Summer is officially here, accompanied by reports of above-average temperatures from around the country. Dehydration is of particular concern at this time of year. Complications can be mild to severe, ranging from mood changes and headaches to heart palpitations, heat stroke, migraines and heart attacks.

We may be dehydrated prior to experiencing symptoms of thirst. Signals and symptoms of dehydration include tiredness, constipation, dry skin, dizziness or light-headedness, reduced tears and decreased or dark urine (1).

Dehydration can also be caused by medications. Diuretics, which are used by many for high blood pressure, heart failure, swelling and other chronic disorders, are primary culprits, especially in elderly patients.

There are inexpensive blood tests to help confirm mild dehydration. Simple blood urea nitrogen (BUN) and creatinine level tests are part of a basic metabolic panel. If each level on its own is high, this indicates there may be dehydration (2). If the ratio of BUN to creatinine is above 20, this is another signal that a patient may be dehydrated.

In addition, elevated sodium, potassium, urea and glucose are good indicators (3). Another way to confirm dehydration is to look at urine sodium concentrations. If they are low, it’s another red flag (2).

Headaches and migraines

Temperature is a potential trigger for headaches and migraine. As the temperature rises by intervals of 9 degrees, the risk for headache and migraines increases by 8 percent (4). This study involved 7,054 participants from one emergency room site. Warmer temperatures can potentially reduce blood volume in the body, causing dilation of the arteries, resulting in higher risk of headaches and migraines.

In another study, those who drank four cups more water had significantly fewer hours of migraine pain than those who drank less (5). Headache intensity decreased as well. Anecdotally, I had a patient who experienced a potentially dehydration-induced migraine after playing sports in the sweltering heat of Florida. He had the classic aura and was treated with hydration, Tylenol and caffeine, which helped avoid much of the suffering.

Heart palpitations

Heart palpations are very common and are broadly felt as a racing heart rate, skipped beat, pounding sensation or fluttering. Dehydration and exercise are contributing factors (6). They occur mainly when we don’t hydrate prior to exercise. All we need to do is drink one glass of water prior to exercise and then drink during exercise to avoid palpitations. Though these are not usually life threatening, they are anxiety producing for patients.

Cardiovascular issues

The Adventist Health Study, an observational study, showed a dose-response curve for men (7). In other words, group one, which drank more than five glasses of water daily, had the least risk of death from heart disease than group two, which drank more than three glasses of water daily. Those in group three, which drank less than two glasses per day, saw the least amount of benefit, comparatively. For women, there was no difference between groups one and two; both fared better than group three.

The reason for this effect, according to the authors, may relate to blood or plasma viscosity (thickness) and fibrinogen, a substance that helps clots form.

In a recently published small study, researchers studied the effects of mild dehydration on healthy males in their 20s (8). The study used intermittent, low-intensity walking to induce a 2 percent hydration deficit among study participants. Then, they provided a low water content diet for the remainder of the day.

Participants showed significantly impaired endothelial function. The endothelium is the inner lining of the blood vessels. Endothelial dysfunction can impair the balance between dilation and constriction of the blood vessels. Why is this important? This dysfunction can contribute to cardiovascular events such as heart attacks. While this study involved only 10 participants, it suggests that even mild dehydration can have a dramatic impact on cardiovascular health.

Ways to remain hydrated

How much water we need to drink depends on circumstances, such as diet, activity levels, environment and other factors. It is not true necessarily that we all should be drinking eight glasses of water a day. In a review article, the authors analyzed the data but did not find adequate studies to suggest that eight glasses is supported in the literature (10). It may actually be too much for some patients.

You may also get a significant amount of water from the foods in your diet. Nutrient-dense diets, like the Mediterranean or DASH diets, have a plant-rich focus. A study mentions that diets with a focus on fruits and vegetables increases water consumption (11). As you may know, 95 percent of their weights is attributed to water. An added benefit is an increased satiety level without eating calorically dense foods.

Mood and energy levels

In another recent study, mild dehydration resulted in decreased concentration, subdued mood, fatigue and headaches in women (9). In this small study, the mean age of participants was 23; they were neither athletes nor highly sedentary. Dehydration was caused by walking on a treadmill with or without taking a diuretic (water pill) prior to the exercise. The authors concluded that adequate hydration was needed, especially during and after exercise.

I would also suggest, from my practice experience, hydration prior to exercise.

The myth: Coffee is dehydrating

In a review, it was suggested that caffeinated coffee and tea don’t increase the risk of dehydration, even though caffeine is a mild diuretic (12). With moderate amounts of caffeine, the liquid has a more hydrating effect than the diuretic effect.

Thus, it is important to stay hydrated to avoid complications — some are serious, but all are uncomfortable. Diet is a great way to ensure that you get the triple effect of high amount of nutrients, increased hydration and sense of feeling satiated without calorie-dense foods. However, don’t go overboard with water consumption, especially if you have congestive heart failure or open-angle glaucoma (13). If you overhydrate with water, you can experience similar symptoms to dehydration. It is a good idea to review your medications with your doctor for possible dehydrating side effects.

References:

(1) mayoclinic.org. (2) uptodate.com. (3) BMJ Open online, Oct 21 2015. (4) Neurology. 2009 Mar 10;72(10):922-927. (5) Handb Clin Neurol. 2010;97:161-172. (7) my.clevelandclinic.org. (7) Am J Epidemiol 2002 May 1; 155:827-833. (8) European Journal of Nutrition online, Feb 10 2016. (9) J. Nutr. February 2012 142: 382-388. (10) AJP – Regu Physiol. 2002;283:R993-R1004. (11) Am J Lifestyle Med. 2011;5(4):316-319. (12) Exerc Sport Sci Rev. 2007;35(3):135-140. (13) Br J Ophthalmol. 2005:89:1298–1301

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.

