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Dr. David Dunaief

By David Dunaief, M.D.

Autoimmune diseases are becoming increasingly common, affecting approximately 23.5 million Americans, with 78 percent of them women. These numbers are expected to continue rising. There are more than 80 conditions with autoimmunity implications (1). These diseases include rheumatoid arthritis (RA), lupus, thyroid (hypo and hyper), psoriasis, multiple sclerosis and inflammatory bowel disease, to mention just a few.

Dr. David Dunaief

Autoimmune diseases are defined by the immune system inappropriately attacking organs, cells and tissues of the body, causing chronic inflammation. Thus, 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). In other words, once you have one, you are much more likely to acquire others.

Drug treatments

The mainstay of treatment is immunosuppressives. For example, 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 are thought to help reduce the underlying inflammation by suppressing the immune system and interfering with inflammatory factors, such as TNF-alpha. The disease-modifying antirheumatic drugs (DMARDs) 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. Remicade’s package insert was approved with approximately two years of data.

So what other methods are available to treat autoimmune diseases? These include medical nutrition therapy using bioactive compounds, which have immunomodulatory (regulation of the immune system) 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. In one study, participants drank the equivalent of about one glass of freshly squeezed orange juice a day with a resultant 49 percent risk reduction in the development of RA (5).

While I have not found studies that specifically tested diet in RA treatment, there are dietary studies that have shown anti-inflammatory effects in other diseases, using biomarkers such as CRP and TNF-alpha. In a study that looked at the Mediterranean-type diet in 112 older patients, there was a significant decrease in inflammatory markers, including CRP (6).

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 (7).

Vitamin D

Vitamin D is ubiquitous in helping to treat and prevent many chronic diseases — autoimmune diseases are no exception. Vitamin D affects over 200 genes, according to Wellcome Trust Centre for Human Genetics at University of Oxford. In the absence of vitamin D, T-cell response, part of the immune system, becomes dysfunctional and uncontrollable, resulting in an increase in multiple sclerosis (MS) and inflammatory bowel disease — Crohn’s and ulcerative colitis. However, when normal levels of vitamin D are conveyed to the vitamin D receptors, proper T-cell functioning is restored with no subsequent autoimmune disease, at least in animal studies (8).

Interestingly, multiple sclerosis patients are notoriously very low in vitamin D, and it is difficult to raise the levels. There was a small study proclaiming that MS patients may need as much as 50,000 IUs of vitamin D2 weekly, and that it was safe (9). I would check with a neurologist specializing in MS before taking such a high dose.

Fish oil

Fish oil helps your immune system by reducing inflammation and improving your blood chemistry.

If you think vitamin D is impressive, fish oil affects as many as 1,040 genes (10). In a randomized clinical study, 1.8 grams of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation had anti-inflammatory affects, 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 (11). 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 (12, 13).

In a study with Crohn’s disease patients, Lactobacillus casei and L. bulgaricus reduced the inflammatory factor, TNF-alpha (14). 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 (15).

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. (16).

Immune system regulation is complex and involves over a 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. 2005 Aug; 82(2):451-455. (6) Am J Clin Nutr. 2009 Jan;89(1):248-256. (7) Chem Biol Interact. 2011 May 20. (8) Prog Biophys Mol Biol. 2006 Sept;92(1):60-64. (9) Am J Clin Nutr. 2007 Sep;86(3):645-651. (10) Am J Clin Nutr. 2009 Aug;90(2):415-424. (11) Drugs. 2003;63(9):845-853. (12) Gut. 2003 Jul;52(7):975-980. (13) Antonie Van Leeuwenhoek 1999 Jul-Nov;76(1-4):279-292. (14) Gut. 2002;51(5):659. (15) Arch Intern Med. 2007;167(5):502-506. (16) 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.

By David Dunaif, M.D.

Dr. David Dunaief

Eczema is a common problem in both children and adults. Therefore, you would think there would be a plethora of research, right? Well, that’s only partly true. While there is a significant amount of research in primarily neonates and some on pediatric patients, there is not a lot of research on adults with eczema. But in my practice, I see a good number of adult patients who present with, among other disorders, eczema.

The prevalence of this disease rivals the prevalence of diabetes. In the United States, more than 10 percent of the adult population is afflicted (1). Twice as many females as males are affected, according to one study (2). Thus, we need more research.

Eczema is also referred to more broadly as atopic dermatitis. The cause is unknown, but it is thought that nature and nurture are both at play (3). Eczema is a chronic inflammatory process that involves symptoms of pruritus (itching) pain, rashes and erythema (redness) (4). There are three different severities: mild, moderate and severe. Adults tend to have eczema closer to the moderate-to-severe range.

Factors that can trigger eczema flare-ups include emotional stress, excessive bathing, dry skin, dry environment and detergent exposure (5). Treatments for eczema run the gamut from over-the-counter creams and lotions to prescription steroid creams to systemic (oral) steroids. Some use phototherapy for severe cases, but the research on phototherapy is scant. Antihistamines are sometimes used to treat the itchiness. Also, lifestyle modifications may play an important role, specifically diet. Two separate studies have shown an association between eczema and fracture, which we will investigate further. Let’s look at the evidence.

Eczema doesn’t just scratch the surface

Eczema causes cracked and irritated skin, but it may also be related to broken bones. In a newly published observational study, results showed that those with eczema had a 44 percent increased risk of injury causing limitation and an even more disturbing 67 percent risk of bone fracture and bone or joint injury for those 30 years and older (6). And if you have both fatigue or insomnia and eczema, you are at higher risk for bone or joint injury than having one or the other alone. Antihistamines may cause more fatigue. One reason for increased fracture risk, the researchers postulate, is the use of corticosteroids in treatment.

Steroids may weaken bone, ligaments and tendons and may cause osteoporosis by decreasing bone mineral density. Chronic inflammation may also contribute to the risk of bone loss. There were 34,500 patients involved in the study ranging in age from 18 to 85.

Another study corroborates these results that eczema increases the risk for sustained injury (7). There was a 48 percent increased risk of fracture at any location in the body and an even greater 87 percent increased risk of fracture in the hip and spine when compared to those who did not have eczema.

Not suprisingly, researchers’ hypotheses for the causes of increased fracture risk were similar to those of the above study: systemic steroid use and chronic inflammation of the disease, itself. The researchers analyzed the database from NHANES 2005-2006, with almost 5,000 patients involved in this study. When oral steroid was given for at least a month, there was a 44 percent increased risk of osteoporosis. For those who have eczema and have been treated with steroids, it may be wise to have a DEXA (bone) scan.

Are supplements the answer?

The thought of supplements somehow seems more appealing for some than medicine. There are two well-known supplements for helping to reduce inflammation, evening primrose oil and borage oil. Are these supplements a good replacement for medications or at least a beneficial addition? The research is really mixed, leaning toward ineffective.

