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Dr. David Dunaief

By David Dunaief, M.D.

 

Dr. David Dunaief

Chronic kidney disease (CKD) is much more common than you think. Those at highest risk for CKD include patients with diabetes, hypertension (high blood pressure) and those with first-degree relatives who have advanced disease. But those are only the ones at highest risk. This brings me to my first question.

Why is chronic kidney disease (CKD) a tricky disease?

Unfortunately, similar to high blood pressure and dyslipidemia (high cholesterol), the disease tends to be asymptomatic, at least initially. Only in the advanced stages do symptoms become distinct, though there can be vague symptoms such as fatigue, malaise and loss of appetite in moderate stages.

What are the stages?

CKD is classified into five stages based on the estimated glomerular filtration rate (eGFR), a way to determine kidney function. Stages 1 and 2 are the early stages, while stages 3a and 3b are the moderate stages, and finally stages 4 and 5 are the advanced stages. This demarcation is based on an eGFR of >60 ml/min for early, 30-59 ml/min for moderate and <30 ml/min for advanced. Stage 5 is end-stage kidney disease or failure.

March is National Kidney Month

Why is CKD important?

The prevalence of the disease is predicted to grow by leaps and bounds in the next 15 years. Presently, approximately 13 percent of those over age 30 in the U.S. population are affected by CKD. In a simulation model, it is expected to reach 16.7 percent prevalence in the year 2030. Currently, those who are ages 30 to 49 have a 54 percent chance of having CKD in their lifetimes; those 50 to 64 years of age, a slightly lower risk of 52 percent; and those 65 years and older, a 42 percent risk (1). Thus, a broad spectrum of people are affected. Another study’s results corroborate these numbers, suggesting almost a 60 percent lifetime risk of at least moderate stage 3a to advanced stage 5 CKD (2). If these numbers are correct, they are impressive, and the disease needs to be addressed. We need to take precautions to prevent the disease and its progression.

Who should be screened?

According to the U.S. Preventive Services Task Force, screening for CKD may not be warranted in the asymptomatic “healthy” population (3). This means people without chronic diseases. The studies are inconclusive in terms of benefits and harms. In order to qualify as CKD, there has to be a minimum of three months of decreased kidney function. This appears to be a paradox: Remember, CKD is asymptomatic generally until the advanced stages. However, there are a number of caveats in the report.

Those who are at highest risk should be screened, including, as I mentioned above, patients with diabetes or hypertension. In an interview on www.Medscape.com entitled “Proteinuria: A Cheaper and Better Cholesterol?” two high-ranking nephrologists suggest that first-degree relatives of advanced CKD patients should also be screened and that those with vague symptoms of fatigue, malaise and/or decreased appetite may also be potential candidates (4). This broadens the asymptomatic population that may benefit from screening.

The fix!

Fortunately, there are several options available, ranging from preventing CKD with specific exercise to slowing the progression with lifestyle changes and medications.

Why exercise?

Here we go again, preaching the benefits of exercise. But what if you don’t really like exercise? It turns out that the results of a study show that walking reduces the risk of death and the need for dialysis by 33 percent and 21 percent, respectively (5). And although some don’t like formal exercise programs, most people agree that walking is enticing.

The most prevalent form of exercise in this study was walking. The results are even more intriguing; they are based on a dose-response curve. In other words, those who walk more often see greater results. So, the participants who walked one to two times per week had a significant 17 percent reduction in death and a 19 percent reduction in kidney replacement therapy, whereas those who walked at least seven times per week experienced a more impressive 59 percent reduction in death and a 44 percent reduction in the risk of dialysis. Those who were in between saw a graded response. There were 6,363 participants for an average duration of 1.3 years.

Protein is important, right?

Yes, protein is important for tissue and muscle health. But when it comes to CKD, more is not necessarily better, and may even be harmful. In a meta-analysis (a group of 10 randomized controlled trials, the gold standard of studies), results showed that the risk of death or treatment with dialysis or kidney transplant was reduced by 32 percent in those who consumed less protein compared to unrestricted protein (6). This meta-analysis used the Cochrane database to search for studies. According to the authors, as few as two patients would need to be treated for a year in order to prevent one from either dying or reaching the need for dialysis or transplant. Unfortunately, the specific quantity of protein consumption that is ideal in CKD patients could not be ascertained since the study was a meta-analysis.

Sodium: How much?

The debate roils on: How much do we need to reduce sodium in order to see an effect? Well, the good news is that in a study, results showed that a modest sodium reduction in our diet may be sufficient to help prevent proteinuria (protein in the urine) (7). Different guidelines recommend sodium intake ranging from fewer than 1500 mg to 2300 mg daily. This particular study says that less than 2000 mg is beneficial, something all of us can achieve.