It is not often that we come across a man who symbolizes so many different facets of life. Muhammad Ali was a fighter, in the literal sense, and his opponents faced an ominous, yet poetic, adversary in the boxing ring. He was also a fighter for racial equality. Ali was larger than life until the boxing ring, the stage where he had the loudest megaphone, took its toll.

Repeated blows to his head, especially to the back of his head, the cerebellar region of the brain responsible for balance and coordination, may have been at least partly responsible for prompting a disease that stole this boxer’s physical prowess and trapped a powerful force in a withering body, leaving him expressionless.

This disease is, of course, Parkinson’s disease. Though it became more and more difficult to move, he remained a fighter in the figurative sense, not allowing a disease to diminish his spirit and bringing hope to others. One of the most moving memories I have of Muhammad Ali is of him lighting the torch to commence the 1996 Summer Olympics in Atlanta, inspiring other athletes.

Parkinson’s disease is a neurodegenerative (the breakdown of brain neurons) disease with the resultant effect of a movement disorder. Most notably, patients with the disease suffer from a collection of symptoms known by the mnemonic TRAP: tremors while resting, rigidity, akinesia/bradykinesia (inability/difficulty to move or slow movements) and postural instability or balance issues. It can also result in a masked face, one that has become expressionless and potentially dementia, depending on the subtype. There are several different subtypes; the diffuse/malignant phenotype has the highest propensity toward cognitive decline (1).

The part of the brain most affected is the basal ganglia, and the prime culprit is dopamine deficiency that occurs in this brain region (2). Why not add back dopamine? Actually, this is the mainstay of medical treatment, but eventually the neurons themselves break down, and the medication becomes less effective.

What are some of the risk factors? These may include head trauma, reduced vitamin D, milk intake, well water, being overweight, high levels of dietary iron and migraine with aura in middle age.

Is there hope? Yes, in the form of medications and deep brain stimulatory surgery, but also with lifestyle modifications. Lifestyle factors include iron, vitamin D, CoQ10 and coffee and teas. The research, unfortunately, is not conclusive, though it is intriguing.

Let’s look at the research.

The role of iron

This heavy metal is potentially harmful for neurodegenerative diseases such as Alzheimer’s disease, macular degeneration, multiple sclerosis and, yes, Parkinson’s disease. The problem is that this heavy metal can cause oxidative damage.

In a small, yet well-designed, randomized controlled trial (RCT), the gold standard of studies, researchers used a chelator to remove iron from the substantia nigra, a specific part of the brain where iron breakdown may be dysfunctional. An iron chelator is a drug that removes the iron. Here, deferiprone (DFP) was used at a modest dose of 30 mg/kg/d (3). This drug was mostly well-tolerated.

The chelator reduced the risk of disease progression significantly on the Unified Parkinson Disease Rating Scale (UPDRS). Participants who were treated sooner had lower levels of iron compared to a group that used the chelator six months later. A specialized MRI was used to measure levels of iron in the brain. This trial was 12 months in duration.

The iron chelator does not affect, nor should it affect, systemic levels of iron, only those in the brain specifically focused on the substantia nigra region. The chelator may work by preventing degradation of the dopamine-containing neurons. It also may be recommended to consume foods that contain less iron.

CoQ10

When we typically think of using CoQ10, a coenzyme found in over-the-counter supplements, it is to compensate for depletion from statin drugs or due to heart failure. Doses range from 100 to 300 mg. However, there is evidence that CoQ10 may be beneficial in Parkinson’s at much higher doses. In an RCT, results showed that those given 1,200 mg of CoQ10 daily reduced the progression of the disease significantly based on UPDRS changes, compared to the placebo group (4). Other doses of 300 and 600 mg showed trends toward benefit but were not significant. This was a 16-month trial in a small population of 80 patients. Though the results for other CoQ10 studies have been mixed, these results are encouraging. Plus, CoQ10 was well-tolerated at even the highest dose. Thus, there may be no downside to trying CoQ10 in those with Parkinson’s disease.

Vitamin D: Good or bad?

In a prospective (forward-looking) study, results show that vitamin D levels measured in the highest quartile reduced the risk of developing Parkinson’s disease by 65 percent, compared to the lowest quartile (5). This is quite impressive, especially since the highest quartile patients had vitamin D levels that were what we would qualify as insufficient, with blood levels of 20 ng/ml, while those in the lowest quartile had deficient blood levels of 10 ng/ml or less. There were over 3,000 patients involved in this study with an age range of 50 to 79.

When we think of vitamin D, we wonder whether it is the chicken or the egg. Let me explain. Many times we are deficient in vitamin D and have a disease, but replacing the vitamin does nothing to help the disease. Well, in this case it does. It turns out that vitamin D may play dual roles of both reducing the risk of Parkinson’s disease and slowing its progression.

In an RCT, results showed that 1,200 IU of vitamin D taken daily, may have reduced the progression of Parkinson’s disease significantly on the UPDRS compared to a placebo over a 12-month duration (6). Also, this amount of vitamin D increased the blood levels by two times from 22.5 to 41.7 ng/ml. There were 121 patients involved in this study with a mean age of 72.

Caffeine, anyone?

What role does caffeine play in Parkinson’s? Potentially a beneficial one. In a prospective observational Finnish study involving almost 30,000 participants over 12 years, results showed that one cup of coffee per day reduced the risk of Parkinson’s disease by 60 percent compared to those who consumed none (7). Three cups of caffeinated tea per day also reduced the risk of Parkinson’s by 59 percent. Caffeine may not be right for everyone; however, in this case, it may be beneficial. Though I would not recommend starting to drink caffeine, I would certainly not dissuade patients from drinking it to help prevent Parkinson’s.

