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Medical Compass

Bones: What is beneficial and what is not?
Dr. David Dunaief

The prevalence of osteoporosis is increasing especially as the population ages. Why is this important? Osteoporosis may lead to increased risk of fracture due to a decrease in bone strength (1). That is what we do know. But what about what we think we know?

For decades we have been told that if we want strong bones, we need to drink milk. Advertising slogans have morphed from “Milk does a body good” to “Got Milk?” to “Milk Life.” Celebrities have worn milk mustaches to show how important it is to our diet. This has been drilled into our brains since we were toddlers. Milk has calcium and is fortified with vitamin D, so milk could only be helpful, right? Not necessarily.

The data is mixed, but studies indicate that milk may not be as beneficial as we have been led to believe. Even worse, it may be harmful. The operative word here is “may.” We will investigate this further. Vitamin D and calcium are good for us. But do supplements help prevent osteoporosis and subsequent fractures? Again the data is mixed, but supplements may not be the answer for those who are not deficient.

Of course, we know which drugs are potentially beneficial for osteoporosis; however, which one works the best for whom may be unclear. There are minimal head-to-head trials comparing different drugs (2). They all have beneficial reductions in fracture risk in patients with osteoporosis, but they also have side effects.

What do the guidelines tell us about those who are at potential risk for osteoporosis and fracture? A study looked at the predictability, or reliability, of the United States Preventive Services Task Force (USPSTF) recommendations for screening patients for osteoporosis. Unfortunately, the study showed that USPSTF guidelines were a nominal improvement over chance (3). In other words, the guidelines were able to predict only 24 percent of patients who ended up developing osteoporosis between the ages of 50 and 64.

Milk — it’s not what you think

Recent studies involving men and women in Sweden showed that milk may be harmful.

The results of a large, observational study involving men and women in Sweden showed that milk may be harmful (4). When comparing those who consumed three or more cups of milk daily to those who consumed less than one, there was a 93 percent increased risk of mortality in women between the ages of 39 and 74. There was also an indication of increased mortality based on dosage.

For every one glass of milk consumed there was a 15 percent increased risk of death in these women. There was a much smaller, but significant, 3 percent per glass increased risk of death in men. Women experienced a small, but significant, increased risk of hip fracture, but no increased risk in overall fracture risk. There was no increased risk of fracture in men, but there was no benefit either. There were higher levels of biomarkers that indicate oxidative stress and inflammation found in the urine.

This study was 20 years in duration and is eye-opening. We cannot make any decisive conclusions, only associations, since it is not a randomized controlled trial. But it does get you thinking. The researchers surmise that milk has high levels of D-galactose, a simple sugar that may increase inflammation and ultimately contribute to this potentially negative effect, whereas other foods have many-fold lower levels of this substance.

Ironically, the USDA recommends that, from 9 years of age through adulthood, we consume three cups of dairy per day (5). This is interesting, since the results from the previous study showed the negative effects at this recommended level of milk consumption. The USDA may want to rethink these guidelines.

Prior studies show milk may not be beneficial for preventing osteoporotic fractures. Specifically, in a meta-analysis that used data from the Nurses’ Health Study for women and the Health Professionals Follow-up Study for men, for each additional glass of milk per day during the teenage years there was a 9 percent increased risk of hip fracture in men only (6). However, this effect was negated when height was taken into account. Neither men nor women saw any benefit from milk consumption in preventing hip fractures. In other words, the milk you drank during your teenage years might not reduce hip fractures later in life.

Calcium disappointments

Unfortunately, it is not only milk that may not be beneficial. There was a meta-analysis that included observational studies and clinical trials. In the meta-analysis involving a group of observational studies, there was no statistically significant improvement in hip fracture risk in those men or women ingesting at least 300 mg of calcium from supplements and/or food on a daily basis (7).

The researchers did not differentiate the types of foods containing calcium. In a group of randomized controlled trials analyzed in the same study, those taking 800 to 1,600 mg of calcium supplements per day also saw no increased benefit in reducing nonvertebral fractures. In fact, in four clinical trials the researchers actually saw an increase in hip fractures among those who took calcium supplements. A weakness of the large multivaried meta-analyses is that vitamin D baseline levels, exercise and phosphate levels were not taken into account.

