vs. high dose

Greater hemorrhagic (bleed) risk is also a concern with daily aspirin regimens greater than 81 mg, which is the equivalent of a single baby aspirin.

Aspirin’s effects are cumulative; therefore, a lower dose is better over the long term. Even 100 mg taken every other day was shown to be effective in trials. There are about 50 million patients who take aspirin chronically in the United States. If these patients all took 325 mg of aspirin per day — an adult dose — it would result in 900,000 major bleeding events per year (JAMA 2007;297:2018-2024). The ideal dose of aspirin to prevent a recurrent stroke is 81 mg.

Lifestyle modifications

On Dec. 20, 2011, I wrote about stroke prevention. A study showed that white fleshy fruits — apples, pears, bananas, etc. — and vegetables — cauliflower, mushrooms, etc. — decreased the risk of ischemic stroke by 52 percent. Not to be left out, the Nurses’ Health study showed that foods with flavanones, found mainly in citrus fruits, decreased the risk of ischemic stroke by 19 percent (Stroke 2012;43:946-951).

The authors suggest that the reasons for the reduction may have to do with the ability of flavanones to reduce inflammation and/or improve blood vessel function. This study involved about 70,000 women with 14 years of follow-up. I mention both of these trials together because of the importance of fruits in prevention of ischemic (clot-based) stroke.

Alcohol’s effect

I am continuously asked about my stand on alcohol consumption. There are definite benefits to drinking alcohol in moderation, and stroke reduction appears to be one. Findings published in March from the Nurses’ Health Study showed a decreased risk of stroke by 17-21 percent in women who consumed between half a glass to one glass of alcohol per day, compared to those who did not (Stroke 2012; 43: 939-945). A serving size is 4 ounces of wine or a 12-ounce beer. This was a very large observational study involving 83,000 women over 26 years.

The authors hypothesize that the effect has to do with improving the lipid profile and/or preventing clot formation. Does this mean if you don’t drink you’re at a disadvantage? Not at all! There are plenty of other lifestyle modifications you can make to reduce your risk equally or more, including eating flavanone-full foods, such as citrus fruits, as well as white fleshy fruits. In addition, the Mediterranean and Dash diets reduce stroke risk. In one recent study, the Mediterranean diet was shown to reduce the risk of ischemic stroke by a resounding 63 percent (J. Nutr. 2011;141(8):1552-1558). Too much alcohol can increase your risk of atrial fibrillation, an arrhythmia that increases stroke risk.

Fiber’s important role

Fiber plays a key role in reducing the risk of a hemorrhagic stroke. In a study involving over 78,000 women, those who consumed the most fiber had a total stroke risk reduction of 34 percent and a 49 percent risk reduction in hemorrhagic stroke. The type of fiber used in this study was cereal fiber, or fiber from whole grains.

Refined grains, however, increased the risk of hemorrhagic stroke twofold (Am J Epidemiol. 2005 Jan 15;161(2):161-9). When eating grains, it is important to have whole grains. Read labels carefully, since some products that claim to have whole grains contain unbleached or bleached wheat flour which are refined.

Fortunately, there are many options to help reduce the risk or the recurrence of a stroke. Ideally, the best option would involve lifestyle modifications. Some patients may need to take statins, even with lifestyle modifications. However, statins’ side-effect profile is dose related. Therefore, if you need to take a statin, lifestyle changes may help lower your dose and avoid harsh side effects. Once you have had a stroke, it is likely that you will remain on at least one medication — low-dose aspirin — since the risk of a second stroke is high.

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, go to the website www.medicalcompassmd.com and/or consult your personal physician.