So, what have we learned? Though medication with dopamine agonists is the gold standard for the treatment of Parkinson’s disease, lifestyle modifications can have a significant impact on both prevention and treatment of this disease. Similar to combination punches from a great boxer like Muhammad Ali, each lifestyle change in isolation may have modest effects, but cumulatively they might pack quite a wallop. The most exciting part is that lifestyle modifications have the potential to slow the progression the disease and thus have a protective effect. Iron chelators specific to the brain may also be very important in disease modification. This also brings vitamin D back into the fold as a potential disease modifier.

References:

(1) JAMA Neurol. 2015;72:863-873. (2) uptodate.com. (3) Antioxid Redox Signal. 2014;10;21(2):195-210. (4) Arch Neurol. 2002;59(10):1541-1550. (5) Arch Neurol. 2010;67(7):808-811. (6) Am J Clin Nutr. 2013;97(5):1004-1013. (7) Mov Disord. 2007;22(15):2242-2248.

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.

Age-related macular degeneration (AMD) is the number one cause of severe central vision loss and blindness in patients over age 65 (1). There are several different stages of AMD. The early stage is referred to as dry. Then, there is the intermediate stage and the late stage, which is made up of two forms: wet (neovascular) and geographic atrophy, an advanced form of the dry.

This is not a lesson in macular degeneration’s pathology, but it is important to understand its rudimentary signs and symptoms. In the early stage, vision is not usually affected. So, how do we know when someone has the disease? Because of drusen, substances composed of cholesterol and proteins. Drusen are described as white-yellowish blobs below the retina, which is found in the back of the eye and can be seen with an indirect ophthalmoscope in a dilated eye exam.

Potentially reversing early-stage disease

For the longest time, we did not know if it were possible to reverse the disease, even in its early stages. However, a recent study’s results suggest we can. The reason is that there may be a relationship between cardiovascular disease (CVD) and AMD. Let me explain. The most common cause of CVD is atherosclerosis, or plaque buildup, made up of cholesterol deposits in the inner lining of the blood vessels. Cholesterol also builds in a layer just below the retina, called Bruch’s membrane. Both diseases also have underlying inflammation.

In this small, prospective (forward-looking) pilot study, treatment with high-dose atorvastatin 80 mg appears to have possibly dissolved the drusen, resulting in reversal of early-stage disease (2). Of the patients treated, approximately 40 percent were deemed responders to the drug. A responder was defined as a greater than 50 percent reduction in drusen volume. And of those, eight of the 10 had a near-complete response after one year. However, it is not clear that reducing drusen volume actually prevents progression. Interestingly both responders and nonresponders had similar blood cholesterol levels.

This was a small trial with only one group and only 23 patients. However, the results are encouraging. Hence, this is the first step toward treating early AMD. Atorvastatin is from the statin family of drugs. It reduces both cholesterol levels and inflammation. However, there are weaknesses with this study such as its small size, lack of placebo group and atorvastatin’s side effects. The study used the highest dose, and more than 20 percent of patients suffered side effects, such as gastrointestinal upset and myalgias, muscle pain. The FDA does not want physicians to start patients on such a high statin dose because of its side effects. This could possibly be offset by taking a supplement, CoQ10 200 mg, since statins deplete CoQ10 levels.

Therefore, the next step is obviously a much larger study to confirm the results, one that may also be a dose-ranging study, to identify the lowest possible dose of atorvastatin or other statins that could achieve the same efficacious results. Interestingly, a vegetable-rich, plant-based diet has similar effects to statins, at least systemically. So, a study could use both diet and statins.

The intermediate stage?

In this stage, drusen have either grown in size and/or there are pigment changes in the retina itself (3). In two randomized controlled trials, the AREDS and AREDS2 studies, results showed that supplements may be able to reduce the risk of disease progression to the late stages, not reverse it (4, 5).

In these studies, specific formulations were used. It turns out that zinc and vitamins C and E may be the most important micronutrients in these supplements. Zinc by itself showed a reduction. The micronutrient doses were vitamin C 452 mg, vitamin E 400 IU, zinc 69.6 mg and copper 2 mg. In the AREDS2 study, the researchers added lutein and zeaxanthin, which reduced the risk of progression further, from 25 to 30 percent, but only in those who did not get significant amounts from their diets. Fish oil in the form of DHA 350 mg and EPA 650 mg did not have any effect in reducing the risk of disease progression.

On an interesting note, zinc also showed that it could reduce the risk of dying from all causes by 27 percent in the AREDS analysis (6).

Caveat emptor when it comes to supplements for AMD. A study examined 11 supplements from five different companies (7). Only four actually contained what was in the AREDS studies. Another important thing to note about the supplements that do contain proper micronutrient amounts is that these supplements do not prevent AMD, nor should they be used in early AMD; they were meant for intermediate AMD. In the medical community, we sometimes make that mistake.

How about the late stage?

As mentioned above, late-stage AMD is made up of two different forms. Fortunately, 85 to 90 percent of AMD is earlier stages of the disease and progression does not always occur. In both forms of advanced AMD, central vision is significantly compromised. However, in the wet (neovascular) type, there are several different intravitreal (into the eye) injection medications that significantly improve vision.

The most commonly used medications include ranibizumab (Lucentis), bevacizumab (Avastin) and aflibercept (Eylea). They prevent the growth of new blood vessels in the eye that may leak and cause significant central vision disruption. All three medications are in a class referred to as VEGF (vascular endothelial growth factor) inhibitors.

