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.

Many of us have inflammation in our bodies, inflammation that is a potential underlying cause for a great number of diseases. Can we demonstrate the level of inflammation by measuring it? The answer is yes, otherwise I would not be writing this article.

One of the most widely studied biomarkers for inflammation is high-sensitivity C-reactive protein (hsCRP), also referred to as CRP. High sensitivity means that we can measure levels as low as 0.3 mg/L more accurately.

What is the significance of the different levels? In heart disease, individuals who have levels less than 1.0 mg/L are in the optimal range for low risk of inflammation. Levels of 1-3 mg/L is the average risk range and greater than 3.0 mg/L is the higher risk profile. Above 10.0 mg/L is less specific to heart disease, although still related, but more likely associated with other causes, such as infection and autoimmune diseases (1, 2). This biomarker is derived from the liver.

CRP is not specific to heart disease, nor is it definitive for risk of the disease. However, the upside is that it may be helpful with risk stratification, which helps us understand where we sit on a heart disease risk spectrum and with progression in other diseases, such as age-related macular degeneration, diabetic retinopathy, depression and autoimmune diseases.

Let’s look at the evidence.

Age-related macular degeneration (AMD)

AMD is the leading cause of blindness in patients over the age of 65 (3). Therefore, it is very important to help define risk stratification for this disease. In a prospective study, the results showed that hsCRP levels were inversely associated with the risk of developing AMD. The group with an hsCRP more than 3.0 mg/L had a 50 percent increased risk of developing overall AMD compared to the optimal group with less than 1.0 mg/L. But even more interestingly, the risk of developing neovascular, or wet, AMD increased to 89 percent in this high-risk group.

The significance of wet AMD is that it is one type of advanced-stage AMD that results in blindness. This study involved five studies where the researchers thawed baseline blood samples from middle-aged participants who had hsCRP levels measured. There were more than 2,000 participants with a follow-up as long as 20 years. According to the study’s authors, annual eye exams and lifestyle modifications, including supplements, may be able to stem this risk by reducing hsCRP.

These results reinforce those of a previous prospective study that showed that elevated hsCRP increased the risk of AMD threefold (4). This study utilized data from the Women’s Health Study, which involved over 27,000 participants. Like the study mentioned above, this one also defrosted blood samples from baseline and looked at follow-up incidence of developing AMD in initially healthy women.

The highest group had hsCRP levels over 5.2 mg/L. Additionally, when analyzing similar cutoffs for high- and low-level hsCRP, as the above trial used, those with hsCRP over 3.0 had an 82 percent increased risk of AMD compared to those with an hsCRP of less than 1.0 mg/L.

Diabetic retinopathy — a complication of diabetes

We know that diabetes affects significantly more than 10 percent of the population and is continuing to rise at a rapid rate. One of the complications of diabetes affects the retina (back of the eye) and is called diabetic retinopathy. This is a leading cause of vision loss (5). One of the reasons for the vision loss is macular edema, or swelling, usually due to rupture of tiny blood vessels below the macula, a portion of the back of the eye responsible for central vision.

The Diabetes Control and Complications Trial (DCCT), a prospective study involving over 1,400 type-1 diabetes patients, showed an 83 percent increased risk of developing clinically significant macular edema in the group with the highest hsCRP levels compared to those with the lowest (6). Although these results were with type-1 diabetes, patients with type-2 diabetes are at equal risk of diabetic retinopathy if glucose levels, or sugars, are not well controlled.

Depression

Depression is a very difficult disease to control and is a tremendous cause of disability. If we can minimize the risk of complications and hospitalizations, this is probably the most effective approach.

Well, it turns out that inflammation is associated with depression. Specifically, in a recent prospective observational trial, rising levels of CRP had a linear relationship with increased risk of hospitalization due to psychological distress and depression (7).

In other words, compared to levels of less than 1 mg/L, those who were 1 to 3 mg/L, 3 to 10 mg/L and greater than 10 mg/L had increased risk from 30 percent  to 84 percent to 127 percent, respectively. This study involved over 70,000 patients.

 What can be done to reduce inflammation?

This is the key question, since we now know that hsCRP is associated with systemic inflammation. In the Nurses’ Health Study, a very large, prospective observational study, the Dietary Approaches to Stop Hypertension (DASH) diet decreased the risk of both heart disease and stroke, which is impressive. The DASH diet also decreases the levels of hsCRP significantly, which was associated with a decrease in clinically meaningful endpoints of stroke and heart disease (8).

The DASH diet is nutrient-dense with an emphasis on fruits, vegetables, nuts, seeds, legumes and whole grains and de-emphasis on processed foods, red meats, sodium and sweet beverages.

Conclusion

As the evidence shows with multiple diseases, hsCRP is a very valuable nonspecific biomarker for inflammation in the body.

To stem the effects of inflammation, reducing hsCRP through lifestyle modifications and drug therapy may be a productive way of reducing risk, slowing progression and even potentially reversing some disease processes.

The DASH diet is a very powerful approach to achieving optimal levels of hsCRP without incurring potential side effects. This is a call to arms to have your levels measured, especially if you are at high risk or have chronic diseases such as heart disease, diabetes, depression and autoimmune diseases. HsCRP is a simple blood test with easy-to-obtain results.

