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Dr. David Dunaif

If you’re missing out on shut-eye, your body will soon show the signs. Stock photo
Getting enough sleep helps clear brain clutter

By David Dunaief, M.D.

Dr. David Dunaief

The brain is the most complex organ, yet what we know about the brain is inverse to its importance.

We do know that certain drugs, head injuries and lifestyle choices negatively impact the brain. There are also numerous disorders and diseases that affect the brain, including neurological (dementia, Parkinson’s, stroke), infectious (meningitis), rheumatologic (lupus and rheumatoid arthritis), cancer (primary and secondary tumors), psychiatric mood disorders (depression, anxiety, schizophrenia), diabetes and heart disease.

These varied diseases tend to have three signs and symptoms in common: They either cause altered mental status, physical weakness or change in mood — or a combination of these.

Probably our greatest fear regarding the brain is cognitive decline. Dementia, whether mild or full-blown Alzheimer’s, is cruel; it robs us of functioning.

Fortunately, there are several studies that show we may be able to prevent cognitive decline by altering modifiable risk factors. They involve rather simple lifestyle changes: sleep, exercise and possibly omega-3s. Let’s look at the evidence.

The impact of clutter

The lack of control over our mental capabilities as we age is what frightens us most. Those who are in their 20s seem to be much sharper and quicker. But are they really?

In a study, German researchers found that educated older people tend to have a larger mental database of words and phrases to pull from since they have been around longer and have more experience (1). When this is factored into the equation, the difference in terms of age-related cognitive decline becomes negligible.

This study involved data mining and creating simulations. It showed that mental slowing may be at least partially related to the amount of clutter or data that we accumulate over the years. The more you know, the harder it becomes to come up with a simple answer to something. We may need a reboot just like a computer. This may be possible through sleep, exercise and omega-3s.

The importance of sleep

Why should we dedicate 33 percent of our lives to sleep? There are several good reasons. One involves clearing the mind, and another involves improving our economic outlook.

For the former, a study shows that sleep may help the brain remove waste, such as those all-too-dangerous beta-amyloid plaques (2). When we have excessive plaque buildup in the brain, it may be a sign of Alzheimer’s. This study was done in mice. When mice were sleeping, the interstitial space (the space between brain gyri, or structures) increased by as much as 60 percent.

This allowed the lymphatic system, with its cerebrospinal fluid, to clear out plaques, toxins and other waste that had developed during waking hours. With the enlargement of the interstitial space during sleep, waste removal was quicker and more thorough, because cerebrospinal fluid could reach much farther into the spaces. A similar effect was seen when the mice were anesthetized.

In another study, done in Australia, results showed that sleep deprivation may have been responsible for an almost 1 percent decline in gross domestic product for the country (3). The reason is obvious: People are not as productive at work when they don’t get enough sleep. They tend to be more irritable, and concentration may be affected. We may be able to turn on and off sleepiness on short-term basis, depending on the environment, but we can’t do this continually.

According to the Centers for Disease Control and Prevention, 4 percent of Americans report having fallen asleep in the past month behind the wheel of a car (4). I hope this hammers home the importance of sleep.

Time to exercise

How can I exercise, when I can’t even get enough sleep? Well there is a study that just may inspire you to exercise.

In the study, which involved rats, those that were not allowed to exercise were found to have rewired neurons in the area of their medulla, the part of the brain involved in breathing and other involuntary activities. There was more sympathetic (excitatory) stimulus that could lead to increased risk of heart disease (5). In rats allowed to exercise regularly, there was no unusual wiring, and sympathetic stimuli remained constant. This may imply that being sedentary has negative effects on both the brain and the heart.

This is intriguing since we used to think that our brain’s plasticity, or ability to grow and connect neurons, was finite and stopped after adolescence. This study’s implication is that a lack of exercise causes unwanted new connections. Of course, these results were done in rats and need to be studied in humans before we can make any definitive suggestions.

Omega-3 fatty acids

In the Women’s Health Initiative Memory Study of Magnetic Resonance Imaging Study, results showed that those postmenopausal women who were in the highest quartile of omega-3 fatty acids had significantly greater brain volume and hippocampal volume than those in the lowest quartile (6). The hippocampus is involved in memory and cognitive function.

Specifically, the researchers looked at the levels of eicosapentaenoic acid and docosahexaenoic acid in red blood cell membranes. The source of the omega-3 fatty acids could either have been from fish or supplementation. The researchers suggest eating fish high in these substances, such as salmon and sardines, since it may not even be the omega-3s that are playing a role but some other substances in the fish.

