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Studies show that taking blood pressure medication at night lowers the risk of diabetes. METRO photo
Controlling sleep-time blood pressure may help

By David Dunaief, M.D.

Dr. David Dunaief

Our understanding of diabetes – its risks and treatment paradigms – is continually evolving. Because so many are affected by diabetes and prediabetes in the U.S., and because the potential health consequences, including significant cardiovascular risks, are so much greater in this population, studies frequently target this population.

To provide a sense of scale, the current rate of diabetes among the U.S. adult population is 13 per-cent, while another estimated 88 million U.S. adults have prediabetes, based on fasting glucose levels (HbA1C) of 5.7 to 6.4 percent (1).

For those with diabetes, cardiovascular risk and severity may not be equal between the sexes. In two trials, women with type 2 diabetes had greater cardiovascular risk than men. In one retrospective study, women with diabetes were hospitalized due to heart attacks at a more significant rate than men, though both had substantial increases in risk, 162 percent and 96 percent, respectively (2).

What may reduce risks of disease and/or complications? Fortunately, we are not without options. These include lifestyle modifications, timing of blood pressure medications, and, oddly, modest wine consumption.

Diet bests Metformin for prevention

All too often in the medical community, we are guilty of reaching for drugs and either overlooking lifestyle modifications or expecting that patients will fail with them. This is a disservice; lifestyle changes may be more effective in preventing this disease. In a head-to-head comparison study, diet plus exercise bested metformin for diabetes prevention (3). This study was performed over 15 years of duration in 2,776 participants who were at high risk for diabetes because they were over-weight or obese and had elevated sugars.

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

Blood pressure medications’ timing

Interestingly, taking blood pressure medications at night has an odd benefit, lowering the risk of diabetes (4). In a study, there was a 57 percent reduction in the risk of developing diabetes in those who took blood pressure medications at night rather than in the morning.

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

The blood pressure medications used in the trial were ACE inhibitors, angiotensin receptor blockers (ARBs) and beta blockers. The first two medications have their effect on the renin-angiotensin-aldosterone system (RAAS) of the kidneys.

According to the researchers, the drugs that blocked RAAS in the kidneys had the most powerful effect on preventing diabetes. Furthermore, when sleep systolic (top number) blood pressure was elevated one standard deviation above the mean, there was a 30 percent increased risk of type 2 diabetes.

Interestingly, the RAAS-blocking drugs are the same drugs that protect kidney function when patients have diabetes.

Reducing complications with wine?

Diabetes patients are often warned to limit or eliminate alcohol. A significant part of the reasoning relates to how the body metabolizes alcohol and sugars. So, the results of a study that showed small amounts of wine could have benefits in reducing diabetes-associated complications among those who were well-controlled sent ripples throughout the medical community.

The CASCADE trial, a randomized controlled trial, considered the gold standard of studies, shows wine may have heart benefits in well-controlled patients with type 2 diabetes by altering the lipid (cholesterol) profile (5).

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

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

Does this mean diabetes patients should start drinking wine? Not necessarily, because this is a small, though well-designed, study. Remember, participants were well-controlled type 2 diabetes patients who generally were nondrinkers.

We need to reverse the trend toward higher diabetes prevalence. Diet and exercise are the first line for prevention. Even a good, but nonideal, diet had better results than medication. A modest amount of wine, especially red, may have effects that reduce cardiovascular risk. Blood pressure medications taken at night, especially those that block RAAS in the kidneys, may help significantly to prevent diabetes.

References:

(1) cdc.gov. (4) Journal of Diabetes and Its Complications 2015;29(5):713-717. (3) Lancet Diabetes Endocrinol. Online Sept. 11, 2015. (4) Diabetologia. Online Sept. 23, 2015. (5) Ann Intern Med. 2015;163(8):569-579.

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

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By David Dunaief, M.D.

Dr. David Dunaief

Heart failure (HF) occurs when the heart’s pumping is not able to keep up with the body’s demands for blood and oxygen and may decompensate. Unlike a heart attack, which is acute, heart failure is a slowly developing disease that may take years to become symptomatic.

As of 2018, there were about 6.2 million Americans living with heart failure, and heart failure was a potential contributing factor in 13.4 percent of deaths (1).

There are two types of heart failure, systolic and diastolic. The basic difference is that the ejection fraction, the output of blood with each contraction of the left ventricle of the heart, is more or less preserved in diastolic HF, while it can be significantly reduced in systolic HF.

We have more evidence-based medicine, or medical research, on systolic heart failure. Fortunately, both types can be diagnosed with the help of an echocardiogram, an ultrasound of the heart. The signs and symptoms may be similar, as well, and include shortness of breath on exertion or when lying down, edema or swelling, reduced exercise tolerance, weakness and fatigue.