References:

(1) uptodate.com. (2) Diabetes Technol Ther. 2006;8(1):28-36. (3) Prog Retin Eye Res. 2007 Nov;26(6):649-673. (4) Arch Ophthalmol. 2007;125(3):300-305. (5) Am J Ophthalmol. 2003;136(1):122-135. (6) JAMA Ophthalmol. 2013 Feb 7;131:1-8. (7) JAMA Psychiatry. 2013;70(2):176-184. (8) Arch Intern Med. 2008;168(7):713-720.

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.

What I am about to say may be hard to comprehend, especially for those who have germaphobic tendencies, which would be most of us, but we harbor microorganisms, or microbes (small organisms), in our body that outnumber our cells by a 10-to-1 ratio, even in healthy individuals. There are over one trillion microorganisms in the body.

These organisms make up what is called the microbiome. It includes bacteria, viruses and single-cell eukaryotes. Our relationship to these organisms is complex, spanning from parasitic (detrimental) to commensalistic (one benefits and the other is not affected) to mutualistic (both benefit). The microbiome is found throughout the body, including the skin, the eyes and the gut. Our focus is going to be on the gut since that is where the majority of the microbiome resides.

What is the importance of the gut microbiome? The short answer is it may have a role in diseases — preventing and promoting them. These diseases include obesity, diabetes, irritable bowel syndrome, autoimmune diseases, such as rheumatoid arthritis and Crohn’s, and infectious diseases, such as colitis.

Similar to the Human Genome Project, which mapped our genes, there is a Human Microbiome Project, launched by the National Institutes of Health in 2007, to map out the composition and diversity of these gut organisms. We are still in the early stages of understanding this vast universe of microbes, yet there are some preliminary studies.

What impacts the microbiome? It is affected by drugs, such as antibiotics that can wipe out the diversity in the microbes, at least in the short term, and by lifestyle modifications, such as diet. Microbiome diversity may be significantly different in distinct geographic locations throughout the world. Also, the birth process — vaginal compared to Cesarean section — may have a significant influence on an organisms’ composition. Let’s look at the evidence.

C-sections and reduced breast-feeding

The mode of birth delivery may be important. While C-sections have become more common, they may have a negative impact on the development of gut microbes. In a recent study, infants who were delivered by C-section had a significant reduction in Escherichia-Shigella and a lack of Bacteroides in their guts, compared to those delivered by vaginal birth (1). This effect was seen mostly in elective C-sections, since emergency C-sections may have some vaginal influence. Elective C-sections may reduce exposure to maternal microbes.

Breast-feeding may be beneficial to the gut flora. Those infants who were breastfed had a significantly lower concentration of the bacterium Clostridium difficile, which causes colitis (infection of the colon) and diarrhea. The non-breast-fed infants had higher levels of Peptostreptococcaceae, part of the family of Clostridium bacteria, which as mentioned, relates to colitis. This was a very small study involving 24 healthy infants divided equally between male and female. Of course, consult your OB/GYN before making a decision on the birth process, especially if there are extenuating circumstances that prohibit vaginal birth. Fortunately, breast-feeding is already being encouraged.

Obesity: From mice and men

Obesity can be one of the most frustrating disorders; most obese patients continually struggle to lose weight. Obese and overweight patients now outnumber malnourished individuals worldwide (2).

I know this will not come as a surprise, but we are a nation with a weight problem; about 70 percent of Americans are overweight or obese. For the longest time, the paradigm for weight loss had been that if you ate fewer calories, you would lose weight. However, extreme low-caloric diets did not seem to have a long-term impact. It turns out that our guts, dominated by bacteria, may play important roles in obesity and weight loss, determining whether we gain or lose weight. Let’s look at the data on obesity.

The results from a study involving human twins and mice are fascinating (3). In each pair of human twins, one was obese and the other was lean. Gut bacteria from obese human twins were transplanted into thin mice. The result: The thin mice became obese. However, when the lean human twins’ gut bacteria were transplanted to thin mice, the mice remained thin.

By pairing sets of human twins, one obese and one thin in each set, with mice that were identical to each other and raised in a sterile setting, researchers limited the confounding effects of environment and genetics on weight.

The most intriguing part of the study compared the effects of diet and gut bacteria. When the mice who had received gut transplants from obese twins were provided gut bacteria from thin twins and given fruit- and vegetable-rich (high in fiber), low-fat diet tablets, they lost significant weight. But they only lost weight when on a good diet; there was no impact on obesity if the diet was not high in fiber and low in saturated fat. The authors believe this suggests that an effective diet may alter the microbiome of obese patients, helping them lose weight. These are exciting, but preliminary, results. It is not clear yet which bacteria may be contributing these effects. However, the authors theorize that some gut bacteria may have a protective effect against weight gain with a high fiber, low saturated fat diet.

This suggests that the diversity of gut bacteria may be a crucial piece of the weight-loss puzzle.

Rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that can be disabling, with patients typically suffering from significant morning stiffness and joint soreness. What if gut bacteria influenced RA risk? In a recent study, the gut bacteria in mice that were made susceptible to RA by deletion of certain genes (HLA-DR genes) were compared to those who were more resistant to developing RA (4). Researchers found that the RA-susceptible mice had a predominance of Clostridium bacteria and that those resistant to RA were dominated by bacteria of the Bifidobacterium genus and the Porphyromonadaceae family. The significance is that the RA-resistant mice bacteria are known for their anti-inflammatory effects.

Although nobody can say what the ideal gut bacteria should consist of, and the research is still evolving when it comes to the microbiome, there are potential ways of influencing this milieu, especially in our gut. While C-sections definitely have their place, vaginal deliveries may be more beneficial to the infants’ gut bacteria than elective C-sections.

Diet composition seems to be important to the composition and diversity of gut bacteria, impacting the development or prevention of diseases, such as obesity and rheumatoid arthritis.

References: (1) CMAJ. 2013;185:373-374. (2) “The Evolution of Obesity”; Johns Hopkins University Press; 2009. (3) Science. 2013;341:1241214. (4) PLoS One. 2012;7:e36095.

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.

COPD, or chronic obstructive pulmonary disease, is the third leading cause of mortality in the United States (1), although it’s not highlighted much in the layman’s press.

COPD is an umbrella term that includes emphysema, chronic bronchitis of more than three months for two consecutive years and/or chronic obstructive asthma. It is an obstructive lung disease that limits airflow. The three most common symptoms of the disease involve shortness of breath, especially on exertion, production of sputum and cough. This disease affects greater than 5 percent of the U.S. population (2).

It tends to be progressive, meaning more frequent and severe exacerbations over time. Since it is a devastating and debilitating chronic disease with no cure, anything that can identify and prevent COPD exacerbations, as well as comorbidities (associated diseases), is critically important.

What are the traditional ways to reduce the risk of and treat COPD exacerbations? The most important step is to stop smoking, since 80 percent of COPD is related to smoking. Supplemental oxygen therapy and medications, such as corticosteroids, bronchodilators (beta-adrenergic agonists and anticholinergics) and antibiotics help to alleviate symptoms (3).

One of the underlying components of COPD may be chronic inflammation (4). Therefore, reducing inflammation may help to stem COPD exacerbations. There are several inflammatory biomarkers that could potentially help predict exacerbations and mortality associated with this disease, such as interleukin-6 (IL-6), C-reactive protein (CRP), leukocyte (white blood cell) count and fibrinogen (a clotting factor of the blood).

How do we reduce inflammation, which may contribute to exacerbations of this disease? Some drugs, such as statins, work partially by reducing inflammation. They may have a role in COPD. Lifestyle changes that include a high-nutrient, anti-inflammatory diet and exercise may also be beneficial.

Let’s look at the evidence.

Biomarkers for inflammation

In a recent population-based study with over 60,000 participants, results show that as three biomarkers (CRP, leukocyte count and fibrinogen) were elevated, the risk of COPD exacerbation increased in a linear manner (5). In other words, the risk of frequent exacerbation increased 20, 70 and 270 percent within the first year as the number of elevated biomarkers increased from one to three, compared to patients who did not have biomarker elevations.

As time progressed beyond the first year of follow-up, risk exacerbation continued to stay high. Patients with all three biomarkers elevated for longer periods had a 150 percent increased risk of frequent exacerbations. These predictions were applicable to patients with stable and with mild COPD.

In an observational study, results showed that when the biomarker IL-6 was elevated at the start of the trial in stable COPD patients, the risk of mortality increased almost 2.7-fold (6). Also, after three years, IL-6 increased significantly. Elevated IL-6 was associated with a worsening of six-minute walking distance, a parameter tied to poor physical performance in COPD patients. However, unlike the previous study, CRP did not show correlation with increased COPD exacerbation risk. This was a small trial, only involving 53 patients. Therefore, the results are preliminary.

These biomarker trials are exciting for their potential to shape treatments based on level of exacerbation risk and mortality, creating more individualized therapies. Their results need to be confirmed in a randomized controlled trial (RCT). Many of these biomarkers mentioned in the two trials are identifiable with simple blood tests at major labs.

Statin effect

Statins have been maligned for their side effects, but their efficacy has been their strong suit. An observational trial showed that statins led to at least a 30 percent reduction in the risk of COPD exacerbations, with the effect based on a dose-dependent curve (7). In other words, as the dose increased, so did the benefit.

Interestingly, even those who had taken the statin previously saw a significant reduction in COPD exacerbation risk. The duration of statin use was not important; a short use of statins, whether presently or previously, had substantial benefit. However, the greatest benefit was seen in those who had been on a medium to high dose or were on the drug currently. The researchers believe that the mechanism of action for statins in this setting has to do with their anti-inflammatory and immune-modulating effects. This was a retrospective (backward-looking) study with over 14,000 participants. We will need a prospective (forward-looking) study and RCT to confirm the results.

Exercise

Exercise is beneficial for almost every circumstance, and COPD is no exception. But did you know that a pedometer might improve results? In a three-month study, those with mild COPD were much more successful at achieving exercise goals and reducing exacerbations and symptoms when they used pedometers, compared to the group given advice alone (8). Pedometers gave patients objective feedback on their level of physical activity, which helped motivate them to achieve the goal of walking 9,000 steps daily. This is a relatively easy way to achieve exercise goals and reduce the risk of COPD exacerbations.