In a recent meta-analysis (involving seven randomized controlled trials, the gold standard of studies), evening primrose oil was no better than placebo in treating eczema (8). The researchers also looked at eight studies of borage oil and found there was no difference from placebo in terms of symptom relief. One positive is that these supplements only had minor side effects. But don’t look to supplements for help.

Where are we on the drug front?

The FDA has given fast track processing to a biologic monoclonal antibody known as dupilumab (9). In trials, the drug has shown promise for treating moderate to severe eczema when topical steroids are not effective. An FDA decision is due by late March (10). We will have to wait for the verdict on this drug in development.

Do probiotics have a place?

When we think of probiotics, we think of taking a pill. However, there are also potentially topical probiotics with atopic dermatitis. In preliminary in-vitro (in a test tube) studies, the results look intriguing and show that topical probiotics from the human microbiome (gut) could potentially work as well as steroids (11). This may be part of the road to treatments of the future. However, this is in very early stage of development.

What about lifestyle modifications?

Cruciferous vegetables including broccoli, celery, kale, cauliflower, bok choy, watercress, cabbage, and arugula may help eczema sufferers.

Wouldn’t it be nice if what we ate could make a difference in eczema? Well, in a study involving pregnant women and their offspring, results showed that when these women ate either a diet high in green and yellow vegetables, beta carotene or citrus fruit there was a significant reduction in the risk of the child having eczema of 59 percent, 48 percent and 47 percent, respectively, when comparing highest to lowest consumption quartiles (12). This was a Japanese study involving over 700 mother-child pairings.

Elimination diets may also play a role. One study’s results showed when eggs were removed from the diet in those who were allergic, according to IgE testing, eczema improved significantly (13).

From an anecdotal perspective, I have seen very good results when treating patients who have eczema with dietary changes. My patient population includes about 15 to 20 percent of patients who suffer some level of eczema. For example, a young adult had eczema mostly on the extremities. When I first met the patient, these were angry, excoriated, erythematous and scratched lesions. However, after several months of a vegetable-rich diet, the patient’s skin had all but cleared.

I also have a personal interest in eczema. I suffered from hand eczema, where my hands would become painful and blotchy and then crack and bleed. This all stopped for me when I altered my diet over 10 years ago.

Eczema exists on a spectrum from annoying to significantly affecting a patient’s quality of life (14). Supplements may not be the solution, at least not borage oil or evening primrose oil. However, there may be promising topical probiotics ahead and medications for the hard to treat. It might be best to avoid long-term systemic steroid use; it could not only impact the skin but also may impact the bone. But don’t wait to treat the disease. Lifestyle modifications appear to be very effective, at least at the anecdotal level.

References: (1) J Allergy Clin Immunol. 2013;132(5):1132-1138. (2) BMC Dermatol. 2013;13(14). (3) Acta Derm Venereol (Stockh) 1985;117 (Suppl.):1-59. (4) uptodate.com. (5) Br J Dermatol. 2006; 1553:504. (6) JAMA Dermatol. 2015;151(1):33-41. (7) J Allergy Clin Immunol. Online Dec. 13, 2014. (8) Cochrane Database Syst Rev. 2013;4:CD004416. (9) Medscape.com. (10) www.medpagetoday.com (11) ACAAI 2014: Abstracts P328 and P329. (12) Allergy. 2010 Jun 1;65(6):758-765. (13) J Am Acad Dermatol. 2004;50(3):391-404. (14) Contact Dermatitis 2008; 59:43-47.

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.

Simple lifestyle changes can make a big difference. Stock photo

By David Dunaief

Dr. David Dunaief

It seems like almost everyone is diagnosed with gastroesophageal reflux disease (GERD), or at least it did in the last few weeks in my practice. I exaggerate, of course, but the pharmaceutical companies do an excellent job of making it appear that way with advertising. Wherever you look there is an advertisement for the treatment of heartburn or indigestion, both of which are related to reflux disease.

GERD, also known as reflux, affects as much as 40 percent of the U.S. population (1). Reflux disease typically results in symptoms of heartburn and regurgitation brought on by stomach contents going backward up the esophagus. For some reason, the lower esophageal sphincter, the valve between the stomach and esophagus, inappropriately relaxes. No one is quite sure why it happens with some people and not others. Of course, a portion of reflux is physiologic (normal functioning), especially after a meal (2).

GERD risk factors are diverse. They range from lifestyle — obesity, smoking cigarettes and diet — to medications, like calcium channel blockers and antihistamines. Other medical conditions, like hiatal hernia and pregnancy, also contribute (3). Diet issues include triggers like spicy foods, peppermint, fried foods and chocolate.

Smoking and salt’s role

One study showed that both smoking and salt consumption added to the risk of GERD significantly (4). Risk increased 70 percent in people who smoked. Surprisingly, people who used table salt regularly saw the same increased risk as seen with smokers. Treatments vary, from lifestyle modifications and medications to surgery for severe, noticeable esophagitis. The goal is to relieve symptoms and prevent complications, such as Barrett’s esophagus, which could lead to esophageal adenocarcinoma. Fortunately, Barrett’s esophagus is not common and adenocarcinoma is even rarer.

Medications

The most common and effective medications for the treatment of GERD are H2 receptor blockers (e.g., Zantac and Tagamet), which partially block acid production, and proton pump inhibitors (e.g., Nexium and Prevacid), which almost completely block acid production (5). Both classes of medicines have two levels: over-the-counter and prescription strength. Here, I will focus on PPIs, for which more than 113 million prescriptions are written every year in the U.S. (6).

PPIs include Nexium (esomeprazole), Prilosec (omeprazole), Protonix (pantoprazole) and Prevacid (lansoprazole). They have demonstrated efficacy for short-term use in the treatment of Helicobacter pylori-induced (bacteria overgrowth in the gut) peptic ulcers, GERD symptoms and complication prevention, and gastric ulcer prophylaxis associated with NSAID use (aspirin, ibuprofen, etc.) as well as upper gastrointestinal bleeds.

However, they are often used long-term as maintenance therapy for GERD. PPIs used to be considered to have mild side-effects. Unfortunately, evidence is showing that this may not be true. Most of the data in the package inserts is based on short-term studies lasting weeks, not years. The landmark study supporting long-term use approval was only one year, not 10 years. Maintenance therapy usually continues over many years.

Side effects that have occurred after years of use are increased risk of bone fractures and calcium malabsorption; Clostridium difficile, a bacterial infection in the intestines; potential B12 deficiencies; and weight gain (7).

