With diabetes, we tend to concentrate on the stabilization of the disease as a whole. This is a good thing. However, there is not enough attention spent on microvascular (small vessel disease) complications of diabetes, specifically diabetic retinopathy, which is an umbrella term. There are at least three different disorders that make up diabetic retinopathy. These are dot and blot hemorrhages, proliferative diabetic retinopathy and diabetic macular edema. The latter two are the most likely disorders to cause vision loss. Our focus for this article will be on diabetic retinopathy as a whole and diabetic macular edema.

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

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

Whew! Did you get all that? If not, to summarize: diabetic macula edema is fluid in the back of the eye that may cause vision loss. DME affects approximately 1 in 25 patients with diabetes according to a recent study (4). However, the results also showed that this number is significantly greater (2.6 times) in blacks compared to non-Hispanic whites. And the highest risk factor for DME was for those with the longest duration of diabetes. Ironically, an oral class of drugs, thiazolidinediones, which includes rosiglitazone (Avandia) and pioglitazone (Actos), used to treat type 2 diabetes may actually increase the risk of DME. However, the results on this are conflicting.

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

In a cross-sectional study (a type of observational study) using NHANES data from 2005-08, among patients with DME, only 45 percent were told by a physician that the diabetes had affected their eyes (6). Approximately 46 percent of patients reported that they had not been to a diabetic nurse educator, nutritionist or dietician in more than a year — or never. The problem is that the symptoms of vision loss don’t necessarily occur until the latter stages of the disorder. According to the authors, there needs to be an awareness campaign about the importance of getting your eyes examined on an annual basis if you have diabetes. Many patients are unaware of the association between vision loss and diabetes.

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

Treatment laser and injection

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

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

Increased risk with diabetes drugs

You would think that drugs to treat type 2 diabetes would prevent DME from occurring as well. However, in the THIN trial, a retrospective (backward-looking) study, a class of diabetes drugs, thiazolidinediones, including Avandia and Actos, actually increased the occurrence of DME compared to those who did not use these oral medications (9). Those receiving these drugs had a 1.3 percent incidence of DME at year one, whereas those who did not had a 0.2 percent incidence. This incidence was persistent through the 10 years of follow-up. To make matters worse, those who received both thiazolidinediones and insulin had an even greater incidence of DME. There were 103,000 diabetes patients reviewed in this trial. It was unclear whether the drugs, because they were second line treatments, or the severity of the diabetes itself may have caused these findings.

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

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

Diet

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

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

References:

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

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to medicalcompassmd.com.

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

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

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

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

In a recent study of centenarians, genetics played a significant role. Characteristics of this group were that they tended to be healthy and then die rapidly, without prolonged suffering (3).

Another benchmark is the amount of health care dollars spent in their last few years. Statistics show that the amount spent for those who were in their 60s and 70s was significantly higher, three times as much, as for centenarians in their last two years (4).

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

Exercise

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

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

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

Diet

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

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

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

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

Inflammation

You may have heard the phrase that inflammation is the basis for more than 80 percent of chronic disease. But how can we quantify this into something tangible? In the Whitehall II study, a specific marker for inflammation was measured, interleukin-6. The study showed that higher levels did not bode well for participants’ longevity (9). In fact, if participants had elevated IL-6 (>2.0 ng/L) at both baseline and at the end of the 10-year follow-up period, their probability of healthy aging decreased by almost half.

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

The bottom line is that, although genetics is important for longevity, so too are lifestyle choices. A small amount of exercise, specifically running, can lead to a substantial increase in healthy lifespan. While calories are not equal, protein from plants may trump protein from animal sources in reducing the risk of mortality from all-cause, diabetes and heart disease.

This does not necessarily mean that one needs to be a vegetarian to see the benefits. IL-6 may be a useful marker for inflammation, which could help predict healthy or unhealthy outcomes. Thus, why not have a discussion with your doctor about testing to see if you have an elevated IL-6? Lifestyle modifications may be able to reduce these levels.

References:

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

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

Niacin has recently become a highly contested drug. In my last article, “Reducing triglycerides,” I mentioned that niacin has powerful effects to treat elevated triglycerides, but that the clinical benefit of this effect is questionable.  Here, I will expand on issues related to niacin.

What is niacin? It is a B vitamin, specifically B3.  It is one of the few supplements that is 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 recent 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). I wrote about this in a separate article entitled “New cholesterol guidelines released,” which can be found on northshoreoflongisland.com.

In a recent 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 non-fatal 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 to 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, both mentioned previously, comparing the benefits of niacin, cholesteryl ester transfer protein inhibitors, and fibrates, the results showed that even though these drugs may raise HDL levels, there was no improvement in terms of cardiovascular endpoints when 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 medicalcompassmd.com and/or consult your personal physician.

Triglycerides is a term that most of us recognize. This substance is part of the lipid (cholesterol) profile. However, this may be the extent of our understanding. Compared to the other substances, HDL (“good” cholesterol) and LDL (“bad” cholesterol), triglycerides are not covered much in the lay press and medical research tends to be less robust than for the other components. If I were to use a baseball analogy, triglycerides are the Mets, who get far less attention than their crosstown rivals, the Yankees.

But are triglycerides any less important? It is unclear whether a high triglyceride level is a biomarker for cardiovascular disease – heart disease and stroke – or an independent risk in its own right (1) (2). This debate has been going on for over 30 years. However, this does not mean it is any less important.

