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.

Aspirin has been around for thousands of years — known as a salicylate — but the form we are most accustomed to was discovered by a scientist named Felix Hoffmann, who worked for Bayer, in 1897 (1). Presently, there are over 100 billion tablets of aspirin consumed worldwide on annual basis (2). It is one of the most broadly accepted prophylactic medications. It has been used for a long time in primary prevention — those who are taking the medication to prevent the disease but don’t have it. Thus, you would think that we know all about aspirin, including its effectiveness as a prophylactic in different diseases and its side effects. However, this is far from reality.

In modern day, aspirin is used mainly for its antiplatelet effects, preventing clots and as an anti-inflammatory rather than for its antipyretic (fever) and analgesic (pain) benefits.

Is it beneficial, or is it oversold and dangerous? Every time we think we know the answer, another new study says the opposite. In other words, for every positive study, there are also negative studies about its side effects and complications.

Aspirin may play a role in a number of diseases, including cardiovascular disease (stroke and heart disease); multiple cancers, such as colorectal cancer and liver cancer; and age-related macular degeneration.

However, there are several risks with aspirin. The two most widely known side effects are gastrointestinal bleed and intracranial hemorrhage, or bleeding in the brain. Let’s look at the evidence.

Cardiovascular disease

Aspirin’s prophylactic role may be in question. We’re certain that aspirin works in primary prevention of cardiovascular disease, right? Why else would we put so many people, who were otherwise healthy, on aspirin? Not so fast. The Food and Drug Administration and recent studies indicate that aspirin may not be effective, or the evidence is inconclusive when comes to benefit outweighing risk.

Bayer AG, the pharmaceutical company, requested a change in the low-dose (baby aspirin or 81 mg.) aspirin label to include prevention of heart attacks. The company wanted to market the drug for those who were otherwise healthy but wanted to prevent a heart attack. The FDA, spurred by this requested change, stated on May 5 that the evidence for using aspirin in primary prevention of cardiovascular disease, including both heart attack and stroke, was not convincing or supportive enough to recommend the drug for this use (3). The FDA also said that the patients who wanted to use it for this indication should talk to their doctor about the risk-benefit ratio.

This response came as a surprise to many in the medical community considering that the American Heart Association, contrary to the FDA, supports aspirin use in in those who are at high risk for cardiovascular disease development. However, the agency did say that those who already have cardiovascular disease should be taking aspirin. But this is secondary prevention that the FDA supports, not primary. If you are already on aspirin for primary prevention, you should discuss it with your doctor before stopping the medication.

This is still a highly controversial issue, but it does not help that the FDA, one of the most respected institutions in medicine, weighed in on the topic to suggest that the risks may outweigh the benefits.

According to a study published in Lancet, the side effects may outweigh the benefits, as the FDA implied (4). Aspirin may also detract from the effectiveness of some cardiovascular risk-reducing classes of blood pressure lowering medications, such as angiotensin-converting enzymes inhibitors, like Lisinopril (5). Another study shows that aspirin is also associated with hearing loss (6).

There is also a suggestion that aspirin may increase the risk of macular degeneration. Let’s investigate this further.

Age-related macular degeneration

A recent observational study suggests that aspirin increases the risk of one type of advanced-stage macular degeneration by almost 2.5-fold in those who used aspirin on a chronic (weekly or more) basis (7). This type of macular degeneration is referred to as wet, or neovascular, AMD. However, there was not an increased risk in a second form of advanced AMD, geographic atrophy. This study followed 2,389 patients for 15 years.

Therefore, we should not use aspirin if patients have a high risk for AMD or have early stage AMD, right? Not necessarily. This study was flawed and difficult to apply to this country; it was done in Australia, and the dose most commonly used was assumed to be 150 mg., but the doses were not quantified. Aspirin does not come in this dose in this country. Also, patients were asked only at the start of the trial how frequently they used aspirin over the last year. Therefore, there was also recall bias.

In another study, aspirin did not show an association with an increased risk of AMD (8). I said it was complicated.

Colorectal cancer

We have thought that aspirin may prevent the occurrence of colorectal cancer. There are some studies suggesting this is the case and others suggesting no effect. But there is a new wrinkle in this discussion. A recent study implies that your DNA may be an important factor to determining whether you will see a benefit from aspirin as a preventive of this cancer (9).

If your genes produce a large amount of an enzyme, 15-PGDH, then there is a significant 50 percent reduction in the risk of developing colorectal cancer in those whose use low-dose aspirin regularly, while those who produce low levels of the enzyme only see a 10 percent reduction in colorectal cancer with aspirin.

