Medical Compass

Statin users tend to neglect dietary guidance.

By David Dunaief, M.D.

High cholesterol affects a great number of Americans 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, guidelines for the treatment of high cholesterol, released in November 2013, suggest that we should. In fact, if followed, these guidelines would 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.

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 risks of diabetes, myalgias (muscle pain), hepatic (liver) toxicity, kidney disorders and negatively affecting memory.

Statins 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.

Statins have been mired in controversy. Stock photo
Statins have been mired in controversy. 

Diet complacency

The “S” in statins does not stand for “superimmune to eating anything.” In a study published 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 percent 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 nonusers 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 lb, the difference between statin users and nonusers 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 lb. 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 — users consumed more calories and gained 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, 2014, New York Times article, “A New Women’s Issue: Statins,” some in the medical community, including the editor of JAMA, focus attention on this tendency, noting 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 were 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 end points 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 prescribing 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

If exercise is beneficial for lowering cardiovascular disease risk and so are statins, the logical presumption might be that the two together would 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):2195-2207. (4) J Am Coll Cardiol. 2013;62(8):709-714.

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

A diet rich in fruits, vegetables, beans, nuts and oily fish may prevent breast cancer. Stock photo

By David Dunaief, M.D.

NFL players are wearing pink shoes and other sportswear this month, making a fashion statement to highlight Breast Cancer Awareness Month. This awareness is critical since annual invasive breast cancer incidence in the U.S. is 246,000 new cases, with approximately 40,000 patients dying from this disease each year (1). The good news is that from 1997 to 2008 there was a trend toward decreased incidence by 1.8 percent (2).

We can all agree that screening has merit. The commercials during NFL games tout that women in their 30s and early 40s have discovered breast cancer with a mammogram, usually after a lump was detected. Does this mean we should be screening earlier? Screening guidelines are based on the general population that is considered “healthy,” meaning no lumps were found, nor is there a personal or family history of breast cancer.

All guidelines hinge on the belief that mammograms are important, but at what age? Here is where divergence occurs; experts can’t agree on age and frequency. The U.S. Preventive Services Task Force recommends mammograms starting at 50 years old, after which time they should be done every other year (3). The American College of Obstetricians and Gynecologists recommends mammograms start at 40 years old and be done annually (4). Your decision should be based on a discussion with your physician.

The best way to treat breast cancer — and just as important as screening — is prevention, whether it is primary, preventing the disease from occurring, or secondary, preventing recurrence. We are always looking for ways to minimize risk. What are some potential ways of doing this? These may include lifestyle modifications, such as diet, exercise, obesity treatment and normalizing cholesterol levels. Additionally, although results are mixed, it seems that bisphosphonates do not reduce the risk of breast cancer nor its recurrence. Let’s look at the evidence.

Bisphosphonates

Bisphosphonates include Fosamax (alendronate), Zometa (zoledronic acid) and Boniva (ibandronate) used to treat osteoporosis. Do they have a role in breast cancer prevention? It depends on the population, and it depends on study quality.

In a meta-analysis involving two randomized controlled trials, results showed there was no benefit from the use of bisphosphonates in reducing breast cancer risk (5). The population used in this study involved postmenopausal women who had osteoporosis, but who did not have a personal history of breast cancer. In other words, the bisphosphonates were being used for primary prevention.

The study was prompted by previous studies that have shown antitumor effects with this class of drugs. This analysis involved over 14,000 women ranging in age from 55 to 89. The two trials were FIT and HORIZON-PFT, with durations of 3.8 and 2.8 years, respectively. The FIT study involved alendronate and the HORIZON-PFT study involved zoledronic acid, with these drugs compared to placebo. The researchers concluded that the data were not evident for the use of bisphosphonates in primary prevention of invasive breast cancer.