Of course medications have a place

We routinely give certain medications, ACE inhibitors or ARBs, to patients who have diabetes to protect their kidneys. What about patients who do not have diabetes? ACEs and ARBs are two classes of anti-hypertensives — high blood pressure medications — that work on the RAAS system of the kidneys, responsible for blood pressure and water balance (8).

Results of a study show that these medications reduced the risk of death significantly in patients with moderate CKD. Most of the patients were considered hypertensive. However, there was a high discontinuation rate among those taking the medication. If you include the discontinuations and regard them as failures, then all who participated showed a 19 percent reduction in risk of death, which was significant. However, if you exclude discontinuations, the results are much more robust with a 63 percent reduction. To get a more realistic picture, the intention-to-treat result (those that include both participants and dropouts) is probably the response that will occur in clinical practice unless the physician is a really good motivator or has very highly motivated patients.

While these two classes of medications, ACE inhibitors and ARBs, are good potential options for protecting the kidneys, they are not the only options. You don’t necessarily have to rely on drug therapies, and there is no downside to lifestyle modifications. Lowering sodium modestly, walking frequently, and lowering your protein consumption may all be viable options, with or without medication, since medication compliance was woeful. Screening for asymptomatic, moderate CKD may lack conclusive studies, but screening should occur in high-risk patients and possibly be on the radar for those with vague symptoms of lethargy as well as aches and pains. Of course, this is a discussion to have with your physician.

References: (1) Am J Kidney Dis. 2015;65(3):403-411. (2) Am J Kidney Dis. 2013;62(2):245-252. (3) Ann Int. Med. 2012;157(8):567-570. (4) www.Medscape.com. (5) Clin J Am Soc Nephrol. 2014;9(7):1183-1189. (6) Cochrane Database Syst Rev. 2009;(3):CD001892. (7) Curr Opin Nephrol Hypertens. 2014;23(6):533-540. (8) J Am Coll Cardiol. 2014;63(7):650-658.

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.

In Europe, lipoic acid is classified as a drug, unlike in the United States, where it is a supplement.
Lipoic acid may have a significant effect on multiple chronic diseases

By David Dunaief, M.D.

Lipoic acid, also known as alpha lipoic acid and thioctic acid, is a noteworthy supplement. I am not a big believer in lots of supplements for several reasons: Diet contributes thousands more nutrients that work symbiotically; in the United States, supplements are not regulated by the FDA, thus there is no official oversight; and research tends to be scant and not well-controlled.

Dr. David Dunaief

So why would I write about lipoic acid? It is a supplement that has scientific data available from randomized controlled trials, which are the gold standard of studies. In Europe, lipoic acid is classified as a drug, unlike the United States, where it is a supplement (1).

Lipoic acid is an antioxidant, helping to prevent free radical damage to cells and tissues, but also is a chelating agent, potentially removing heavy metals from the body. Lipoic acid is involved in generating energy for cells; it is an important cofactor for the mitochondria, the cell’s powerhouse. It may also boost glutathione production, a powerful antioxidant in the liver (1). We produce small amounts of lipoic acid in our bodies naturally. Lipoic acid may be important in chronic diseases, including Alzheimer’s, multiple sclerosis and diabetic peripheral neuropathy. Let’s look at the evidence.

Diabetic peripheral neuropathy

Diabetic peripheral neuropathy, or diabetic neuropathy, involves oxidative stress and occurs in up to half the population with diabetes. One in five patients, when diagnosed, will already have peripheral neuropathy. The most common type is distal symmetric polyneuropathy — damage to nerves on both sides of the body in similar locations. It causes burning pain, numbness, weakness and pins and needles in the extremities (2).

The best studies with lipoic acid focus on peripheral neuropathy with diabetes. In a double-blinded, randomized controlled trial (SYDNEY I), results showed that the total treatment score had improved significantly more for those receiving 600 mg lipoic acid by intravenous therapy compared to the placebo group (3). Also, individual symptoms of numbness, burning pain and prickling significantly improved in the group treated with lipoic acid compared to placebo.

The study involved 120 diabetes patients with stage 2 neuropathy. Its weakness was its duration; it was a very short trial, about three weeks. The author concluded that this therapy would be a good adjunct for those suffering diabetic neuropathy.

In a follow-up to this study (SYDNEY II), the design and the results were the same (4). In other words, in a second double-blinded, placebo-controlled trial, the lipoic acid treatment group showed significantly better results than the placebo group. There were 180 patients with a similarly short duration of five weeks.