When exercising, we are told to vary our exercise routines on regular basis. One study demonstrates that this may be especially important for COPD patients (9). Results show that nonlinear periodization exercise (NLPE) training is better than traditional routines of endurance and resistance training in severe COPD patients. The goal of NLPE is to regularly alter the time spent working out, the number of sets, the number of repetitions and the intensity of the workout on a regular basis.

This study was randomized, involved 110 patients, and was three months in duration. Significantly more severe COPD patients achieved their exercise goals using NLPE than the traditional approach. The group that used NLPE also had an improved quality of life response. The researchers believe that compliance with an NLPE-type program is mostly likely going to be greater because patients seem to enjoy it more.

Chronic inflammation may play a central role in COPD exacerbation. Nonspecific inflammatory biomarkers are potentially valuable for providing more personalized approach to therapy. Drugs that can control inflammation, such as statins, show promise. But don’t forget the importance of lifestyle changes, such as quitting smoking and committing to an exercise regimen that is varied and/or involves the use of a pedometer. And potentially a high-nutrient, anti-inflammatory diet will also contribute positively to reducing the frequency and severity of COPD exacerbations.

References:

(1) Natl Vital Stat Rep. 2011 Dec.;59(10):1-126. (2) MMWR Morb Mortal Wkly Rep. 2012;61:938. (3) N Engl J Med. 2002;346:988-994. (4) www.goldcopd.org. (5) JAMA. 2013;309:2353-2361. (6) Respiratory Research. 2013;14:24. (7) Am J Med. 2013 Jul;126:598-606. (8) ATS 2013 International Conference: Abstract A1360. (9) Am J Respir Crit Care Med. 2013; online Feb. 28.

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.

What is mild cognitive impairment (MCI)? It is a good question, for the parameters are fuzzy. MCI is a hodgepodge of terminology including amnestic and nonamnestic types, with the amnestic type possibly leading to dementia. It is defined as a disorder, but not a disease, that is between normal aging and dementia. As a disorder, it may be more easily reversed. The number of people affected is difficult to pin down, but estimates range from 14  to 22 percent of the U.S. population aged 70 and older (1). Risk factors for MCI include increased age; family history; chronic diseases including heart disease, high blood pressure and diabetes; drug therapies; and lifestyle (2).

So is being overweight potentially detrimental, or is it being underweight? In short, when you are obese and lose weight, it actually decreases your risk. It is not difficult to understand when you put it into context, which we will do.

Also, are there ways to decrease your risk? Well, I already mentioned one, weight loss for the obese patient. I will delineate how weight loss could be both beneficial and detrimental. Another is a twist on a Mediterranean-type diet.

So without further ado, let’s look at the research. Most of the studies refer to dementia; remember, MCI is a malady not a disease; therefore it is harder to find specific studies relating to increased risk.

Increased weight

Rarely does it seem that being overweight or obese is beneficial. Dementia is no exception. I know I am using the risk of dementia study, but I want to demonstrate that the overweight and obese individuals, who now make up at least two-thirds of the U.S. population, are jeopardizing their cognitive abilities.

In an observational study using the Swedish Twin Registry, results showed that being overweight or obese in midlife significantly increased dementia risk — a 71 percent increase in the overweight patient and an almost fourfold increase in the obese (3). This may be a powerful reason to watch your weight at any age.

Underweight

If being obese or overweight may be harmful, what about being underweight? According to the results of a retrospective (backward-looking) study from the UK Clinical Practice Research Datalink, those who are underweight have a 34 percent increased risk of dementia and are at greater risk than those who are overweight or obese (4). In fact, this study suggests that those who are overweight and obese are at lower risk for dementia than even those who are normal weight.

But wait, how can that be? Didn’t the study above suggest that being overweight was bad? First impression says that either the study focusing on overweight/obese patients was wrong or this study has a caveat. Well, the latter is the case. In fact, the researchers did not delineate among potential causes for patients to be underweight or even normal weight. Many times, patients are underweight or normal weight at middle to advanced years due to weight loss-inducing chronic diseases, such as cancer and autoimmune diseases. Underweight was defined as a BMI <20 kg/m2. Other previous studies also contradict the obesity paradox seen in this study.

Unintended weight loss

In one recent study, results demonstrated that unintended weight loss from midlife to later life is a potentially ominous sign for increased risk of mild cognitive impairment (5). There was a statistically significant difference between those who were at higher risk of developing MCI because of greater unintentional weight loss and those who did not experience as much weight loss. The absolute difference was 0.8 kg and the increased risk was 4 percent; however, in a subgroup with a 5-kg weight loss every 10 years, there was an almost 25 percent increased risk of mild cognitive impairment. At the beginning of the study, none of the patients had MCI, and the average age was 70 years. The researchers used retrospective data to compile weight loss from midlife.

Possible solutions to the rescue

What can be done about this? There are lifestyle changes, including dietary changes and weight loss that may help to reduce   the risk or even reverse MCI.

Weight loss, intentional that is!