What are triglycerides? The most rudimentary explanation is that they are a kind of fat in the blood. Alcohol, sugars and excess calorie consumption may be converted into triglycerides.

Risk factors for high triglycerides include obesity, smoking, a high carbohydrate diet, uncontrolled diabetes, hypothyroidism (underactive thyroid), cirrhosis (liver disease), excessive alcohol consumption and some medications (3).

What levels are normal and what are considered elevated? According to the American Heart Association, optimal levels are <100 mg/dL; however, less than 150 mg/dL is considered within normal range. Borderline triglycerides are 150-199 mg/dL, high levels are 200-499 mg/dL and very high are >500 mg/dL (3).

While medicines that focus on triglycerides, fibrates and niacin, have the ability to lower them significantly, it is questionable whether this reduction results in clinical benefits, like reducing the risk of cardiovascular events. The ACCORD Study, a randomized controlled trial, questioned the effectiveness of medication; when these therapies were added to statins in type 2 diabetes patients, they did not further reduce the risk of cardiovascular disease and events (4). Instead, it seems that lifestyle modifications may be the best way to control triglyceride levels.

Let’s look at the evidence.

Exercise – timing and intensity

If you need a reason to exercise, here is really good one. I frequently see questions pertaining to optimal exercise timing and intensity. Most of the answers are vague, and the research is not specific. However, hold on to your hats, because a recent study may give the timing and intensity answer, at least in terms of triglycerides.

Study results showed that walking a modest distance with alacrity and light weight training approximately an hour after eating (postprandial) reduced triglyceride levels by 72 percent (5). However, if patients did the same workout prior to eating, then postprandial triglycerides were reduced by 25 percent. This is still good, but not as impressive. Participants walked a modest distance of just over one mile (2 kilometers). This was a small pilot study of 10 young healthy adults for a very short duration. The results are intriguing nonetheless, since there are few data that give specifics on optimal amount and timing of exercise.

Exercise trumps calorie restriction

There is good news for those who want to lower their triglycerides: calorie restriction may not the best answer. In other words, you don’t have to torture yourself by cutting calories down to some ridiculously low level to get an effect. We probably should be looking at exercise and carbohydrate intake instead.

In a well-controlled trial, results showed that those who walked and maintained 60 percent of their maximum heart rate, which is a modest level, showed an almost one-third reduction in triglycerides compared to the control group (maintain caloric intake and no exercise expenditure) (6). Those who restricted their calorie intake saw no difference compared to the control. This was a small study of 11 young adult women.

Thus, calorie restriction was trumped by exercise as a way to potentially reduce triglyceride levels.

Carbohydrate reduction not calorie restriction

In addition, when calorie restriction was compared to carbohydrate reduction, results showed that carbohydrate reduction was more effective at lowering triglycerides (7). In this small but well-designed study, patients with nonalcoholic fatty liver disease were randomized to either a lower calorie (1200-1500 kcal/day) or lower carbohydrate (20 g/day) diet. Both groups significantly reduced triglycerides, but the lower carbohydrate group reduced triglycerides by 55 percent versus 28 percent for the lower calorie group. The reason for this difference may have to do with oxidation in the liver and the body as a whole. Both groups lost similar amounts of weight, so weight could not be considered a confounding or complicating factor. However, the weakness of this study was its duration of only two weeks.

Fasting versus nonfasting blood tests

The paradigm has been that, when cholesterol levels are drawn, fasting levels provide a more accurate reading. Except this may not be true.

In a new analysis, fasting may not be necessary when it comes to cholesterol levels. NHANES III data suggests that nonfasting and fasting levels yield similar results related to all-cause mortality and cardiovascular mortality risk. The LDL levels were similarly predictive regardless of whether a patient had fasted or not. The researchers used 4,299 pairs of fasting and nonfasting cholesterol levels. The duration of follow-up was strong, with a mean of 14 years (8).

Why is this relevant? Triglycerides are an intricate part of a cholesterol profile. With regards to stroke risk assessment, nonfasting triglycerides possibly may be more valuable than fasting. In a study involving 13,596 participants, results showed that, as nonfasting triglycerides rose, the risk of stroke also rose significantly (9). Compared to those who had levels below 89 mg/dL (the control), those with 89-176 mg/dL had a 1.3-fold increased risk of cardiovascular events, whereas those within the range of 177-265 mg/dL had a twofold increase, and women in the highest group (>443 mg/dL) had an almost fourfold increase. The results were similar for men, but not quite as robust at the higher end with a threefold increase.

The benefit of nonfasting is that it is more realistic and, according to the authors, also involves remnants of VLDL and chylomicrons, other components of the cholesterol profile that interact with triglycerides and may affect the inner part (endothelium) of the arteries.

What have we learned? Triglycerides need to be discussed, just as we review HDL and LDL levels regularly. Elevated triglycerides may result in heart disease or stroke. The higher the levels, the more likely there will be increased risk of mortality – both all-cause and cardiovascular. Therefore, we ideally should reduce levels to less than 100 mg/dL.

Lifestyle modifications using carbohydrate restriction and modest levels of exercise after a meal may be the way to go to the best results, though the studies are small and need more research. Nonfasting levels may be as important as fasting levels when it comes to triglycerides and the cholesterol profile as a whole; they potentially give a more realistic view of cardiovascular risk, since we don’t live in a vacuum and fast all day.