Major lifestyle risk factors for heart failure include obesity; smoking; poor diet, including consuming too much sodium; being sedentary; and drinking alcohol excessively. Pre-existing conditions that are significant risk factors include diabetes, coronary artery disease and high blood pressure.

Typically, heart failure is treated with blood pressure medications, such as beta blockers, ACE inhibitors and angiotensin receptor blockers. We are going to look at how diet, iron and the supplement CoQ10 impact heart failure.

Antioxidant diet’s impact

If we look beyond the usual risk factors mentioned above, oxidative stress may play an important role as a contributor to HF. Oxidative stress is thought to result in damage to the inner lining of the blood vessels, or endothelium, oxidation of cholesterol molecules and a decrease in nitric oxide, which helps vasodilate blood vessels.

In a population-based, prospective (forward-looking) study, called the Swedish Mammography Cohort, results show that a diet rich in antioxidants reduces the risk of developing HF (2). In the group that consumed the most nutrient-dense foods, there was a significant 42 percent reduction in the development of HF, compared to the group that consumed the least. According to the authors, the antioxidants were derived mainly from fruits, vegetables, whole grains, coffee and chocolate. Fruits and vegetables were responsible for the majority of the effect.

This nutrient-dense approach to diet increased oxygen radical absorption capacity. Oxygen radicals have been implicated in cellular and DNA damage, potentially as a result of increasing chronic inflammation. What makes this study so impressive is that it is the first of its kind to investigate antioxidants from the diet and their impacts on heart failure prevention.

This was a large study, involving 33,713 women, with good duration — follow-up was 11.3 years. There are limitations to this study, because it is observational and the population involved only women. Still, the results are very exciting, and it is unlikely there is a downside to applying this approach to the population at large.

CoQ10 benefits

Coenzyme Q10 is a substance produced by the body that helps the mitochondria (the powerhouse of the cell) produce energy. It is thought of as an antioxidant. 

Results of the Q-SYMBIO study, a randomized double-blind control trial, showed an almost 50 percent reduction in the risk of all-cause mortality and 50 percent fewer cardiac events with CoQ10 supplementation (3). This one randomized controlled trial followed 420 patients for two years who had severe heart failure. This involved using 100 mg of CoQ10 three times a day compared to placebo.

The lead author goes as far as to suggest that CoQ10 should be part of the paradigm of treatment. CoQ10 is the first supplement to show survival benefits in heart failure.

This study’s rigor is impressive; it assesses the supplement as if it were a drug. A subsequent 2019 sub-group analysis of Q-SYMBIO confirmed the short- and long-term effects and also found a significant improvement in left ventricular ejection fraction among CoQ10 therapy adherents (4).

A meta-analysis involving 13 studies of CoQ10 supplementation with HF confirmed that CoQ10 resulted in ejection fraction improvements among patients with less severe stages of HF, although the authors suggest that studies with more diverse demographics and that refine and compare dose responses are warranted (5). If you have heart failure, you may want to discuss CoQ10 supplementation with your physician.

Iron deficiency challenges

An observational study that followed 753 heart failure patients for almost two years showed that iron deficiency without anemia increased the risk of mortality in heart failure patients by 42 percent (6).

In this study, iron deficiency was defined as a ferritin level less than 100 μg/L (the storage of iron) or, alternately, transferrin saturation less than 20 percent (the transport of iron) with a ferritin level in the range 100–299 μg/L.

The authors conclude that iron deficiency is potentially more predictive of clinical outcomes than anemia, contributes to the severity of HF and is common in these patients. Thus, it behooves us to try to prevent heart failure through dietary changes, including high levels of antioxidants, because it is not easy to reverse the disease. Those with HF should have their ferritin and iron levels checked, for these are correctable.

Based on study results, CoQ10 appears to be a compelling therapy to reduce risk of further complications and potentially death. Consult with your doctor before taking CoQ10 or any other supplements.

References:

(1) cdc.gov. (2) Am J Med. 2013 Jun:126(6):494-500. (3) JACC Heart Fail. 2014 Dec;2(6):641-649. (4) Cardiol J. 2019;26(2):147-156. (5) Am J Clin Nutr. 2013 Feb; 97(2): 268–275. (6) Am Heart J. 2013;165(4):575-582.

Dr. David 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. 

In recent studies, apples, bananas and pears were shown to reduce COPD. Pixabay photo
Lung health is affected by simple diet and exercise changes

By David Dunaief, M.D.

Dr. David Dunaief

The COVID-19 pandemic has raised many people’s awareness of the importance of lung function. Its consequences are especially severe for those with chronic obstructive lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma, as well as those who smoke and vape.

What can we do to strengthen our lungs? We can improve lung function with simple lifestyle modifications including exercising, eating a plant-based diet with a focus on fruits and vegetables, expanding lung capacity with an incentive spirometer, and quitting smoking and vaping, which damage the lungs (1). Not only people with compromised lungs will benefit; studies suggest everyone will benefit.