On the flip side to unintended weight loss, there is intentional weight loss in those who are obese. In a recent randomized controlled trial (RCT), results showed that those who were treated with a calorie-restricted diet saw improvements in language, memory and executive functioning (allows one to complete tasks or reach goals) compared to those in the conventional medicine treatment group without diet counseling (6). The study population had a mean age of 68 and included 80 participants with 40 participants in each arm. It was composed of 80 percent women. Those in both groups were obese, ranging in BMI from obese to morbidly obese, 30-49.5 kg/m2.

The goal was to reach 10 percent weight loss with most of these women, though that was not achieved. This study used a calorie-restricted diet to achieve weight loss. About 40 percent of the participants did lose 5 percent of weight during the study’s one-year duration. The good news: Even with this modest 5 percent weight loss, there was improvement in cognition, especially verbal memory, which involves remembering words and utilizing language skills. The more weight they lost, the better they did cognitively (a dose-response curve). This is encouraging for a follow-up study with more significant weight loss.

Mediterranean diet with extra fat

Recently, we have been furiously debating the importance of fat in the diet. In an RCT, results showed that adding extra virgin olive oil (EVOO) or nuts to the Mediterranean-type diet increased participants’ cognitive functioning (7). There were three groups; all were on the Mediterranean diet, but the two treatment groups differed — one had added EVOO and the other had added nuts.

Interestingly, nuts and olive oil had different effects. The group that had nuts, consisting of one ounce per day of a mixture of almonds, walnuts and hazelnuts, saw an improvement in word memory.

Meanwhile, those in the EVOO group saw more gains in thought processing, executive functioning in the frontal cortex. The EVOO group consumed five tablespoons of olive oil a day, or one liter a week. This is a large amount of olive oil. Remember, though, that the brain is made up of 70 percent fat. There were a total of 447 study participants with a mean age of 67 years, and the study duration was pretty long at approximately four years. No participant had mild cognitive impairment at the start of the trial, though they were at high risk for cardiovascular disease.

Although there was significant improvement in cognition in the treatment groups compared to the control, there was no difference in occurrence of MCI.  Overall incidence of MCI was very small across the groups. A good follow-up study might be a group eating a Mediterranean diet with olive oil plus nuts.

A diet high in “good” fats, especially a Mediterranean-type diet with either nuts or olive oil, appears to be beneficial to improve cognition in older adults.

References:

(1) Arch Neurol. 1999;56(3):303; Ann Intern Med. 2008;148(6):427. (2) uptodate.com. (3) Neurology. 2011;76(18):1568-1574. (4) Lancet Diabetes Endocrinol. 2015;3(6):431-436. (5) JAMA Neurol. online Feb. 1, 2016. (6) J Clin Endocrinol Metab. online Dec. 29, 2015. (7) JAMA Intern Med. 2015 Jul;175(7):1094-1103

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.

Reflux (GERD) disease, sometimes referred to as heartburn, though this is more of a symptom, is one of the most commonly treated diseases. Continuing with that theme, proton pump inhibitors (PPIs), which have become household names, are one of the top-10 drug classes prescribed or taken in the United States. In fact, CDC data shows that use has grown precipitously in the last 10 years in those ages 55 to 64, from 9 percent of the population to 16 percent (1). This is a 78 percent increase in the number of prescriptions for these drugs.

In 2010, there were 147 million prescriptions filled for PPIs (2). The class of drugs includes Prevacid (lansoprazole), Prilosec (omeprazole), Nexium (esomeprazole), Protonix (pantoprazole) and Aciphex (rabeprazole). This growth may not capture the fact that several of these medications are now available over the counter.

I remember when PPIs were touted as having one of the cleanest side-effect profiles. This may still be true, if we are using them correctly for reflux disease. They are supposed to be used for the short term. This can range from 7 to 14 days for over-the-counter PPIs to 4 to 8 weeks for prescription PPIs.

Why did we not know that this class of drugs might be associated with chronic kidney disease, dementia, bone fractures and Clostridium difficile (a bacterial infection of the gastrointestinal tract) before they were approved? Well, if you look at the manufacturers’ package inserts for these drugs, the trials, such as for Protonix, were no longer than a year (3), yet we are putting patients on these medications for decades. And the longer people are on them, the more complications arise.

Typical symptoms of reflux are heartburn and/or regurgitation. Atypical symptoms include coughing and throat clearing. But these atypical symptoms may not be as common as you might think. In fact, in one study, coughing and throat clearing taken together only resulted in a very small portion of patients having reflux disease (4). Having one of these two symptoms showed a slightly higher risk of reflux, but very modest.

Let’s look at some of the research.

Though PPIs may increase the risk of a number of complications, keep in mind that none of the data are from randomized controlled trials (RCTs), which are the gold standard of studies, but mostly observational studies that suggest an association, but not a link. Long-term RCTs to determine side effects are prohibitively expensive.