The good news is that eye injections originally had to be done every four weeks. However, trials have shown that the injections can be used as needed or on a treat-and-extend basis (8). In other words, injection frequency can be individualized.

Is prevention possible?

When it comes to AMD, prevention is possible with lifestyle modifications. Study after study shows this. The basis for this effect is a high-nutrient diet that includes vegetables, fruits and fish. Exercise also plays an equally important role. Here are two studies to reinforce this.

In the Rotterdam Study I, a prospective (forward-looking) observational study, results showed an almost 50 percent reduction in risk of developing either early AMD or late-stage AMD (9). The components of the diet included at least seven ounces of vegetables per day, at least two servings of fruit per day and two servings of fatty fish per week. Sadly, only 3.5 percent were able to consume this very modest combination of servings. Two servings of fatty fish, by itself, reduced risk 26 percent. The study had 4,797 participants who were at least 55 years old, and it had a mean duration of nine years.

In the CAREDS study, results showed that both exercise and a plant-based diet, separately or on their own, had similarly impressive potential protective effects, reducing risk by approximately 50 percent (10). Diet, plus exercise and not smoking, decreased risk even more, by a whopping 71 percent. Again, congruous with the diet above, these results were based on a Mediterranean-type diet. There were 1,313 female participants, ages 55 to 74 at the study’s start, and a six-year study duration.

The bottom line is that the use of statin medications may be a new approach to preventing progression and possibly reversing early-stage macular degeneration. But the tried and true method of prevention is lifestyle modifications including a high-nutrient, plant-based diet, with the addition of fish, as well as exercise.

References:

(1) Ophthalmology 2008; 115:116–126. (2) EBioMedicine. 2016;5:198-203. (3) nei.nih.gov/health/maculardegen/armdfacts. (4) Arch Ophthalmol. 2001;119(10):1417-1436. (5) JAMA. 2013;309(19):2005-2015. (6) Arch Ophthalmol. 2004;122(5):716-726. (7) Ophthalmology. 2015;122(3):595-599. (8) Int Ophthalmol Clin. 2015;55(4):103-112. (9) ARVO 2015; Abstract 3762-C0004. (10) Arch Ophthalmol. 2011;129(4):470-480

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.

Atrial fibrillation (AFib) is the most common arrhythmia, an abnormal or irregular heartbeat, found in the U.S. Unfortunately, it can be very complicated to treat. Though there are several options, including medications and invasive procedures, it mostly boils down to symptomatic treatment, rather than treating or reversing underlying causes.

What is AFib? It is an electrical malfunction that affects the atria, the two upper chambers of the heart, causing them to beat “irregularly irregular.” This means there is no set pattern, which affects the rhythm and potentially causes a rapid heart rate. The result of this may be insufficient blood supply throughout the body.

Complications that may occur can be severely debilitating, such as stroke or even death. AFib’s prevalence is expected to more than double by 2030 (1). Risk factors include age (the older we get, the higher the probability), obesity, high blood pressure, premature atrial contractions and diabetes.

AFib is not always symptomatic; however, when it is, symptoms include shortness of breath, chest discomfort, light-headedness, fatigue and confusion. This arrhythmia can be diagnosed by electrocardiogram, but more likely with a 24-hour Holter monitor. The difficulty in diagnosing AFib sometimes is that it can be intermittent.

There may be a better way to diagnose AFib. In a recent study, the Zio Patch, worn for 14 days, was more likely to show arrhythmia than a 24-hour Holter monitor (2). The Zio Patch is a waterproof adhesive patch on the chest, worn like a Band-Aid, with one ECG lead.  While 50 percent of patients found the Holter monitor to be unobtrusive, almost all patients found the Zio Patch comfortable.

There are two main types of AFib, paroxysmal and persistent. Paroxysmal is acute, or sudden, and lasts for less than seven days, usually less than 24 hours. It tends to occur with greater frequency over time, but comes and goes. Persistent AFib is when it continues past seven days (3). AFib is a progressive disease, meaning it only gets worse, especially without treatment.

Medications are meant to treat either the rate or rhythm or prevent strokes from occurring. Medications that treat rate include beta blockers, like metoprolol, and calcium channel blockers, such as diltiazem (Cardizem). Examples of medications that treat rhythm are amiodarone and sotalol. Then there are anticoagulants that are meant to prevent stroke, such as warfarin and some newer medications, dabigatran (Pradaxa), rivaroxaban (Xarelto) and apixaban (Eliquis). The newer anticoagulants are easier to administer but may have higher bleeding risks, in some circumstances with no antidote.

There is also ablation, an invasive procedure that requires threading a catheter through an artery, usually the femoral artery located in the groin, to reach the heart. In one type of ablation, the inappropriate nodes firing in the walls of the atria are ablated, or destroyed, using radiofrequency. This procedure causes scarring of atrial tissue. When successful, patients may no longer need medication.

Premature atrial contractions

Premature atrial contractions (PACs), abnormal extra beats that occur in the atrium, may be a predictor of atrial fibrillation. In a recent study, PACs alone, when compared to the Framingham AF risk algorithm (a conglomeration of risk factors that excludes PACs) resulted in higher risk of AFib (4). When there were more than 32 abnormal beats/hour, there was a significantly greater risk of AFib after 15 years of PACs. When taken together, PACs and the Framingham model were able to predict AFib risk better at 10 years out as well. Also, when the number of PACs doubled overall in patients, there was a 17 percent increased risk of AFib.