COPD and diet

Several studies demonstrate that higher consumption of fiber from plants decreases the risk of COPD in smokers and ex-smokers. Bear with me, because the studies were done with men or women, not both at the same time. In one study of men, for example, results showed that higher fiber intake was associated with significant 48 percent reductions in COPD incidence in smokers and 38 percent incidence reductions in ex-smokers (3). The high-fiber group ate at least 36.8 grams per day, compared to the low-fiber group, which ate less than 23.7 grams per day. Fiber sources were fruits, vegetables and whole grain, essentially a whole foods plant-based diet. The high-fiber group was still below the American Dietetic Association-recommended 38 grams per day. This is within our grasp. 

In another study, women had a highly significant 37 percent decreased risk of COPD among those who consumed at least 2.5 serving of fruit per day compared to those who consumed less than 0.8 servings per day (4). The highlighted fruits shown to reduce COPD in both men and women included apples, bananas, and pears.

Asthma and diet

In a randomized controlled trial of asthma patients, results show that after 14 days those who ate a low-antioxidant diet had less lung function compared to those who ate a high-antioxidant diet (2). Researchers measured lung function with one-second forced expiratory volume (FEV1) and predicted forced vital capacity (FVC). 

Additionally, those who were in the low-antioxidant diet group also had higher inflammation at 14 weeks, as measured using a c-reactive protein (CRP) biomarker. Those who were in the low-antioxidant group also were over two-times more likely to have an asthma exacerbation.

The good news is that the difference in behavior between the high- and low-antioxidant groups was small. The high-antioxidant group had a modest five servings of vegetables and two servings of fruit daily, while the low-antioxidant group ate no more than two servings of vegetables and one serving of fruit daily. 

Carotenoid supplementation, instead of antioxidant foods, made no difference in inflammation. The authors concluded that an increase in carotenoids from diet has a clinically significant impact on asthma and can be seen in a very short period. 

Incentive spirometry

What is an incentive spirometer? It’s a device that helps expand the lungs by inhaling through a tube and causing a ball or multiple balls to rise. This opens the alveoli and may help you breathe better. 

Incentive spirometry has been used for patients with pneumonia, those who have chest or abdominal surgery and those with asthma or COPD, but it has also been useful for healthy participants (5). A small study showed that those who trained with an incentive spirometer for two weeks increased their vital capacity, right and left chest wall motion, and right diaphragm motion. This means it improved lung function and respiratory motion. Participants were 10 non-smoking healthy adults who were instructed to take five sets of five deep breaths twice a day, totaling 50 deep breaths per day. The brands used in the study are inexpensive and easily accessible, such as Teleflex’s Triflo II.

In another small, two-month study of 27 patients with COPD, the incentive spirometer improved blood gasses, such as partial pressure carbon dioxide and oxygen, in COPD patients with exacerbation (6). The authors concluded that it may improve quality of life for COPD patients.  

Exercise

Exercise can have a direct impact on lung function. In a study involving healthy women ages 65 years and older, results showed that 20 minutes of high-intensity exercise three times a day improved FEV1 and FVC, both indicators of lung function, in as little as 12 weeks (7). Participants began with a 15-minute warm-up, then 20 minutes of high-intensity exercise on a treadmill, followed by 15 minutes of cool-down with stretching.

What is impressive is that it was done in older adults, not those in their twenties and not in elite athletes.

Note that you don’t need a treadmill to do aerobic exercise. You can walk up steps or steep hills in your neighborhood, do jumping jacks, or even dance in your living room. Whatever you choose, you want to increase your heart rate and expand your lungs. If this is new for you, consult a physician and start slowly. You’ll find that your stamina improves rather quickly over time.

We all should be working to strengthen our lungs, regardless of COVID-19. This three-pronged approach of lifestyle modifications – diet, exercise and incentive spirometer – can help without expending significant time or expense.

References:

(1) Public Health Rep. 2011 Mar-Apr; 126(2): 158-159. (2) Am J Clin Nutr. 2012 Sep;96(3):534-43.(3)Epidemiology Mar 2018;29(2):254-260. (4)Int J Epidemiol Dec 1 2018;47(6);1897-1909. (5)Ann Rehabil Med. Jun 2015;39(3):360-365. (6)Respirology. Jun 2005;10(3):349-53.(7)J Phys Ther Sci. Aug 2017;29(8):1454-1457. 

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

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Excess fat contributes to increased inflammation

By David Dunaief, M.D.

Dr. David Dunaief

Obesity is an ongoing struggle for many in the United States. If you, like many, put on some extra pounds during the past 18 months, it’s even more concerning.

Obesity is a disease unto itself and is defined by a BMI (body mass index) of >30 kg/m2, but obesity can also be defined by excess body fat, which is more important than BMI.

