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Dr. David Dunaief

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The decision to take a statin is an important one. Stock photo
Fatigue and cataracts are downsides

By David Dunaief, M.D.

Dr. David Dunaief

Statins are one of the most commonly prescribed medications in the United States. Yet, some in the medical community believe that more patients should be on this class of drugs while others think it is one of the most overprescribed medications. Suffice to say, this is one of the most polarizing topics in medicine — probably rightfully so.

The debate is over primary prevention with statins. Primary prevention is treating people with high cholesterol and/or inflammation who may be at risk for a cardiovascular event, such as a stroke or heart attack.

Fortunately, most physicians would agree that statins have their place in secondary prevention — treating patients who have had a stroke or heart attack already or have coronary artery disease.

We are going to look at benefits and risks for the patient population that could take statins for primary prevention. On one side, we have the statin as Rocky Balboa, coming out to fight off cancer risk, both overall and esophageal, as well as improving quality of life and glaucoma. On the other, we have the statin as Evel Knievel, demonstrating that reckless heroics don’t provide longevity, but they do increase diabetes risk, promote fatigue and increase cataracts. Let’s look at some of the evidence.

Effect on cancer

A study published in The New England Journal of Medicine involved 300,000 Danish participants and investigated 13 cancers. It showed that statin users may have a 15 percent decreased risk of death from cancer (1). This is exciting news.

However, there were major limitations with the study. First, the researchers did not control for smoking, which we know is a large contributor to cancer. Second, it was unknown which of the statin-using population might have received conventional cancer treatments, such as radiation and chemotherapy. Third, the dose of statins did not correlate to risk reduction. In fact, those who took 1 to 75 percent of prescribed statin levels showed more benefit in terms of cancer mortality risk than those who took more. We need a better-designed trial that is prospective (forward looking) to determine whether there really is an effect. I would say that Rocky Balboa came out of this fight pretty banged up.

Another study showed that statins may play a role in reducing the risk of esophageal cancer. This is important, since esophageal cancer, especially adenocarcinoma that develops from Barrett’s esophagus, is on the rise. The results showed a 28 percent risk reduction in this type of cancer. The authors of the study surmise that statins may have a protective effect. This was a meta-analysis of 13 observational studies (2).

Although there is an association, these results need to be confirmed with randomized controlled trials. Remember, aspirin has about the same 30 percent reduction in colorectal cancer, yet is not recommended solely for this use because of side effects.

Eye diseases: mixed results

In two common eye diseases, glaucoma and cataracts, statins have vastly different results. In one study, statins were shown to decrease the risk of glaucoma by 5 percent over one year and 9 percent over two years (3). It is encouraging that the longer the duration of statin use, the greater the positive effect on preventing glaucoma.

Statins also help to slow glaucoma progression in patients suspected of having early-stage disease at about the same rate. This was a retrospective (backward-looking or looking in the past) study analyzing statin use with patients at risk for open-angle glaucoma. There is a need for prospective (forward-looking) studies. With cataracts, it is a completely different story. Statins increase the risk of cataracts by over 50 percent, as shown in the Waterloo Eye Study (4). Statins exacerbate the risk of cataracts in an already high-risk group: diabetes patients.

Quality of life and longevity: a mixed bag

In a meta-analysis involving 11 randomized controlled trials, considered the gold standard of studies, statins did not reduce the risk of all-cause mortality in moderate to high-risk primary prevention participants (5). This study analysis involved over 65,000 participants with high cholesterol and at significant risk for heart disease.

However, in this same study, participants at high risk of coronary heart disease saw a substantial improvement in their quality of life with statins. In other words, the risk of a nonfatal heart attack was reduced by more than half and nonfatal strokes by almost half, avoiding the potentially disabling effects of these cardiovascular events.

Fatigue effect

Some of my patients who are on statins ask if statins can cause fatigue. A randomized controlled trial published in the Archives of Internal Medicine reinforces the idea that statins increase the possibility of fatigue (6).

Women, especially, complained of lower energy levels, both overall and on exertion, when they were blindly assigned to a statin-taking group. The trial was composed of three groups: two that took statins, simvastatin 20 mg and pravastatin 40 mg; and a placebo group. The participants were at least 20 years old and had LDL (bad) cholesterol of 115 to 190 mg/dl, with less than 100 mg/dl considered ideal.

In conclusion, some individuals who are at high risk for cardiovascular disease may need a statin, but with the evidence presented, it is more likely that statins are overprescribed in primary prevention. Evidence of the best results points to lifestyle modification, with or without statins, and all patients with elevated LDL (bad) cholesterol should make changes that include a nutrient-dense diet and a reduction in fat intake, as well as exercise.

References:

(1) N Engl J Med 2012;367:1792-1802. (2) Clin Gastroenterol Hepatol. 2013 Jun; 11(6):620–629. (3) Ophthalmology 2012;119(10):2074-2081. (4) Optom Vis Sci 2012;89:1165-1171. (5) Arch Intern Med 2010;170(12):1024-1031. (6) Arch Intern Med 2012;172(15):1180-1182.

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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While vitamin D may not be a cure-all, it may play an integral role with many disorders. Stock photo
Recent trial results question supplementation benefits

By David Dunaief, M.D.

Dr. David Dunaief

Vitamin D is one the most widely publicized and important supplements. We get vitamin D from the sun, food and supplements. With our days rapidly shortening here in the Northeast, let’s explore what we know about vitamin D supplementation.

There is no question that, if you have low levels of vitamin D, replacing it is important. Previous studies have shown that it 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 in, their meaning for vitamin D becomes murkier. For instance, is the sun the best source of 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 geographic locations, 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. For adults, the Institute of Medicine recommends more than 20 ng/dl, and The Endocrine Society recommends at least 30 ng/dl.