The role of obesity

There is good news and bad news with obesity in regards to AFib. Let’s first talk about the bad news. In studies, those who are obese are at significantly increased risk. In the Framingham Heart Study, the risk of developing AFib was 52 percent greater in men who were obese and 46 percent greater in women who were obese when compared to those of normal weight (5). Obesity is defined as a BMI >30 kg/m2, and normal weight as a BMI <25 kg/m2. There were over 5,000 participants in this study with a follow-up of 13 years. The Danish Diet, Cancer and Health Study reinforces these results by showing that obese men were at a greater than twofold increased risk of developing AFib, and obese women were at a twofold increased risk (6).

Now the good news: Weight loss may help reduce the frequency of AFib episodes. That’s right; weight loss could be a simple treatment for this very dangerous arrhythmia. In a recent randomized controlled trial, the gold standard of studies, those in the intervention group lost significantly more weight, 14 kg (32 pounds) versus 3.6 kg (eight pounds), and saw a significant reduction in atrial fibrillation severity score (AFSS) compared to those in the control group (7). There were 150 patients involved in the study.

AFSS includes duration, severity and frequency of atrial fibrillation. All three components in the AFSS were reduced in the intervention group compared to the control group. There was a 692-minute decrease in the time spent in AFib over 12 months in the intervention arm, whereas there was a 419-minute increase in the time in AFib in the control group. These results are potentially very powerful; this is the first study to demonstrate that managing risk factors may actually help manage the disease.

Caffeine

According to a recent meta-analysis (a group of six population-based studies) done in China, caffeine does not increase, and may even decrease, the risk of AFib (8). The study did not reach statistical significance. The authors surmised that drinking coffee on a regular basis may be beneficial because caffeine has antifibrosis properties. Fibrosis is the occurrence of excess fibrous tissue, in this case, in the atria, which most likely will have deleterious effects. Atrial fibrosis could be a preliminary contributing step to AFib. Since these were population-based studies, only an association can be made with this discovery, rather than a hard and fast link. Still, this is a surprising result.

However, in those who already have AFib, it seems that caffeine may exacerbate the frequency of symptomatic occurrences, at least anecdotally. With my patients, when we reduce or discontinue substances that have caffeine, such as coffee, tea and chocolate, the number of episodes of AFib seems to decline. I have also heard similar stories from my colleagues and their patients. So, think twice before running out and getting a cup of quantified coffee if you have AFib. What we really need are randomized controlled studies done in patients with AFib, comparing people who consume caffeine regularly to those who have decreased or discontinued the substance.

The bottom line is this: If there were ever a reason needed for obese patients to lose weight, treating atrial fibrillation should be on the top of the list, especially since it is such a dangerous disease with potentially severe complications.

References:

(1) Am J Cardiol. 2013 Oct. 15;112:1142-1147. (2) Am J Med. 2014 Jan.;127:95.e11-7. (3) Uptodate.com. (4) Ann Intern Med. 2013;159:721-728. (5) JAMA. 2004;292:2471-2477. (6) Am J Med. 2005;118:489-495. (7) JAMA. 2013;310:2050-2060. (8) Canadian J Cardiol online. 2014 Jan. 6.

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, go to the website www.medicalcompassmd.com or consult your personal physician.

Niacin has become a highly contested drug. It has powerful effects to treat elevated triglycerides, but the clinical benefit of this effect is questionable.

What is niacin? It is a B vitamin, specifically B3. It is one of the few supplements regulated by the FDA in higher doses as a medication. It is also known as nicotinic acid and is a coenzyme involved in oxidation-reduction, where electrons are exchanged. These reactions provide a source of energy for organisms (1).

Just like with triglycerides, niacin seems to have a powerful effect on HDL “good” cholesterol, by raising HDL levels as much 30-35 percent (2). While this is an impressive number, once again, it has become debatable whether this raising of HDL is clinically beneficial.

In several trials, niacin showed unexpectedly disappointing results in reducing the potential for cardiovascular disease and events. It also demonstrated significant side effects. In other words, this is not a harmless drug.

Interestingly, as the benefit of niacin for cardiovascular disease has been debated, the number of scripts has increased almost threefold, or 200 percent, in the seven years from 2002 to 2009, according to IMS data for both the U.S. and Canada (3). The majority of the scripts were for extended-release niacin (Niaspan). The rest were mainly for Simcor (simvastatin-niacin combination) and Advicor (lovastatin-niacin combination). Let’s look at the evidence.

Is raising HDL beneficial or not?

The paradigm has always been that higher HDL is better, but this may not be the case. It is not the first time that HDL’s protectiveness has been debated. An observational study showed that those who have genetically high levels of HDL may not benefit any more than those with normal levels (4).

In a randomized controlled trial, the HPS2-THRIVE study, the results showed an increase of 6 mg/dL in HDL levels and a decrease of 10 mg/dL in LDL, “bad” cholesterol when extended-release niacin plus laropiprant was added to statin therapy (5). This is considered by some to be a relatively small change. Also, there was no reduction in vascular events seen with the combination, even though there was improvement in both HDL and LDL when compared to the placebo.

Laropiprant is a drug used to help reduce the flushing with niacin. The dose used was 2 g of extended-release niacin and 40 mg of laropiprant. The demographics included a patient population that had vascular disease, and therefore was at greater risk of vascular events, such as nonfatal heart attacks, strokes, arterial revascularization and mortality from cardiovascular disease. There were over 25,000 patients involved in the study, and its duration was 3.9 years. LDL was already low in the participants at the start of the trial.