Vitamin D benefit

Finally, though the data is not always consistent for vitamin D, when it comes to fracture prevention, it appears it may be valuable. In a meta-analysis (involving 11 randomized controlled trials), vitamin D supplementation resulted in a reduction in fractures (8). When patients were given a median dose of 800 IUs (ranging from 792 to 2,000 IUs) of vitamin D daily, there was a significant 14 percent reduction in nonvertebral fractures and an even greater 30 percent reduction in hip fractures in those 65 years and over. However, vitamin D in lower levels showed no significant ability to reduce fracture risk.

Just because something in medicine is a paradigm does not mean it’s correct. Milk may be an example of this. Also, ironically, the “Milk Life” slogan may need an overhaul, especially in women between the ages of 39 and 74 years old, where there is a potential increased risk of mortality. No definitive statement can be made about calcium, although even in randomized controlled trials with supplements there seemed to be no significant benefit. Of course, the patients in these trials were not necessarily deficient in calcium or vitamin D.

In order to get benefit from vitamin D supplementation to prevent fracture, patients may need at least 800 IUs per day, which is the Institute of Medicine’s recommended amount for a relatively similar population as in the study. Also, different drugs have different benefits and side effect profiles.

Remember that studies, though imperfect, are better than tradition alone. Prevention and treatment therefore should be individualized, and deficiency in vitamin D or calcium should usually be treated, of course. Please, talk to your doctor before adding or changing any supplements.

References: (1) JAMA. 2001;285:785-795. (2) Ann Intern Med. 2014;161(10):711-723. (3) NAMS 2014 Meeting: Abstract S-13. Oct. 16, 2014. (4) BMJ 2014;349:g6015. (5) choosemyplate.gov. (6) JAMA Pediatr. 2014;168(1):54-60. (7) Am J Clin Nutr. 2007 Dec;86(6):1780-1790. (8) N Engl J Med. 2012 Aug. 2;367(5):481.

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 recent studies, whole fruit was shown to actually reduce the risk of type 2 diabetes.
Some surprising results about lifestyle

By David Dunaief, M.D.

Most of us know that type 2 diabetes is an epidemic in America and continues to grow. Type 2 diabetes was thought to be an adult-onset disease, but more and more children and adolescents are affected as well. The most recent statistics show that 50 percent of teens with diabetes between the ages of 15 and 19 have type 2 (1). Thus, this disease is pervasive throughout the population.

Let’s test our diabetes IQ. See if you can determine whether the following items are true or false.

•Whole fruit should be limited or avoided.

•Soy has detrimental effects with diabetes.

•Plant fiber provides too many carbohydrates.

•Coffee consumption contributes to diabetes.

•Bariatric surgery is an alternative to lifestyle changes.

My goal is to help debunk type 2 diabetes myths. All of these statements are false. Let’s look at the evidence.

Fruit

Fruit, whether whole fruit or fruit juice, has always been thought of as taboo for those with diabetes. This is only partially true. Yes, fruit juice should be avoided because it does raise or spike glucose (sugar) levels. The same does not hold true for whole fruit. Studies have demonstrated that patients with diabetes don’t experience a spike in sugar levels whether they limit the number of fruits consumed or have an abundance of fruit (2). In another study, whole fruit actually was shown to reduce the risk of type 2 diabetes (3).

In yet another study, researchers looked at different whole fruits to determine their impacts on glucose levels. They found that berries reduced glucose levels the most, but even bananas and grapes reduced these levels (4) — that’s right, bananas and grapes, two fruits people associate with spiking sugar levels and increasing carbohydrate load. The only fruit that seemed to have a mildly negative impact on sugars was cantaloupe. Fruit is not synonymous with sugar. One of the reasons for the beneficial effect is the flavonoids, or plant micronutrients, but another is the fiber.