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 (1).

However, a small randomized controlled trial (RCT), the gold standard of studies, called the cardioprotective effects of vitamin D into question (2). 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 2,500 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 end points.

Long-awaited VITAL study results for cancer and cardiovascular events

Most trials relating to vitamin D are observational, which provides associations, but not links. However, results of the VITAL study, a large, five-year RCT looking at the effects of vitamin D and omega-3s on cardiovascular disease and cancer were just published this week (3). Study results were disappointing, finding that daily vitamin D3 supplementation at 2000 IUs did not reduce the incidence of cancers (prostate, breast or colorectal) or of major cardiovascular events.

Mortality decreased

In a meta-analysis of a group of eight studies, vitamin D with calcium reduced the mortality rate in the elderly, whereas vitamin D alone did not (5). 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 amounts of 300,000 to 500,000 IUs once a year, rather than taken daily. This has different effects.

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/dl, compared to those below this level, in the Study of Osteoporotic Fractures (4).

This association held true at baseline and after 4.5 years of observation. If the women dropped below 30 ng/dl 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.

USPSTF recommendations

The U.S. Preventive Services Task Force recommends against giving “healthy” postmenopausal women vitamin D, calcium or the combination of vitamin D 400 IUs plus calcium 1,000 mg to prevent fractures, and it found inadequate evidence of fracture prevention at higher levels (6). The supplement combination does not seem to reduce fractures, but does increase 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. But as I mentioned previously, the recent VITAL study did not show any benefit for cancer prevention.

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. But it is also important not to raise the levels too high. The range that I tell my patients is between 30 and 55 ng/dl, depending on their circumstances — those who are healthy and those who have chronic diseases and what type of chronic diseases.

References:

(1) Circulation. 2008 Jan 29;117(4):503-511. (2) PLoS One. 2012;7(5):e36617. (3) NEJM. 2018 published online Nov. 10, 2018. (4) J Women’s Health (Larchmt). 2012 Jun 25. (5) J Clin Endocrinol Metabol. online May 17, 2012. (6) JAMA. 2018;319(15):1592-1599.

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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Regular exercise helps prevent or manage a wide range of health problems and concerns. Stock photo
The real benefits of exercise

By David Dunaief, M.D.

Dr. David Dunaief

With holiday dinners right around the corner, what would be a better topic than exercise? To quell our guilt about Thanksgiving dinner indiscretions, many of us will resolve to exercise to burn off the calories from this seismic meal and the smaller, calorically dense aftershock meals, whether with a vigorous family football game or with a more modest walk.

Unfortunately, exercise without dietary changes may not actually help many people lose weight, no matter what the intensity or the duration (1). If it does help, it may only modestly reduce fat mass and weight for the majority of people. However, it may be helpful with weight maintenance. Therefore, it may be more important to think about what you are eating than to succumb to the rationalization that you can eat with abandon during the holidays and work it off later.

Don’t give up on exercise just yet, though. There is very good news: Exercise does have beneficial effects on a wide range of conditions, including chronic kidney disease, cognitive decline, diabetes, cardiovascular disease, osteoporosis, fatigue, insomnia and depression.

Let’s look at the evidence.

Weight loss attenuated

The well-known weight-loss paradigm in medicine is that when more calories are burned than consumed, we will tip the scale in favor of weight loss. The greater the negative balance with exercise, the greater the loss. However, the results of a study say otherwise. They show that in premenopausal women there was neither weight nor fat loss from exercise (2). This involved 81 women over a short duration, 12 weeks. All of the women were overweight to obese, although there was great variability in weight.

However, more than two-thirds of the women (55) gained a mean of 1 kilogram, or 2.2 pounds, of fat mass by the end of the study. There were a few who gained 10 pounds of predominantly fat. Significant variability was seen among the participants, ranging from significant weight loss to substantial weight gain. These women were told to exercise at the American College of Sports Medicine’s optimal level of intensity (3). This is to walk 30 minutes on a treadmill three times a week at 70 percent VO2max — maximum oxygen consumption during exercise — or, in other words, a moderately intense pace. 

The good news is that the women were in better aerobic shape by the end of the study and that women who had lost weight at the four-week mark were more likely to continue to do so by the end of the study. This was a preliminary study, so no definitive conclusions can be made.

Other studies have shown modest weight loss. For instance, in a meta-analysis involving 14 randomized controlled trials — the gold standard of studies — results showed that there was a disappointing amount of weight loss with exercise alone (4). In six months, patients lost a mean of 1.6 kilograms, or 3.5 pounds, and at 12 months, participants lost 1.7 kilograms, or about 3.75 pounds.

Weight maintenance

However, exercise may be valuable in weight maintenance, according to observational studies. Premenopausal women who exercised at least 30 minutes a day were significantly less likely to regain lost weight (5). When exercise was added to diet, women were able to maintain 30 percent more weight loss than with diet alone after a year in a prospective study (6).

Chronic kidney disease

As just one example of exercise’s impact on disease, let’s look at chronic kidney disease (CKD), which affects 14 percent of adults in the United States, according to the Centers for Disease Control and Prevention (7). The U.S. Preventive Services Task Force has indicated that there is insufficient evidence to treat asymptomatic CKD. In fact, the American College of Physicians has said that asymptomatic CKD, which includes stages 3a and 3b, or moderate disease levels, should not be screened for, since the treatment risks outweigh the benefits, and lead to false positive results and unnecessary treatments (8).

However, in a trial, results showed that walking regularly could reduce the risk of kidney replacement therapy and death in patients who have moderate to severe CKD, stages 3-5 (9). Yes, this includes stage 3, which most likely is asymptomatic. There was a 21 percent reduction in the risk of kidney replacement therapy and a 33 percent reduction in the risk of death when walkers were compared to nonwalkers.