To make matters worse, the serious side effects were greater with the extended-release niacin compared to the placebo. There was a greater propensity toward diabetes — 32 percent relative increase — as well as exacerbation of diabetes — 55 percent increase in impaired sugar or glucose control — in patients who already had the disease. There were also increases in ulcers and diarrhea by 28 percent, muscle damage and gout by 26 percent, rashes and ulcerations by 67 percent, gastrointestinal bleeding or other bleeds by 38 percent and infection rates by 22 percent. Using niacin to raise HDL may be ineffective, at least in vascular patients, those with atherosclerosis, who already have low LDL. It does not foretell what happens in patients with high LDL at the start.

Other studies have shown questionable efficacy and increased adverse events with niacin use in raising HDL levels to limit cardiovascular events. In the AIM-HIGH study, similarly disappointing results were seen. When extended-release niacin was added for patients with stable coronary artery disease, high triglycerides and low HDL who were already on statins, there was no clinical change in cardiovascular events (6).

Also, there were more serious adverse effects seen in the niacin group compared to the placebo group in a post-hoc analysis (7). These side effects included gastrointestinal disorders, infection, and infestations. However, there was no difference in bleed or hemorrhage, though the absolute number was small.

In yet another study, this a meta-analysis of 39 studies, including HPS2-THRIVE and AIM-HIGH, comparing the benefits of niacin, cholesteryl ester transfer protein inhibitors and fibrates, results showed that even though these drugs may raise HDL levels, there was no improvement in terms of cardiovascular end points when they were added to statin therapy (8). There were about 117,000 patients involved in the meta-analysis. The drugs and drug classes, niacin, CETP and fibrates, did not demonstrate any reduction in all-cause mortality or coronary heart disease mortality, nor did they reduce heart attacks or stroke risk. These drugs were added to statins as adjunct therapy.

Possible HDL explanation

Investigating a theory as to why raising HDL may not be effective when using niacin, a small study looked at cholesterol efflux capacity — the ability of HDL to garner cholesterol from macrophages, a type of white blood cells, compared to the HDL inflammatory index (9). The results showed that cholesterol efflux capacity may be a better indicator for vascular disease than HDL levels. There was an increase in HDL-C, where C stands for cholesterol, but no change in HDL inflammatory index, nor cholesterol efflux capacity, when niacin was used.

In conclusion, if you are on niacin to raise HDL levels and are already on a statin, you may want to talk to your physician about the evidence that refutes the clinical benefits in reducing cardiovascular events. The European Union has recently banned the use of niacin-laropiprant combination (10). Niacin alone does not seem to be harmless either. Whether HDL is as important as we thought is now in debate. Know that a change in a biomarker, such as HDL levels, is not synonymous with better clinical outcomes. This disappointing clinical result also holds true for niacin’s effects on triglycerides.

This article is only addressing niacin in regard to HDL and the cholesterol profile in general, not other roles for the drug. Of course, never discontinue your medication without first discussing it with your doctor.

References:

(1) “Present Knowledge in Nutrition,” 10th ed. 2012;293-306. (2) Arch Intern Med. 1994;154:1586-1595. (3) JAMA Intern Med. 2013;173:1379-1381. (4) Lancet online. 2012 May 17. (5) New Engl J Med. 2014;371:203-212. (6) New Engl J Med. 2011;365:2255-2267. (7) New Engl J Med. 2014;371:288-290. (8) BMJ 2014;349:g4379. (9) J Am Coll Cardiol. 2013;62:1909-1910. (10) European Medicines Agency 2013 Jan. 18.

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, go to the website www.medicalcompassmd.com or consult your personal physician.

After winter ends, we look forward to mild temperatures. The days get longer, trees and flowers bud and bloom, and grass becomes lush and green. It seems like heaven. But for people who suffer from seasonal allergic rhinitis, hay fever, seasonal allergies or whatever you would like to call it, life can be downright miserable. You probably can rate an allergy season with your own built-in personal barometer, the sneeze factor. How many times are you, your friends or your colleagues sneezing?

Approximately 19.1 million adult Americans have had a diagnosis of seasonal allergies within the past year, about 8 percent of the population, and an additional 6.1 million children have this disorder, or about 8.4 percent, according to the Centers for Disease Control and Prevention (1). Sadly, considering the number of people it affects, only a paltry amount of research has been published.

The triggers for allergies are diverse. They include pollen from leafy trees and shrubs, the lush grass and the beautiful flowering plants and weeds, with the majority from ragweed (mostly in the fall), as well as fungus (summer and fall) (2).

What sparks allergies within the body? A chain reaction occurs in seasonal allergy sufferers. When foreign substances such as allergens (pollen in this case) interact with immunoglobulin E (IgE), antibodies that are part of our immune system, it causes mast cells in the body’s tissues to degrade and release inflammatory mediators. These include histamines, leukotrienes and eosinophils in those who are susceptible. In other words, it is an allergic inflammatory response.

The revved up immune system then responds with sneezing; red, itchy and watery eyes; scratchy throat; congestion; sinus headaches; postnasal drip; runny nose; diminished taste and smell; and even coughing (3). Basically, it emulates a cold, but without the virus. If symptoms last more than 10 days and are recurrent, then it is more than likely you have allergies.

Risk factors for seasonal allergies are tied most strongly to family history and to having other personal allergies, such as eczema or food allergies, but also may include cigarette exposure, being male and, possibly, diet (4). If allergic rhinitis is not properly treated, complications such as ear infections, sinusitis, irritated throat, insomnia, chronic fatigue, headaches and even asthma can result (5).

To treat allergic rhinitis, we have a host of medications from classes including intranasal glucocorticoids (steroids), oral antihistamines, allergy shots, decongestants, antihistamine and decongestant eye drops and leukotriene modifiers (second-line only). Let’s look at the evidence.