It’s never too late to improve brain function. You can still be sharp at a ripe old age. Although we have a lot to learn about the functioning of the brain, we know that there are relatively simple ways we can positively influence it.

References:

(1) Top Cogn Sci. 2014 Jan.;6:5-42. (2) Science. 2013 Oct. 18;342:373-377. (3) Sleep. 2006 Mar.;29:299-305. (4) cdc.gov. (5) J Comp Neurol. 2014 Feb. 15;522:499-513. (6) Neurology. 2014;82:435-442.

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.

The pancreas is about 6 inches long and sits across the back of the abdomen, behind the stomach.
Increasing vegetable intake may improve outcomes
Dr. David Dunaief

By David Dunaief, M.D.

Everyone has heard of pancreatic cancer, but pancreatitis is a significantly more common disease in gastroenterology and seems to be on an upward projection. Ironically, this disease gets almost no coverage in the general press. In the United States, it is among the top reasons for patients to be admitted to the hospital (1).

Now that I have your attention, let’s define pancreatitis. A rudimentary definition is an inflammation of the pancreas. There are both acute and chronic forms. We are going to address the acute — abrupt and of short duration — form. There are three acute types: mild, moderate and severe. Those with the mild type don’t have organ failure, whereas those with moderate acute pancreatitis experience short-term or transient (less than 48 hours) organ failure. Those with the severe type have persistent organ failure. One in five patients present with moderate or severe levels (2).

What are the symptoms?

In order to diagnosis this disease, the American College of Gastroenterology guidelines suggest that two of three symptoms be present. The three symptoms include severe abdominal pain; increased enzymes, amylase or lipase, that are at least three times greater than normal; and radiologic imaging (ultrasound, CT, MRI, abdominal and chest X-rays) that shows characteristic findings for this disease (3). Most of the time, the abdominal pain is in the central upper abdomen near the stomach (epigastric), and it may also present with pain in the right upper quadrant of the abdomen (4). Approximately 90 percent of patients may also experience nausea and vomiting (5). In half of patients, there may also be pain that radiates to the back.

What are the risk factors?

There is a multitude of risk factors for acute pancreatitis. These include gallstones, alcohol, obesity and, to a much lesser degree, drugs. Gallstones and alcohol may cause up to 75 percent of the cases (2). Many of the other cases of acute pancreatitis are considered idiopathic (of unknown causes). Although medications are potentially responsible for between 1.4 and 5.3 percent of cases, making it rare, the number of medications implicated is diverse (6, 7). These include certain classes of diabetes therapies, some antibiotics — Flagyl (metronidazole) and tetracycline — and immunosuppressive drugs used to treat ailments like autoimmune diseases. Even calcium may potentially increase the risk.

Obesity effects

When given a multiple-choice question for risk factors that includes obesity as one of the answers, it’s a safe bet to choose that answer. Pancreatitis is no exception. However, in a recent study, using the Swedish Mammography Cohort and the Cohort of Swedish Men, results showed that central obesity is an important risk factor, not body mass index or obesity overall (8). In other words, it is fat in the belly that is very important, since this may increase risk more than twofold for the occurrence of a first-time acute pancreatitis episode. Those who had a waist circumference of greater than 105 cm (41 inches) experienced this significantly increased risk compared to those who had a waist circumference of 75 to 85 cm (29.5 to 33.5 inches). The association between central obesity and acute pancreatitis occurred in both gallbladder-induced and non-gallbladder-induced disease. There were 68,158 patients involved in the study, which had a median duration of 12 years. Remember that waistline is measured from the navel, not from the hips. This may be a surprising wake-up call for some.

Mortality risks

What makes acute pancreatitis so noteworthy and potentially dangerous is that the rate of organ failure and mortality is surprisingly high. One study found that the risk of mortality was 5 percent overall. This statistic broke out into a smaller percentage for mild acute pancreatitis and a greater percentage for severe acute pancreatitis, 1.5 and 17 percent, respectively (9). This was a prospective (forward-looking) observational trial involving 1,005 patients. However, in another study, when patients were hospitalized for this disease, the mortality rate was even higher, at 10 percent overall (10).

Diabetes risks

The pancreas is a critical organ for balancing glucose (sugar) in the body. In a recent meta-analysis (involving 24 observational trials), results showed that more than one-third of patients diagnosed with acute pancreatitis went on to develop prediabetes or diabetes (11). Within the first year, 15 percent of patients were newly diagnosed with diabetes. After five years, it was even worse; the risk of diabetes increased 2.7-fold. If we can reduce the risk of pancreatitis, we may also help reduce the risk of diabetes.