Why include this study? There were several important differences. One was that lipoic acid was given in oral supplements, rather than intravenously. Thus, this is a more practical approach. Another difference is that there were three doses tested for lipoic acid: 600, 1,200 and 1,800 mg. Interestingly, all of them had similar efficacy. However, the higher doses had more side effects of nausea, vomiting and vertigo, again without increased effectiveness. This suggests that an oral dose of 600 mg lipoic acid may help treat diabetic peripheral neuropathy.

Dementia and Alzheimer’s

In a recent randomized, placebo-controlled trial involving Alzheimer’s patients, results were significantly better for lipoic acid (600-mg oral dose) in combination with fish oil, compared to fish oil alone or to placebo (5). The amount of fish oil used was 3 grams daily containing 675 mg docosahexaenoic acid and 975 mg eicosapentaenoic acid of the triglyceride formulation.

The duration of this pilot study was 12 months with 39 patients, and the primary end point was a change in an oxidative stress biomarker, which did not show statistical significance. However, and very importantly, the secondary end point was significant: slowing the progression of cognitive and functional decline with the combination of fish oil and lipoic acid. Minimental status and instrumental activities of daily living declined less in the combination treatment group. This was encouraging, although we need larger trials.

However, another study showed 900 mg lipoic acid in combination with 800 IU daily of vitamin E (alpha tocopherol strain) and 500 mg vitamin C actually mildly reduced an oxidative stress biomarker but had a negative impact on Alzheimer’s disease by increasing cognitive decline on a minimental status exam (6). What we don’t know is whether the combination of supplements in this study produced the disappointing effects or if an individual supplement was the cause. It is unclear since the supplements were tested in combination. The study duration was 16 weeks and involved 78 moderate to severe Alzheimer’s patients.

Multiple sclerosis

In a study involving rats, giving them high doses of lipoic acid resulted in slowing of the progression of multiple sclerosis-type disease (7). The mechanism by which this may have occurred involved blocking the number of inflammatory white blood cells allowed to enter the cerebrospinal fluid in the brain and spinal cord by reducing the enzymatic activity of factors such as matrix metalloproteinases.

I know this sounds confusing, but the important point is that this may relate to a human trial with 30 patients that showed reduction in the enzyme MMP (8). Thus, it could potentially slow the progression of multiple sclerosis. This is purely connecting the dots. We need a large-scale trial that looks at clinical outcomes of progression in MS, not just enzyme levels. The oral dose used in this study was 1,200 to 2,400 mg lipoic acid per day.

Interestingly, the 1,200-mg dose used in the human trial was comparable to the high dose that showed slowed progression in the rat study (9). This only whets the appetite and suggests potential. So, we have lots of data. What do we know? In diabetic neuropathy, 600 mg oral lipoic acid may be beneficial. However, in Alzheimer’s the jury is still out, although 600 mg lipoic acid in combination with fish oil has potential to slow the cognitive decline in Alzheimer’s disease. It also may have a role in multiple sclerosis with an oral dose of 1,200 mg, though this is early data.

Always discuss the options with your physician before taking a supplement; in the wrong combinations and doses, supplements potentially may be harmful. The good news is that it has a relatively clean safety profile. If you do take lipoic acid, know that food interferes with its absorption, so it should be taken on an empty stomach (1).

References: (1) lpi.oregonstate.edu. (2) emedicine.medscape.com. (3) Diabetes Care. 2003;26:770-776. (4) Diabetes Care. 2006;29:2365-2370. (5) J Alzheimer’s Dis. 2014;38:111-120. (6) Arch Neurol. 2012;69:836-841. (7) J Neuroimmunol. 2002;131:104-114. (8) Mult Scler. 2005;11:159-165. (9) Mult Scler. 2010;16:387-397.

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.

CoQ10 is the first new ‘drug’ in over a decade to show survival benefits in heart failure.
A supplement reduces the risk of cardiovascular events

By David Dunaief, M.D.

Heart attacks and heart disease get a lot of attention, but chronic heart failure is something that tends to be overlooked by the press. The reason may be that heart failure is not acute like a heart attack.

Dr. David Dunaief

To clarify by using an analogy, a heart attack is like a tidal wave whereas heart failure is like a tsunami. You don’t know it is coming until it may be too late. Heart failure is an insidious (slowly developing) disease and thus may take years before it becomes symptomatic. It also increases the risk of heart attack and death.