Walking had an impressive impact; results were based on a dose-response curve. In other words, the more frequently patients walked in the week, the better the probability of preventing complications. Those who walked between one and two times per week had 17 and 19 percent reductions in death and kidney replacement therapy, respectively, while those who walked at least seven times per week saw 44 and 59 percent reductions in death and kidney replacement. These are substantial results. The authors concluded that the effectiveness of walking on CKD was independent of kidney function, age or other diseases.

Therefore, while it is important to enjoy the holidays, it is food choices, not exercise, that will have the greatest impact on our weight and body composition. However, exercise is extremely beneficial for preventing progression of chronic disorders, such as CKD.

So, by all means, exercise during the holidays, but also focus on more nutrient-dense foods. At a minimum, strike a balance rather than eating purely calorically dense foods. You won’t be able to exercise them away.

References:

(1) uptodate.com. (2) J Strength Cond Res. Online Oct. 28, 2014. (3) ACSM.org. (4) Am J Med. 2011;124(8):747. (5) Obesity (Silver Spring). 2010;18(1):167. (6) Int J Obes Relat Metab Disord. 1997;21(10):941. (7) cdc.gov. (8) Ann Intern Med. online October 21, 2013. (9) Clin J Am Soc Nephrol. 2014 Jul;9(7):1183-1189.

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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Stock photo
Key lifestyle choices may reduce your risk significantly

By David Dunaief, M.D.

Dr. David Dunaief

Happy “Movember!” The Movember Foundation is in its 11th year of raising awareness and research money for men’s health issues (1). What better time to discuss prostate cancer prevention?

The best way to avoid prostate cancer is through lifestyle modifications, which means learning about both detrimental and beneficial approaches. There are a host of things that may increase your risk and others that may decrease your likelihood of prostate cancer. Your family history does not mean you can’t alter gene expression with the choices you make.

What may increase the risk of prostate cancer? Contributing factors include obesity, animal fat and supplements, such as vitamin E and selenium. Equally as important, factors that may reduce risk include vegetables, especially cruciferous, and tomato sauce or cooked tomatoes.

Vitamin E and selenium

In the SELECT trial, a randomized clinical trial (RCT), a dose of 400 mg of vitamin E actually increased the risk of prostate cancer by 17 percent (2). Though significant, this is not a tremendous clinical effect. It does show that vitamin E should not be used for prevention of prostate cancer. Interestingly, in this study, selenium may have helped to reduce the mortality risk in the selenium plus vitamin E arm, but selenium trended toward a slight increased risk when taken alone. Therefore, I would not recommend that men take selenium or vitamin E for prevention.

Obesity

Obesity showed conflicting results, prompting the study authors to analyze the results further. According to a review of the literature, obesity may slightly decrease the risk of nonaggressive prostate cancer, however increase risk of aggressive disease (3). Don’t think this means that obesity has protective effects. It’s quite the contrary. The authors attribute the lower incidence of nonaggressive prostate cancer to the possibility that it is more difficult to detect the disease in obese men, since larger prostates make biopsies less effective. What the results tell us is that those who are obese have a greater risk of dying from prostate cancer when it is diagnosed.

Animal fat, red and processed meats

The risk of developing prostate cancer increases with age. Stock photo

It seems there is a direct effect between the amount of animal fat we consume and incidence of prostate cancer. In the Health Professionals Follow-up Study, a large observational study, those who consumed the highest amount of animal fat had a 63 percent increased risk, compared to those who consumed the least (4).

Here is the kicker: It was not just the percent increase that was important, but the fact that it was an increase in advanced or metastatic prostate cancer. Also, in this study, red meat had an even greater, approximately 2.5-fold, increased risk of advanced disease. If you are going to eat red meat, I recommend decreased frequency, like lean meat once every two weeks or once a month.

In another large, prospective (forward-looking) observational study, the authors concluded that red and processed meats increase the risk of advanced prostate cancer through heme iron, barbecuing/grilling and nitrate/nitrite content (5).

Omega-3s paradox

When we think of omega-3 fatty acids or fish oil, we think “protective” or “beneficial.” However, these may increase the risk of prostate cancer, according to one epidemiological study (6). This study, called the Prostate Cancer Prevention Trial, involving a seven-year follow-up period, showed that docosahexaenoic acid (DHA), a form of omega-3 fatty acid, increased the risk of high-grade disease 2.5-fold. This finding was unexpected. If you choose to eat fish, salmon or sardines in water with no salt are among the best choices.

Lycopene – found in tomato sauce

Tomato sauce has been shown to potentially reduce the risk of prostate cancer. However, uncooked tomatoes have not shown beneficial effects. This may be because, in order to release lycopene, the tomatoes need to be cooked (7). It is believed that lycopene, which is a type of carotenoid found in tomatoes, is central to this benefit.

In a prospective (forward-looking) study involving 47,365 men who were followed for 12 years, the risk of prostate cancer was reduced by 16 percent (8). The primary source of lycopene in this study was tomato sauce. When the authors looked at tomato sauce alone, they saw a reduction in risk of 23 percent when comparing those who consumed at least two servings a week to those who consumed less than one serving a month. The reduction in severe, or metastatic, prostate cancer risk was even greater, at 35 percent. There was a statistically significant reduction in risk with a very modest amount of tomato sauce.

In the Health Professionals Follow-up Study, the results were similar, with a 21 percent reduction in the risk of prostate cancer (9). Again, tomato sauce was the predominant food responsible for this effect. This was another large observational study with 47,894 participants. Although tomato sauce may be beneficial, many brands are loaded with salt. I recommend to patients that they either make their own sauce or purchase a sauce with no salt, such as one made by Eden Organics.