Poor COVID-19 outcomes have been associated with obesity, especially in the U.S. In a study involving 5700 hospitalized COVID-19 patients in the NYC area, the most common comorbidities were obesity, high blood pressure and diabetes (1). Of those who were hospitalized, 41.7% were obese.

In a study in China, results showed that those who were overweight were 86 percent more likely to have severe COVID-19 pneumonia, and that percentage increases to 142 percent when obesity is reached (2).

In fact, one study’s authors suggested quarantining should be longer in obese patients because of the potential for prolonged viral shedding compared to those in the normal range for weight (3).

And though age is a risk factor for COVID-19, among those younger than 60 and obese, there is a two-times increased risk of being admitted to the hospital, according to a 3,615-patient study at NYU Langone Health (4).

While these studies do not test specifically for the more recent variants, I would expect the results are similar.

Why is risk for severe COVID-19 higher with obesity? 

According to the prevailing theory, obesity may interfere with mechanical aspects of breathing, thus increasing airway resistance and make gas in exchange more difficult in the lung. It may also impede on lung volume by exerting pressure on the lungs and may involve weaker muscles necessary for respiration (5).

Why is excess fat more important than BMI? 

First, some who have elevated BMI may not have a significant amount of fat; they may actually have more innate muscle. More than 25 percent of my patient population is “solidly built,” which means they have greater muscle mass as well as too much excess fat. Visceral fat is the most important, since it’s the fat that lines the organs, including the lungs.

For another, fat cells have adipokines, specific cell communicators found in fat cells that communicate with other fat cells but also other systems such as the brain, immune system, muscles, and liver. Adipokines can be mediators of both inflammation and insulin resistance, according to an endocrinology study (6). In a study of over 4,000 patients with COVID-19, the author suggests that inflammation among obese patients may be an exacerbating factor for hospitalizations and severe illness (7). 

If we defined obesity as being outside the normal fat range – normal ranges are roughly 11-22 percent for men and 22-34 percent for women – then close to 70 percent of Americans are obese.

Inflammation reduction and weight-loss combined

In a randomized controlled trial with 75 participants comparing a plant-based diet to a control diet, there was a greater than 14 lbs. weight reduction and roughly 10 lbs. fat reduction over a 14-week period (8). Of the weight lost, about 70 percent was excess fat. Remember, excess body fat, through adipokines, may be inflammatory and increase the risk of severe COVID-19. 

The weight reduction with a plant-based approach may involve the increase in fiber, reduction in dietary fat and increased burning of calories after the meal, according to Physician’s Committee for Responsible Medicine (PCRM) (9).

You also want a diet that has been shown to reduce inflammation.

We recently published a study involving 16 patients from my clinical practice. It shows that those who ate a whole food plant-based LIFE (low inflammatory foods everyday) diet over a seven-day period had a significant decrease in inflammation measured by hsCRP (high sensitivity c-reactive protein). This occurred in those who completely changed their diets to the LIFE diet, but also occurred in those who simply added a greens and fruit-based smoothie daily to their existing diet (10).

In my practice, I have seen a number of patients lose a substantial amount of weight, but also body fat, over a short period. For instance, a 70-year-old male lost 19 lbs. of weight and 12 lbs. of body fat over a six-week period. His inflammation, which was very high to start, dropped substantially to the border of optimal levels, using hsCRP as the inflammation measurement. This patient and many others have seen tandem reductions in both weight and inflammation. To boot, this was a cardiac patient whose cardiologist had considered a stent, but later said he did not need it after reducing his inflammation.

If the continuing COVID-19 concerns do not convince you that losing excess fat is important, then consider that obesity contributes to, or is associated with, many other chronic diseases like cardiovascular disease, high blood pressure, and high cholesterol, which also contribute to severe COVID-19. Thus, there is an imperative to lose excess body fat.

References:

(1) JAMA. online April 22, 2020. (2) Clin Med (Lond). 2020 Jul; 20(4): e109–e113. (3) Acta Diabetol. 2020 Apr 5: 1–6. (4) Clin Infect Dis. 2020 Jul 28;71(15):896-897. (5) Chron. Respir. Dis. 5, 233–242 (2008). (6) Front Endocrinol (Lausanne). 2013; 4:71. (7) MedRxiv.com. (8) Nutr Diabetes. 2018; 8: 58. (9) Inter Journal of Disease Reversal and Prevention 2019;1:1. (10) Am J of Lifestyle Med. online Oct. 5, 2020.

Dr. David 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. 

Photo courtesy of Brandpoint
Increased fall risk is a consequence of sleep apnea

By David Dunaief, M.D.

Dr. David Dunaief

Sleep is critical for physical and mental health, yet many struggle to get quality, restful sleep. For those with obstructive sleep apnea (OSA), quality sleep is elusive. This can cause serious physical and mental health impacts.