References:

(1) Circulation. 2011;123:2292-2333. (2) N Engl J Med. 1980;302:1383–1389. (3) nlm.nih.gov. (4) N Engl J Med. 2010;362:1563-1574. (5) Med Sci Sports Exerc. 2013;45(2):245-252. (6) Med Sci Sports Exerc. 2013;45(3):455-461. (7) Am J Clin Nutr. 2011;93(5):1048-1052. (8) Circulation Online. 2014 July 11. (9) JAMA 2008;300:2142-2152.

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 medicalcompassmd.com or consult your personal physician.

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

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

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

Let’s look at the evidence.

Diabetic peripheral neuropathy

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

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

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

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

Why include this study? There were several important differences. One was that lipoic acid was given in oral supplements, rather than intravenously. Thus, this is a more practical approach. Another difference is that there were three doses tested for lipoic acid: 600 mg, 1200 mg and 1800 mg. Interestingly, all of them had similar efficacy. However, the higher doses had more side effects of nausea, vomiting and vertigo, again without increased effectiveness. This suggests that an oral dose of 600 mg of lipoic acid may help treat diabetic peripheral neuropathy.

Dementia and Alzheimer’s

In a recent randomized, placebo-controlled trial involving Alzheimer’s patients, results were significantly better for lipoic acid (600 mg oral dose) in combination with fish oil, compared to fish oil alone or to placebo (5). The amount of fish oil used was 3 grams daily containing 675 mg of docosahexaenoic acid and 975 mg of eicosapentaenoic acid of the triglyceride formulation. The duration of this pilot study was 12 months with 39 patients, and the primary endpoint was a change in an oxidative stress biomarker, which did not show statistical significance. However, and very importantly, the secondary endpoint was significant: slowing the progression of cognitive and functional decline with the combination of fish oil and lipoic acid. Mini-mental status and instrumental activities of daily living declined less in the combination treatment group. This was encouraging, although we need larger trials.

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

Multiple sclerosis

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

I know this sounds confusing, but the important point is that this may relate to a human trial with 30 patients that showed reduction in the enzyme MMP (8). Thus, it could potentially slow the progression of multiple sclerosis. This is purely connecting the dots. We need a large-scale trial that looks at clinical outcomes of progression in MS, not just enzyme levels. The oral dose used in this study was 1200 mg to 2400 mg of lipoic acid per day.

Interestingly, the 1200 mg dose used in the human trial was comparable to the high dose that showed slowed progression in the rat study (9). This only whets the appetite and suggests potential.

So, we have lots of data. What do we know? In diabetic neuropathy, 600 mg of oral lipoic acid may be beneficial. However, in Alzheimer’s the jury is still out, although 600 mg of lipoic acid in combination with fish oil has potential to slow the cognitive decline in Alzheimer’s disease. It also may have a role in MS with an oral dose of 1200 mg, though this is early data.

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

References:

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

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

Fat in the diet is a highly complicated issue. For decades, we have adopted the notion that fat may be the enemy and, therefore, we should eat a low-fat diet. But is this really true? The answer is that we all need fat, but the sources are important.

The cover of Time magazine’s June 23 edition exclaimed in big yellow letters to “Eat Butter. Scientists labeled fat the enemy. Why they were wrong” (1). It also included a picture of a curl of butter, in case you had forgotten what butter looked like. This cover is provocative and tantalizing. However, it does a disservice to the article itself and to the general population who may have seen it.

The article, itself, is well written. Its focus is not mainly on butter, but rather on different types of fats, saturated and unsaturated. The author Bryan Walsh does make salient points, but my objection is mainly that many of these points are buried deep within a five-page, three-column, single-spaced article among comments that are not necessarily substantiated. You have to wade through paragraph after paragraph to get to some these points. Reading the first page is not good enough.

Let’s look at a few studies presented in the article.

Study: Different types of fat — saturated and unsaturated with heart disease.

There was a recent meta-analysis (a group of 72 studies including both observational and randomized controlled trials) that looked at whether different types of fat had an impact on cardiovascular health (2). The results showed that saturated fats, omega-6 polyunsaturated fats and monounsaturated fats were most likely not harmful and that omega-3 polyunsaturated fats were potentially beneficial. However, trans fatty acids were shown to be potentially harmful, with a 17 percent increased risk of cardiovascular disease outcomes such as heart attacks and heart disease.

While this is an interesting study, there are some significant flaws that need to be highlighted.

1. The conclusions in the study don’t match or only partially match. Let me explain. There is a conclusion in the abstract (a synopsis or summary of the study) and a conclusion in the body of the study. The abstract concludes that polyunsaturated fats, including omega-3 fatty acids, are not necessarily beneficial while saturated fat may not be harmful. In the body of the study, the authors conclude that omega-3 fatty acids significantly reduce cardiovascular events. Why is this important? Many physicians are bombarded by studies and may only have time to read the abstract. Thus, this could wrongly influence the physician.

2. The source of fat is never differentiated in the study. In other words, the saturated fats which are deemed harmless may be from foods or supplements that contain both unsaturated fats and saturated fats or from foods that contain only saturated fats. We see benefit in plant-based foods that have multiple types of fats — saturated and unsaturated — such as olive oil, nuts, seeds and avocado. However, most animal fats, like red meat, pork and chicken, contain only saturated fats. The exception is fish, which contains multiple types of fats.