The best way to treat allergy attacks is to prevent them, but this is an arduous process that can mean closing yourself out from the enjoyment of spring by literally closing the windows, using the air-conditioning, and using recycling vents in your car.

The recent guidelines for treating seasonal allergic rhinitis with medications suggest that intranasal corticosteroids (steroids) should be used when quality of life is affected. If there is itchiness and sneezing, then second-generation oral antihistamines may be appropriate (6). Two well-known inhaled steroids that do not require a prescription are Nasocort (triamcinolone) and Flonase (fluticasone propionate). There does not seem to be a significant difference between them (7). While inhaled steroids are probably most effective in treating and preventing symptoms, they need to be used every day.

Oral antihistamines, on the other hand, can be taken on an as-needed basis. Second-generation antihistamines have less sleepiness as a side effect than first-generation antihistamines. They include loratadine (Claritin), cetirizine (Zyrtec) and fexofenadine (Allegra).

Surprisingly good news

Seasonal allergic rhinitis may actually be beneficial for longevity. In a recent study involving more than 200,000 participants, results showed that those who had allergies had a 25 percent reduction in the risk of heart attacks, a 19 percent reduction in strokes, and a whopping 49 percent reduction in mortality (8). Remember two things: this is an observational trial, which means that it is not the best of trials. Don’t wish allergies on yourself. The reason for this effect may be at least partially attributable to the type of white blood cell expressed in the immune system.

In other words, type 2 T helper (Th2) lymphocytes (white blood cells) are elevated with allergies instead of type 1 T helper (Th1) lymphocytes. Why is this important? Th2 is known to decrease cardiovascular disease, while Th1 is known to possibly increase cardiovascular disease. Unfortunately, the same cannot be said about asthma, where cardiovascular events are increased by 36 percent.

Alternative treatments

Butterbur (Petasites hybridus), an herb, may not just be for migraines. There are several small studies that indicate its efficacy in treating hay fever. In fact, in one study, results show that butterbur was as effective as cetirizine (Zyrtec) in treating this disorder (9). This was a small, randomized, controlled trial involving 131 patients.

In another randomized, controlled trial, results showed that high doses of butterbur — 1 tablet given three times a day — was significantly more effective than placebo (10). The side effects were similar in the placebo group and the butterbur group. The researchers used butterbur Ze339 (carbon dioxide extract from the leaves of Petasites hybridus L., 8 mg petasines per tablet) in the trial. The authors concluded that butterbur would be potentially useful for intermittent allergic rhinitis. The duration of treatment for this study was two weeks.

Still another study, this one a post-marketing study done as a follow-up to the previous study, showed that with butterbur Ze339, symptoms improved in 90 percent of patients with allergic rhinitis (11). Interestingly, anti-allergic medications were co-administered in about half of the patient population, with no additional benefit over butterbur alone. There were 580 patients in this study, and the duration was two weeks.

Gastrointestinal upset occurred as the most common side effect in 3.8 percent of the population.

The caveats to the use of butterbur are several. First, the studies were short in duration. Second, the leaf extract used in these studies was free of pyrrolizidine alkaloids (PAs); this is very important since PAs may not be safe. Third, the dose was well-measured, which may not be the case with over-the-counter extracts. Fourth, you need to ask about interactions with prescription medications.

Diet

While there are no significant studies on diet, there is one review of literature that suggests that a plant-based diet may reduce symptoms of allergies, specifically rhinoconjunctivitis, affecting the nose and eyes, as well as eczema and asthma. This is according to the International Study of Asthma and Allergies in Childhood study in 13- to 14-year-old teens (12). In my clinical practice, I have seen patients who suffer from seasonal allergies improve and even reverse the course of allergies over time with a vegetable-rich, plant-based diet possibly due to an anti-inflammatory effect.

While allergies can be miserable, there are a significant number of over-the-counter and prescription options to help to reduce symptoms. Diet may play a role in the disease process by reducing inflammation, though there are no formal studies. There does seem to be promise with some herbs, especially butterbur. However, alternative supplements and herbs lack large, randomized clinical trials with long durations. Always consult your doctor before starting any supplements, herbs or over-the-counter medications.

References: (1) CDC.gov. (2) acaai.org/allergies/types/pollen-allergy. (3) Allergy Clin Immunol. 2003;112(6):1021-1031. (4) umm.edu. (5) J Allergy Clin Immunol. 2010;125(1):16-29. (6) Otolaryngol Head Neck Surg. online February 2, 2015. (7) Otolaryngol Head Neck Surg. 2003;129(1):16. (8) AAAAI 2014: Abstract 811. (9) BMJ 2002;324:144. (10) Arch Otolaryngol Head Neck Surg. 2004;130(12):1381-1386. (11) Adv Ther. 2006;23(2):373-384. (12) Eur Respir J. 2001;17(3):436-443.

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, go to the website www.medicalcompassmd.com or consult your personal physician.

The lipid or cholesterol profile is one of the most common batteries of blood tests. Why? Abnormal cholesterol levels may have an integral role in exacerbating a number of chronic diseases. These diseases are some of the most common, including atherosclerosis (hardening of the arteries), cardiovascular disease (heart disease and stroke) and vascular dementia. It’s even thought to be a component of age-related macular degeneration, the number one cause of vision loss in those who are at least age 60 in industrialized countries (1).

Let’s delve into the components that make up the cholesterol profile. The lipid panel is made up of several different components. These include total cholesterol, HDL or “good cholesterol,” LDL or “bad cholesterol” and triglycerides. Many people focus more on total cholesterol, HDL, and LDL and less on triglycerides. We worry about whether the levels are high enough for HDL and are low enough for total cholesterol and LDL. Is this the proper focus? With total cholesterol and LDL, this seems to be appropriate.