Fracture risks

There has been a debate about whether PPIs contribute to fracture risk. The Nurses’ Health Study, a prospective (forward-looking) study involving approximately 80,000 postmenopausal women, showed a 40 percent overall increased risk of hip fracture in long-term users (more than two years’ duration) compared to nonusers (8). Risk was especially high in women who also smoked or had a history of smoking, with a 50 percent increased risk. Those who never smoked did not experience significant increased fracture risk. The reason for the increased risk may be due partially to malabsorption of calcium, since stomach acid is needed to effectively metabolize calcium.

In the Women’s Health Initiative, a prospective study that followed 130,000 postmenopausal women between the ages of 50 and 79, hip fracture risk did not increase among PPI users, but the risks for wrist, forearm and spine were significantly increased (9). The study duration was approximately eight years.

Bacterial infection

The FDA warned that patients who use PPIs may be at increased risk of a bacterial infection called C. difficile. This is a serious infection that occurs in the intestines and requires treatment with antibiotics. Unfortunately, it only responds to a few antibiotics and that number is dwindling. In the FDA’s meta-analysis, 23 of 28 studies showed increased risk of infection. Patients need to contact their physicians if they develop diarrhea when taking PPIs and the diarrhea doesn’t improve (10).

B12 deficiencies

Suppressing hydrochloric acid produced in the stomach may result in malabsorption issues if turned off for long periods of time. In a study where PPIs were associated with B12 malabsorption, it usually took at least three years duration to cause this effect. B12 was not absorbed properly from food, but the PPIs did not affect B12 levels from supplementation (11). Therefore, if you are taking a PPI chronically, it is worth getting your B12 and methylmalonic acid (a metabolite of B12) levels checked and discussing possible supplementation with your physician if you have a deficiency.

My recommendations would be to use PPIs short-term, except with careful monitoring by your physician. If you choose medications for GERD management, H2 blockers might be a better choice, since they only partially block acid. Lifestyle modifications may also be appropriate in some of the disorders, with or without PPIs. Consult your physician before stopping PPIs since there may be rebound hyperacidity (high acid produced) if they are stopped abruptly.

Lifestyle modifications

A number of modifications can improve GERD, such as raising the head of the bed about six inches, not eating prior to bedtime and obesity treatment, to name a few (12). In the same study already mentioned with smoking and salt, fiber and exercise both had the opposite effect, reducing the risk of GERD (5). This was a prospective (forward-looking) trial. The analysis by Journal Watch suggests that the fiber effect may be due to its ability to reduce nitric oxide production, a relaxant for the lower esophageal sphincter (13).

Obesity

In one study, obesity exacerbated GERD. What was interesting about the study is that researchers used manometry, which measures pressure, to show that obesity increases the pressure on the lower esophageal sphincter significantly (14). Intragastric (within the stomach) pressures were higher in both overweight and obese patients on inspiration and on expiration, compared to those with normal body mass index. This is yet another reason to lose weight.

Eating prior to bed — myth or reality?

Though it may be simple, it is one of the most powerful modifications we can make to avoid GERD. There was a study that showed a 700 percent increased risk of GERD for those who ate within three hours of bedtime, compared to those who ate four hours or more prior to bedtime. Of note, this is 10 times the increased risk of the smoking effect (15). Therefore, it is best to not eat right before bed and to avoid “midnight snacks.” Although there are a number of ways to treat GERD, the most comprehensive have to do with modifiable risk factors. Drugs have their place in the arsenal of choices, but lifestyle changes are the first and most effective approach in many instances.

References:

(1) Gut 2005;54(5):710. (2) Gastroenterol Clin North Am. 1996;25(1):75. (3) emedicinehealth.com. (4) Gut 2004 Dec.; 53:1730-1735. (5) Gastroenterology. 2008;135(4):1392. (6) JW Gen Med. Jun. 8, 2011. (7) World J Gastroenterol. 2009;15(38):4794–4798. (8) BMJ 2012;344:e372. (9) Arch Intern Med. 2010;170(9):765-771. (10) www.FDA.gov/safety/medwatch/safetyinformation. (11) Linus Pauling Institute; lpi.oregonstate.edu. (12) Arch Intern Med. 2006;166:965-971. (13) JWatch Gastro. Feb. 16, 2005. (14) Gastroenterology 2006 Mar.; 130:639-49. (15) Am J Gastroenterol. 2005 Dec.;100(12):2633-2636.

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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By David Dunaief, M.D.

I’m sure we all can agree that type 2 diabetes is an epidemic that needs to be discussed again. Again, because this disease is just not going away. There are a number of different drug classes to treat diabetes, and these classes keep on growing in number and diversity; each has its merits and drawbacks. Since there are so many drugs and drug classes, you will need a scorecard to keep track.

When we talk about this disease, the first thing that comes to mind is glucose levels, or sugar, which is what defines having diabetes. However, we are going to look beyond the sugars to the nonglycemic effects.

What do I mean by this? There seems to be a renaissance occurring where there is a focus in drug trials on the treatment of diabetes complications rather than just the lowering of sugars. Some of the complications that we will investigate include cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). Several drugs may reduce the risk of cardiovascular disease (CVD) mortality. Diabetes patients who have cardiovascular disease are more likely to die about 12 years prematurely (1). However, new research suggests that relatively new diabetes drugs reduce the risk of CVD mortality. These include empagliflozin (Jardiance), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and liraglutide, a glucagon-like peptide-1 (GLP1) receptor agonist. There is also a third, older drug that has shown CVD risk benefit, metformin. Though these drugs are not without their caveats. Liraglutide has also been shown to potentially reduce the risk of nonalcoholic fatty liver disease.

In fact, the American College of Physicians has recently updated its recommendations on the treatment of type 2 diabetes with oral medications (2). The first line continues to be metformin, the tried and true. The favored second-line drugs to add to metformin may be the SGLT2 cotransporter inhibitors, such as empagliflozin, or DPP-4 inhibitors, such as sitagliptin. The sulfonylureas class, such as glimepiride, and thiazolidinediones class, such as pioglitazone, are also consider second line but not as favorable. GLP1 receptor agonists, such as liraglutide, are not on the list, since they are injectable medications. There are always downsides to drug therapy, and diabetes drugs are no exception. Drawbacks include expense with newer drugs, as well as adverse side effects with all of these drugs, new and old. Though empagliflozin has been shown to reduce CVD mortality, others in the same class have been shown to increase the risk of acute kidney failure.

Before I go any further, I want to state that lifestyle modifications including a plant-based diet and exercise are likely the most powerful tools we have in treating, preventing and reversing diabetes. So, I am not a proponent of diabetes drugs. But, there are many patients who could and do benefit from drug therapy. Lifestyle modifications should always be a significant component whether on drugs or not. Recently, plant-based diets were ranked highly for treating and preventing diabetes in U.S. News and World Report, with the DASH (dietary approach to stop hypertension) diet ranked number one and the Mediterranean diet number two (3), although rankings are not the be-all and end-all. Let’s look at the evidence.

New diabetes drugs may reduce cardiovascular mortality.