Sleep apnea is an abnormal pause in breathing that occurs at least five times an hour while sleeping and can be caused by either airway obstruction (OSA), brain signal failure (central sleep apnea), or a combination of these two (complex sleep apnea). Estimates indicate that approximately 30 million people suffer from sleep apnea in the United States (1). 

Here, our focus is on OSA, which can be classified as either mild, moderate or severe. It’s estimated that 80 percent of moderate and severe OSA are undiagnosed.

Risk factors for OSA include chronic nasal congestion, large neck circumference, excess weight or obesity, alcohol use, smoking and a family history (2). Fortunately, many of the risk factors are modifiable.

Significant symptoms of OSA include daytime fatigue, loud snoring, breathing cessation observed by another, impaired concentration and morning headaches. These symptoms, while significant, are not the worst problems. OSA is also associated with a list of serious consequences, such as cardiovascular disease, high blood pressure and depression.

Fortunately, we have an arsenal of treatment options, including continuous positive airway pressure (CPAP) devices; oral appliances; lifestyle modifications, such as diet, exercise, smoking cessation and reduced alcohol intake; and some medications.

Cardiovascular disease risk

In an observational study, the risk of cardiovascular mortality increased in a linear fashion with the severity of OSA (3). In other words, in those with mild-to-moderate untreated sleep apnea, there was a 60 percent increased risk of death; and in the severe group, this risk jumped considerably, 250 percent. However, the good news is that treating patients with CPAP considerably decreased their risk by 81 percent for mild-to-moderate patients and 45 percent for severe OSA patients. This study involved 1,116 women over a six-year duration.

Another observational study with male subjects showed similar risks of cardiovascular disease with sleep apnea and benefits of CPAP treatment (4). There were more than 1,500 men in this study with a 10-year follow-up. The authors concluded that severe sleep apnea increases the risk of nonfatal and fatal cardiovascular events, and CPAP was effective in stemming these occurrences.

In a third study, this time involving the elderly, OSA increased the risk of cardiovascular death in mild-to-moderate patients and in those with severe OSA by 38 and 125 percent, respectively (5). But, as in the previous studies, CPAP decreased the risk in both groups significantly. In the elderly, an increased risk of falls, cognitive decline and difficult-to-control high blood pressure may be signs of OSA.

Cancer association

In sleep apnea patients under age 65, a study showed an increased risk of cancer (6). The authors believe that intermittent low levels of oxygen, which are caused by the many frequent short bouts of breathing cessation during sleep, may be responsible for the development of tumors and their subsequent growth.

The greater the percentage of time patients spend in hypoxia (low oxygen) at night, the greater the risk of cancer. For those patients with more than 12 percent low-oxygen levels at night, there is a twofold increased risk of cancer development when compared to those with less than 1.2 percent low-oxygen levels.

Male sexual function

It appears that erectile dysfunction (ED) may also be associated with OSA. CPAP may decrease this incidence. This was demonstrated in a small study involving 92 men with ED (7). The surprising aspect of this study was that, at baseline, the participants were overweight, not obese, on average and were young, at 45 years old. In those with mild OSA, the CPAP had a beneficial effect in over half of the men. For those with moderate and severe OSA, the effect was still significant, though not as robust, at 29 and 27 percent, respectively.

Dietary approach

Although CPAP can be quite effective, it may not be well tolerated by everyone. In some of my patients, their goal is to discontinue their CPAP. Diet may be an alternative to CPAP, or may be used in combination with CPAP.

In a small study of those with moderate-to-severe OSA levels, a low-energy diet showed positive results. A low-energy diet implies a low-calorie approach, such as a diet that is plant-based and nutrient-rich. It makes sense, since weight loss is important. In the study, almost 50 percent of those who followed this type of diet were able to discontinue CPAP (8). The results endured for at least one year.

The bottom line is that if you think you or someone else is suffering from sleep apnea, it is very important to go to a sleep lab to be evaluated, and then go to your doctor for a follow-up. Don’t suffer from sleep apnea and, more importantly, don’t let obstructive sleep apnea cause severe complications, possibly robbing you of more than sleep. There are effective treatments.

References:

(1) sleepapnea.org. (2) JAMA. 2004;291(16):2013. (3) Ann Intern Med. 2012 Jan 17;156(2):115-122. (4) Lancet. 2005 Mar 19-25;365(9464):1046-1053. (5) Am J Respir Crit Care Med. 2012;186(9):909-916. (6) Am J Respir Crit Care Med. 2012 Nov. 15. (7) APSS annual meeting: abstract No. 0574. (8) BMJ. 2011;342:d3017.

Dr. David 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. 

Eating a high-fiber breakfast cereal is a great way to start. METRO photo
Increasing fiber intake may help modulate the immune system

By David Dunaief, M.D.