Also, unlike the Time cover story, the study NEVER mentions butter, cheese or red meat. Therefore, the commentary by the press is based on an extrapolation that cannot and should not be made: that eating butter, cheese and red meat maybe harmless and possibly beneficial.

3. The populations of the studies differed at the starts of the different trials. In other words, some were healthy participants, some were high-risk patients and some already had cardiovascular disease. The main thing these studies had in common was that cardiovascular disease outcomes were an endpoint, but it did not have to be the primary, or main, endpoint. Thus, cardiovascular disease outcomes may not have been the main thrust of all the studies that made up the meta-analysis.

4. A meta-analysis by definition is difficult to perform because researchers combine results from studies that were designed and performed differently from one another. In this meta-analysis, the authors combine the results of observational trials that may have used different types of fat intake from food or from supplements. Usually, supplements, like fish oil, involve both saturated and unsaturated fats, and they may have different effects than food.

5. Finally, the study does not tell us what those who ate lower saturated and unsaturated fats ate instead. For example, it compared those who ate high saturated fats to those who ate low saturated fats. What did the group who ate lower saturated fat eat instead of fat? Was it carbohydrates? If so, were they fries, whole grains or sweet potatoes?

The Time cover article goes on to mention the Mediterranean diet and its beneficial effects with heart disease. There was a recent randomized controlled study, the gold standard of studies, called the
PREDIMED trial, with results that showed that participants who ate a Mediterranean diet with added olive oil or mixed nuts had a 30 percent decreased risk of cardiovascular disease than those in the control arm who were advised to follow a “low-fat” diet (3). The Mediterranean diet emphasizes vegetables, fruits, whole intact grains, beans, legumes and fish, as well as olive oil and nuts. This was not a low-fat diet. It contained both saturated and unsaturated fats, including polyunsaturated and monounsaturated fatty acids. The caveat to these results is that the “low-fat” group was not actually able to maintain a low-fat diet, but instead ate more like the standard American diet with no restrictions.

Interestingly, researchers using the same Mediterranean diet study, PREDIMED, showed that higher dietary intake of magnesium reduced the risk of cardiovascular mortality risk by 34 percent (4). They compared those in the highest intake of dietary magnesium with those in the lowest. These participants had a high risk of cardiovascular disease. Foods rich in magnesium include dark green leafy vegetables, such as spinach, as well as nuts, seeds, fish, beans, lentils and avocados.

In conclusion, the sources of fats matter. To run out and eat a cheeseburger, without the bun of course, would be to have misunderstood this article and the flaws in the meta-analysis and to have focused only on the cover of the Time magazine article. The take-home message should be that we need some fats in our diet, but that the sources of these fats are critical. Diet quality is of the utmost importance in reducing disease (5), so put that cheeseburger out of your mind. Many studies have shown that the Mediterranean diet helps reduce the risk of cardiovascular events. For some, this may include the addition of more olive oil and nuts.

References:

(1) Time.com. (2) Ann Intern Med. 2014;160:398-406. (3) N Engl J Med. 2013;368:1279-1290. (4) J Nutr. 2014;144:55-60. (5) Lancet. 2014;383:1999-2007.

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 medicalcompassmd.com or consult your personal physician.

When we refer to diabetes, we think of its complications. It may lead to microvascular maladies that affect vision (retinopathy), the kidneys (nephropathy) and the limbs (peripheral neuropathy), as well as macrovascular diseases such as heart disease and heart attacks. These are important reasons to prevent and treat it.

However, diabetes, in and of itself, is complicated. For example, in the ACCORD trial, we treated diabetes patients aggressively with medication trying to get their HbA1C (three-month sugars) to below 6.0 percent rather than the standard 7.0 percent, because we thought lower would mean fewer complications. According to the results, the patients who were treated more aggressively had a higher risk of mortality (1).

We know that in type 2 diabetes, the first line of therapy beyond lifestyle modifications is metformin. But when that is not enough, we also know that insulin is the most powerful treatment for decreasing glucose, or sugar, levels. But are insulin therapies the best drugs to use? Well, it turns out that they may have more risk of death compared to another drug class, sulfonylureas (e.g., Glucotrol, Amaryl). However, sulfonylureas, along with another drug class, thiazolidinediones (e.g., Avandia, Actos), may increase the risk of fractures. Sulfonylureas and insulin each have also been associated with increased risk of hypoglycemia (low sugar).

Diabetes is also associated with depression. The prevailing thought has been that having diabetes may contribute to depression. However, the association may be related to another common factor, inflammation.

If that were not enough to make your head spin, the Centers for Disease Control reports that one-quarter of patients don’t even know they have diabetes (2). And for people over the age of 20, 33 percent have prediabetes, defined as sugar levels between normal and diabetes, with fasting sugar of 100-125 mg/dl or HbA1C of 5.7-6.4 percent. However, there is good news as it relates to lifestyle modification. Let’s look at the evidence.

Medications: insulin versus
sulfonylurea

Two of the most common medications for the treatment of diabetes, referred to as second-line therapies since they would be used after metformin, are insulin and sulfonylureas. In a recent observational comparative effectiveness trial with patients already on metformin, results showed that  when insulin was added compared to when sulfonylureas were added, there was a 44 percent increased risk of all-cause mortality and a 30 percent increased risk of cardiovascular outcomes including heart attack, stroke or all-cause death (3).