Drug benefit on cardiovascular disease

As I mentioned, there are two new drugs, empagliflozin and liraglutide, and one older drug, metformin, that have shown potentially beneficial effects on the macrovascular portion of diabetes treatment and prevention — cardiovascular disease. For the longest time, most diabetes drug trials were focused only on reducing sugars, not on clinical end points.

Empagliflozin

In a the EMPA-REG OUTCOME trial, a randomized, double-blind, placebo-controlled trial, results showed that empagliflozin reduces the risk of cardiovascular mortality (heart attack or stroke) by a relative 38 percent compared to placebo in patients with type 2 diabetes and cardiovascular disease (4). There was also a 32 percent reduction in all-cause mortality compared to the placebo group. Two different doses of empagliflozin were used with similar results, 10 mg and 25 mg once a day. There were 7,020 patients with a duration of 3.1 years. Most of those in the placebo arm were on statin (cholesterol) drugs, ACE inhibitors (blood pressure medication) and aspirin.

The FDA approved this drug for the prevention of heart attacks and strokes in diabetes patients with known cardiovascular disease (5). However, the FDA advisory board only narrowly recommended the drug for this label (6). The label change is based on one trial, and the mechanism for CVD mortality reduction is unclear. However, there are several pitfalls to this study. Empagliflozin was compared to placebo, rather than the usual standard of care, and these patients had cardiovascular disease, which means that we don’t know if the benefit actually holds true in those without CVD. Interestingly, the placebo group’s HbA1C was 8.2 percent at the trial’s end, while the treatment group was reduced to 7.8 percent, neither of which is considered controlling the sugar levels. The treatment group saw a 0.5 percent reduction in HbA1C, which is not overwhelming.

In terms of adverse reactions, empagliflozin increases the risk of urinary tract infections and diabetic ketoacidosis, since sugar is excreted through the urine. In fact, the FDA warned that two drugs from the same class as empagliflozin increase the risk of acute renal failure. These are canagliflozin (Invokana) and dapagliflozin (Farxiga) (5).

Liraglutide

In the LEADER trial, a randomized controlled trial, results showed that liraglutide 1.8 mg subcutaneous injection daily decreased the risk of CVD mortality by a significant 22 percent compared to placebo plus standard care after 3 years (7). This is the highest tolerated dose. This trial involved over 9,000 type 2 diabetes patients at high risk for CVD. Liraglutide also showed a 2.3-kg (5-lb) weight reduction and 0.4 percent HbA1C drop compared to placebo by the 3-year mark. The duration of trial was 3.5 to 5 years. The most significant side effects were gastrointestinal and increased heart rate. In another study, results showed that liraglutide reduced the liver fat in 57 NAFLD patients who were not adequately controlled on metformin, insulin or sulfonylureas (8). After six months, the liver fat in these patients decreased by 33 percent. The patients also lost almost 8 lb of weight and reduced HbA1C by 1.6 percent from 9.8 to 7.3.

Metformin

In a retrospective (backward-looking) study of over 250,000 diabetes patients, there was a greater than 40 percent reduction in cardiovascular events or mortality with metformin compared to sulfonylureas (9). However, a retrospective study is not the most reliable.

Triglyceride-lowering drug reduces CVD

Fenofibrate, which had been shown not to be of benefit, may actually help reduce CVD in a specific group of diabetes patients. In a recent analysis of the ACCORDION trial, a subset of data suggests that diabetes patients with triglycerides >204 mg/dL and HDL <34 mg/dL, when treated with fenofibrate in addition to statins, saw a 27 percent significant reduction in cardiovascular events (10). This was an observational study that requires confirmation with a randomized controlled trial. Thus, there may be a use, though a narrow one, for fenofibrate.

It is potentially exciting that drugs may reduce cardiovascular mortality in diabetes patients. If you do chose one or more of these drug therapies after discussing it with your physician, remember these drugs are in addition to continuing to work on diet and on exercise — the cornerstone of therapy.

References: (1) JAMA. 2015;314(1):52-60. (2) Ann Intern Med. online Jan. 3, 2017. (3) usnews.com. (4) N Engl J Med 2015; 373:2117-2128. (5) FDA.gov. (6) Medscape.com. (7) N Engl J Med 2016; 375:311-322. (8) J Clin Endocrinol Metab. Online Oct. 12, 2016. (9) Ann Intern Med. 2012 Nov. 6;157(9):601-610. (10) JAMA Cardiology online Dec. 28, 2016.

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.

By David Dunaief, M.D.

Dr. David Dunaief

When we think of losing weight, calories are usually the first thing that comes to mind. We know that the more calories we consume, the greater our risk of becoming overweight or obese and developing many chronic diseases, including top killers such as heart disease, diabetes and cancer. Despite this awareness, obesity and chronic diseases are on the rise according to the Centers for Disease Control and Prevention.

How can this be the case? I am usually focused on the quality of foods, rather than calories, and I will delve into this area as well, but we suffer from misconceptions and lack of awareness when it comes to calories. The minefield of calories needs to be placed in context. In this article, we will put calories into context, as they relate to exercise, and help to elucidate the effects of mindful and distracted eating. Let’s look at the studies.

Impact of energy expenditure

One of the most common misconceptions is that if we exercise, we can be more lax about what we are eating. But researchers in a recent study found that this was not the case (1). The results showed that when menu items were associated with exercise expenditures, consumers tended to make better choices and ultimately eat fewer calories. In other words, the amount of exercise needed to burn calories was paired on the menu with food options, resulting in a significant reduction in overall consumption.

The example that the authors gave was that of a four-ounce cheeseburger, which required that women walk with alacrity for two hours in order to burn off the calories. Those study participants who had menus and exercise expenditure data provided simultaneously, compared to those who did not have the exercise data, chose items that resulted in a reduction of approximately 140 calories, 763 versus 902 kcals.

Even more interestingly, study participants not only picked lower calorie items, but they ate less of those items. Although this was a small preliminary study, the results were quite impactful. The effect is that calories become a conscious decision rooted in context, rather than an abstract choice.

The importance of mindful eating

Most of us like to think we are multitaskers. However, when eating, multitasking may be a hazard. In a meta-analysis (a group of 24 studies), researchers found that when participants were distracted while eating, they consumed significantly more calories immediately during this time period, regardless of dietary constraints (2).

This distracted eating also had an impact on subsequent meals, increasing the amount of food eaten at a later time period, while attentive eating reduced calories eaten in subsequent meals by approximately 10 percent. Distracted eating resulted in greater than 25 percent more calories consumed for the day. When participants were cognizant of the amount of food they were consuming, and when they later summoned memories of their previous eating, there was a vast improvement in this process.

The authors concluded that reducing distracted eating may be a method to help in both weight loss and weight management, providing an approach that does not necessitate calorie counting. These results are encouraging, since calorie counting frustrates many who are watching their weight over the long term.