In a previous meta-analysis of two observational studies from the Women’s Health Initiative, results showed that bisphosphonates did indeed reduce the risk of invasive breast cancer in patients by as much as 32 percent (6). These results were statistically significant. However, there was an increase in risk of ductal carcinoma in situ (precancer cases) that was not explainable. These studies included over 150,000 patients with no breast cancer history. The patient type was similar to that used in the more current trial mentioned above. According to the authors, this suggested that bisphosphonates may have an antitumor effect. But not so fast!

The disparity in the above two bisphosphonate studies has to do with trial type. Randomized controlled trials are better designed than observational trials. Therefore, it is more likely that bisphosphonates do not work in reducing breast cancer risk in patients without a history of breast cancer or, in other words, in primary prevention.

In a third study, a meta-analysis (group of 36 post-hoc analyses — after trials were previously concluded) using bisphosphonates, results showed that zoledronic acid significantly reduced mortality risk, by as much as 17 percent, in those patients with early breast cancer (7). This benefit was seen in postmenopausal women but not in premenopausal women. The difference between this study and the previous study was the population. This was a trial for secondary prevention, where patients had a personal history of cancer.

However, in a RCT, the results showed that those with early breast cancer did not benefit overall from zoledronic acid in conjunction with standard treatments for this disease (8). The moral of the story: RCTs are needed to confirm results, and they don’t always coincide with other studies.

Exercise

We know exercise is important in diseases and breast cancer is no exception. In an observational trial, exercise reduced breast cancer risk in postmenopausal women significantly (9). These women exercised moderately; they walked four hours a week. The researchers stressed that it is never too late to exercise, since the effect was seen over four years. If they exercised previously, but not recently, for instance, five to nine years ago, no benefit was seen.

To make matters worse, only about one-third of women get the recommended level of exercise every week: 30 minutes for five days a week. Once diagnosed with breast cancer, women tend to exercise less, not more. The NFL, which does an admirable job of highlighting Breast Cancer Awareness Month, should go a step further and focus on the importance of exercise to prevent breast cancer or its recurrence, much as it has done to help motivate kids to exercise with it Play 60 campaign.

Soy intake

Contrary to popular belief, soy may be beneficial in reducing breast cancer risk. In a meta-analysis (a group of eight observational studies), those who consumed more soy saw a significant reduction in breast cancer compared to those who consumed less (10). There was a dose-response curve among three groups: high intake of >20 mg per day, moderate intake of 10 mg and low intake of <5 mg.

Those in the highest group had a 29 percent reduced risk, and those in the moderate group had a 12 percent reduced risk, when compared to those who consumed the least. Why have we not seen this in U.S. trials? The level of soy used in U.S. trials is a fraction of what is used in Asian trials. The benefit from soy is thought to come from isoflavones, plant-rich nutrients.

Western vs. Mediterranean diets

A Mediterranean diet may decrease the risk of breast cancer significantly.
A Mediterranean diet may decrease the risk of breast cancer significantly.

In an observational study, results showed that, while the Western diet increases breast cancer risk by 46 percent, the Spanish Mediterranean diet has the inverse effect, decreasing risk by 44 percent (11). The effect of the Mediterranean diet was even more powerful in triple-negative tumors, which tend to be difficult to treat. The authors concluded that diets rich in fruits, vegetables, beans, nuts and oily fish were potentially beneficial.

Hooray for Breast Cancer Awareness Month stressing the importance of mammographies and breast self-exams. However, we need to give significantly more attention to prevention of breast cancer and its recurrence. Through potentially more soy intake, as well as a Mediterranean diet and modest exercise, we may be able to accelerate the trend toward a lower breast cancer incidence.

References: (1) breastcancer.org. (2) J Natl Cancer Inst. 2011;103:714-736. (3) Ann Intern Med. 2009;151:716-726. (4) Obstet Gynecol. 2011;118:372-382. (5) JAMA Inter Med online. 2014 Aug. 11. (6) J Clin Oncol. 2010;28:3582-3590. (7) 2013 SABCS: Abstract S4-07. (8) Lancet Oncol. 2014;15:997-1006. (9) Cancer Epidemiol Biomarkers Prev online. 2014 Aug. 11. (10) Br J Cancer. 2008;98:9-14. (11) Br J Cancer. 2014;111:1454-1462.