Fiber

We know fiber is important in a host of diseases, and it is not any different in diabetes. In the Nurses’ Health Study and NHS II, two very large prospective (forward-looking) observational studies, plant fiber was shown to help reduce the risk of type 2 diabetes (5). Researchers looked at lignans, a type of plant fiber, specifically examining the metabolites enterodiol and enterolactone. They found that patients with type 2 diabetes have substantially lower levels of these metabolites in their urine, compared to the control group without diabetes. There was a linear, or direct, relationship between the amount of metabolites and the reduction in risk for diabetes. The authors therefore encourage patients to eat more of a plant-based diet to get this benefit.

Foods with lignans include: flaxseed; sesame seeds; cruciferous vegetables, such as broccoli and cauliflower; and an assortment of fruits and grains (6). The researchers could not determine which plants contributed the most benefit. They believe the effect is from antioxidant activity.

Soy and kidney function

Soy sometimes has a negative association. However, in diabetes patients with nephropathy (kidney damage or disease), soy consumption showed improvements in kidney function (7). There were significant reductions in urinary creatinine levels and reductions of proteinuria (protein in the urine), both signs that the kidneys are beginning to function better.

This was a small but randomized controlled trial, considered the gold standard of studies, over a four-year period with 41 participants. The control group’s diet consisted of 70 percent animal protein and 30 percent vegetable protein, while the treatment group’s consisted of 35 percent animal protein, 35 percent textured soy protein and 30 percent vegetable protein.

This is very important since diabetes patient are 20 to 40 times more likely to develop nephropathy than those without diabetes (8). It appears that soy protein may put substantially less stress on the kidneys than animal protein. This negative effect with animal protein may be due to higher levels of phosphorus. However, those who have hypothyroidism should be cautious or avoid soy since it may suppress thyroid functioning.

Coffee

Coffee is a staple in America and in my household. It is one thing my wife would never let me consider taking away. Well, she and the rest of the coffee-drinking portion of the country can breathe a big sigh of relief when it comes to diabetes.

There is a meta-analysis (involving 28 prospective studies) that shows coffee decreases the risk of developing diabetes (9). It was a dose-dependent effect; two cups decreased the risk more than one cup. Interestingly, it did not matter whether it contained caffeine or was decaffeinated. This suggests that caffeine is not necessarily the driving force behind the effect of coffee on diabetes.

The authors surmise that other compounds, including lignans, which have antioxidant effects, may play an important role. The duration of the studies ranged from 10 months to 20 years, and the database was searched from 1966 to 2013, with over one million participants.

Bariatric surgery

In recent years, bariatric surgery has grown in prevalence for treating severely obese (BMI>35 kg/m²) and obese (BMI >30 kg/m²) diabetes patients. In a meta-analysis of bariatric surgery (involving 16 RCTs and observational studies), the procedure illustrated better results than conventional medicines over a 17-month follow-up period in treating HbA1C (three-month blood glucose measure), fasting blood glucose and weight loss (10). During this time period, 72 percent of those patients treated with bariatric surgery went into diabetes remission and had significant weight loss.

However, after 10 years without proper management involving lifestyle changes, only 36 percent remained in remission with diabetes, and a significant number regained weight. Thus, whether one chooses bariatric surgery or not, altering diet and exercise are critical to maintain long-term benefits.

There is still a lot to be learned with diabetes, but our understanding of how to manage lifestyle modifications, specifically diet, is becoming clearer. The take-home messages are: Don’t avoid whole fruit; soy is potentially valuable; fiber from plants may play a very powerful role in preventing and treating diabetes; and coffee may help prevent diabetes.

Thus, the overarching theme is that you can’t necessarily go wrong with a plant-based diet focused on fruits, vegetables, beans and legumes. And if you choose a medical approach, bariatric surgery is a viable option, but don’t forget that you need to make significant lifestyle changes to increase the likely durability over 10 or more years.

References: (1) JAMA. 2007;297:2716-2724. (2) Nutr J. 2013 Mar. 5;12:29. (3) Am J Clin Nutr. 2012 Apr.;95:925-933. (4) BMJ online 2013 Aug. 29. (5) Diabetes Care. online 2014 Feb. 18. (6) Br J Nutr. 2005;93:393–402. (7) Diabetes Care. 2008;31:648-654. (8) N Engl J Med. 1993;328:1676–1685. (9) Diabetes Care. 2014;37:569-586. (10) Obes Surg. 2014;24:437-455.

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

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 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.