The perils of eating out

Most of us eat out at least once in a while. In many cultures, it is a way to socialize. However, as much as we would like to control what goes into our food, we lose that control when eating out. In a study that focused on children, the results showed that when they ate out, they consumed more calories, especially from fats and sugars (3).

Of the 9,000 teenagers involved in the study, between 24 and 42 percent had gone to a fast-food establishment and 7 to 18 percent had eaten in sit-down restaurants when asked about 24-hour recall of their diets on two separate occasions.

Researchers calculated that this resulted in increases of 310 calories and 267 calories from fast-food and sit-down restaurants, respectively. This is not to say we shouldn’t eat out or that children should not eat out, but that we should have more awareness of the impact of our food choices. For example, many municipalities now require calories be displayed in chain restaurants.

Quality of calories

Blueberries are one of the most nutrient dense and highest antioxidant foods in the world.

It is important to be aware of the calories we are consuming, not only from the quantitative perspective but also from a perspective that includes the quality of those calories. In another study involving children, the results showed that those offered vegetables for snacks during the time that they were watching television needed significantly fewer calories to become satiated than when given potato chips (4). The authors commented that this was true for overweight and obese children as well, however, they were more likely to be offered unhealthy snacks, like potato chips.

In a study published in JAMA in June 2012, the authors state that we should not restrict one type of nutrient over another but rather focus on quality of nutrients consumed (5). In my practice, I find that when my patients follow a vegetable-rich, nutrient-dense diet, one of the wonderful “side effects” they experience is a reduction or complete suppression of food cravings. As far as mindless eating goes, I suggest if you are going to snack while working, watching TV or doing some other activity, then snack on a nutrient-dense, low-calorie food, such as carrots, blueberries or blackberries. If you don’t remember how many vegetables or berries that you ate, you can take heart in knowing it’s beneficial. It can also be helpful to keep a log of what you’ve eaten for the day, to increase your cognizance of distracted eating.

Therefore, rather than counting calories and becoming frustrated by the process, be aware of the impact of your food choices. Why not get the most benefit out of lifestyle modifications with the least amount of effort? Rather than having to exercise more to try to compensate, if you actively choose nutrient-dense, low-calorie foods, the goal of maintaining or losing weight, as well as preventing or potentially reversing chronic diseases, becomes attainable through a much less painful and laborious process.

References: (1) J Exp Biol. 2013; Abstract 367.2. (2) Am J Clin Nutr. 2013 April;97:728-742. (3) JAMA Pediatr. 2013;167:14-20. (4) Pediatrics. 2013;131:22-29. (5) JAMA 2012; 307:2627-2634.

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.

Skip the cookies and milk this year and reach for a piece of fruit or vegetable instead.

By Dr. David Dunaief

Dear Santa,

This time of year, people around the world are no doubt sending you lists of things they want through emails, blogs, tweets and old-fashioned letters. In the spirit of giving, I’d like to offer you ­— and maybe your reindeer — some advice.

David Dunaief, M.D.

Let’s face it: You aren’t exactly the model of good health. Think about the example you’re setting for all those people whose faces light up when they imagine you shimmying down their chimneys. You have what I’d describe as an abnormally high BMI (body mass index). To put it bluntly, you’re not just fat, you’re obese. Since you are a role model to millions, this sends the wrong message.

We already have an epidemic of overweight kids, leading to an ever increasing number of type 2 diabetics at younger and younger ages. From 2005 to 2007, according to the CDC and NIH, the prevalence of diabetes increased by an alarming rate of three million cases in the U.S. The rate is only getting worse. It complicates the issue that approximately two-thirds of the U.S. population is overweight and/or obese. This is just one of many reasons we need you as a shining beacon of health.

Obesity has a much higher risk of shortening a person’s life span, not to mention quality of life and self-image. The most dangerous type of obesity is an increase in visceral adipose tissue, which means central belly fat. An easy way to tell if someone is too rotund is if a man’s waist line, measured from the navel, is greater than or equal to 40 inches and for a woman is greater than or equal to 35 inches. The chances of diseases such as pancreatic cancer, breast cancer, liver cancer and heart disease increase dramatically with this increased fat.

Santa, here is a chance for you to lead by example (and, maybe, by summer, to fit into those skinny jeans you hide in the back of your closet). Think of the advantages to you of being slimmer and trimmer. For one thing, Santa, you would be so much more efficient if you were fit. Studies show that with a plant-based diet, focusing on fruits and vegetables, people can reverse atherosclerosis, clogging of the arteries.

The importance of a good diet not only helps you lose weight but avoid strokes, heart attacks, peripheral vascular diseases, etc. But you don’t have to be vegetarian; you just have to increase your fruits, vegetables and whole grain foods significantly. With a simple change, like eating a handful of raw nuts a day, you can reduce your risk of heart disease by half. Santa, future generations need you. Losing weight will also change your center of gravity, so your belly doesn’t pull you forward. This will make it easier for you to keep your balance on those steep, icy rooftops.

Skiing is a great way to get fit.

Exercise will help, as well. Maybe for the first continent or so, you might want to consider walking or jogging alongside the sleigh. As you exercise, you’ll start to tighten your abs and slowly see fat disappear from your mid-section, reducing risk and practicing preventive medicine. Your fans everywhere leave you cookies and milk when you deliver presents. It’s a tough cycle to break, but break it you must. You — and your fans — need to see a healthier Santa. You might let slip that the modern Santa enjoys fruits, especially berries, and veggies, with an emphasis on cruciferous veggies like broccoli florets dipped in humus, which have substantial antioxidant qualities and can help reverse disease.

As for your loyal fans, you could place fitness videos under the tree. In fact, you and your elves could make workout videos for those of us who need them, and we could follow along as you showed us “12 Days of Workouts with Santa and Friends.” Who knows, you might become a modern version of Jane Fonda or Richard Simmons!

How about giving athletic equipment, such as baseball gloves, baseballs, footballs and basketballs, instead of video games? You could even give wearable devices that track step counts and bike routes or stuff gift certificates for dance lessons into people’s stockings. These might influence the recipients to be more active.

By doing all this, you might also have the kind of energy that will make it easier for you to steal a base or two in this season’s North Pole Athletic League’s Softball Team. The elves don’t even bother holding you on base anymore, do they?

The benefits to a healthier Santa will ripple across the world. Think about something much closer to home, even. Your reindeer won’t have to work so hard. You might also fit extra presents in your sleigh. And Santa, you will be sending kids and adults the world over the right message about taking control of their health through nutrition and exercise. That’s the best gift you could give!

As you become more active, you’ll find that you have more energy all year round, not just on Christmas Eve. If you start soon, Santa, maybe by next year, you’ll find yourself parking the sleigh farther away and skipping from chimney to chimney.