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

Full-fat and low-fat cheeses are no better for you than refined grains. Stock photo

By David Dunaief, M.D.

We are constantly redefining or at least tweaking our diets. We were told that fats were the culprit for cardiovascular disease (CVD). That the root cause was saturated fats, specifically. However, a recent study showed the sugar industry had a strong influence on the medical and scientific communities in the 1960s and 1970s, influencing this perception (1).

Why is this all important? Well, for one thing, about one out every two “healthy” 30-year-olds in the United States will most likely develop CVD in their lifetime (2). This is a sobering statistic. For another, CVD is still the reigning notorious champion when it comes to the top spot for deaths in this country. Except, this disease is preventable, for the most part.

What can prevent CVD? You guessed it, lifestyle modifications, including changes in our diet, exercise and smoking cessation. There is no better demonstration of this than what I refer to as the “new” China Study, which was done through the Harvard T.H. Chan School of Public Health. I call it “new,” because T. Colin Campbell published a book in 2013 with the same name pertaining to the benefits of the Chinese diet in certain provinces. However, the wealthier China has become in the last few decades by opening its borders, the more it has adopted a Western hemisphere-type lifestyle, and the worse its health has become overall. In a recent study published in the Journal of the American College of Cardiology, results show that over 20 years the rate of CVD has increased dramatically in China, and it is likely to continue worsening over time (3). High blood pressure, elevated “bad” cholesterol LDL levels, blood glucose (sugars), sedentary lifestyle and obesity were the most significant contributors to this rise. In 1979 about 8 percent of the population had high blood pressure, but by 2010, more than one-third of the population did.

Does this sound familiar? It should, since this is due to adopting a Western-type diet. The researchers highlighted increased consumption of red meat and soda, an increasingly sedentary lifestyle and, unlike us, half the population still smokes. But you can see just how powerful the effects of lifestyle are on the world’s largest population. There were 26,000 people and nine provinces involved.

Cardiologist embraces fat

We are going to focus on one area, diet. What is the most productive diet for preventing cardiovascular disease? In a recent New York Times article, entitled “An Unconventional Cardiologist Promotes a High-Fat Diet,” published on Aug. 23, 2016, the British cardiologist suggests that we should embrace fats, including saturated fats (4). He has bulletproof coffee for breakfast, with one tablespoon of butter and one tablespoon of coconut oil added to his coffee. He also promotes full-fat cheese as opposed to low-fat cheese. These are foods that contain 100 percent saturated fats. He believes dairy can protect against heart disease. Before you get yourself in a lather, either in agreement or in disgust, let’s look at the evidence.

The Cheesy Study

Alert! Before you read any further, know that this study was sponsored by the dairy industry in Denmark. Having said this, this study would presumably agree with the unconventional cardiologist. The results showed that full-fat cheese was equivalent to low-fat cheese and to carbohydrates when it came to blood chemistries for cardiovascular disease, as well as to waist circumference (5). These markers included cholesterol, LDL “bad” cholesterol levels, fasting glucose levels and insulin. There were three groups in this study: those who consumed three ounces of full-fat cheese, low-fat cheese or refined bread and jam. The authors suggested that full-fat cheese may be part of a healthy diet. This means we can eat full-fat cheese, right? NOT SO FAST.

The study was faulty. The control arm was refined carbohydrates. And since both cheeses had similar results to the refined carbohydrates, the more appropriate conclusion is that full-fat and low-fat cheeses are no better for you than refined grains.

What about dairy fat?