Heart failure occurs in about 20 percent of the population over the age of 40 (1). There are about 5.8 million Americans with heart failure (2). Not surprisingly, incidence of heart failure increases with age (3).

Heart failure (HF) occurs when the heart’s pumping is not able to keep up with the body’s demands and may decompensate. It is a complicated topic, for there are two types — systolic heart failure and diastolic heart failure. The basic difference is that the ejection fraction, the output of blood with each contraction of the left ventricle of the heart, is more or less preserved in diastolic HF, while it can be significantly reduced in systolic HF.

We have more evidence-based medicine, or medical research, on systolic heart failure. Fortunately, both types can be diagnosed with the help of an echocardiogram, an ultrasound of the heart. The signs and symptoms may be similar, as well, and include shortness of breath on exertion or when lying down; edema or swelling; reduced exercise tolerance; weakness and fatigue. The risk factors for heart failure include diabetes, coronary artery disease, high blood pressure, obesity, smoking, heart attacks and valvular disease.

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

Effect of diet

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

In a population-based, prospective (forward-looking) study, called the Swedish Mammography Cohort, results show that a diet rich in antioxidants reduces the risk of developing HF (4). In the group that consumed the most nutrient-dense foods, there was a significant 42 percent (p<0.001) reduction in the development of HF, compared to the group that consumed the least. According to the authors, the antioxidants were derived mainly from fruits, vegetables, whole grains, coffee and chocolate. Fruits and vegetables were responsible for the majority of the effect.

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

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

CoQ10 supplementation

Coenzyme Q10 is a substance produced by the body that helps the mitochondria (the powerhouse of the cell) produce energy. It is thought of as an antioxidant. In a meta-analysis (group of 13 studies), the results showed that supplementation with CoQ10 may help improve functioning in patients with heart failure (5). This may occur because of a modest rise in ejection fraction functioning. It seems to be important in systolic heart failure. Supplementation with CoQ10 may help to reduce its severity.

The doses used in the meta-analysis ranged from 60 mg to 300 mg. Interestingly, those that were less than or equal to 100 mg showed statistical significance, while higher doses did not reach statistical significance. This CoQ10 meta-analysis was small. It covered 13 studies and fewer than 300 patients.

Like some other supplements, CoQ10 has potential benefits, but more study is needed. Because there are no studies showing significant deleterious effects, which doesn’t mean there won’t be, it is worth starting HF patients with comprised ejection fractions on 100 mg CoQ10 and titrating up, as long as patients can tolerate it, although the next study would suggest 300 mg was the appropriate dose.

CoQ10 — a well-run study

Results of the Q-SYMBIO study, a randomized controlled trial, the gold standard of studies, showed an almost 50 percent reduction in the risk of all-cause mortality and 50 percent fewer cardiac events with CoQ10 supplementation (6). This one randomized controlled trial followed 420 patients for two years who had severe heart failure. This involved using 100 mg of CoQ10 three times a day compared to placebo.

The lead author goes as far as to suggest that CoQ10 should be part of the paradigm of treatment. This the first new “drug” in over a decade to show survival benefits in heart failure. Thus, if you have heart failure, you may want to discuss CoQ10 with your doctor.

Iron deficiency

Anemia and iron deficiency are not synonymous, since iron deficiency can occur without anemia. A recent observational study that followed 753 heart failure patients for almost two years showed that iron deficiency without anemia increased the risk of mortality in heart failure patients by 42 percent (7).

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

The authors conclude that iron deficiency is potentially more predictive of clinical outcomes than anemia, contributes to the severity of HF, and is common in these patients. Thus, it behooves us to try to prevent heart failure through dietary changes, including high levels of antioxidants, because it is not easy to reverse the disease. Those with HF should have their ferritin and iron levels checked, for these are correctable. I am not typically a supplement advocate; however, based on the latest results, CoQ10 seems like a compelling therapy to reduce risk of further complications and potentially death. Consult with your doctor before taking CoQ10 or any other supplements, especially if you have heart failure.

References: (1) Circulation. 2002;106(24):3068. (2) Circulation. 2010;121(7):e46. (3) J Am Coll Cardiol. 2003;41(2):21. (4) Am J Med. 2013 Jun:126(6):494-500. (5) Am J Clin Nutr. 2013 Feb;97(2):268-275. (6) JACC Heart Fail. 2014 Dec;2(6):641-649. (7) Am Heart J. 2013;165(4):575-582.

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.

A nutrient-dense, plant-based diet that intensively controls blood sugar is likely to decrease the risk of diabetic retinopathy complication. Stock photo
Diabetic retinopathy is a leading cause of blindness.

By David Dunaief, M.D.