PPI and kidney disease

In two separate studies, results showed that there was an increase in chronic kidney disease with prolonged PPI use (5). All of the patients started the study with normal kidney function based on glomerular filtration rate (GFR). In the Atherosclerosis Risk in Communities (ARIC) study, there was a 50 percent increased risk of chronic kidney disease, while the Geisinger Health System cohort study found there was a modest 17 percent increased risk. The first study had a 13-year duration, and the second had about a six-year duration. Both demonstrated a modest, but statistically significant, increased risk of chronic kidney disease. But as you can see, the medications were used on a chronic basis for years. In an accompanying editorial to these published studies, the author suggests that there is overuse of the medications or that they are used beyond the resolution of symptoms and suggests starting with diet and lifestyle modifications as well as a milder drug class, H2 blockers (6).

PPI and dementia

A recent German study looked at health records from a large public insurer and found there was a 44 percent increased risk of dementia in the elderly who were using PPIs, compared to those who were not (7). These patients were at least age 75. The authors surmise that PPIs may cross the coveted blood-brain barrier and have effects by potentially increasing beta-amyloid levels, markers for dementia. With occasional use, meaning once every 18 months for a few weeks to a few months, there was a much lower increased risk of 16 percent. The researchers also suggested that PPIs may be significantly overprescribed in the elderly. Unfortunately, there were confounding factors that may have conflated the risk, such as multiple drug use, having diabetes, or patient also having depression or a stroke history. Researchers also did not take into account family history of dementia, high blood pressure or excessive alcohol use, all of which have effects on dementia occurrence.

PPI and bone fractures

In a recent meta-analysis (a group of 18 observational studies), results showed that PPIs can increase the risk of hip fractures, spine fractures and any-site fractures (8). Interestingly, when it came to bone fractures, it did not make a difference whether patients were taking PPIs for more or less than a year. How much less than a year was not delineated. They found increased fracture risks of 58, 26 and 33 percent for spine, hip and any site, respectively. It is not clear what may potentially increase the risk; however, it has been proposed that it may have to do with calcium absorption through the gut. PPIs reduce the amount of acid, which may be needed to absorb insoluble calcium salts. In another study, seven days of PPIs were shown to lower the absorption of calcium carbonate supplements when taken without food (9).

Need for magnesium

PPIs may have lower absorption effects on several electrolytes including magnesium, calcium and B12. There were two recent studies on magnesium. In one observational study, PPIs combined with diuretics caused a 73 percent increased risk of hospitalization due to low magnesium (10). Diuretics are water pills that are commonly used in disorders such as high blood pressure, heart failure and swelling.

Another study confirmed these results. In this second study, which was a meta-analysis (a group of nine studies), PPIs increased the risk of low magnesium in patients by 43 percent, and when researchers looked only at higher quality studies, the risk increased to 63 percent (11). The authors note that a significant reduction in magnesium could lead to cardiovascular events.

The bottom line is even though some PPIs are over-the-counter and some are prescription medications, it is best if you confer with your doctor before starting them. You may not need PPIs, but rather a milder medication referred to as H2 blockers (Zantac, Pepcid). Even better, start with lifestyle modifications including diet, not eating later at night, raising the head of the bed, losing weight and stopping smoking, if needed, and then consider medications (12). If you do need medications, know that PPIs don’t give immediate relief and should only be taken for a short duration: 7 to 14 days, according to the FDA (13), without a doctor’s consult, and 4 to 8 weeks with one. Most of the problems occur with long-term use.

References:

(1) cdc.gov. (2) PLoS Med. 2014;11(9):e1001736. (3) protonix.com. (4) J Clin Gastroenterol. Online Jul 18, 2015. (5) JAMA Intern Med. 2016;176(2). (6) JAMA Intern Med. 2016;176(2):172-174. (7) JAMA Neurol. online Feb 15, 2016. (8) Osteoporos Int. online Oct 13, 2015. (9) Am J Med. 118:778-781. (10) PLoS Med. 2014;11(9):e1001736. (11) Ren Fail. 2015;37(7):1237-1241. (12) Am J Gastroenterol 2015; 110:393–400. (13) fda.gov.

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.

Cardiovascular disease is anything but boring; what we know about it is constantly evolving. New information comes along all the time, which on the whole is a good thing. Even though this disease has been on the decline, it is still the number one killer of Americans, responsible for about one million deaths per year (1). However, not all studies nor all analyses on the topic are created equal. Therefore, I thought it apropos to present a quiz on cardiovascular disease myths and truths.

Saturated fat

Most of the medical community has been under the impression that saturated fat is not good for us. We need to limit our intake to no more than 10 percent of our diet. But is this true? The results of a meta-analysis (a group of 72 randomized clinical trials and observational studies) challenge this paradigm (2). While saturated fat did not decrease the risk of cardiovascular disease, it did not significantly increase the risk either. Also, the results showed that trans fats increase the risk of this disease. Of course, trans fats are a processed fat, so this is something that most of us would agree upon. And in the clinical trials portion of the meta-analysis, omega-3 and omega-6 polyunsaturated fats did not significantly reduce the risk of cardiovascular disease.

Does this mean that we can go back to eating saturated fats with impunity? Well, there were weaknesses and flaws with this study. The authors only looked at the one dimension of fat. Their comparison was based on the upper third of intake of one type of fat versus the lower third of intake of the same type of fat (whether it was saturated fat or a type of unsaturated fat). It did not consider whether saturated fat was substituted with refined grains or unsaturated fatty acids. Also, what was the source of saturated fats, animal or plant, and did these sources also contain unsaturated fats as well, like olive oil or nuts, which contain good fats? Therefore, there are many unanswered questions and potentially several significant flaws with this study.