In a meta-analysis (involving three studies — the Professional Follow-Up Study and the Nurses’ Health Studies 1 and 2), the results refute the claim that dairy fat is beneficial for preventing CVD (6). The results show that substituting a small portion of energy intake from dairy fat with polyunsaturated fats results in a 24 percent reduction in CVD risk. And doing the same with vegetable fats in replacement of dairy fat resulted in a 10 percent reduction in risk. Dairy fat was slightly better when compared to other animal fat.

This meta-analysis involved observational studies with a duration of at least 20 years and involving more than 200,000 men and women. There needs to be a large randomized controlled trial. But, I would not rush to eat cheese, whether it was the full-fat or low-fat variety. Nor would I drink bulletproof coffee anytime soon.

Saturated fat: not so good

In a recent meta-analysis (involving three studies run by the Harvard School of Public Health), replacing just 5 percent of saturated fats with both mono- and polyunsaturated fats resulted in a substantial reduction in the risk of mortality, 27 and 13 percent, respectively (7). This is a blow to the theory that saturated fats are not harmful to your health. Also, the highest quintile of poly- and monounsaturated fat intake, compared to lowest, showed reductions in mortality that were significant, 19 and 11 percent, respectively. Again, this is an observational conglomeration of studies, using the same studies as with the dairy results above. This analysis suggests that the unconventional cardiologist’s approach is not the one you want to take.

The good news diet!

Here is the good news diet. In a recent randomized controlled trial (RCT), the gold standard of studies, results showed that high levels of polyphenols reduce the risk of cardiovascular disease (8). Polyphenols are from foods such as vegetables, fruits, berries especially and, yes, chocolate. The researchers divided the study population into two groups, high and low polyphenol intake. The biomarkers used for this study were endothelial (inner lining of the blood vessel) dependent and independent vasodilators. The more dilated the blood vessel, the lower the hypertension and the lower the CVD risk. These patients had hypertension, a risk factor for CVD. Those who consumed high levels of polyphenols had higher levels of nutrients such as carotenoids and vitamin C in their blood.

Is fish useful?

In a study, results show that eating a modest amount of fish decreases the risk of death from CVD by more than one-third (9). What is a modest amount? Consume fish once or twice a week. You want to focus on fish that are rich in omega 3s — docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These are fatty fish with plenty of unsaturated fats, such as salmon. Thus, more of a Mediterranean-style diet, involving fruits and vegetables, as well as mono- and polyunsaturated fats in the forms of olive oil, nuts, avocado and fish may reduce the risk of CVD, while a more traditional American diet, with lots of pure saturated fats and refined carbohydrates may have the opposite effect. The reason we can’t say for sure that pure saturated fat should be avoided is that there has not been a large randomized controlled trial. However, many studies continually point in this direction.

References: (1) JAMA Intern Med. online Sept. 12, 2016. (2) Lancet. 2014;383(9932):1899-1911. (3) J Am Coll Cardiol. 2016;68(8):818-833. (4) NYTimes.com. (5) Am J Clin Nutr. 2016;104(4):973-981. (6) Am J Clin Nutr. Online Aug. 24, 2016. (7) JAMA Intern Med. 2016;176(8):1134-1145. (8) Heart. 2016;102(17):1371-1379. (9) JAMA. 2007;297(6):590.

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

Exercise and diet are key to losing weight.

By David Dunaief, M.D.

The more we seem to know about obesity as a chronic disease, classified this way first by the American Medical Association, the worse we in the medical community seem to have done to prevent and treat it and its complications. There are more obese people now than those who are overweight (1). Why would it be so difficult to treat a disease that has a simple solution, lose weight? How hard could that be, right?

If it were so simple to lose weight, we would not have an epidemic on our hands. We compete with internal and external forces, including forces from the food industry working to influence us every day. What is the problem with being obese? The issue with weight is not about vanity. The issue is that obesity creates medical complications and is second only to smoking in causing premature deaths (2). The research implies that weight loss in obese patients reduces the risk of death (3).