Does this mean we should not use insulin? No. There were limitations to this study. Though it was more sophisticated with its comparative effectiveness design, it was still retrospective, which is not as strong as some other study types and may involve bias. The only conclusion that can be made is that insulin when used with metformin had an association with, but not a link to, significantly negative side effects versus sulfonylureas. These patients were followed for a median of 14 months. We need prospective studies, especially randomized controlled studies. However, the results are intriguing. It makes you think twice before reaching for insulin as a second-line therapy.

Medications: sulfonylureas and thiazolidinediones

Does this mean that we know what to use for second-line therapy? Not necessarily. In a recent study, both sulfonylureas and thiazolidinediones showed a significantly increased risk of fractures. There was a 9 percent increase in fracture risk with sulfonylureas and a 40 percent increased risk with thiazolidinediones when each was compared to metformin (4). The good news is that other drug classes were tested and did not show statistically significant elevated risk occurrences. This was also a retrospective observational study so the same study limitations apply, most importantly, bias and confounding factors.

Depression

To complicate matters further, diabetes and depressive symptoms are associated with each other, but not in the way you might think. According to a recent study, these two maladies may not be a classic chicken-and-egg argument, but rather a common denominator; inflammation may be the culprit that is at least partially responsible for both diseases processes (5).

The researchers found that six biomarkers of inflammation were increased in patients with both diabetes and depressive symptoms. These inflammatory markers include C-reactive protein, tumor necrosis factor alpha, triglycerides, white blood cells, interleukin 1 (IL-1B and IL-1RA) and monocyte chemotactic protein-1. Ultimately, if they are both caused by inflammation to varying degrees, then theoretically if we reduced inflammation it may give us beneficial results for both diseases. This is important, since those with both diseases may have a two times greater likelihood of death, according to the authors. They also note that lifestyle modifications, including diet and exercise, are the best way to reduce inflammation. The study involved 1227 newly diagnosed diabetes patients.

Heart attack

Both men and women with diabetes are at increased risk of heart attacks. However, in a recent meta-analysis (group of 64 studies) involving over 800,000 patients, the results surprisingly show that women with diabetes are at a significantly greater risk of having a heart attack than men (6). In fact, these women were at a 44 percent increased risk of having fatal and nonfatal cardiovascular events compared to their male counterparts. The reason for this, according to the authors, was that women may already be in poorer health before the onset of diabetes. What to do?

Exercise: games

We tell patients to exercise, but many of us know just how difficult it can be to motivate ourselves to do this. Video games may provide the needed spark. In a randomized controlled trial, the gold standard of studies, those who used Wii Fit Plus saw improvements in their diabetes parameters compared to those who were given usual care (7). Results included significant decreases in their HbA1C, fasting blood sugars and weight. These results were seen in just three months. There were also improvements in daily physical activity, quality of life and depressive symptoms that are so commonly associated with diabetes. Family members were also likely to get involved in the Wii with the patient, creating a natural support network. Interestingly, after 12 weeks, those in the control group were then given the Wii Fit Plus and followed for an additional 12 weeks. They saw similar benefits. The authors called this “exergaming.”

Ultimately, we should do a really good job with lifestyle modifications and if that is not enough add metformin, because we know that both have much greater upsides and very few downsides compared to many other diabetes treatments. Exercise can even be fun, as shown by the exergaming study. However, if insulin or other medications are needed, while there are treatment guidelines, it really comes down to a case-by-case decision to be made by the patient and doctor.

References:

(1) N Engl J Med. 2008;358:2545-2559. (2) cdc.gov/diabetes. (3) JAMA. 2014;311:2288-2296. (4) ADA 2014 Scientific Sessions;165-OR. (5) Diabetes Care Online. 2014 May 19. (6) Diabetologia Online. 2014 May. (7) BMC Endocr Disord. 2013;13:57.

•If you would like to see a specific topic covered in Medical Compass, please email [email protected].

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 medicalcompassmd.com or consult your personal physician.

Last week, I wrote about heart disease and mentioned that hypertension, better known as high blood pressure, is one of its contributing risk factors. I would like to go into more depth on hypertension, for approximately 33 percent of Americans are afflicted, according to the latest statistics from the Centers for Disease Control. (1)

What could we possibly learn about blood pressure that we have not already heard? New information is always coming out on this common disease. Studies are teaching us about diagnostic techniques and timing, as well as consequences of hypertension and its treatment.

Let’s look at the evidence.

Technique

When you go to the doctor’s office, they usually take your blood pressure first. But do they take readings in both arms and, if so, have you wondered why? I take blood pressure readings in both arms, and when one of my longtime patients asked me why, I joked that I need the practice. In truth, it’s because there may be significant benefit from taking readings in both arms.

An analysis of the Framingham Heart Study and Offspring Study showed that when the blood pressure was taken in both arms, if there was a difference of more than 10 mm Hg in the systolic (top number) blood pressure, then there may be an increased risk for the development of cardiovascular disease — stroke and heart disease. (2)  This is a simple technique that may give an indication of who is at greater cardiovascular disease risk. In fact, when this interarm blood pressure comparison showed a 10 mm Hg difference, it allowed the researchers to identify an almost 40 percent increased risk of having a cardiac event, such as a stroke or a heart attack, with minimal extra effort expended.