Dr. David Dunaief

When the immune system attacks the body’s own organs, cells and tissues and causes chronic inflammation, we classify it as an autoimmune disease. However, this umbrella term refers to more than 80 different diseases (1). Some are familiar names, like type 1 diabetes, lupus, rheumatoid arthritis (RA), psoriasis, multiple sclerosis, and inflammatory bowel disease. Others, like Lambert-Eaton myasthenic syndrome and Cogan syndrome, are less well-known.

Chronic inflammation is 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 are at high risk for acquiring others. Autoimmune diseases disproportionately affect women, although men do also get them.

Drug treatments

The mainstay treatment is immunosuppressives. In RA, for example, where there is swelling of joints bilaterally, a 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. Disease-modifying anti-rheumatic drugs (DMARDs), a class that also includes Plaquenil (hydroxychloroquine), may slow or stop the progression of joint destruction and increase physical functioning.

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 required 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 clinical trials; however, many patients are prescribed these therapies for 20 or more years.

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

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. Several studies have also tested dietary interventions in RA treatment (5). Included were fasting followed by a vegetarian diet; a vegan diet; and a Mediterranean diet, among others. All mentioned here showed decreases in inflammatory markers, including CRP, and improvements in joint pain and other quality of life concerns.

Fish oil supplementation

Fish oil helps your immune system by reducing inflammation and improving your blood chemistry, affecting as many as 1,040 genes (6). 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 (7). 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 (8, 9).

In a study with Crohn’s disease patients, L. casei and L. bulgaricus reduced the inflammatory factor TNF-alpha (10). 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 intake

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 (11). 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 (12).

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) Front Nutr. 2017; 4: 52. (6) Am J Clin Nutr. 2009 Aug;90(2):415-424. (7) Drugs. 2003;63(9):845-853. (8) Gut. 2003 Jul;52(7):975-980. (9) Antonie Van Leeuwenhoek 1999 Jul-Nov;76(1-4):279-292. (10) Gut. 2002;51(5):659. (11) Arch Intern Med. 2007;167(5):502-506. (12) Nutr Metab (Lond). 2010 May 13;7:42.

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

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Stress management and diet can have positive effects

By David Dunaief, MD

Dr. David Dunaief

According to estimates, 10 to 15 percent of the population suffers from irritable bowel syndrome (IBS) symptoms, although only five to seven percent have been diagnosed (1).

Symptoms can directly affect quality of life. They include abdominal pain, cramping, bloating, constipation and diarrhea.

Diagnosing IBS is challenging. While the general perception is that IBS symptoms are somewhat vague, there are discrete criteria physicians use to provide a diagnosis it and eliminate more serious possibilities.

The Rome IV criteria comprise an international effort to help diagnose and treat functional gastrointestinal disorders. Using these criteria in combination with a careful history and physical exam helps provide a diagnosis.

So, what can be done to improve IBS? There are a number of possibilities.

Mental state

The “brain-gut” connection is real. It refers to the direct connection between mental state, such as nervousness or anxiety, to gastrointestinal issues, and vice versa.

Mindfulness-based stress reduction was used in a small, but randomized, eight-week clinical trial with IBS (2). Those in the mindfulness group (treatment group) showed statistically significant results in decreased severity of symptoms compared to the control group, both immediately after training and three months post-therapy.

Those in the treatment group were instructed to do meditation, gentle yoga and “body scanning” — focusing on one area of the body for muscle tension detection. The control group attended an IBS support group once a week.

A preliminary study has suggested there may be a link between IBS and migraine and tension-type headaches. The study of 320 participants, 107 with migraine, 107 with IBS, 53 with episodic tension-type headaches (ETTH), and 53 healthy individuals, identified significant occurrence crossover among those with migraine, IBS and ETTH. Researchers also found that these three groups had at least one gene that was different from that of healthy participants. Their hope is that this information will lead to more robust studies that could result in new treatment options (3).

Gluten

In a small randomized clinical trial, patients who were given gluten were more likely to complain of uncontrolled symptoms than those who were given a placebo, 68 percent vs. 40 percent, respectively.

These results were highly statistically significant (4). The authors concluded that nonceliac gluten intolerance may exist. Gluten sensitivity may be an important factor in the pathogenesis of some IBS patients (5).

I suggest to my patients that they might want to start avoiding gluten and then add it back into their diets slowly to see the results.

Fructose

Some IBS patients may suffer from fructose intolerance. In a prospective (forward-looking) study, IBS researchers used a breath test to examine this possibility. The results were dose dependent. When patients were given a 10 percent fructose solution, only 39 percent tested positive for fructose intolerance, but when they were given a 33 percent solution, 88 percent of patients tested positive.

The symptoms of fructose intolerance included flatus, abdominal pain, bloating, belching and alternating bowel habits. The authors concluded that avoidance of fructose may reduce symptoms in IBS patients (6).

According to another study, about one-third of IBS patients are fructose intolerant. When on a fructose-restricted diet, symptoms appeared to improve (7). Foods with high levels of fructose include certain fruits, like apples and pears, but not bananas.