But with HDL it is becoming more complicated; it is less about how high the levels are and more about the functionality of HDL. There are drugs that increase HDL levels, such as niacin and the fibrates, without significantly reducing cardiovascular events. This was demonstrated in the AIM-HIGH trial (2). In this trial, niacin added to a statin drug increased HDL levels and decreased triglyceride levels without a change in the primary end point of cardiovascular outcomes. Thus, they were deemed less than satisfactory and the trial was abruptly ended. However, triglycerides get the short end of the stick. Just look lack of coverage in the mainstream media.

We will look at the different components of the lipid panel and the supposed roles they play in our health.

Let’s look at the research.

HDL — the good cholesterol that may not be so good

For years, when patients have been told their total cholesterol and LDL are high, they have asked if their HDL levels compensate for this. Of course, we in the medical community are partially to blame for fueling this thinking. More and more studies point to the importance of HDL functionality rather than the level.

In a recent study investigating a specific gene variant or mutation, those who had very high levels of HDL, a mean of 106 mg/dL, and two copies of a P376L mutation, had an increased risk of heart disease (3). In a population of 300 participants with this very high level of HDL, only one had this mutation.

When the investigators broadened the number to 1,282 participants, the results were the same. Results were consistent when they looked at a meta-analysis of 300,000 participants with high HDL. Carriers of the gene mutation, meaning they had one copy instead of two, were at a 79 percent increased risk of heart disease. Those who had this gene mutation were mostly Ashkenazi Jews of European descent. The good news is that this gene mutation is rare. However, it does show that in certain circumstances, HDL is not always good.

Lest you become too relaxed about this study, since the occurrence was uncommon, another study’s results showed that there is a U-shaped curve when it comes to HDL levels (4). In other words, those on the lowest and the highest ends of HDL levels had higher risk of death from both cardiovascular and noncardiovascular death. There were associations among HDL and other factors, like vegetable and fruit consumption, high blood pressure, diabetes, age and sex. Thus, HDL may not by itself be an indicator of heart disease death risk as suggested by the investigators in the trial. This was a large population-based study with over 600,000 participants.

In a third study, results showed that functionality is more important than HDL level (5). What is called the cholesterol-efflux capacity may be central to HDL functionality. This technique calibrates the reverse transport of cholesterol. Cholesterol is removed from a type of white blood cell in the wall of the artery, put back into the bloodstream and removed by the liver. The importance of the functionality is that a higher cholesterol-efflux capacity results in a lower risk of cardiovascular disease. In other words, you may not be able to rely on HDL levels to determine cardioprotective effects.

Triglycerides should get their due

Triglycerides need their 15 minutes of fame, just like the rest of the cholesterol profile; triglycerides may be an independent risk factor for cardiovascular disease. In a recent study, results showed that triglycerides are an independent risk factor for all-cause mortality in those with heart disease (6). But even more interesting is that those with high normal levels, those between 100 and 150 mg/dL, have a significantly increased risk of cardiovascular death. In other words, those who are still within normal limits, but at the upper end, should consider reducing their levels.

The results also showed a dose-dependent curve; the higher the levels of triglycerides, the higher the risk of death from cardiovascular disease. Measurements used included borderline high of 150-199 mg/dL, moderately high of 200-499 mg/dL and very high of >500 mg/dL. This was a secondary prevention trial, meaning the patients already had heart disease. Unfortunately, a disproportionate number of patients were men, 81 percent. However, this study had a strong duration of 22 years with data based on 15,000 patients. The weakness of this trial was its inability to control for confounders such as sickness, treatments and cause of death. Still, this signifies that triglycerides have an important role in our health.

Triglycerides are affected by diet. The elements in the diet that raise levels include sugars, grains — for some even whole grains — and starchy vegetables.

What about whole eggs? Good, bad or neutral?

Today, the debates in the medical community over eggs’ merits, detriments or neutrality continue. In a recent observational trial from Finland, results show that one egg a day did not increase the risk of heart disease (7). Whew, now we can put that debate behind us and eat eggs, right? NOT SO FAST! While the strength of the trial was its very impressive duration of 21 years, the weaknesses of the trial were huge. First, participants were asked for a four-day dietary history at the start of the trial and then never again. It was assumed that they were eating the same foods over this long time period. Second, there were no blood tests taken specifically for the study. In other words, there are no cholesterol levels for the trial. So we don’t know if one egg a day — and remember we’re making a gigantic assumption that they did eat one egg a day — had any negative impact on cholesterol levels. Third, this study population did not include women. There were 1,032 men involved. Having said all this, you could try an egg a day. However, I would highly recommend a physician’s supervision.

In my practice, I had several patients eat two eggs a day, and their total cholesterol levels went up by approximately 100 mg/dL in one month. But this is anecdotal data from my clinical experience.

In conclusion, don’t think you’re safe if you have a high HDL level. It is best to lower your triglycerides to below 100 mg/dL, and an effective way to do this is by reducing sugars, grains and starchy vegetables in your diet. However, there is subset data suggesting that the fibrate class of drugs may have benefit in those who have triglycerides of at least 500 mg/dL (6).

References:

(1) www.nlm.nih.gov. (2) N Engl J Med 2011; 365:2255-2267. (3) Science 2016; 351:1166-1171. (4) AHA 2015 Scientific Sessions; Nov. 10, 2015. (5) N Engl J Med. 2014;371(25):2383-2393. (6) Circ Cardiovasc Qual Outcomes 2016;9:100-108. (7) Am J Clin Nutr. 2016;103(3):895-901.

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, go to the website www.medicalcompassmd.com or consult your personal physician.