Vegetable effects

Vegetables, especially cruciferous vegetables, reduce the risk of prostate cancer significantly. In a case-control study (comparing those with and without disease), participants who consumed at least three servings of cruciferous vegetables per week, versus those who consumed less than one per week, saw a 41 percent reduction in prostate cancer risk (10). What’s even more impressive is the effect was twice that of tomato sauce, yet the intake was similarly modest. Cruciferous vegetables include broccoli, cauliflower, bok choy, kale and arugula, to name a few.

When it comes to preventing prostate cancer, lifestyle modification, including making dietary changes, can reduce your risk significantly.

References:

(1) www.movember.com. (2) JAMA. 2011; 306: 1549-1556. (3) Epidemiol Rev. 2007;29:88. (4) J Natl Cancer Inst. 1993;85(19):1571. (5) Am J Epidemiol. 2009;170(9):1165. (6) Am J Epidemiol. 2011 Jun 15;173(12):1429-1439. (7) Exp Biol Med (Maywood). 2002; 227:914-919. (8) J Natl Cancer Inst. 2002;94(5):391. (9) Exp Biol Med (Maywood). 2002; 227:852-859; Int. J. Cancer. 2007;121: 1571–1578. (10) J Natl Cancer Inst. 2000;92(1):61.

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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Type 2 diabetes is a lifestyle disease — our food choices can either prevent or promote diabetes. Stock photo
Dietary changes are worth the effort

By David Dunaief, M.D.

Dr. David Dunaief

Lifestyle modifications are the most effective way to tackle Type 2 diabetes and its complications. Many in the medical community agree that a combination of diet and exercise is the best approach. However, American Diabetes Association (ADA) guidelines recommend that patients with new onset disease start by combining lifestyle changes with the medication metformin. 

The thinking behind this approach is that too many patients fail on diet alone, and it’s important to reduce glucose (sugar) levels as soon as possible. According to the guidelines’ authors, for most individuals with Type 2 diabetes, lifestyle interventions fail to achieve or maintain metabolic goals, either because of failure to lose weight, weight regain, progressive disease or a combination of factors (1). 

I agree that it is not easy to change your lifestyle, but I also think that, for highly motivated patients, the benefits far outweigh the challenges. Not only can we treat this disease, but we can also prevent its complications, such as heart disease, which are so difficult to treat with medications. 

Type 2 diabetes is caused in large part by poor nutrition. Yes, some people have a higher propensity than others, but if compliant on a diet regimen, you can dramatically reduce your risk. And, while medications may help manage diabetes, they also have varying degrees of undesirable side effects. With lifestyle modifications, though, there are only positive effects.

What type of diet regimen may be used to prevent Type 2 diabetes?

The regimen that has achieved the best results is a plant-based diet rich in vegetables, beans and legumes, nuts and seeds, whole grains and fruits. It also may include animal products with an emphasis on fish. This is a diet that emphasizes good fats, those with lots of omega 3 fatty acids, and is low in saturated fat. The data suggest that antioxidants, such as carotenoids, which can be found in multiple foods in this diet, play an integral role in preventing the disease (2).

A randomized clinical trial, called the PREDIMED study, published in the journal Diabetes Care in January 2011, showed that a Mediterranean-type diet, such as described above, reduced the risk of Type 2 diabetes by 52 percent, when compared to a low-fat diet (3). The incredible part was that these results were seen over a short four years, with negligent weight loss among the trial groups. In other words, the Mediterranean-type diet’s effects extend beyond a change in body mass index. 

An observational study showed that those with the highest compliance with a Mediterranean-type diet had a dramatic risk reduction for developing diabetes of 83 percent (4).

What about treatment?

A study published in the American Journal of Clinical Nutrition showed a low-fat vegan diet had twice the effectiveness in lowering glucose levels, compared to the traditional ADA diet (5). Both groups lost about the same amount of weight. Again, it shows that there is more than just weight loss involved in effective dietary regimens for this disease.

Can we reverse Type 2 diabetes?

In a study I authored in collaboration with Dr. Joel Fuhrman and the University of Pennsylvania Medical Center, results showed that 62 percent of participants who followed a high-nutrient density diet, similar to the Mediterranean-type diet, achieved normal glycemic (sugar) levels (6). Thus, they became nondiabetic. 

Even more impressive, participants were able to reduce the number of overall medications from four to one and discontinue all of their diabetic medications, except for one participant. Of those with high blood pressure, the mean blood pressure was normal at the last data point of the study. There was also significant improvement in the lipid profiles of participants.

These are very positive results for both prevention and treatment of Type 2 diabetes and its complications. The caveat is that it is not easy and takes highly motivated individuals. However, the results are well worth the effort.

References:

(1) Diabetes Care 2018 Jan; 41(Supplement 1): S73-S85. (2) Am J Clin Nutr June 2003 77(6):1434-1441. (3) Diabetes Care 2011(34):14-19. (4) BMJ. 2008 Jun 14;336(7657):1348–1351. (5) Am J Clin Nutr May 2009 89(5):1588S-1596S. (6) Open Jnl Prev Med Aug 2012 2(3):364-371.

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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Fish oil may help with a range of medical conditions including reducing inflammation. Stock photo
Focus on nutritional options for improving outcomes

By David Dunaief, M.D.

Dr. David Dunaief

Autoimmune diseases affect approximately 23.5 million Americans, most of them women. More than 80 conditions have autoimmunity implications (1). Among the most common are rheumatoid arthritis (RA), lupus, thyroid (hypo and hyper), psoriasis, multiple sclerosis and inflammatory bowel disease. In all autoimmune diseases, the immune system inappropriately attacks organs, cells and tissues of the body, causing chronic inflammation, the main consequence of immune system dysfunction, and it is the underlying theme tying these diseases together. Unfortunately, autoimmune diseases tend to cluster (2). Once you have one, you will  likely acquire others.