Surgical treatments

Gallstones and gallbladder sludge are major risk factors, accounting for 35 to 40 percent of acute pancreatitis incidence (12). Gallstones are thought to cause pancreatitis by temporarily blocking the duct shared by the pancreas and gallbladder that leads into the small intestine. When the liver enzyme ALT is elevated threefold (measured through a simple blood test), it has a positive predictive value of 95 percent that it is indeed gallstone-induced pancreatitis (13). If it is gallstone-induced, surgery plays an important role in helping to resolve pancreatitis and prevent recurrence of acute pancreatitis. In a recent study, results showed that surgery to remove the gallbladder was better than medical treatment when comparing hospitalized patients with this disease (14). Surgery trumped medical treatment in terms of outcomes, complication rates, length of stay in the hospital and overall cost for patients with mild acute pancreatitis. This was a retrospective (backward-looking) study with 102 patients.

Can diet have an impact?

The short answer is: Yes. What foods specifically? In a large, prospective observational study, results showed that there was a direct linear relationship between those who consumed vegetables and a decreased risk of nongallstone acute pancreatitis (15). For every two serving of vegetables, there was 17 percent drop in the risk of pancreatitis. Those who consumed the most vegetables — the highest quintile (4.6 servings per day) — had a 44 percent reduction in disease risk, compared to those who were in the lowest quintile (0.8 servings per day). There were 80,000 participants involved in the study with an 11-year follow-up. The authors surmise that the reason for this effect with vegetables may have to do with their antioxidant properties, since acute pancreatitis increases oxidative stress on the pancreas.

References: (1) Gastroenterology. 2012;143:1179-1187. (2) www.uptodate.com. (3) Am J Gastroenterol. 2013;108:1400-1415. (4) JAMA. 2004;291:2865-2868. (5) Am J Gastroenterol. 2006;101:2379-2400. (6) Gut. 1995;37:565-567. (7) Dig Dis Sci. 2010;55:2977-2981. (8) Am J Gastroenterol. 2013;108:133-139. (9) Dig Liver Dis. 2004;36:205-211. (10) Dig Dis Sci. 1985;30:573-574. (11) Gut. 2014;63:818-831. (12) Gastroenterology. 2007;132:2022-2044. (13) Am J Gastroenterol. 1994;89:1863-1866. (14) Am J Surg online. 2014 Sept. 20. (15) Gut. 2013;62:1187-1192.

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.

Rheumatoid arthritis causes pain, stiffness and swelling of the joints.

By David Dunaief, M.D.

Rheumatoid arthritis (RA) is one of many autoimmune diseases where the body’s immune system begins to attack the body’s own tissue. RA results in systemic (throughout the body) inflammation, which initially affects the synovium (lining) of the small joints in both the hand and the feet bilaterally, as well as the wrists and ankles (1). It causes pain, stiffness and swelling of the joints.

RA, like most autoimmune diseases, affects significantly more women than men and can be incredibly debilitating (2). It affects approximately 1 percent of the U.S. population (3). Fortunately, treatments have helped to significantly improve sufferers’ quality of life.

Dr. David Dunaief
Dr. David Dunaief

RA may be treated initially with acetaminophen and NSAIDs (such as ibuprofen), depending on its severity. To help stop progression and preserve the joints, disease-modifying anti-rheumatic drugs (known as DMARDs) may be used. They are considered the gold standard of treatment for RA and include methotrexate, which has been around the longest and is a first-line therapy; plaquenil (hydroxycholorquine); and TNF inhibitors, such as Enbrel (etanercept), Humira (adalimumab) and Remicade (infliximab).

DMARDs work by reducing inflammation and acting as immunosuppressives, basically tamping down or suppressing the immune system. These drugs have helped RA patients improve their quality of life, preserving joint integrity and causing RA to go into remission. The goal of these drugs is to reduce synovitis, or inflammation in the joints, helping to lessen joint damage. They can be quite effective. Unfortunately, compliance can be an issue. In addition, corticosteroids can be used to suppress inflammation.

The yin and yang of medications

In a meta-analysis (a group of 28 studies), the results showed that DMARDs reduced the risk of cardiovascular events by up to 30 percent, while NSAIDs and corticosteroids increased the risk (4). However, oral steroids have been found to increase the risk of heart complications, approximately a 50 percent rise in risk. This may be one reason rheumatologists encourage their RA patients to discontinue oral steroid treatments as quickly as possible.