Dr. David Dunaief

With diabetes, we tend to concentrate on stabilization of the disease as a whole. This is a good thing. However, there is not enough attention spent on microvascular (small vessel disease) complications of diabetes, specifically diabetic retinopathy (negativity affecting blood vessels in the back of the eye), which is an umbrella term.

This disease, a complication of diabetes that is related to sugar control, can lead to blurred vision and blindness. There are at least three different disorders that make up diabetic retinopathy. These are dot and blot hemorrhages, proliferative diabetic retinopathy and diabetic macular edema. The latter two are the most likely disorders to cause vision loss. Our focus for this article will be on diabetic retinopathy as a whole and on diabetic macular edema.

Diabetic retinopathy is the No. 1 cause of vision loss in those who are of working age, 25 to 74 years old (1). Risk factors include duration of diabetes, glucose (sugars) that is not well-controlled, smoking, high blood pressure, kidney disease, pregnancy and high cholesterol (2).

What is diabetic macula edema, also referred to as DME? This disorder is edema, or swelling, due to extracellular fluid accumulating in the macula (3). The macula is a yellowish oval spot in the central portion of the retina — in the inner segment of the back of the eye — and it is sensitive to light. The macula is the region with greatest visual acuity. Hence, when fluid builds up from blood vessels leaking, there is potential loss of vision.

Whew! Did you get all that? If not, to summarize: Diabetic macula edema is fluid in the back of the eye that may cause vision loss. The highest risk factor for DME was for those with the longest duration of diabetes (4). Ironically, an oral class of drugs, thiazolidinediones, which includes rosiglitazone (Avandia) and pioglitazone (Actos), used to treat type 2 diabetes may actually increase the risk of DME. However, the results on this are conflicting.

DME is traditionally treated with lasers. But intravitreal (intraocular — within the eye) injections of a medication known as ranibizumab (Lucentis) may be as effective as laser. Studies suggest that injections alone may be as effective as injections plus laser treatments, though the studies are in no way definitive. Unfortunately, many patients are diagnosed with DME after it has already caused vision loss. If not treated after having DME for a year or more, patients can experience permanent loss of vision (5).

In a cross-sectional study (a type of observational study) using NHANES data from 2005-2008, among patients with DME, only 45 percent were told by a physician that the diabetes had affected their eyes (6). Approximately 46 percent of patients reported that they had not been to a diabetic nurse educator, nutritionist or dietician in more than a year — or never.

The problem is that the symptoms of vision loss don’t necessarily occur until the latter stages of the disorder. According to the authors, there needs to be an awareness campaign about the importance of getting your eyes examined on an annual basis if you have diabetes. Many patients are unaware of the association between vision loss and diabetes.

According to a study, there is good news in that the percentage of patients reporting visual impairment from 1997 to 2010 decreased (7). However, the absolute number of patients with vision loss has actually continued to grow, but at a lesser rate than diabetes as a disease has grown.

Treatment options: lasers and injections

There seems to be a potential paradigm shift in the making for the treatment of DME. Traditionally, patients had been treated with lasers. The results from a randomized controlled trial, the gold standard of studies, showed that intravitreal (delivery directly into the eye) injections with ranibizumab, whether given prompt laser treatments or treatments delayed for at least 24 weeks, were equally effective in treating DME (8).

In fact, some in the delayed group, 56 patients or about half, never even required laser treatments at all. Unfortunately, intravitreal injections may be used as frequently as every four weeks. Though in practice, ophthalmologists generally are able to inject patients with the drug less frequently. However, the advantage of receiving prompt laser treatments along with the injections was a reduction in the median number of injections.

Increased risk with diabetes drugs

You would think that drugs to treat type 2 diabetes would prevent DME from occurring as well. However, in the THIN trial, a retrospective (backward-looking) study, a class of diabetes drugs, thiazolidinediones, which includes Avandia and Actos, actually increased the occurrence of DME compared to those who did not use these oral medications (9). Those receiving these drugs had a 1.3 percent incidence of DME at year 1, whereas those who did not had a 0.2 percent incidence. This incidence was persistent through the 10 years of follow-up.

To make matters worse, those who received both thiazolidinediones and insulin had an even greater incidence of DME. There were 103,000 diabetes patients reviewed in this trial. It was unclear whether the drugs, because they were second-line treatments, or the severity of the diabetes itself may have caused these findings.

This is in contrast to a previous ACCORD eye substudy, a cross-sectional analysis, which did not show an association between thiazolidinediones and DME (10). This study involved review of 3,473 participants who had photographs taken of the fundus (the back of the eye).