Lactose

Another small study found that about one-quarter of patients with IBS also have lactose intolerance. Two things are at play here. One, it is very difficult to differentiate the symptoms of lactose intolerance from IBS. The other is that most IBS trials are small and there is a need for larger trials.

Of the IBS patients who were also lactose intolerant, there was a marked improvement in symptomatology at both six weeks and five years when placed on a lactose-restrictive diet (8).

Though small, the trial results were statistical significant, which is impressive. Both the durability and the compliance were excellent, and visits to outpatient clinics were reduced by 75 percent. This demonstrates that it is most probably worthwhile to test patients for lactose intolerance who have IBS.

Probiotics

Treatment with probiotics from a study that reviewed 42 trials shows that there may be a benefit to probiotics, although the endpoints were different in each trial. The good news is that most of the trials reached one of their endpoints (9).

Probiotics do show promise, including the two most common strains, Lactobacilli and Bifidobacteri, which were covered in the review.

All of the above gives IBS patients a sense of hope that there are options for treatments that involve modest lifestyle changes. I believe there needs to be a strong patient-doctor connection in order to choose the appropriate options that result in the greatest symptom reduction.

References:

(1) American College of Gastroenterology [GI.org]. (2) Am J Gastroenterol. 2011 Sep;106(9):1678-1688. (3) American Academy of Neurology 2016, Abstract 3367. (4) Am J Gastroenterol. 2011 Mar;106(3):508-514. (5) Am J Gastroenterol. 2011 Mar;106(3):516-518. (6) Am J Gastroenterol. 2003 June;98(6):1348-1353. (7) J Clin Gastroenterol. 2008 Mar;42(3):233-238. (8) Eur J Gastroen-terol Hepatol. 2001 Aug;13(8):941-944. (9) Aliment Pharmacol Ther. 2012 Feb;35(4):403-413.

Dr. David 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. 

About 70% of people with Parkinson’s experience a tremor at some point in the disease. Stock photo
Much new research focuses on dietary approaches

By David Dunaief

Dr. David Dunaief

Parkinson’s disease is a neurodegenerative disease, most often associated with a movement disorder, or tremors. According to the Parkinson’s Foundation, roughly 60,000 Americans are diagnosed with Parkinson’s disease (PD) each year, and approximately one million Americans are living with PD (1).

Patients with PD suffer from a collection of symptoms caused by the breakdown of brain neurons. In medicine, we know the most common symptoms 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.

There are several different subtypes of PD; the diffuse/malignant phenotype has the highest propensity toward cognitive decline (2).

There’s a lot we still don’t know about the causes of PD; however, 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.

The part of the brain most affected is the basal ganglia, and the prime culprit is dopamine deficiency that occurs in this brain region (3). Adding back dopamine has been the mainstay of medical treatment, but eventually the neurons themselves break down, and the medication becomes less effective. 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.

Reducing iron in the brain

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 (4). This drug was mostly well-tolerated.

The chelator reduced the risk of disease progression significantly on the Unified Parkinson Disease Rating Scale (UPDRS) during the 12-month study. 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.

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.

Does CoQ10 slow progression?

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. Typical 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 (5). 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. Unfortunately, results for other CoQ10 studies have been mixed. In this study, CoQ10 was well-tolerated at even the highest dose. Thus, there may be no downside to trying CoQ10 in those with PD.

Is Vitamin D part of the puzzle?

In a prospective 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 (6). 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.

While many times we are deficient in vitamin D and have a disease, replacing the vitamin does nothing to help the disease. Here, it does. 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 (7). Also, this amount of vitamin D increased the blood levels by almost 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 their impact could be significant. The most exciting part is that lifestyle modifications have the potential to slow the disease progression and thus have a protective effect.

References:

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

Dr. David 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. 

The standard American diet is very low in nutrients. METRO photo
Nutrient intake is stunningly low in the United States

By David Dunaief, M.D.

Dr. David Dunaief

Most chronic diseases, including common killers, such as heart disease, stroke, diabetes and some cancers, can potentially be prevented, modified and even reversed with a focus on nutrients, according to the Centers for Disease Control and Prevention (CDC). 

Here’s a stunning statistic: 60 percent of American adults have a chronic disease, with 40 percent of adults having more than one (1). This is likely a factor in the slowing pace of life expectancy increases in the U.S., which have plateaued in the past decade at around 78.8 years old (2).

The truth is that many Americans are malnourished, regardless of socioeconomic status and, in many cases, despite being overweight or obese. The definition of malnourished is insufficient nutrition, which in the U.S. results from low levels of much-needed nutrients. Sadly, the standard American diet is very low in nutrients, so many have at least moderate malnutrition.