In an observational study, the results reaffirmed that corticosteroids increased the risk of a heart attack in RA patients, this time by 68 percent (5). The study involved over 8,000 patients with a follow-up of nine years. Interestingly, there was a dose-response curve. In other words, the results also showed that for every 5-mg increase in dosage, there was a corresponding 14 percent increase in heart attack risk.

The downside of using immunosuppressive drugs

Unfortunately, DMARDs have significant adverse effects. In 2011, the FDA found there were 100 cases of Listeria and Legionella pneumonia infections associated with these drugs. Therefore, a black-box warning was placed on all TNF inhibitors cautioning about serious or life-threatening side effects, such as opportunistic infections — more likely in combination with other immunosuppressives — and malignancy. The median duration that patients were on the drugs when they experienced infections was about 10 months. However, most patients were also on methotrexate and steroids at the time of infection.

Anecdotally, I had a patient who had previously developed pneumonia twice, multiple basal-cell carcinomas and one episode of melanoma. These were all attributed to use of a TNF inhibitor.

Skin cancer risk

In 2009, the FDA warned that there is an increased risk of cancer after about 30 months of treatment, especially with TNF inhibitors. A 2011 meta-analysis (a group of 28 studies) found that TNF inhibitors may increase the risk of cancers, including skin cancers (6). In four of the studies, there was a 45 percent elevated risk of developing skin cancer other than melanoma. However, in data pooled from two of the studies, there was a 79 percent greater chance of developing melanoma. All the studies in this analysis were observational studies, and the absolute risk of developing cancer is small. The good news is that this analysis did not appear to show increased risk of lymphoma.

Cardiovascular disease

Patients with RA are at a threefold increased risk of developing coronary artery disease, compared to the general population (7). Those RA patients who stopped taking statins for high cholesterol and/or heart disease had a 60 percent increased risk of cardiovascular mortality and a 79 percent increased risk of all-cause death after three months (8). Though statins have their pitfalls, they can be potentially lifesaving in the right context. Don’t discontinue statins before consulting your physician.

Additional complications from RA

RA can also affect organs and the surrounding tissue. Thus, complications from RA include heart disease, stroke, atrial fibrillation, chronic obstructive pulmonary disease, fracture risk, as well as uveitis and scleritis (inflammatory disorders of the eye).

Nonpharmacologic approaches

Exercise and fish oil have shown reductions in symptomatology and joint inflammation. In a meta-analysis (a group of 17 trials), omega-3 fish oil reduced joint pain intensity, as reported by patients, minutes of morning stiffness, number of painful joints and NSAID use significantly (9). The dose was at least 2.7 g of EPA plus DHA in the omega-3 fish oil and took at least 12 weeks of treatment to see a benefit. Exercise is also important to relieve joint pain and stiffness. In a meta-analysis of 14 studies, there was a 69 percent reduction in pain with aerobic exercise (10). Understandably, however, a study found that 42 percent of RA patients don’t work out at the recommended minimum of 10 minutes of moderate exercise daily (11). The reasons were that half were either not motivated or believed that exercise had no benefit.

Prevention

In the Iowa Women’s Health Study, results showed that supplemental vitamin D decreased the risk of RA by 34 percent (12). This study involved almost 30,000 women followed over an 11-year period.

The best way to treat an autoimmune disease like rheumatoid arthritis is to prevent it with an anti-inflammatory diet, exercise and omega-3 fish oil. Barring that, however, it is encouraging that DMARD treatments may be effective at half the dose once the disease has been suppressed significantly. Therefore, a low-dose pharmacological approach coupled with nonpharmacological lifestyle adjustments may produce the best outcomes with the fewest adverse reactions.

References: (1) www.ncbi.nlm.nih.gov. (2) www.mayoclinic.com. (3) Arthritis Rheum. 2008;58:15-25. (4) Ann Rheum Dis 2015;74(3):480-489. (5) Rheumatology 2013;52:68-75. (6) Ann Rheum Dis. 2011 Nov;70(11):1895-1904. (7) Ann Rheum Dis. 2007;66(1):70. (8) Arthritis Care Res [Hoboken]. 2012 Mar 29. (9) Pain. 2007 May;129(1-2):210-223. (10) Br J Sports Med. 2011;45(12):1008-1009. (11) Arthritis Care Res [Hoboken]. 2012 Apr;64(4):488-493. (12) Arthritis Rheum. 2004 Jan;50(1):72-77.

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.