The reason is that aspirin and the enzyme both help control prostaglandins, which can be inflammatory. Together, the combination seems to have a profound effect on risk reduction. About half of the population produces significant amounts of the enzyme. You can test for this enzyme through colon biopsy during a routine colonoscopy. Therefore, targeted aspirin use may be the answer in colorectal cancer prevention.

Aspirin is obviously a tricky topic. At best, it prevents one in five cardiovascular events — stroke and heart attacks. This number comes from those who already have cardiovascular disease, and this may not be the case for primary prevention. Because aspirin has significant side effects, it is best not to depend on it for prevention in “healthy” individuals until there is solid data that it is an effective agent. However, it may make sense to prevent colorectal cancer in those who have complementary DNA, but we need larger, well-controlled trials confirm these results. As always, consult with your doctor before starting or stopping an aspirin regimen.

References:

(1) Tex Heart Inst J. 2007;34:179-186. (2) Proc Natl Acad Sci USA. 2002;99:13371-13373. (3) fda.gov. (4) Lancet. 2009;374:878. (5) J Am Coll Cardiol. 2001;38:1950-1956. (6) Am J Med. 2010;123:231-237. (7) JAMA Intern Med. 2013;173:258-264. (8) PLoS ONE. 2013;8:e58821. (9) Sci Transl Med. 2014;6:233re2.

• 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.

High cholesterol affects a great deal of Americans – millions upon millions (a modified homage to the late, great scientist Carl Sagan), and cuts across many demographics, affecting young and old and those in between.  When we think of hyperlipidemia (high cholesterol), what do you think is the mainstay of medical treatment?  If you said, “statins,” you would be correct. 

Do statins deserve this central role in treatment?  They have been convincingly shown in studies to significantly lower cholesterol, and they play an important role for those who have cardiovascular disease.  However, should we be using statins as liberally as we have?  Well, the new guidelines for the treatment of high cholesterol, which came out in Nov. 2013, suggest that we should.  In fact, these guidelines would most likely increase the use of this medication, especially in those over the age of 60.  Some in the medical community have even joked that statins might as well be put in the drinking water.  To read more about the guidelines, please see my November 20, 2013 article, entitled “New cholesterol guidelines released,” online at northshoreoflongisland.com.

This is a medication that patients may be on for life.  I don’t know about you, but that thought sends chills down my spine.  We know all medications have pros and cons.  Statins are no exception; they have been mired in controversy.

For one thing, they have side effects.  These include possibly increasing the risk of diabetes, myalgias (muscle pain), hepatic (liver) toxicity, kidney disorders and negatively affecting memory.

They also may reduce the benefits of exercise, and they may not be as effective in women as they are in men.

Because statins are such effective cholesterol-lowering medications, does this mean that patients on these drugs may become complacent with their diets?   A new study indicates that this is exactly what might be happening.

Let’s look at the evidence.

Diet complacency

The “S” in statins does not stand for “super immune to eating anything.”  In a newly published study in JAMA Internal Medicine, results show that those who are taking statins tend to eat more calories and fats and, ultimately, increase their (body mass index) by gaining weight, compared to those who were not taking statins. (1)  In fact, in this study that used 11 years of NHANES data, results showed that there were a 14 percent increase in fat intake and an almost 10 percen increase in overall calorie intake among statin users.  This resulted in a BMI that rose by 1.3 percent in those on statins, while in non-users over the same period, BMI only rose by 0.4 percent.

In other words, if you took an average male who was 5 feet 9 inches and weighed 200 lbs., the difference between statin users and non-users would be the difference between obesity and being just below obesity.  Those on statins were consuming about 200 extra calories a day.  This increase in calorie consumption occurred after they were placed on statins.   Their weight also increased by 6.6 to 11 lbs.  This is especially concerning to the researchers, since the guidelines for statin use call for a prudent diet to help reduce fat and calorie intake with the ultimate goal of reducing weight. 

However, the opposite was found to have happened – consuming more calories and gaining more weight. This is an observational study with over 27,000 participants, therefore no firm conclusions can be made.  However, statins are not a license to gorge at the all-you-can-eat buffet line.  We already know that statins may increase the risk of diabetes.  Why worsen this risk with dietary indiscretions that are harmful to your BMI?  As an aside, the authors note that this increased calorie and fat consumption may be a contributing reason for the increased risk of diabetes with statins, but it’s too early to tell.

Impact on women

We tend to clump data together from trials that focus predominantly on one demographic, in this case men, and apply the results broadly to both men and women.  However, in a May 5 article in the New York Times, some in the medical community, including the editor of JAMA, note that this may be a mistake. (2)  According to the dissenters, the thought process is that women have been underrepresented in statin trials, and cholesterol may not play the same role in women as it does in men.  Yet almost half of the patients treated with statins are women.  These physicians referring to the use of statins in primary prevention, or in those who have high cholesterol, but who do not have documented heart disease.