Mark Bittman, a popular columnist for The New York Times, referenced this meta-analysis as his justification for promoting butter and other sources of saturated animal fat, such as cheese, pork and the skin from chicken. Many of his articles in the past have contributed to the health and wellness of his readers. In this case, I think he does a disservice to his readers, making statements that are dangerous and hopefully will not result in more cardiovascular disease.

The meta-analysis above, which Bittman uses to buoy his arguments, does not differentiate among plant or animal saturated fat sources. But in one that does, the researchers found saturated fats from animal sources increased cholesterol and the risk of cardiovascular disease (3). In another study, specifically using unsaturated fats in place of saturated fat reduced the risk of cardiovascular disease (4, 5).

Fish oil

There is whole industry built around fish oil and reducing the risk of cardiovascular disease. Yet the data don’t seem to confirm this theory. In the latest study, the age-related eye disease study 2 (AREDS2), unfortunately, 1 gram of fish oil (long-chain omega-3 fatty acids) daily did not demonstrate any benefit in the prevention of cardiovascular disease nor its resultant mortality (6). This study was done over a five-year period in the elderly with macular degeneration. The cardiovascular primary end point was a tangential portion of the ophthalmic AREDS2. This does not mean that fish, itself, falls into that same category, but for now there does not seem to be a need to take fish oil supplements for heart disease, except potentially for those with very high triglycerides. Fish oil, at best, is controversial; at worst, it has no benefit with cardiovascular disease.

Fiber

We know that fiber tends to be important for a number of diseases, and cardiovascular disease does not appear to be an exception. In a meta-analysis, involving 22 observational studies, the results showed a linear relationship between fiber intake and decreased risk for developing cardiovascular disease (7). In other words, for every 7 grams of fiber consumed, there was 9 percent reduced risk in developing the disease. It did not matter the source of the fiber from plant foods; vegetables, grains and fruit all decreased the risk of cardiovascular disease. This did not involve supplemental fiber, like that found in Fiber One or Metamucil.

To give you an idea about how easy it is to get a significant amount of fiber, one cup of lentils has 15.6 grams of fiber, one cup of raspberries or green peas has almost 9 grams and one medium-size apple has 4.4 grams. Americans are sorely deficient in fiber (8).

We typically get between 8 to 14 grams of fiber so we have a lot of room for improvement. The American Dietetic Association recommends 25 grams of fiber for women and 40 grams for men, but I advocate 40 grams for both.

Diet soda

A 2014 presentation at the American College of Cardiology examined the Women’s Health Initiative: The study suggests that diet soda may increase the risk of heart disease (9). In those drinking two or more cans per day, defined as 12 ounces per can, there was a 30 percent increased risk of a cardiovascular event, such as a stroke or heart attack, but an even greater risk of cardiovascular mortality, 50 percent, over 10 years. These results took into account confounding factors like smoking, diabetes, high blood pressure and obesity. This study involved over 56,000 postmenopausal women for an almost nine-year duration.

Vitamin D

The results of an observational study in the elderly suggest that vitamin D deficiency may be associated with cardiovascular disease risk. The study showed that those whose vitamin D levels were low had increased inflammation, demonstrated by elevated biomarkers including C-reactive protein (CRP) (10). This biomarker is related to inflammation of the heart, though it is not as specific as one would hope.

Beware in regards to saturated fat. If a study looks like an outlier or too good to be true, then it probably is. I would not run out and get a cheeseburger just yet. However, study after study has shown benefit with fiber. So if you want to reduce the risk of cardiovascular disease, consume as much whole food fiber as possible. Also, since we live in the Northeast, consider taking at least 1000 IUs of vitamin D daily. This is a simple way to help thwart the risk of the number one killer.

References:

(1) uptodate.com. (2) Ann Intern Med. 2014;160(6):398-406. (3) JAMA 1986;256(20):2623. (4) Am J Clin Nutr. 2009;99(5):1425-1432. (5) Cochrane Database Syst Rev. 2012:5;CD002137. (6) JAMA Intern Med. Online March 17, 2014. (7) BMJ 2013; 347:f6879. (8) Am J Med. 2013 Dec;126(12):1059-1067.e1-4. (9) ACC Scientific Sessions 2014; Abstract 917-05. (10) J Clin Endocrinol Metab online February 24, 2014.

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.

Not surprisingly, osteoarthritis is widespread. The more common joints affected are the knees, hips and hands. There are three types of treatment for this disease: surgery, involving joint replacements of the hips or knees; medications; and nonpharmacologic approaches. The most commonly used first-line medications are acetaminophen and nonsteroidal anti-inflammatory drugs, such as ibuprofen. Unfortunately, medications mostly treat the symptoms of pain and inflammation.

However, the primary objectives in treating osteoarthritis should also include improving quality of life, slowing progression of the disease process and reducing its disabling effects (1).