Wishing you good health in the coming year,

David

P.S. I could really use a new baseball glove, if you have a little extra room in your sleigh.

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.

Dementia symptoms include impairments in thinking, communicating, and memory. Stock photo

By David Dunaief, M.D.

When you hear the word dementia, what is your reaction? Is it fear, anxiety or an association with a family member or friend? The majority of dementia is Alzheimer’s, which comprises about 60 to 80 percent of dementia incidence (1). There is also vascular dementia and Parkinson’s-induced dementia, as well as others. Then there are precursors to dementia, such as mild cognitive impairment, that have a high risk of leading to this disorder.

Dr. David Dunaief
Dr. David Dunaief

Encouraging data

There is good news! A recent study, the Health and Retirement Study (HRS), a prospective (forward-looking) observational study, suggested that dementia incidence has declined (2). This was a big surprise, since predictions were for significant growth. Dementia declined by 24 percent from 2000 to 2012. There were over 10,000 participants 65 years old and older at both the 2000 and 2012 comparison surveys. There was also a decrease in mild cognitive impairment that was statistically significant. However, the reason for the decline is not clear. The researchers can only point to more education as the predominant factor. They surmise that more treatment and prevention of risk factors for cardiovascular disease may have played a role.

So how is dementia defined?

According to the American Psychiatric Association’s DSM-5 (“Diagnostic and Statistical Manual of Mental Disorders,” Fifth Edition), dementia is a decline in cognition involving one or more cognitive domains. In addition to memory, these domains can include learning, executive function, language, social cognition, perceptual-motor and complex attention (3).

What can be done to further reduce dementia’s prevalence?

Knowing some of the factors that may increase and decrease dementia risk is a good start. Those that raise the risk of dementia include higher blood pressure (hypertension), higher heart rate, depression, calcium supplements in stroke patients and prostate cancer treatment with androgen deprivation therapy (ADT).

What abates risk?

This includes lifestyle modifications with diet and exercise. A diet shown to be effective in prevention and treatment of dementia is referred to as the MIND (Mediterranean–DASH intervention for neurodegenerative delay) diet, which is a combination of the Mediterranean-type and Dietary Approaches to Stop Hypertension (DASH) diets. Surprisingly, there is also a cocktail of supplements that may have beneficial effects.

How does medication to treat dementia, specifically Alzheimer’s, fit into this paradigm?

It is not that I was ignoring this issue. Our present medications are not effective enough to slow the disease progression by clinically significant outcomes. But what about the medications in the pipeline? The two hottest areas are focusing on tau tangles and amyloid plaques. Recently, drugs targeting tau tangles from TauRx Therapeutics and amyloid plaques from Eli Lilly failed to achieve their primary clinical end points during trials. There may be hope for these different classes of drugs, but don’t hold your breath. The plaques and tangles may be signs of Alzheimer’s dementia rather than causes. Several experts in the field are not surprised by the results.

Let’s look at the evidence.

The quandary that is blood pressure

If ever you needed a reason to control high blood pressure, the fact that it may contribute to dementia should be a motivator. In the recent Framingham Heart Study, Offspring Cohort, a prospective observational study, results showed that high blood pressure in midlife — looking specifically at systolic (top number) blood pressure (SBP) — increased the risk for dementia by 70 percent (4). Even worse, those who were controlled with blood pressure medications in midlife also had significant risk for dementia.

There were 1,440 patients involved in the study over a 16-year period with an examination every four years. Then, those patients who were free of dementia were examined for another eight years. Results showed a 107-patient incidence of dementia, of which half were on blood pressure medications. And when there was a rapid drop in SBP from midlife to late in life, there was a 62 percent increased risk, to boot. Thus, the moral of the story is that lifestyle changes to either prevent high blood pressure or to get off medications may be the most appropriate route to reducing this risk factor.

Prostate cancer inflates dementia risk

Actually, the title above does not do justice to prostate cancer. It is not the prostate cancer, but the treatment for prostate cancer, androgen deprivation therapy (ADT), that may increase the risk of dementia by greater than twofold (5). Treatment duration played a role: those who had a year or more of ADT were at higher risk. ADT suppresses production of the male hormones testosterone and dihydrotestosterone. The study involved over 9,000 men with a 3.4-year mean duration; however, it was a retrospective (backward-looking) analysis and requires a more rigorous prospective study design to confirm the results. Thus, though the results are only suggestive, they are intriguing.

Calcium supplements — not so good

In terms of dementia, the Prospective Population Study of Women and H70 Birth Cohort trial has shown that calcium supplements, especially when given to patients who have a history of stroke, increase the risk of dementia by greater than sixfold (6). Those who had white matter lesions in the brain also had an increased risk. The population involved 700 elderly women, with 98 given calcium supplements. How do we reduce this risk? Easy: Don’t give calcium supplements to those who have had a stroke. This brings more controversy to taking calcium supplements, especially for women. You are better off getting calcium from foods, especially plant-based foods.

The MIND diet to the rescue

In a recent study, results showed that the MIND diet reduced the risk of Alzheimer’s dementia by 53 percent in those who were adherent. It also showed a greater than one-third reduction in dementia risk in those who only partially followed the diet (7). There were over 900 participants between the ages of 58 and 98 in the study, which had a 4.5-year duration. When we talk about lifestyle modifications, the problem is that sometimes patients find diets too difficult to follow. The MIND diet was ranked one of the easiest to follow. It involves a very modest amount of predominantly plant-based foods, such as two servings of vegetables daily — one green leafy. If that is not enough, the MIND diet has shown the ability to slow the progression of cognitive decline in those individuals who do not have full-blown dementia (8).

Supplement cocktail

To whet your appetite, a recent study involving transgenic growth hormone mice (which have accelerated aging and demonstrate cognitive decline) showed a cocktail of supplements helped decrease the risk of brain deterioration and function usually seen with aging and in severe Alzheimer’s dementia (9). The cocktail contained vitamins, minerals and nutraceuticals, such as bioflavonoids, garlic, cod liver oil, beta carotene, green tea extract and flax seed. Each compound by itself is not considered to be significant, but taken together they seem to have beneficial effects for dementia prevention in mice.

The reasons for dementia may involve mitochondrial dysfunction, oxidative stress and inflammation that are potentially being modified by these supplements. Hopefully, there will be more to come on this subject. It comes down to the fact that lifestyle modifications, whether in terms of reducing risk or slowing the progression of the disease, trump current medications and those furthest along in the drug pipeline. There may also be a role for a supplement cocktail, though it’s too early to tell. The MIND diet has shown some impressive results that suggest powerful effects.