Drug treatments

The mainstay of treatment is immunosuppressives. In RA where there is swelling of joints bilaterally, the typical drug regimen includes methotrexate and TNF (tumor necrosis factor) alpha inhibitors, like Remicade (infliximab). These therapies seem to reduce underlying inflammation by suppressing the immune system and interfering with inflammatory factors, such as TNF-alpha. The disease-modifying anti-rheumatic drugs may slow or stop the progression of joint destruction and increase physical functioning. Remicade reduces C-reactive protein (CRP), a biomarker of inflammation.

However, there are several concerning factors with these drugs. First, the side effect profile is substantial. It includes the risk of cancers, opportunistic infections and even death, according to black box warnings (the strongest warning by the FDA) (3). Opportunistic infections include diseases like tuberculosis and invasive fungal infections. It is no surprise that suppressing the immune system would result in increased infection rates. Nor is it surprising that cancer rates would increase, since the immune system helps to fend off malignancies. In fact, a study showed that after 10 years of therapy, the risk of cancer increased by approximately fourfold with the use of immunosuppressives (4).

Second, these drugs were tested and approved using short-term randomized clinical trials, but many patients are put on these therapies for 20 or more years. 

So what other methods are available to treat autoimmune diseases? These include medical nutrition therapy using bioactive compounds, which have immunomodulatory (immune system regulation) effects on inflammatory factors and on gene expression and supplementation.

Nutrition and inflammation

Raising the level of beta-cryptoxanthin, a carotenoid bioactive food component, by a modest amount has a substantial impact in preventing RA. While I have not found studies that specifically tested diet in RA treatment, there is a study that looked at the Mediterranean-type diet in 112 older patients where there was a significant decrease in inflammatory markers, including CRP (5).

In another study, participants showed a substantial reduction in CRP with increased flavonoid levels, an antioxidant, from vegetables and apples. Astaxanthin, a carotenoid found in fish, was shown to significantly reduce a host of inflammatory factors in mice, including TNF-alpha (6).

Fish oil

Fish oil may help with a range of medical conditions including reducing inflammation.
Stock photo

Fish oil helps your immune system by reducing inflammation and improving your blood chemistry, affecting as many as 1,040 genes (7). In a randomized clinical study, 1.8 grams of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation had anti-inflammatory effects, suppressing cell signals and transcription factors (proteins involved with gene expression) that are pro-inflammatory, such as NFkB.

In RA patients, fish oil helps suppress cartilage degradative enzymes, while also having an anti-inflammatory effect (8). When treating patients with autoimmune disease, I typically suggest about 2 grams of EPA plus DHA to help regulate their immune systems. Don’t take these high doses of fish oil without consulting your doctor, since fish oil may have blood thinning effects.

Probiotic supplements

The gut contains approximately 70 percent of your immune system. Probiotics, by populating the gut with live beneficial microorganisms, have immune-modulating effects that decrease inflammation and thus are appropriate for autoimmune diseases. Lactobacillus salvirus and Bifidobacterium longum infantis are two strains that were shown to have positive effects (9, 10).

In a study with Crohn’s disease patients, L. casei and L. bulgaricus reduced the inflammatory factor, TNF-alpha (11). To provide balance, I recommend probiotics with Lactobacillus to my patients, especially with autoimmune diseases that affect the intestines, like Crohn’s and ulcerative colitis.

Fiber

Fiber has been shown to modulate inflammation by reducing biomarkers, such as CRP. In two separate clinical trials, fiber either reduced or prevented high CRP in patients. In one, a randomized clinical trial, 30 grams, or about 1 ounce, of fiber daily from either dietary sources or supplements reduced CRP significantly compared to placebo (12).

In the second trial, which was observational, participants who consumed the highest amount of dietary fiber (greater than 19.5 grams) had reductions in a vast number of inflammatory factors, including CRP, interleukin-1 (IL-1), interleukin-6 (IL-6) and TNF-alpha (13).

Immune system regulation is complex and involves over 1,000 genes, as well as many biomarkers. Dysfunction results in inflammation and potentially autoimmune disease. We know the immune system is highly influenced by bioactive compounds found in high nutrient foods and supplements. Therefore, bioactive compounds may work in tandem with medications and/or may provide the ability to reset the immune system through immunomodulatory effects and thus treat and prevent autoimmune diseases.

References:

(1) niaid.nih.gov. (2) J Autoimmun. 2007;29(1):1. (3) epocrates.com. (4) J Rheumatol 1999;26(8):1705-1714. (5) Am J Clin Nutr. 2009 Jan;89(1):248-256. (6) Chem Biol Interact. 2011 May 20. (7) Am J Clin Nutr. 2009 Aug;90(2):415-424. (8) Drugs. 2003;63(9):845-853. (9) Gut. 2003 Jul;52(7):975-980. (10) Antonie Van Leeuwenhoek 1999 Jul-Nov;76(1-4):279-292. (11) Gut. 2002;51(5):659. (12) Arch Intern Med. 2007;167(5):502-506. (13) Nutr Metab (Lond). 2010 May 13;7:42.

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

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Recent research focuses on modest lifestyle changes

By David Dunaief, M.D.

Dr. David Dunaief

Parkinson’s disease has burst into the public consciousness in recent years. It is a neurodegenerative (the breakdown of brain neurons) disease with the resultant effect of a movement disorder. 

Most notably, patients with the disease suffer from a collection of symptoms known by the mnemonic TRAP: tremors while resting, rigidity, akinesia/bradykinesia (inability/difficulty to move or slow movements) and postural instability or balance issues. It can also result in a masked face, one that has become expressionless, and potentially dementia, depending on the subtype. There are several different subtypes; the diffuse/malignant phenotype has the highest propensity toward cognitive decline (1).