What does this ultimately mean? Both of these studies were not without weaknesses. It was not clear how long the patients had been using the thiazolidinediones in either study or whether their sugars were controlled and to what degree. The researchers were also unable to control for all other possible confounding factors (11). Thus, there needs to be a prospective (forward-looking) trial done to sort out these results.

Diet

The risk of progression of diabetic retinopathy was significantly lower with intensive blood sugar controls using medications, one of the few positive highlights of the ACCORD trial (12). Medication-induced intensive blood sugar control also resulted in more increased mortality and no significant change in cardiovascular events. But an inference can be made: A nutrient-dense, plant-based diet that intensively controls blood sugar is likely to decrease the risk of diabetic retinopathy complications (13, 14).

The best way to avoid diabetic retinopathy is obviously to prevent diabetes. Barring that, it’s to have sugars well controlled. If you or someone you know has diabetes, it is imperative that they get a yearly eye exam from an ophthalmologist so that DME and diabetic retinopathy, in general, is detected as early as possible, before permanent vision loss can occur. It is especially important for those diabetes patients who are taking the oral diabetes class thiazolidinediones, which include rosiglitazone (Avandia) and pioglitazone (Actos).

References: (1) Diabetes Care. 2014;37 (Supplement 1):S14-S80. (2) JAMA. 2010;304:649-656. (3) www.uptodate.com. (4) JAMA Ophthalmol online. 2014 Aug. 14. (5) www.aao.org/ppp. (6) JAMA Ophthalmol. 2014;132:168-173. (7) Morb Mortal Wkly Rep. 2011;60:1549-1553. (8) ASRS. Presented 2014 Aug. 11. (9) Arch Intern Med. 2012;172:1005-1011. (10) Arch Ophthalmol. 2010 March;128:312-318. (11) Arch Intern Med. 2012;172:1011-1013. (12) www.nei.nih.gov. (13) OJPM. 2012;2:364-371. (14) Am J Clin Nutr. 2009;89:1588S-1596S.

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.

Studies show that even moderate exercise can significantly lower mortality risk when compared with no physical activity at all.

Reducing inflammation is part of this process.

By David Dunaief, M.D.

Dr. David Dunaief

When asked what was more important, longevity or healthy aging (quality of life), more people choose the latter. Why would you want to live a long life but be miserable? Well, it turns out the two components are not mutually exclusive. I would like you to ponder the possibility of a third choice, “all of the above.” Would you change your answer and, instead of making a difficult choice between the first two, choose the third?

I frequently use the example of Jack LaLanne, a man best known for popularizing fitness. He followed and preached a healthy lifestyle, which included diet and exercise. He was quite a motivator for many and ahead of his time. He died at the ripe old age of 96.

This brings me to my next point, which is that the number of 90-year-olds is growing by leaps and bounds. According to the National Institutes of Health, those who were more than 90 years old increased by 2.5 times over a 30-year period from 1980 to 2010 (1). This group is among what researchers refer to as the “oldest-old,” which includes those aged 85 and older.

What do these people have in common? According to one study, they tend to have fewer chronic morbidities or diseases. Thus, they tend to have a better quality of life with a greater physical functioning and mental acuity (2).

In a study of centenarians, genetics played a significant role. Characteristics of this group were that they tended to be healthy and then die rapidly, without prolonged suffering (3). Another benchmark is the amount of health care dollars spent in their last few years. Statistics show that the amount spent for those who were in their 60s and 70s was significantly higher, three times as much, as for centenarians in their last two years (4).

Factors that predict one’s ability to reach this exclusive club may involve both genetics and lifestyle choices. One group of people in the U.S. that lives longer lives on average than most is Seventh-day Adventists. We will explore why this might be the case and what lifestyle factors could increase our potential to maximize our healthy longevity. Exercise and diet may be key components of this answer. Now that we have set the tone, let’s look at the research.

Exercise

For all those who don’t have time to exercise or don’t want to spend the time, this next study is for you. We are told time and time again to exercise. But how much do we need, and how can we get the best quality? In a 2014 study, the results showed that 5 to 10 minutes of daily running, regardless of the pace, can have a significant impact on life span by decreasing cardiovascular mortality and all-cause mortality (5).

Amazingly, even if participants ran fewer than six miles per week at a pace slower than 10-minute miles, and even if they ran only one to two days a week, there was still a decrease in mortality compared to nonrunners. Here is the kicker: Those who ran for this very short amount of time potentially added three years to their life span. There were 55,137 participants ranging in age from 18 to 100 years old.