I regularly test patients’ carotenoid levels. Carotenoids are nutrients that are incredibly important for tissue and organ health. They are measurable and give the practitioner a sense of whether the patient may lack potentially disease-fighting nutrients. Testing is often covered by insurance if the patient is diagnosed with moderate malnutrition. A high nutrient intake dietary approach can resolve the situation and increase, among others, carotenoid levels.

High nutrient intake is important

A high nutrient intake diet is an approach that focuses on micronutrients, which literally means small nutrients, including antioxidants and phytochemicals – plant nutrients. Micronutrients are bioactive compounds found mostly in foods and some supplements. While fiber is not considered a micronutrient, it also has significant disease modifying effects. Micronutrients interact with each other in synergistic ways, meaning the sum is greater than the parts. Diets that are plant-rich raise the levels of micronutrients considerably in patients.

In a 2017 study that included 73,700 men and women who were participants in the Nurses’ Health Study and the Health Professionals Follow-up Study, participants’ diets were rated over a 12-year period using three established dietary scores: the Alternate Healthy Eating Index–2010 score, the Alternate Mediterranean Diet score, and the Dietary Approaches to Stop Hypertension (DASH) diet score (3).

A 20 percent increase in diet scores (indicating an improved quality of diet) was significantly associated with a reduction in total mortality of 8 to 17 percent, depending on whether two or three scoring methods were used. Participants who maintained a high-quality diet over a 12-year period reduced their risk of death by 9 to 14 percent more than participants with consistently low diet scores over time. By contrast, worsening diet quality over 12 years was associated with an increase in mortality of 6 to 12 percent. Not surprisingly, longer periods of healthy eating had a greater effect than shorter periods.

This study reinforces the findings of the Greek EPIC trial, a large prospective (forward-looking) cohort study, where the Mediterranean-type diet decreased mortality significantly – the better the compliance, the greater the effect (4). The most powerful dietary components were the fruits, vegetables, nuts, olive oil, legumes and moderate alcohol intake. Low consumption of meat also contributed to the beneficial effects. Dairy and cereals had a neutral or minimal effect.

Quality of life

Quality of life is also important, though. Let’s examine some studies that examine the impact of diet on diseases that may reduce our quality of life as we age.

A study showed olive oil reduces the risk of stroke by 41 percent (5). The authors attribute this effect at least partially to oleic acid, a bioactive compound found in olive oil. While olive oil is important, I recommend limiting olive oil to one tablespoon a day. There are 120 calories per tablespoon of olive oil, all of them fat. If you eat too much, even of good fat, it defeats the purpose. The authors commented that the Mediterranean-type diet had only recently been used in trials with neurologic diseases and results suggest benefits in several disorders, such as Alzheimer’s. 

In a case-control study that compared those with and without disease, high intake of antioxidants from food was associated with a significant decrease in the risk of early Age-related Macular Degeneration (AMD), even when participants had a genetic predisposition for the disease (6). AMD is the leading cause of blindness in those 55 years or older.

There were 2,167 people enrolled in the study with several different genetic variations that made them high risk for AMD. Those with a highest nutrient intake, including B-carotene, zinc, lutein, zeaxanthin, EPA and DHA- substances found in fish, had an inverse relationship with risk of early AMD. Nutrients, thus, may play a role in modifying gene expression. 

Though many Americans are malnourished, nutrients that are effective and available can alter this predicament. Hopefully, with a focus on a high nutrient intake, we can improve life expectancy and, on an individual level, improve our quality of life.

References:

(1) cdc.gov. (2) macrotrends.net. (3) N Engl J Med 2017; 377:143-153. (4) BMJ. 2009;338:b2337. (5) Neurology June 15, 2011. (6) Arch Ophthalmol. 2011;129(6):758-766.

Dr. David 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. 

METRO photo
Avoid calcium supplements and fortified foods

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 have no symptoms, but more often they 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, 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 non-contrast 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 <4mm pass spontaneously. Location is an important factor as well, with stones closest to the opening of the urethra more likely to pass (3). In the case of a stone too large to pass naturally, a urologist may use surgery, ultrasound, or a combination of methods to break it into smaller pieces, so it can be passed.

Stay hydrated

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).

 

Consume calcium from diet, not supplements

Pain from kidney stones can be intermittent or constant, ranging from dull to extremely painful.

One of the simplest methods is to reduce your intake of calcium supplements, including foods fortified with calcium. There are two types of stones. Calcium oxalate is the dominant one, occurring approximately 80 percent of the time (5). Calcium supplements, therefore, 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.

Reduce sodium

Another modifiable risk factor is sodium. It’s important to reduce sodium for many reasons, but 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.

Pain from kidney stones can be intermittent or constant, ranging from dull to extremely painful. METRO photo

Limit animal protein

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 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).

Reduce blood pressure naturally

Some medical conditions may increase the likelihood of stone formation. For example, in a cross-sectional study 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 with medications; 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 January 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;63:1817–23. (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. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com. 

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