Dairy and milk

When we think of dairy, specifically milk, there are two distinct camps: One believes in the benefits, and the other thinks it may contribute to disease. In this case they both may be at least partly correct. In the Osteoarthritis Initiative study, an observational study of over 2,100 patients, results showed that low-fat (1 percent) and nonfat milk may slow the progression of osteoarthritis (2). The researchers looked specifically at joint space narrowing that occurs in those with affected knee joints. Radiographic imaging changes were used at baseline and then to follow the patients for up to 12 to 48 months for changes. Compared to those who did not drink milk, patients who did saw significantly less narrowing of knee joint space.

Was it a dose-dependent response? Not necessarily. Specifically, those who drank less than three glasses/week and those who drank four to six glasses/week both saw slower progression of joint space narrowing of 0.09 mm. Seven to 10 glasses/week resulted in a 0.12 mm preservation. However, those who drank more than 10 glasses/week saw less beneficial effect, 0.06 mm preservation compared to those who did not drink milk. Interestingly, there was no benefit seen in men or with the consumption of cheese or yogurt.

However, there are significant flaws with this study. First, the patients were only asked about their dietary intake of milk at baseline; therefore their consumption could have changed during the study. Second, there was a recall bias; patients were asked to recall their weekly milk consumption for the previous 12 months before the study began. I don’t know about you, but I can’t recall my intake of specific foods for the last week, let alone for the past year. Third, there could have been confounding factors, such as orange consumption.

Oddly, this was not a dose-response curve, since the most milk consumption had less beneficial effect than lower amounts. Also, why were these effects only seen in women? Finally, researchers could not explain why low-fat or nonfat milk had this potential benefit, but cheese was detrimental and yogurt did not show benefit. We are left with more questions than answers.

Would I recommend consuming low-fat or nonfat milk? Not necessarily, but I may not dissuade osteoarthritis patients from drinking it. There are very few approaches that slow the progression of joint space narrowing.

Vitamin D

Over the last five years or so, the medical community has gone from believing that vitamin D was potentially the solution to many diseases to wondering whether, in some cases, low levels were indicative of disease, but repletion was not a change-maker. Well, in a recent randomized controlled trial, the gold standard of studies, vitamin D had no beneficial symptom relief, nor any disease-modifying effects (3). This two-year study of almost 150 men and women raised blood levels of vitamin D on average to 36 ng/ml, which is considered respectable. Researchers used MRI and X-rays to track their results.

Glucosamine

There is raging debate about whether glucosamine is an effective treatment for osteoarthritis. In the latest installment, there was a RCT, the results of which showed that glucosamine hydrochloride was not effective in treating osteoarthritis (4). In the trial, 201 patients with either mild or moderate knee pain drank diet lemonade with or without 1500 mg of glucosamine hydrochloride.

There was no difference in cartilage changes in the knee nor in pain relief in those in the placebo or treatment groups over a six-month duration. Bone marrow lesions also did not improve with the glucosamine group. The researchers used 3T MRI scans (an advanced radiologic imaging technique) to follow the patients’ disease progression. This does not mean that glucosamine does not work for some patients. Different formulations, such as glucosamine sulfate, were not used in this study.

Weight

This could not be an article on osteoarthritis if I did not talk about weight. Do you remember analogies from the SATs? Well here is one for you: Weight loss, weight loss, weight loss is to osteoarthritis as location, location, location is to real estate. In a recent study involving 112 obese patients, there was not only a reduction of knee symptoms in those who lost weight, but there was also disease modification, with reduction in the loss of cartilage volume around the medial tibia (5).

On the other hand, those who gained weight saw the inverse effect. A reduction of tibial cartilage is potentially associated with the need for knee replacement. The relationship was almost one-to-one; for every 1 percent of weight lost, there was a 1.2 mm3 preservation of medial tibial cartilage volume, while the exact opposite was true with weight gain.

Exercise and diet

In a recent study, diet and exercise trumped the effects of diet or exercise alone (6). Patients with osteoarthritis of the knee who lost at least 10 percent of their body weight experienced significant improvements in function and a 50 percent reduction in pain, as well as reduction in inflammation, compared to those who lost 5 to 10 percent and those who lost less than 5 percent. This study was a well-designed, randomized controlled single-blinded study with a duration of 18 months.

Researchers used a biomarker — IL6 — to measure inflammation. The diet and exercise group and the diet-only group lost significantly more weight than the exercise-only group, 23.3 pounds and 19.6 pounds versus 4 pounds. The diet portion consisted of a meal replacement shake for breakfast and lunch and then a vegetable-rich, low-fat dinner. Low-calorie meals replaced the shakes after six months. The exercise regimen included one hour of a combination of weight training and walking with alacrity three times per week.

Therefore, concentrate on lifestyle modifications if you want to see potentially disease-modifying effects. These include both exercise and diet. In terms of low-fat or nonfat milk, while the study had numerous flaws, if you drink milk, you might continue for the sake of osteoarthritis, but stay on the low end of consumption. And remember, the best potential effects shown are with weight loss and with a vegetable-rich diet.

References:

(1) uptodate.com. (2) Arthritis Care Res online. 2014 April 6. (3) JAMA. 2013;309:155-162. (4) Arthritis Rheum online. 2014 March 10. (5) Ann Rheum Dis online. 2014 Feb. 11. (6) JAMA. 2013;310:1263-1273.

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.