An accompanying editorial to this study noted that more than 50 percent of people in the United States do not meet the current recommendation of at least 30 minutes of moderate exercise per day (6). Thus, this recent study suggests an easier target that may still provide significant benefits.

Diet

A long-standing paradigm is that we need to eat sufficient animal protein. However, there have been cracks developing in this façade of late, especially as it relates to longevity. In an observational study using NHANES III data, results show that those who ate a high-protein diet (greater than 20 percent from protein) had a twofold increased risk of all-cause mortality, a four times increased risk of cancer mortality and a four times increased risk of dying from diabetes (7). This was over a considerable duration of 18 years and involved almost 7,000 participants ranging in age at the start of the study from 50 to 65.

However, this did not hold true if the protein source was from plants. In fact, a high-protein plant diet may reduce the risks, not increase them. The reason for this effect, according to the authors, is that animal protein may increase insulin growth factor-1 and growth hormones that have detrimental effects on the body.

Interestingly, those who are over the age of 65 may benefit from more animal protein in reducing the risk of cancer. However, there was a significantly increased risk of diabetes mortality across all age groups eating a high animal protein diet. The researchers therefore concluded that lower animal protein may be wise at least during middle age.

The Adventists Health Study 2 trial reinforced this data. It looked at Seventh-day Adventists, a group whose emphasis is on a plant-based diet, and found that those who ate animal protein up to once a week had a significantly reduced risk of dying over the next six years compared to those who were more frequent meat eaters (8). This was an observational trial with over 73,000 participants and a median age of 57 years old.

Inflammation

You may have heard the phrase that inflammation is the basis for more than 80 percent of chronic disease. But how can we quantify this into something tangible?

In the Whitehall II study, a specific marker for inflammation was measured, interleukin-6. The study showed that higher levels did not bode well for participants’ longevity (9). In fact, if participants had elevated IL-6 (>2.0 ng/L) at both baseline and at the end of the 10-year follow-up period, their probability of healthy aging decreased by almost half.

The takeaway from this study is that IL-6 is a relatively common biomarker for inflammation that can be measured with a simple blood test offered by most major laboratories. This study involved 3,044 participants over the age of 35 who did not have a stroke, heart attack or cancer at the beginning of the study.

The bottom line is that, although genetics are important for longevity, so too are lifestyle choices. A small amount of exercise, specifically running, can lead to a substantial increase in healthy life span. While calories are not equal, protein from plants may trump protein from animal sources in reducing the risk of mortality from all causes, from diabetes and from heart disease. This does not necessarily mean that one needs to be a vegetarian to see the benefits. IL-6 may be a useful marker for inflammation, which could help predict healthy or unhealthy outcomes. Therefore, why not have a discussion with your doctor about testing to see if you have an elevated IL-6? Lifestyle modifications may be able to reduce these levels.

References: (1) nia.nih.gov. (2) J Am Geriatr Soc. 2009;57:432-440. (3) Future of Genomic Medicine (FoGM) VII. Presented March 7, 2014. (4) CDC.gov. (5) J Am Coll Cardiol. 2014;64:472-481. (6) J Am Coll Cardiol. 2014;64:482-484. (7) Cell Metab. 2014;19:407-417. (8) JAMA Intern Med. 2013;173:1230-1238. (9) CMAJ. 2013;185:E763-E770.

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.

Cocoa components reduce cardiovascular risk

By David Dunaief, M.D.

Dr. David Dunaief

Valentine’s Day is one of the wonderful things about winter. For many, it lifts the mood and spirit. A traditional gift is chocolate. But do the benefits of chocolate go beyond Valentine’s Day? The short answer is yes, which is good news for chocolate lovers. However, we are not talking about filled chocolates, but primarily dark chocolate and cocoa powder.

The health benefits of chocolate are derived in large part from its flavonoid content — compounds that are produced by plants. These health benefits are seen in cardiovascular disease, including stroke, heart disease and high blood pressure. This is ironic, since many chocolate boxes are shaped as hearts. Unfortunately, it is not necessarily the chocolates that come in these boxes that are beneficial.

Let’s look at the evidence.

Effect on heart failure

Heart failure is very difficult to reverse. Therefore, the best approach is prevention, and dark chocolate may be one weapon in this crusade. In the Swedish Mammography Cohort study, those women who consumed dark chocolate saw a reduction in heart failure (1). The results were on a dose-response curve, but only to a point. Those women who consumed two to three servings of dark chocolate a month had a 26 percent reduction in the risk of heart failure.