References: (1) uptodate.com. (2) JAMA Intern Med. online Nov. 21, 2016. (3) uptodate.com. (4) American Neurological Association (ANA) 2016 Annual Meeting. Abstract M148. (5) JAMA Oncol. online Oct. 13, 2016. (6) Neurology. online Aug. 17, 2016. (7) Alzheimers Dement. 2015;11:1007-1014. (8) Alzheimers Dement. 2015;11:1015-1022. (9) Environ Mol Mutagen. online May 20, 2016.

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.

Consuming white fleshy fruits such as pears may decrease ischemic stroke risk by as much as 52 percent.

By David Dunaief, M.D.

Stroke remains one of the top five causes of mortality and morbidity in the United States (1). As a result, we have a wealth of studies that inform us on issues ranging from identifying chronic diseases that increase stroke risk to examining the roles of medications and lifestyle in managing risk.

Impact of chronic diseases

There are several studies that show chronic diseases — such as age-related macular degeneration, rheumatoid arthritis and migraine with aura — increase the risk for stroke. Therefore, patients with these diseases must be monitored.

In the ARIC study, stroke risk was approximately 50 percent greater in patients who had AMD compared to those who did not — 7.6 percent versus 4.9 percent, respectively (2). This increase was seen in both types of stroke: ischemic (complete blockage of blood flow in the brain) and hemorrhagic (bleeding in the brain). The risk was greater for hemorrhagic stroke than for ischemic, 2.64 vs. 1.42 times increased risk.

However, there was a smaller overall number of hemorrhagic strokes, which may have skewed the results. This was a 13-year observational study involving 591 patients, ages 45 to 64, who were diagnosed with AMD. Most patients had early AMD. If you have AMD, you should be followed closely by both an ophthalmologist and a primary care physician.

Rheumatoid arthritis (RA)

In an observational study, patients with RA had a 30 percent increased risk of stroke, and those under 50 years old with RA had a threefold elevated risk (3). This study involved 18,247 patients followed for a 13-year period. There was also a 40 percent increased risk of atrial fibrillation (AF), a type of arrhythmia or irregular heartbeat. Generally, AF causes increased stroke risk; however, the authors were not sure if AF contributed to the increased risk of stroke seen here. They suggested checking regularly for AF in RA patients, and they surmised that inflammation may be an underlying cause for the higher number of stroke events.

Migraine with aura

In the Women’s Health Study, an observational study, the risk of stroke increased twofold in women who had migraine with aura (4). Only about 20 percent of migraines include an aura, and the incidence of stroke in this population is still rather rare, so put this in context (5).

Medications with beneficial effects

Two medications have shown positive impacts on reducing stroke risk: statins and valsartan. Statins are used to lower cholesterol and inflammation, and valsartan is used to treat high blood pressure. Statins do have side effects, such as increased risks of diabetes, cognitive impairment and myopathy (muscle pain). However, used in the right setting, statins are very effective. In one study, there was reduced mortality from stroke in patients who were on statins at the time of the event (6). Patients who were on a statin to treat high cholesterol had an almost sixfold reduction in mortality, compared to those with high cholesterol who were not on therapy.

There was also significant mortality reduction in those on a statin without high cholesterol, but with diabetes or heart disease. The authors surmise that this result might be from an anti-inflammatory effect of the statins. Of course, if you have side effects, you should contact your physician immediately.

Valsartan is an angiotensin II receptor blocker that works on the kidney to reduce blood pressure. However, in the post-hoc analysis (looking back at a completed trial) of the Kyoto Heart Study data, valsartan used as an add-on to other blood pressure medications showed a significant reduction, 41 percent, in the risk of stroke and other cardiovascular events for patients who have coronary artery disease (7).

It is important to recognize that chronic disease increases stroke risk. High blood pressure and high cholesterol are two of the most significant risk factors. Fortunately, statins can reduce cholesterol, and valsartan may be a valuable add-on to prevent stroke in those patients with coronary artery disease.

Medication combination: negative impact

There are two anti-platelet medications that are sometimes given together in the hopes of reducing stroke recurrence — aspirin and Plavix (clopidogrel). The assumption is that these medications together will work better than either alone. However, in a randomized controlled trial, the gold standard of studies, this combination not only didn’t demonstrate efficacy improvement but significantly increased the risk of major bleed and death (8, 9).

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

Aspirin: low dose vs. high dose

Greater hemorrhagic (bleed) risk is also a concern with daily aspirin regimens greater than 81 mg, which is the equivalent of a single baby aspirin. Aspirin’s effects are cumulative; therefore, a lower dose is better over the long term. Even 100 mg taken every other day was shown to be effective in trials. There are about 50 million patients who take aspirin chronically in the United States. If these patients all took 325 mg of aspirin per day — an adult dose — it would result in 900,000 major bleeding events per year (10).

Lifestyle modifications

A prospective study of 20,000 participants showed that consuming white fleshy fruits — apples, pears, bananas, etc. — and vegetables — cauliflower, mushrooms, etc. — decreased ischemic stroke risk by 52 percent (11). Additionally, the Nurses’ Health Study showed that foods with flavanones, found mainly in citrus fruits, decreased the risk of ischemic stroke by 19 percent (12). The authors suggest that the reasons for the reduction may have to do with the ability of flavanones to reduce inflammation and/or improve blood vessel function. I mention both of these trials together because of the importance of fruits in prevention of ischemic (clot-based) stroke.

Fiber’s important role

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

Refined grains, however, increased the risk of hemorrhagic stroke twofold (13). When eating grains, it is important to have whole grains. Read labels carefully, since some products that claim to have whole grains contain unbleached or bleached wheat flour, which is refined.

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

References: (1) cdc.gov. (2) Stroke online April 2012. (3) BMJ 2012; Mar 8;344:e1257. (4) Neurology 2008 Aug 12; 71:505. (5) Neurology. 2009;73(8):576. (6) AAN conference: April 2012. (7) Am J Cardiol 2012; 109(9):1308-1314. (8) ISC 2012; Abstract LB 9-4504; (9) www.clinicaltrials.gov NCT00059306. (10) JAMA 2007;297:2018-2024. (11) Stroke. 2011; 42: 3190-3195. (12) J. Nutr. 2011;141(8):1552-1558. (13) Am J Epidemiol. 2005 Jan 15;161(2):161-169.

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.

By Dr. David Dunaief

Prostate cancer is the second most common cancer in men, after skin cancer. The American Cancer Society estimates that, in 2016, there will be almost 190,000 new prostate cancer diagnoses in the United States and just over 26,000 deaths (1). What better time to discuss prostate cancer prevention than in “Movember,” a month dedicated to raising awareness of men’s health issues?

The best way to avoid prostate cancer is through lifestyle modifications, which means garnering knowledge 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 genetics or family history do 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, tomato sauce or cooked tomatoes, soy and even coffee.

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 meat and processed meats

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. 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 (4). 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.

However, this does not mean that men should cut back on fish consumption; the effects of omega-3s on heart disease prevention are significant, and heart disease is far more prevalent. Also, this is only one study finding. 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 effect

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.