So, the next time you go to the doctor’s office, you might want to ask if they would take your blood pressure in both arms to give you and your doctor a potential preliminary indication of increased cardiovascular disease risk.

Timing

When do we get our blood pressure taken? For most of us it is usually at the doctor’s office in the middle of the day. This may not be the most effective reading. Nighttime blood pressure readings may be the most accurate, according to a recent study. (3)  This was a meta-analysis (a group of nine observational studies) involving over 13,000 patients. Neither the clinical nor daytime readings correlated significantly with cardiovascular events when multiple confounding variables were taken into account, while every 10 mm Hg increase at night had a more significant predictive value.

Twenty-four ambulatory blood pressures readings were taken with these patients, which means these were standardized readings. Does this mean that nighttime readings are more important? Not necessarily, but it is an interesting finding. With my patients, if blood pressure is high in my office, I suggest that patients take their blood pressure at home, both in the morning and at night, and send me readings on a weekly basis. However, at least one of the readings should be taken before antihypertensive medications are taken, since they will alter readings.

Salt impact

There has always been a debate about whether salt really plays a role in high blood pressure and heart disease. The latest installment in this argument is a compelling British study called the Health Survey from England. It implicates sodium as one potential factor exacerbating the risk for high blood pressure and, ultimately, cardiovascular disease. (4)  The results show that when salt intake was reduced by an average of 15 percent, there was a significant blood pressure reduction and that this reduction may be at least partially responsible for a 40 percent reduction in stroke mortality and a 42 percent reduction in heart disease mortality.

The graphs of sodium reduction mimicked the line graphs for the reductions in deaths from stroke and heart disease. One potential study weakness was that physical activity was not taken into account. However, a strength of this study was that they measured salt intake through 24-hour urine tests. Most of our dietary salt comes from processed foods that we least suspect, such as breads, pastas, and cheeses.

Age-related macular degeneration

When we think of blood pressure-lowering medications, we don’t usually consider age-related macular degeneration as a potential side effect. However, in the Beaver Dam Eye Study, those patients who were taking blood pressure medications were at a significant 72 percent overall risk of developing early stage AMD. (5)  It did not matter which class of blood pressure-lowering drug the patient was using, all had similar effects: calcium channel blockers, beta blockers, diuretics, and angiotensin receptor blockers. However, the researchers indicated that they could not determine whether the blood pressure or the blood pressure medication was the potential contributing factor. In addition, another study that was presented at the Association for Research in Vision and Ophthalmology in May, 2013 actually suggests the opposite — that blood pressure medications may reduce the risk of AMD. (6)  However, this was a retrospective (backward-looking) study, and it has yet to be published.

This is a controversial topic. If you are on blood pressure medications and are more than 65 years old, I would recommend that you get yearly eye exams by your ophthalmologist.

Fall risk

As we age, falling risk seems to increase. A recent study shows that blood pressure medications significantly increase fall risk in the elderly. (7)  Overall, 9 percent of these patients on blood pressure medications were seriously injured when they fell. Those who were considered moderate users of these medications had a 40 percent increased risk of fall. But, interestingly, those who were consider high-intensity users had a slightly less robust risk of fall (28 percent) than the moderate users. The researchers used the Medicare database with 5,000 participants as their data source. The average age of the participants in the study was 80.

Does this mean that we should discontinue blood pressure medications in this population? Not necessarily. This should be assessed at an individual level between the patient and the doctor. Also, one weakness of this study was that there was no dose-response curve. In other words, as the dosage increased with high blood pressure medications, one would expect a greater fall risk. However, the opposite was true.

In conclusion, we have some simple, easy-to-implement, takeaways. First, consider monitoring blood pressure in both arms, since a difference can mean an increased risk of cardiovascular events. Reduce your salt intake; it appears that many people may be sensitive to salt, as shown by the British study. If you do take blood pressure medications and are at least 65 years old, take steps to reduce the risk of falling and have annual ophthalmic exams to check for AMD.

References:

(1) CDC.gov/blood pressure.  (2) Am J Med. 2014 Mar;127(3):209-15.  (3) J Am Soc Hypertens 2014; 8:e59.  (4) BMJ Open 2014;4:e004549.  (5) Ophthalmology online April 30, 2014.  (6) ARVO 2013 Annual Meeting: presentation.  (7) JAMA Intern Med. 2014;174(4):588-595.

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 medicalcompassmd.com or consult your personal physician.

In my May 22 article, entitled “Detecting various heart attack symptoms,” I wrote about unusual symptoms that may indicate a myocardial infarction (heart attack) and the importance of knowing these atypical major symptoms beyond chest pain. This is not an easy task. I thought a good follow-up to that article would be one that focused on preventable risk factors.

The good news, as I mentioned previously, is that we have made great strides in reducing mortality from heart attacks. When we compare cardiovascular disease — heart disease and stroke — mortality rates from 1975 to the present, there is a substantial decline of approximately one-quarter. However, if we look at these rates since 1990, the rate of decline has slowed. (1)

Plus, one in 10 visits to the emergency room are related to potential heart attack symptoms. Luckily, only 10 to 20 percent of these patients actually are having a heart attack. (2)  We need to reduce our risk factors to improve this scenario.

Some risk factors are obvious. Others are not. The obvious ones include age (men at least 45 years old and women at least 55 years old), family history, high cholesterol, high blood pressure, obesity, sedentary lifestyle, diabetes, and smoking. Less obvious risk factors include gout, atrial fibrillation, and osteoarthritis. Lifestyle modifications, including a high-fiber diet and exercise, also may help allay the risks.