For the dark chocolate lovers, it gets even better. Women who consumed one to two servings per week had an even greater reduction of 32 percent. However, those who ate more than these amounts actually lost the benefit in heart failure reduction and may have increased risk. With a serving (1 ounce) a day, there was actually a 23 percent increased risk.

This study was a prospective (forward-looking) observational study that involved more than 30,000 women over a long duration, nine years. The authors comment that chocolate has a downside of too much fat and calories and, if eaten in large quantities, it may interfere with eating other beneficial foods, such as fruits and vegetables. The positive effects are most likely from the flavonols, a subset of flavonoids, which come from the cocoa solids — the chocolate minus the cocoa butter.

Impact on mortality from heart attacks

In a two-year observational study, results showed that chocolate seemed to reduce the risk of cardiac death after a first heart attack (2). Again, the effects were based on a dose-response curve, but unlike the previous study, there was no increased risk beyond a certain modest frequency.

Those who consumed chocolate up to once a week saw a 44 percent reduction in risk of death, and those who ate the most chocolate — two or more times per week — saw the most effect, with 66 percent reduced risk. And finally, even those who consumed one serving of chocolate less than once per month saw a 27 percent reduction in death, compared to those who consumed no chocolate.

The study did not mention dark or milk chocolate; however, this was another study that took place in Sweden. In Sweden, milk chocolate has substantially more cocoa solids, and thus flavonols, than that manufactured for the U.S. There were over 1,100 patients involved in this study, and none of them had a history of diabetes, which is important to emphasize.

Stroke reduction

I don’t know anyone who does not want to reduce the risk of stroke. We tell patients to avoid sodium in order to control blood pressure and reduce their risk. Initially, sodium reduction is a difficult thing to acclimate to — and one that people fear. However, it turns out that eating chocolate may reduce the risk of stroke, so this is something you can use to balance out the lifestyle changes.

In yet another study, the Cohort of Swedish Men, which involved over 37,000 men, there was an inverse relationship between chocolate consumption in men and the risk of stroke (3). Those who ate at least two servings of chocolate a week benefited the most with a 17 percent reduction in both major types of stroke — ischemic and hemorrhagic — compared to those who consumed the least amount of chocolate. Although the reduction does not sound tremendous, compare this to aspirin, which reduces stroke risk by 20 percent. However, chocolate consumption study was observational, not the gold standard randomized controlled trial, like aspirin studies.

Blood pressure

One of the most common maladies, especially in people over 50, is high blood pressure. So, whatever we can do to lower blood pressure levels is important, including decreasing sodium levels, exercising and even eating flavonoid-rich cocoa.

In a meta-analysis (a group of 20 RCTs), flavonoid-rich cocoa reduced both systolic (top number) and diastolic (bottom number) blood pressure significantly: −2.77 mm Hg and −2.20 mm Hg, respectively (4). These studies involved healthy participants, who are sometimes the most difficult in whom to show a significant reduction, since their blood pressure is not high initially. One of the weaknesses of this meta-analysis is that the trials were short, between two and 18 weeks.

Why chocolate has an effect

Consuming a small amount of dark chocolate twice a week may lower the risk of heart disease.

Chocolate has compounds called flavonoids. The darker the chocolate, the more flavonoids there are. These flavonoids have potential antioxidant, antiplatelet and anti-inflammatory effects.

In a small, randomized controlled trial comparing 22 heart transplant patients, those who received dark flavonoid-rich chocolate, compared to a cocoa-free control group, had greater vasodilation (enlargement) of coronary arteries two hours after consumption (5). There was also a decrease in the aggregation, or adhesion, of platelets, one of the primary substances in forming clots. The authors concluded that dark chocolate may also cause a reduction in oxidative stress.

It’s great that chocolate, mainly dark, and cocoa powder have such substantial effects in cardiovascular disease. However, certain patients should avoid chocolate such as those with reflux disease, allergies to chocolate and diabetes. Be aware that Dutch-processed, or alkalized, cocoa powder may have lower flavonoid levels and is best avoided. Also, the darker the chocolate is, the higher the flavonoid levels. I suggest that the chocolate be at least 60 to 70 percent dark.

Moderation is the key, for all chocolate contains a lot of calories and fat. Based on the studies, two servings a week are probably where you will see the most cardiovascular benefits. Happy Post-Valentine’s Day!

References: (1) Circ Heart Fail. 2010;3(5):612-616. (2) J Intern Med. 2009;266(3):248-257. (3) Neurology. 2012;79:1223-1229. (4) Cochrane Database Syst Rev. 2012:15;8:CD008893. (5) Circulation. 2007 Nov 20;116(21):2376-2382.

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.

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.