Life-threatening complications from obesity include multiple cancers, heart disease, stroke, diabetes, and nonalcoholic fatty liver disease. Is there something we can do about it? Simply, yes. Weight loss may have to do, at least in part, with the timing of when we eat. Also, exercise may help us increase lean muscle mass while decreasing body fat. Diet, of course, is important. A Mediterranean diet has only been shown to help with weight loss, not contribute to weight gain. There is too much doom and gloom about obesity. We need to focus on possible solutions first! Let’s look at the research.

Timing! Timing! Timing!

We have always been told not to eat late at night. Is there some truth to this, or is it an old wives’ tale? Well, it may be partially true; however, it may have more to do with how many hours we have access to food during a 24-hour period. Let me explain. In a recent study involving mice, results showed that those mice restricted to a 12-hour food consumption period in a 24-hour day were thinner than those allowed to eat anytime during the 24 hours. They may also have had reversal of metabolic disease, such as type 2 diabetes, in those mice who had pre-existing disease (4). Those that had access 24/7 became more obese and chronically ill. It did not matter which diet the mice ate.

Timing/access to food was the most important factor over the 38-week study. In fact, those that were initially given 24-hour access and then switched to the 12-hour limited access actually lost weight! Surprisingly, those that were limited to 12-hour food access could even cheat occasionally on the weekends, and it did not have a negative impact on their results. There were four diet groups — high fat and sucrose (a type of sugar), high fat, high fructose and typical diet. Of course, we are not mice. However, these are encouraging results.

Restricting eating to 12 consecutive hours during the day doesn’t seem like too much of a hardship. Now we need a randomized controlled trial in humans. In the meantime, I would suggest implementing these findings, even though we are not mice. There is no downside. In a previous study by the same research group, results showed that mice who had eight hours of access to food during a 24-hour period also showed considerably better results than those that had 24-hour access (5). Both mice groups were fed high-fat diets. The only difference was that one group was time restricted to eight hours of food exposure. The food-restricted mice saw an increase in prevention of metabolic parameters including diabetes, obesity and liver disease. The results also showed that restricting time to food decreased inflammation and improved energy expenditure. However, eight hours is more difficult to manage than 12 hours of access to food in a 24-hour cycle.

Mediterranean-type diet to the rescue

The Mediterranean diet has been valuable for a number of different chronic diseases, and obesity is no exception. In a meta-analysis (involving 16 randomized controlled trials, the gold standard of studies), the results showed that the Mediterranean-type diet was significantly better at helping patients lose weight when compared to a control diet (6). The longer the participants were on a Mediterranean-type diet, the greater the weight loss. Thus, this type of diet seems to get better with time. The meta-analysis involved over 3,000 participants. In none of the studies did any group on the Mediterranean diet gain weight.

Cancer is a weighty topic

We are always looking for cures for cancer. It is one of the more prevalent conglomerations of diseases. What might exacerbate cancer risk? If you guessed obesity, you would be right. Interestingly, it may have to do with duration of obesity that increases risk for cancer. This applies to multiple types of cancer. In a recent study, results showed that eight more cancers are associated with being overweight and obese, according to the International Agency for Research on Cancer (IARC), including mostly gastrointestinal cancers (liver, gallbladder, stomach and pancreas), as well as meningioma, thyroid, multiple myeloma and ovarian cancers (7). As we know, ovarian and pancreatic cancers tend to present with symptoms in the later stages and so are more lethal. This is added to the five cancers already known to be associated with obesity: esophageal, colorectal, uterine and post-menopausal breast cancers, plus renal cell carcinoma (kidney cancer).