Lest you think their views are based solely on opinion or anecdotal data from clinical experience, this data on women was from the JUPITER trial, which looked at almost 7,000 initially healthy female participants. (3)  Statins did benefit women by reducing the occurrence of chest pain and reducing the number of stent placements and bypass surgeries, but they did not reach the primary endpoints of showing statistical significance in reducing the occurrence of a first heart attack, stroke or death.

The caveat is that there were not a large number of cardiovascular events – heart attacks, strokes or death – that occurred in either the treatment group or the control group. These results were in women over the age of 60.  This may give slight pause when giving statins.  By no means do I think these physicians are advocating to not give women statins, just that we may want to weigh the benefits and risks on a case-by-case basis.

Tamping down exercise benefits

Since exercise is beneficial for lowering cardiovascular disease risk and statins are as well, the logical presumption might be that the two together might create a synergistic effect that is greater than the two alone – or at least an added benefit from combining the two.  Unfortunately, what seems straightforward is not always the case.  In a small, yet randomized controlled trial, participants who were put on statins and monitored for cardiopulmonary exercise saw a blunted aerobic effect compared to the control group, which exercised without the medication. (4) In the treatment group, there was a marginal 1.5 percent improvement with aerobic exercise, while the control group experienced a much more robust 10 percent gain. The reason for this disappointing discrepancy is that statins seem to interrupt the enzymes that are responsible for making the mitochondria (the powerhouse or energy source for the cell) more efficient.  The most troubling aspect of this trial is that the participants chosen were out of shape, overweight individuals in need of aerobic exercise.

Whether or not a patient, male or female, is placed on cholesterol-lowering medication, one thing is clear: there is a strong need to make sure that lifestyle modifications are always emphasized to help reduce the risk of cardiovascular disease to its lowest levels.  But the quandary becomes what to do with statins and exercise.  And statins, as powerful and effective as they may be, still do have side effects, may reduce exercise benefits, and may not have the same effects for women.  Thus, they may not be appropriate for everyone.  A healthy diet and exercise, however, are appropriate for all.

References:

1 JAMA Intern Med. online April 24, 2014.  2 nytimes.com.   3 N Engl J Med. 2008 Nov 20;359(21):2195-207.  4 J Am Coll Cardiol. 2013;62(8):709-14.

* 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.

Cancer, a word that for decades was whispered as taboo, has become front and center in the medical community. Cancer is the No. 1 killer of Americans, at least those less than 85 years old, even ahead of cardiovascular disease (1). We have thought that diet may be an important component in preventing cancer. Is diet a plausible approach?

A recent article published in The New York Times on April 21, titled “An Apple a Day, and Other Myths,” questions the validity of diet in the prevention of cancer. This article covers cancer in general, which is a huge and daunting topic. The article’s author references a comment by Dr. Walter Willett, a professor and chair of the Harvard School of Public Health’s nutrition department, as indicating that the research is inconsistent when it comes to fruits and vegetables. The article goes on to state that even fiber and fats may not play significant roles in cancer.

I don’t necessarily disagree with their assessment. However, I would like to emphasize that Willett also commented that there are no large, well-controlled diet studies. This leaves the door open for the possibility that diet does have an impact on cancer prevention. I would like to respond.

As Willett hinted, the problem with answering this question may lie with the studies themselves. The problem with diet studies in cancer, in particular, are that they rely mainly on either retrospective (backward-looking) or prospective (forward-looking) observational studies.

Observational studies have many weaknesses. Among them is recall bias, or the ability of subjects to remember what they did. Durability is also a problem; the studies are not long enough, especially with cancer, which may take decades to develop. Confounding factors and patient adherence are other challenges, as are the designs and endpoints of the studies (2). Plus, randomized controlled trials are very difficult and expensive to do since it’s difficult and much less effective to reduce the thousands of compounds in food into a focus on one nutrient.

Let’s look at the evidence.

The EPIC trial

Considered the largest of the nutrition studies is the European Prospective Investigation into Cancer and Nutrition. It is part of what the author is using to demonstrate his point that fruits and vegetables may not be effective, at least in breast cancer. This portion of the study involved almost 300,000 women from eight different European nations (3). Results showed that there was no significant difference in breast cancer occurrence between the highest quintile of fruit and vegetable consumption group compared to the lowest. The median duration was 5.4 years.

Does this study place doubt in the diet approach to cancer? Possibly, but read on. The most significant strength was its size. However, there were also many weaknesses. The researchers were trying to minimize confounding factors, but there were eight countries involved, with many different cultures, making it almost impossible to control. It is not clear if participants were asked what they were eating more often than at the study’s start. Risk stratification was also not clear; which women, for example, might have had a family history of the disease.