The part of the brain most affected is the basal ganglia, and the prime culprit is dopamine deficiency that occurs in this brain region (2). Why not add back dopamine? Actually, this is the mainstay of medical treatment, but eventually the neurons themselves break down, and the medication becomes less effective.

Risk factors may include head trauma, reduced vitamin D, milk intake, well water, being overweight, high levels of dietary iron and migraine with aura in middle age.

Is there hope? Yes, in the form of medications and deep brain stimulatory surgery, but also with lifestyle modifications. Lifestyle factors include iron, vitamin D and CoQ10. The research, unfortunately, is not conclusive, though it is intriguing.

Let’s look at the research.

The role of iron

This heavy metal is potentially harmful for neurodegenerative diseases such as Alzheimer’s disease, macular degeneration, multiple sclerosis and, yes, Parkinson’s disease. The problem is that this heavy metal can cause oxidative damage.

In a small, yet well-designed, randomized controlled trial (RCT), researchers used a chelator to remove iron from the substantia nigra, a specific part of the brain where iron breakdown may be dysfunctional. An iron chelator is a drug that removes the iron. Here, deferiprone (DFP) was used at a modest dose of 30 mg/kg/d (3). This drug was mostly well tolerated.

The chelator reduced the risk of disease progression significantly on the Unified Parkinson Disease Rating Scale (UPDRS). 

Participants who were treated sooner had lower levels of iron compared to a group that used the chelator six months later. A specialized MRI was used to measure levels of iron in the brain. This trial was 12 months in duration.

The iron chelator does not affect, nor should it affect, systemic levels of iron, only those in the brain specifically focused on the substantia nigra region. The chelator may work by preventing degradation of the dopamine-containing neurons. It also may be recommended to consume foods that contain less iron.

CoQ10

When we typically think of using CoQ10, a coenzyme found in over-the-counter supplements, it is to compensate for depletion from statin drugs or due to heart failure. Doses range from 100 to 300 mg. However, there is evidence that CoQ10 may be beneficial in Parkinson’s at much higher doses. 

In an RCT, results showed that those given 1,200 mg of CoQ10 daily reduced the progression of the disease significantly based on UPDRS changes, compared to the placebo group (4). Other doses of 300 and 600 mg showed trends toward benefit but were not significant. This was a 16-month trial in a small population of 80 patients. Though the results for other CoQ10 studies have been mixed, these results are encouraging. Plus, CoQ10 was well tolerated at even the highest dose. Thus, there may be no downside to trying CoQ10 in those with Parkinson’s disease.

Vitamin D: Good or bad?

In a prospective (forward-looking) study, results show that vitamin D levels measured in the highest quartile reduced the risk of developing Parkinson’s disease by 65 percent, compared to the lowest quartile (5). This is quite impressive, especially since the highest quartile patients had vitamin D levels that were what we would qualify as insufficient, with blood levels of 20 ng/ml, while those in the lowest quartile had deficient blood levels of 10 ng/ml or less. There were over 3,000 patients involved in this study with an age range of 50 to 79.

When we think of vitamin D, we wonder whether it is the chicken or the egg. Let me explain. Many times we are deficient in vitamin D and have a disease, but replacing the vitamin does nothing to help the disease. Well, in this case it does. It turns out that vitamin D may play dual roles of both reducing the risk of Parkinson’s disease and slowing its progression.

In an RCT, results showed that 1,200 IU of vitamin D taken daily may have reduced the progression of Parkinson’s disease significantly on the UPDRS compared to a placebo over a 12-month duration (6). Also, this amount of vitamin D increased the blood levels by two times from 22.5 to 41.7 ng/ml. There were 121 patients involved in this study with a mean age of 72.

So, what have we learned? Though medication with dopamine agonists is the gold standard for the treatment of Parkinson’s disease, lifestyle modifications can have a significant impact on both prevention and treatment of this disease. Each lifestyle change in isolation may have modest effects, but cumulatively they might pack quite a wallop. The most exciting part is that lifestyle modifications have the potential to slow the progression of the disease and thus have a protective effect. Iron chelators specific to the brain may also be very important in disease modification. This also brings vitamin D back into the fold as a potential disease modifier.

References:

(1) JAMA Neurol. 2015;72:863-873. (2) uptodate.com. (3) Antioxid Redox Signal. 2014;10;21(2):195-210. (4) Arch Neurol. 2002;59(10):1541-1550. (5) Arch Neurol. 2010;67(7):808-811. (6) Am J Clin Nutr. 2013;97(5):1004-1013.

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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Placing one foot in front of the other can lead to impressive mental and physical benefits. Stock photo
Benefits are seen with modest exercise

By Dr. David Dunaief

Dr. David Dunaief

There is great emphasis on exercise. We have heard it is good for us ever since we were children in gym class striving for the presidential fitness award. 

The average reaction, unfortunately, is an aversion to exercise. As kids, many of us tried to get out of gym class, and as adults, we “want” to exercise, but we “don’t have time.” The result of this is a nation of couch potatoes. I once heard that the couch is the worst deep-fried food. It perpetuates inactivity, especially when watching TV. Even sleeping burns more calories.

I think part of the problem is that we don’t know what type of exercise is best and how long and frequently to do it. 

Well, guess what? There is an easy way to get tremendous benefit with very little time involved. You don’t need expensive equipment, and you don’t have to join a gym. You can sharpen your wits with your feet.

Jane Brody has written in The New York Times’ Science Times about Esther Tuttle. Esther was 99 years old, sharp as a tack and was independently mobile, with no aids needed. She continued to stay active by walking in the morning for 30 minutes and then walking again in the afternoon. The skeptic might say that this is a nice story, but its value is anecdotal at best. 