The reasons for this association may have to do with the dysregulation of sex hormone breakdown and increased inflammation associated with body fat. According to the IARC, losing weight may be a way to reduce cancer risk, although studies that have shown this effect have been animal studies. However, this is pretty good motivation to lose weight. In another study, the results show the longer the duration of obesity, the greater the risk of developing cancer (8). According to the study results, for every 10 years of being overweight/obese, there was an additional 7 percent increase in the risk for several different cancers. The study involved over 70,000 postmenopausal women for a mean duration of 12.6 years.

Finally, the beverage industry’s black eye

A recent scientific review found that Coca-Cola and PepsiCo have spent millions and millions of dollars trying to influence medical organizations and public health institutions. They have put these groups in precarious situations by offering them money to help fund their organizations’ work, while asking them to back down on pressing issues such as a soda tax (9). The American Academy of Nutrition and Dietetics is, unfortunately, an example. However, the Institute of Medicine (IOM) has said that research shows soda has a strong association with the obesity epidemic (10). The moral of the story: We can and need to do a better job treating obese patients. One possible way to lose weight may be to restrict our access to food to the same 12-hour period each 24-hour cycle. Also, a Mediterranean diet has only been shown to cause weight loss, not weight gain.

References: (1) cdc.gov. (2) Lancet. online July 13, 2016. (3) Obes Rev. 2007;8(6):503-513. (4) Cell Metab. 2014;20(6): 991–1005. (5) Cell Metab. 2012;15(6):848-860. (6) Metab Syndr Relat Disord. 2011 Feb;9(1):1-12. (7) N Engl J Med. 2016;375:794-798. (8) PLoS Med. online August 16, 2016. (9) Am J Prev Med. online October 10, 2016. (10) hsph.harvard.edu/nutritionsource/sugary-drinks-fact-sheet.

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

Not all carbs are created equal. Photo by Heidi Sutton

By David Dunaief

It’s a persistent question: Should we minimize our carbohydrate consumption? Unfortunately, it depends on a number of factors including the type of carbohydrate and your family and personal history of chronic disease such as diabetes, cardiovascular disease, obesity, high triglycerides and hypertension. If this seems complicated and confusing to you, you are not alone. We have been bamboozled, railroaded or whatever term you like about carbohydrates for decades.

The body is like a chemistry set in that it turns many different types of carbohydrates into sugar. In other words, most of the sugar we consume is not what we add to food, but rather the food that our bodies turn into sugar. This is what’s so dangerous because it raises our blood sugar level.

The FDA has recently tried to quantify the amount of sugar we should consume on a daily basis (1). The agency recommends that we get no more than 50 grams of ADDED sugar a day. This seems like an easy task, for who would add 14.5 teaspoons of sugar to their food or drink in a day? Ah, but there is a catch: It includes processed foods such as refined carbohydrates and beverages. In fact, one can of soda may be enough to reach the upper limits of this recommendation.

We have been told for years that fats, especially saturated fats, were the enemy. Remember the food pyramid? The USDA had grains as its foundation for the longest time. Why would this be? Well, as it turns out, this is not a conspiracy theory but an actual scheme by the sugar industry to influence what we ate. They blamed fats as the cause for chronic diseases. However, they were very tricky in their approach, influencing scientists in the 1960s and 1970s with a small amount money, as was recently disclosed in a medical journal. We will discuss this in more detail.

Not all carbs are created equal

Carbohydrates come in many different forms. It depends on how much fiber they contain and whether they’re in liquid or solid form (2). Don’t focus on whether the carbohydrates are soluble or insoluble, complex or simple.

What is important is that some carbs don’t raise our blood sugar levels, while others have a much higher propensity to raise them. The carbs that don’t, or are less likely to, include fruits, nonstarchy vegetables, beans, legumes, pasta made from beans and tofu. With these, for the most part, you can eat a plentiful amount and may help prevent and even reverse chronic diseases such as diabetes, cardiovascular disease and obesity. However, carbs that raise our blood sugar are grains, especially refined grains, starchy vegetables like potatoes, fruit juice, sweets, bread, grain pasta, dried fruit, alcohol, soda, condiments and sauces. Let’s look at the evidence.