Beneficial studies with fruits and vegetables

Also using the same EPIC study, results showed that fruit may have a statistically significant impact on lung cancer (4). Results showed that there was a 40 percent decrease in the risk of developing lung cancer in those that were in the highest quintile of fruit consumption, compared to those in the lowest quintile. However, vegetables did not have an impact. The results were most pronounced in the Northern European region. I did say the answer was complex.

Ironically, it seems that some other studies, mostly smaller studies, show potentially beneficial effects from fruits and vegetables. This may be because it is very difficult to run an intensive, well-controlled, large study.

Prostate cancer

Dr. Dean Ornish, a professor of medicine at University of California, San Francisco Medical School, has done several well-designed pilot studies with prostate cancer. His research has a focus on how lifestyle affects genes. In one of the studies, results of lifestyle modifications showed a significant increase in telomere length over a five-year period (5). Telomeres are found on the end of our chromosomes; they help prevent the cell from aging, becoming unstable and dying. Shorter telomeres may have an association with diseases, such as cancer, aging and morbidity (sickness). Interestingly, the better patients adhered to the lifestyle modifications, the more telomere growth they experienced. However, in the control group, telomeres decreased in size over time. There were 10 patients in the lifestyle (treatment) group and 25 patients in the control group — those who followed an active surveillance-only approach.

In an earlier study with 30 patients, there were over 500 changes in gene expression in the treatment group. Of these, 453 genes were downregulated, or turned off, and 48 genes were upregulated, or turned on (6). The most interesting part is that these changes in gene transcription occurred over just a three-month period with lifestyle modifications.

In both studies, the patients had prostate cancer that was deemed at low risk of progressing into advanced or malignant prostate cancer. These patients had refused immediate conventional therapy including hormones, radiation and surgery. In both studies, the results were determined by prostate biopsy. These studies involved intensive lifestyle modifications that included a low-fat, plant-based, vegetable-rich diet. But as the researchers pointed out, there is a need for larger randomized controlled trials to confirm these results.

Cruciferous vegetables

A meta-analysis involving a group of 24 case-control studies and 11 observational studies, both types of observational trials, showed a significant reduction in colorectal cancer (7). This meta-analysis looked at the effects of cruciferous vegetables, also sometimes referred to as dark green, leafy vegetables.

In another study that involved a case-control observational design, cruciferous vegetables were shown to significantly decrease the risk of developing multiple cancers, including esophageal, oral cavity/pharynx, breast, kidney and colorectal cancers (8). There was also a trend that did not reach statistical significance for preventing endometrial, prostate, liver, ovarian and pancreatic cancers. The most interesting part is that the comparison was modest, contrasting consumption of at least one cruciferous vegetable a week with none or less than one a month. However, we need large, randomized trials using cruciferous vegetables to confirm these results.

In conclusion, it would appear that the data are mixed in terms of the effectiveness of fruit and vegetables in preventing cancer or its progression. The large studies have flaws, and pilot studies require larger studies to validate them. However, imperfect as they are, there are results that indicate that diet modification may be effective in preventing cancer. I don’t think we should throw out the baby with the bath water.

There is no reason not to consume significant amounts of fruits and vegetables in the hopes that it will have positive effects on preventing cancer and its progression. There is no downside, especially if the small studies are correct.

References:

(1) CA Cancer J Clin. 2011;61:212-236. (2) Nat Rev Cancer. 2008;8:694-703. (3) JAMA. 2005;293:183-193. (4) Int J Cancer. 2004 Jan. 10;108:269-276. (5) Lancet Oncol. 2013 Oct.;14:1112-1120. (6) Proc Natl Acad Sci USA. 2008 June 17;105:8369-8374. (7) Ann Oncol. 2013 April;24:1079-1087. (8) Ann Oncol. 2012 Aug.;23:2198-2203.

• 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.

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).

What are the most productive approaches to treatment? This is good time to test your knowledge. This will hopefully get you thinking and make you an active participant for the evidence to follow. There are three responses to choose from: True (T), False (F) and Unclear (U) — a new twist, because I want to keep you on your toes.

1) Dairy is effective in the treatment of osteoarthritis.

2) Low-fat and nonfat milk have potentially disease-modifying effects.

3) Vitamin D is a necessary supplement in this disease.

4) Glucosamine is an effective treatment.

5) Weight loss may provide symptom relief and disease-modifying effects.

6) Diet and exercise are more important than either alone.

So how do you think you did? The answers are as follows: 1) F, 2) U, 3) F, 4) U, 5) T and 6) T.

Let’s look at the evidence.

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.

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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.