Let’s look at the evidence.

Obesity

On a board exam in medicine, if smoking is one of the choices with disease risk, you can’t go wrong by choosing it. Well, it appears that the same axiom holds true for obesity. But how substantial a risk factor is obesity? In the Copenhagen General Population Study, results showed an increased heart attack risk in obese (BMI >30 kg/m²) individuals with or without metabolic syndrome (high blood pressure, high cholesterol and high sugar) and in those who were overweight (BMI >25 kg/m²). (3)  The risk of heart attack increased in direct proportion to weight. Specifically, there was a 26 percent increase in heart attack risk for those who were overweight and an 88 percent increase in risk for those who were obese without metabolic syndrome. This study had a follow-up of 3.6 years.

It is true that those with metabolic syndrome and obesity together had the highest risk. But, it is quite surprising that obesity, by itself, can increase heart attack risk when a person is “metabolically healthy.” Since this was an observational trial, we can only make an association, but if it is true, then there may not be such thing as a “metabolically healthy” obese patient. Therefore, if you are obese, it is really important to lose weight.

Sedentary lifestyle

If obesity were not enough of a wake-up call, let’s look at another aspect of lifestyle: the impact of being sedentary. A recent observational study found that activity levels had a surprisingly high impact on heart disease risk. (4)  Of four key factors — weight, blood pressure, smoking and physical inactivity — age was the determinant as to which one had the most negative effect on women’s heart disease risk. Those under the age of 30 saw smoking as most negatively impactful. For those over the age of 30, lack of exercise became the most dominant risk factor for heart disease, including heart attacks.

For women over the age of 70, the study found that increasing physical activity may have a greater positive impact than addressing high blood pressure, losing weight, or even quitting smoking. However, since high blood pressure was self-reported and not necessarily measured in a doctor’s office, it may have been underestimated as a risk factor for heart disease. Nonetheless, the researchers indicated that women should make sure they exercise on a regular basis to most significantly reduce heart disease risk.

Osteoarthritis

The prevailing thought with osteoarthritis is that it is best to suffer with hip or knee pain as long as possible before having surgery. But when do we cross the line and potentially need joint replacement? Well, in a recent study, those with osteoarthritis of the hip or knee joints that caused difficulty walking on a flat surface were at substantially greater risk of cardiovascular events, including heart attack. (5)  Those who had surgery for the affected joint saw a substantially reduced heart attack risk. It is important to address the causes of osteoarthritis to improve mobility, whether with surgery or other treatments.

Gout

When we think of gout, we relate it to kidney stones. But gout increases the risk of heart attacks by 82 percent, according to an observational study. (6)  Gout tends to affect patients more when they are older, but the risk of heart attack with gout is greater in those who are younger, ages 45 to 69, than in those over 70. What can we do to reduce these risk factors?

There have been studies showing that fiber decreases the risk of heart attacks. However, does fiber still matter when someone has a heart attack? In a recent analysis using data from the Nurses’ Health Study and the Health Professional Follow-up Study, results showed that higher fiber plays an important role in reducing the risk of death after a heart attack. (7)  Those who consumed the most fiber, compared to the least, had a 25 percent reduction in post-heart attack mortality. Even more impressive is the fact that those who increased their fiber after the cardiovascular event had a 31 percent reduction in mortality risk. In this analysis, it seemed that more of the benefit came from fiber found in cereal. The most intriguing part of the study was the dose response. For every 10 g increase in fiber consumption, there was a 15 percent reduction in the risk of post-heart attack mortality. Since we get too little fiber anyway, this should be an easy fix.

Lifestyle modifications are so important. In the Nurses’ Health Study, which followed 120,000 women for 20 years, those who routinely exercised, ate a quality diet, did not smoke and were a healthy weight demonstrated a whopping 84 percent reduction in the risk of a cardiovascular events such as heart attacks. (8)

What have we learned? We can substantially reduce the risk of heart attacks and even potentially the risk of death after sustaining a heart attack with lifestyle modifications that include weight loss, physical activity, and diet — with, in this case, a focus on fiber. While there are a number of diseases that contribute to heart attack risk, most of them are modifiable. With disabling osteoarthritis, addressing the causes of difficulty with mobility may also help reduce heart attack risk.

References:

(1) Heart. 1998;81(4):380.  (2) JAMA Intern Med. 2014;174(2):241-249.  (3) JAMA Intern Med. 2014;174(1):15-22.  (4) Br J Sports Med. 2014, May 8. (5) Presented Research: World Congress on OA, 2014.  (6) Rheumatology (Oxford). 2013 Dec;52(12):2251-9.  (7) BMJ. 2014;348:g2659.  (8) N Engl J Med. 2000;343(1):16.

• If you would like to see a specific topic covered in Medical Compass, please email [email protected].

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 medicalcompassmd.com or consult your personal physician.

Heart disease is the most common chronic disease in America. When we refer to heart disease, it is an umbrella term of which heart attacks are one component. Fortunately, the number of heart attacks has decreased over the last several decades, as have deaths from heart attacks. However, there are still 720,000 heart attacks every year, and more than two-thirds are first heart attacks (1).