Where does coffee fit in?

Surprisingly, coffee may reduce the risk of prostate cancer. It was recently shown in the Health Professionals Follow-Up Study, where there was a dose-response curve. In other words, the more coffee consumed, the lower the risk. Even those who consumed one to three cups a day saw a 30 percent reduction in the risk of lethal prostate cancers, whether the coffee was caffeinated or decaffeinated (11). Coffee contains bioactive compounds, such as phenolic acids, which have antioxidant effects.

There is a caveat. Although, in this study, more was better, that is not always true in many other studies. Therefore, I would not recommend drinking more than three cups per day, because of other potentially detrimental effects. I think it is apt to finish with two thoughts. Aaron Katz, M.D., from Columbia University Medical Center, had it right when he mentioned that lifestyle modification was important. He was talking about those with early-stage prostate cancer. However, the same philosophy can be applied to prevention of prostate cancer. My goal in writing this article was to arm you with the knowledge you need to start protecting yourself or your loved ones today.

References: (1) www.cancer.org. (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. (11) J Natl Cancer Inst. 2011;103:876-884.

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

Statin users tend to neglect dietary guidance.

By David Dunaief, M.D.

High cholesterol affects a great number of Americans and cuts across many demographics, affecting young and old and those in between. When we think of hyperlipidemia (high cholesterol), what do you think is the mainstay of medical treatment? If you said “statins” you would be correct.

Do statins deserve this central role in treatment? They have been convincingly shown in studies to significantly lower cholesterol, and they play an important role for those who have cardiovascular disease. However, should we be using statins as liberally as we have? Well, guidelines for the treatment of high cholesterol, released in November 2013, suggest that we should. In fact, if followed, these guidelines would increase the use of this medication, especially in those over the age of 60. Some in the medical community have even joked that statins might as well be put in the drinking water.

This is a medication that patients may be on for life. I don’t know about you, but that thought sends chills down my spine. We know all medications have pros and cons. Statins are no exception; they have been mired in controversy. For one thing, they have side effects. These include possibly increasing the risks of diabetes, myalgias (muscle pain), hepatic (liver) toxicity, kidney disorders and negatively affecting memory.

Statins also may reduce the benefits of exercise, and they may not be as effective in women as they are in men. Because statins are such effective cholesterol-lowering medications, does this mean that patients on these drugs may become complacent with their diets? A new study indicates that this is exactly what might be happening. Let’s look at the evidence.

Statins have been mired in controversy. Stock photo
Statins have been mired in controversy. 

Diet complacency

The “S” in statins does not stand for “superimmune to eating anything.” In a study published in JAMA Internal Medicine, results show that those who are taking statins tend to eat more calories and fats and, ultimately, increase their [body mass index] by gaining weight compared to those who were not taking statins (1).

In fact, in this study that used 11 years of NHANES data, results showed that there were a 14 percent increase in fat intake and an almost 10 percent increase in overall calorie intake among statin users. This resulted in a BMI that rose by 1.3 percent in those on statins, while in nonusers over the same period BMI only rose by 0.4 percent.

In other words, if you took an average male who was 5 feet 9 inches and weighed 200 lb, the difference between statin users and nonusers would be the difference between obesity and being just below obesity. Those on statins were consuming about 200 extra calories a day. This increase in calorie consumption occurred after they were placed on statins. Their weight also increased by 6.6 to 11 lb. This is especially concerning to the researchers, since the guidelines for statin use call for a prudent diet to help reduce fat and calorie intake with the ultimate goal of reducing weight.

However, the opposite was found to have happened — users consumed more calories and gained more weight. This is an observational study with over 27,000 participants, therefore no firm conclusions can be made. However, statins are not a license to gorge at the all-you-can-eat buffet line. We already know that statins may increase the risk of diabetes. Why worsen this risk with dietary indiscretions that are harmful to your BMI?

As an aside, the authors note that this increased calorie and fat consumption may be a contributing reason for the increased risk of diabetes with statins, but it’s too early to tell.

Impact on women

We tend to clump data together from trials that focus predominantly on one demographic, in this case men, and apply the results broadly to both men and women. However, in a May 5, 2014, New York Times article, “A New Women’s Issue: Statins,” some in the medical community, including the editor of JAMA, focus attention on this tendency, noting that this may be a mistake (2).

According to the dissenters, the thought process is that women have been underrepresented in statin trials, and cholesterol may not play the same role in women as it does in men. Yet almost half of the patients treated with statins are women. These physicians were referring to the use of statins in primary prevention, or in those who have high cholesterol but who do not have documented heart disease.

Lest you think their views are based solely on opinion or anecdotal data from clinical experience, this data on women was from the JUPITER trial, which looked at almost 7,000 initially healthy female participants (3). Statins did benefit women by reducing the occurrence of chest pain and reducing the number of stent placements and bypass surgeries, but they did not reach the primary end points of showing statistical significance in reducing the occurrence of a first heart attack, stroke or death.

The caveat is that there were not a large number of cardiovascular events — heart attacks, strokes or death — that occurred in either the treatment group or the control group. These results were in women over the age of 60. This may give slight pause when prescribing statins. By no means do I think these physicians are advocating to not give women statins, just that we may want to weigh the benefits and risks on a case-by-case basis.

Tamping down exercise benefits

If exercise is beneficial for lowering cardiovascular disease risk and so are statins, the logical presumption might be that the two together would create a synergistic effect that is greater than the two alone — or at least an added benefit from combining the two. Unfortunately, what seems straightforward is not always the case.

In a small, yet randomized controlled trial, participants who were put on statins and monitored for cardiopulmonary exercise saw a blunted aerobic effect compared to the control group, which exercised without the medication (4). In the treatment group, there was a marginal 1.5 percent improvement with aerobic exercise, while the control group experienced a much more robust 10 percent gain.

The reason for this disappointing discrepancy is that statins seem to interrupt the enzymes that are responsible for making the mitochondria (the powerhouse or energy source for the cell) more efficient. The most troubling aspect of this trial is that the participants chosen were out-of-shape, overweight individuals in need of aerobic exercise.

Whether or not a patient, male or female, is placed on cholesterol-lowering medication, one thing is clear: There is a strong need to make sure that lifestyle modifications are always emphasized to help reduce the risk of cardiovascular disease to its lowest levels. But the quandary becomes what to do with statins and exercise. And statins, as powerful and effective as they may be, still do have side effects, may reduce exercise benefits and may not have the same effects for women. Thus, they may not be appropriate for everyone. A healthy diet and exercise, however, are appropriate for all.

References: (1) JAMA Intern Med. online April 24, 2014. (2) nytimes.com. (3) N Engl J Med. 2008 Nov 20;359(21):2195-2207. (4) J Am Coll Cardiol. 2013;62(8):709-714.

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.