Well, evidence-based medicine backs up her claim that walking is a rudimentary and simple way to get exercise that shows incredible benefits. One mile of walking a day will help keep the doctor away. 

Walking has a powerful effect on preserving brain function and even growing certain areas of the brain (1). Walking between six and nine miles a week, or just one mile a day, reduced the risk of cognitive impairment over 13 years and actually increased the amount of gray matter tissue in the brain over nine years.

Those participants who had an increase in brain tissue volume had a substantially reduced risk of developing cognitive impairment. Interestingly, the parts of the brain that grew included the hippocampus, involved with memory, and the frontal cortex, involved with short-term memory and executive decision making. There were 299 participants who had a mean age of 78 and were dementia free at the start of the trial. Imagine if you started earlier? 

In yet another study, moderate exercise reduced the risk of mild cognitive impairment with exercise begun in mid-to-late life (2). 

Even better news is that, if you’re pressed for time or if you’re building up your stamina, you can split a mile into two half-mile increments. How long does it take you to walk a half-mile? You’ll be surprised at how much better you will  feel — and how much sharper your thinking is.

If you ratchet up the exercise to running, a study showed that mood improves, mollifying anger (3). The act of running actually increases your serotonin levels, a hormone that, when low, can make people agitated or angry. So exercise may actually help you get your aggressions out.

Walking has other benefits as well. We’ve all heard about the importance of doing weight-bearing exercise to prevent osteoporosis and osteoporotic fractures. The movie “WALL-E” even did a spoof on this, projecting a future where people lived in their movable recliners. The result was a human skeletal structure that had receded over the generations from lack of use. Although it was tongue in cheek, it wasn’t too far from the truth; if you don’t use them, bones weaken and break. Walking is a weight-bearing exercise that helps strengthen your joints, bones and muscles. 

So remember, use your feet to keep your mind sharp. Activities like walking will help you keep a positive attitude, preserve your bones and help increase the plasticity of your brain.

References: 

(1) Neurology Oct 2010, 75 (16) 1415-1422. (2) Arch Neurol. 2010;67(1):80-86. (3) J Sport Exerc Psychol. 2010 Apr;32(2):253-261.

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.

We invite you to check out our new weekly Medical Compass MD Health Videos on Times Beacon Record News Media’s website, www.tbrnewsmedia.com.

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There are serious side effects of NSAIDs and Tylenol

Dr. David Dunaief

Most of us keep a few key items in our medicine cabinets. In addition to aspirin, among these are usually NSAIDs (non-steroidal anti-inflammatory drugs) and acetaminophen (Tylenol). We often use them for relief of pain, fever or inflammation. Familiar NSAIDs include ibuprofen (Advil, Motrin) and naproxen sodium (Aleve). It is estimated that more than 17 million people use NSAIDs on a daily basis. According to a poll of these regular users of over-the-counter (OTC) NSAIDs, a substantial number — 60 percent — were unaware of their dangerous side effects (1).

Acetaminophen is used frequently, as well. On a weekly basis, one quarter of Americans take it. 

We think of these drugs as relatively benign. In fact, I find that unless I specifically ask about their use, most patients don’t include them on a list of their medications on a patient registration form. 

NSAIDs: The statistics

Unfortunately, NSAIDs, according to the Centers for Disease Control and Prevention, are responsible for 7,600 deaths annually and 10 times that number in hospitalizations (2). These are not medications that should be taken lightly. NSAIDs increase the risk of several maladies, including erectile dysfunction, heart attacks, gastrointestinal bleeds, exacerbation of diverticular disease and chronic arrhythmias (abnormal heartbeats). In some instances, the cardiovascular effects can be fatal. 

NSAIDs: Studies demonstrating adverse side effects

In a case control (epidemiologic, retrospective) study using the UK Primary Care Database, chronic users of NSAIDs have a significantly increased risk of a serious arrhythmia (abnormal heartbeat) called atrial fibrillation (3). Patients were between 40 and 89 years of age. 

Interestingly, chronic users were defined as patients who took NSAIDs for more than 30 days. Those patients who used NSAIDs more than 30 days had a 57 percent increased risk of atrial fibrillation. A Danish study reinforces these results after the first month of use (4). This is not very long to have such a substantial risk. For patients who used NSAIDs longer than one year, the risk increased to 80 percent. Caution should be used when prescribing NSAIDs or when taking them OTC. Atrial fibrillation is not an easy disease to treat.

NSAIDs also increase the risk of mortality in chronic users. Older patients who have heart disease or hypertension (high blood pressure) and are chronic NSAIDs users are at increased risk of death, according to an observational study (5). Compared to those who never or infrequently used them over about 2.5 years, chronic users had a greater than twofold increase in death due to cardiovascular causes. High blood pressure was not a factor, since the chronic users actually had lower blood pressure. Yet I have seen with my patients that NSAIDs can increase blood pressure. 

Is acetaminophen the answer?

Acetaminophen does not cause gastrointestinal bleeds, arrhythmias and deaths due to cardiovascular events that NSAIDs can. However, the Food & Drug Administration announced in 2011 that acetaminophen should not exceed 325 mg every four to six hours when used as a prescription combination pain reliever (6). The goal is to reduce and avoid severe injury to the liver, which can potentially cause liver failure. 

There is an intriguing paradox with acetaminophen: Hospitals typically dispense regular-strength 325-mg doses of the drug, whereas OTC doses frequently are found in extra-strength 500-mg tablets, and often the suggested dose is two tablets, or 1 gram. Patients should not take more than 4 grams a day to lower their risk of liver damage. The 4-gram amount sounds like a significant quantity, but it translates into two pills of extra-strength Tylenol every six hours.