How can we further improve these statistics and save more lives? By increasing awareness and education about heart attacks. It is a multifaceted approach: recognizing the symptoms and knowing what to do if you think you’re having a heart attack.

If you think someone is having a heart attack, call 911 as quickly as possible and have the patient chew an adult aspirin (325 mg) or four baby aspirin. In my May 15 article, I wrote that the Food and Drug Administration does not recommend aspirin for primary prevention of a heart attack. Please note that the use of aspirin in this case is for treatment of a potential heart attack, not prevention. It is also very important to know the risk factors and how to potentially modify them.

What are the symptoms of a heart attack? The main symptom is chest pain, which most people don’t have trouble recognizing. However, there are a number of other, more subtle, symptoms such as discomfort or pain in the jaw, neck, back, arms and epigastric, or upper abdominal, area; as well as nausea, shortness of breath, sweating, lightheadedness and tachycardia (racing heart rate). One problem is that less than one-third of people know these other major symptoms (2). About 10 percent of patients present with atypical symptoms — without chest pain according to one study (3).

It is not only difficult for the patient, but also for the medical community, especially the emergency room, to determine who is having a heart attack. Fortunately, approximately 80 to 85 percent of chest pain sufferers are not having a heart attack, but more likely having indigestion, reflux or other nonlife-threatening ailments.

There has been a raging debate about whether men and women have different symptoms when it comes to heart attacks. Several studies speak to this topic.

Let’s look at the evidence.

There is data showing that, although men have heart attacks more commonly, women are more likely to die from a heart attack (4). In a Swedish prospective (forward-looking) study, after having a heart attack, a significantly greater number of women died in-hospital or near term compared to men. The women received reperfusion therapy, artery opening treatment that consisted of medications or invasive procedures, less often than the men.

However, recurrent heart attacks occurred at the same rate, regardless of sex. Both men and women had similar findings on an electrocardiogram; they both had what we call ST elevations. This was a study involving approximately 54,000 heart attack patients, with one-third of them being women.

One theory about why women are treated less aggressively when first presenting in the ER is that they have different and more subtle symptoms, even chest pain symptoms may be different. Women’s symptoms may include pain in the lower portion of the chest or upper portion of the abdomen and maybe significantly less severe pain that could radiate or spread to the arms. But, is this true? Not according to several recent studies.

In one observational study, results showed that, though there were some subtle differences in chest pain, on the whole, when men and women presented with this main symptom, it was of a similar nature (5). There were 34 chest pain characteristic questions used to determine if a difference existed. These included location, quality or type of pain and duration. Of these, there was some small amount of divergence: the duration was shorter for a man (2 to 30 minutes), and pain subsided more for men than for women. The study included approximately 2,500 patients, all of whom had chest pain. The authors concluded that determination of heart attacks with chest pain symptoms should not factor in the sex of patients.

This trial involved an older population; patients were a median age of 70 for women and 59 for men, with more men having had a prior heart attack. This was a conspicuous weakness of an otherwise mostly solid study, since age and previous heart attack history are important factors.

Therefore, I thought it apt to present another observational study with a younger population, where there was no significant difference in age; the median age of both men and women was 49. In this GENESIS-PRAXY study, results show that chest pain remained the most prevalent presenting symptom in both men and women (6). However, of the patients who presented without distinct chest pain and with less-specific EKG findings (non-ST elevations), significantly more were women than men. Those who did not have chest pain symptoms may have had some of the following symptoms: back discomfort, weakness, discomfort or pain in the throat, neck, right arm and/or shoulder, flushing, nausea, vomiting and headache.

If the patients did not have chest pain, regardless of sex, the symptoms were, unfortunately, diffuse and nonspecific. The researchers were looking at acute coronary syndrome, which encompasses heart attacks. In this case, independent risk factors for nonchest pain-related disease included both tachycardia (rapid heart rate) and being female. The authors concluded that there need to be better ways to calibrate nonchest pain symptoms.

Some studies imply that as much as 35 percent of patients do not present with chest pain as their primary complaint (7).

So what have we learned about heart attack symptoms? The simplest lessons are that most patients have chest pain, and that both men and women have similar types of chest pain. However, this is where the simplicity stops and the complexity begins. The percentage of patients who present without chest pain seems to vary significantly depending on the study — ranging from less than 10 percent to 35 percent. Therefore, it is even hard to quantify the number of non
chest pain heart attacks. This is why it is even more important to be aware of the symptoms. Nonchest pain heart attacks have a bevy of diffuse symptoms, including obscure pain, nausea, shortness of breath and lightheadedness. This is seen in both men and women, although it occurs more often in women. When it comes to heart attacks, suspicion should be based on the same symptoms for both sexes. Therefore, know the symptoms, for it may be your life or a loved one that depends on it.

In my next article on June 5, we will discuss the risk factors associated with heart attacks, prevention and potential lifestyle modifications for the treatment of heart attacks, and the traditional medical regimen.

References:

(1) Circulation. 2014;128. (2) MMWR. 2008;57:175–179. (3) Chest. 2004;126:461-469. (4) Int J Cardiol. 2013;168:1041-1047. (5) JAMA Intern Med. 2014 Feb. 1;174:241-249. (6) JAMA Intern Med. 2013;173:1863-1871. (7) JAMA. 2012;307:813-822.

• If you would like to see a specific topic covered in Medical Compass, please email [email protected].

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 medicalcompassmd.com and/or consult your personal physician.