I have patients who have taken three pills at one time thinking that, since it is OTC, exceeding the dose is okay. Unfortunately, this is not true. 

The FDA’s recommendations for limiting the dose result from a conglomeration of data. For instance, one study that showed acute liver failure was due primarily to unintentional overdoses of acetaminophen (7). Accidental overdosing is more likely to occur when taking acetaminophen at the same time as a combination sinus, cough or cold remedy that also contains acetaminophen. Over-the-counter cold medications can contain acetaminophen. 

In order to be aware of potentially adverse events, you have to be your own best advocate and read labels. Remember to tell your physician if you are taking OTC medications. If you are a chronic user of NSAIDs because of underlying inflammation, you may find an anti-inflammatory diet, which is usually plant-based, is an effective alternative.

References: 

(1) J Rheumatol. 2005;32;2218-2224. (2) Annals of Internal Medicine, 1997;127:429-438. (3) Arch Intern Med. 2010;170(16):1450-1455. (4) BMJ 2011;343:d3450. (5) Am J Med. 2011 Jul;124(7):614-620. (6) FDA.gov. (7) Am J Gastroenterol. 2007;102:2459-2463. 

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.

٭We invite you to check out our new weekly Medical Compass MD Health Videos on Times Beacon Record News Media’s website, www.tbrnewsmedia.com.٭

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The best protection against kidney stones is a combination of low sodium and high fluid intake. Stock photo
Calcium from supplements may increase risk of kidney stone formation

By David Dunaief, M.D.

Dr. David Dunaief

Kidney stones are relatively common, occurring more often in men than women (1). I have seen many patients who have a history of forming these stones. Unfortunately, once a patient forms one stone, the incidence of another increases significantly over time. However, there are several ways to reduce your risk.

Kidney stones, or nephrolithiasis, can be asymptomatic (no symptoms at all) or may present with the classic symptoms of blood in the urine and colicky pain. Pain can be intermittent or constant, ranging from dull to extremely painful, described by some as being worse than giving birth or being shot or burned. 

The pain may radiate from the kidneys to the bladder and even to the groin in males, depending on the obstruction (2). Stones are usually diagnosed through clinical suspicion and abdominal X-rays and/or noncontrast CT scans.

Unfortunately, the first line treatment for passing kidney stones — at least small ones — involves supportive care. This means that patients are given pain medications and plenty of fluids until the stone(s) pass. Usually stones that are <4 mm pass spontaneously. Location is an important factor as well, with stones closest to the opening of the urethra more likely to pass (3).

Prevention is the way to go

The good news is there are lifestyle changes that can reduce the risk of kidney stones. First, it is very important to stay hydrated, drinking plenty of fluids, especially if you have a history of stone formation (4).

One of the easiest methods is to significantly reduce your intake of calcium supplements, including foods fortified with calcium. There are two types of stones, with calcium oxalate being the dominant one, occurring approximately 80 percent of the time (5). Calcium supplements increase the risk of kidney stones. When physicians started treating women for osteoporosis with calcium supplements, the rate of kidney stones increased by 37 percent (6). 

According to findings from the Nurses’ Health Study, those who consumed highest amount of supplemental calcium were 20 percent more likely to have kidney stones than those who consumed the lowest amount (7). It did not matter whether participants were taking calcium citrate or calcium carbonate supplements.

Interestingly, calcium from dietary sources actually has the opposite effect, decreasing risk. In the same study, those participants who consumed the highest amount of dietary calcium had a 35 percent reduction in risk, compared to those who were in the lowest group. Calcium intake should not be too low, for that also increases kidney stone risk. However, the source of calcium is a key to preventing kidney stones. 

Another modifiable risk factor is sodium. It’s important to reduce sodium for many reasons, and this provides one more. Again, in the Nurses’ Health Study, participants who consumed 4.5 g sodium per day had a 30 percent higher risk of kidney stones than those who consumed 1.5 g per day (7). The reason is that increased sodium causes increased urinary excretion of calcium. When there is more calcium going through the kidneys, there is a higher chance of stones. 

Animal protein also seems to play a role. In a five-year, randomized clinical trial, men who consumed small amounts of animal protein, approximately two ounces per day, and lower sodium were 51 percent less likely to experience a kidney stone than those who consumed low amounts of calcium (8). These were men who had a history of stone formation. The reason that animal protein may increase the risk of calcium oxalate stones more than vegetable protein is that its higher sulfur content produces more acid, which is neutralized by release of calcium from the bone (9).

Some medical conditions may increase the likelihood of stone formation. For example, in a cross-sectional study (a certain population during a specific period) with Italian men, those with high blood pressure had a two times greater risk of kidney stones than those who had a normal blood pressure (10). Amazingly, it did not matter if the patients were treated for high blood pressure; the risk remained. This is just one more reason to treat the underlying cause of blood pressure, not the symptoms.

The most productive way to avoid the potentially excruciating experience of kidney stones is to make these relatively simple lifestyle changes. The more changes that you implement, the lower your risk of stones.

References: 

(1) Kidney Int. 1979;16(5):624. (2) emedicine Jan 1, 2008. (3) J Urol. 2006;175(2):575. (4) J Urol. 1996;155(3):839. (5) N Engl J Med. 2004;350(7):684. (6) Kidney Int 2003;63:1817–1823. (7) Ann Intern Med. 1997;126(7):497-504. (8) N Engl J Med. 2002 Jan 10;346(2):77-84. (9) J Clin Endocrinol Metab. 1988;66(1):140. (10) BMJ. 1990;300(6734):1234. 

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.

٭We invite you to check out our new weekly Medical Compass MD Health Videos on Times Beacon Record News Media’s website, www.tbrnewsmedia.com.٭

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