Sugar industry manipulation

You wouldn’t think we could be fooled by the sugar industry or distracted into thinking that saturated fats are what’s detrimental, not carbohydrates, and in their simplest form, sugars. This is just what the sugar industry did. A recent article in JAMA flushes this out (3).

The Sugar Research Foundation, the predecessor to the Sugar Association, paid three Harvard scientists to focus on fat and cholesterol as contributing factors to the rise in heart disease, not sugar. The resulting low-fat diet craze led to products loaded with sugar, like Snackwell cookies.

How much did they pay the researchers? A paltry $50,000 total in current monetary value. One of the scientists involved became the director of nutrition at the USDA. While the sugar industry and Harvard scientists in the 1960s may have conspired to downplay the dangers of sugar, strong evidence has now come to light that sugar, especially refined sugar, plays a role in heart disease and many other chronic diseases. However, this does not exonerate foods with high levels of saturated fat such as animal products.

We could never fall for this again, right? Well, that is what Coca-Cola was hoping to repeat recently by paying scientists millions of dollars to blame exercise, not diet, for the increase in heart disease, diabetes and obesity (4). This was recently revealed in a New York Times article entitled, “Coca-Cola Funds Scientists Who Shift Blame for Obesity Away From Bad Diets.” The Global Energy Balance Network, a nonprofit advocacy group, was influenced by the funding from Coke. In fact, a 2013 peer-reviewed journal article argued similar ridiculous assertions (5). It was subsequently amended to note the funding by Coca-Cola. The difference is that scientists now have to disclose any paid industry associations when published in a peer-reviewed journal, unlike in the 1960s and 1970s.

Starchy vegetables — be leery!

It is not only refined grains that are a problem. Another is starchy vegetables, in this case potatoes. In a recent study, results showed that potatoes increased the risk of diabetes, while replacing them with whole grains may decrease this risk (6). Those who ate less than two to four servings of starchy vegetables per week had a 7 percent increased diabetes risk, and those who ate at least seven servings per week had a 33 percent increased risk. Those who consumed french fries had even higher risks for diabetes. This was a meta-analysis including data from three prestigious sources, the Health Professional Follow-up Study and The Nurses’ Health Study I and II, involving almost 200,000 men and women across the three studies with a minimum duration of 20 years.

Here is the corker: It did not matter what type of potato they were eating! Although I could not find data that delineated the different types of potato, this may imply sweet potato.

Whole fruit vs. nonstarchy veggies vs. starchy veggies

Many people who want to lose weight find the task to be downright daunting. The following may provide motivation. In a study, results showed that eating whole fruit helped people lose weight. Nonstarchy vegetables also had similar results; however, starchy vegetables caused people to put on the pounds (7). The fruits included berries, pears and apples. The vegetables with the most positive weight-loss impact were cauliflower and soy/tofu. Starchy vegetables included corn and potatoes. This was a meta-analysis involving three studies and over 130,000 men and women.

Clinical example — what a surprise!

In my practice, I had been encouraging patients to eat starchy vegetables that were high in a class of nutrients known as carotenoids. These starchy vegetables include sweet potato, acorn squash, butternut squash, spaghetti squash, pumpkin and corn. Well, it turns out that a number of my patients indeed had higher nutrient levels in their blood, but unfortunately had no decrease in the inflammatory marker, C-reactive protein (CRP), that usually accompanies this effect. Even worse, their triglycerides, insulin levels and HbA1C, a measure of three-month sugars, were actually elevated and they could not lose weight.

The moral of the story is that we don’t have to be on a low-carb diet. Instead, we should focus on consuming carbohydrates that may prevent and reverse disease, such as fruits, nonstarchy vegetables and beans, while trying to minimize those that would potentially have the opposite effect, including starchy vegetables, disappointingly. The response to carbohydrates tends to depend on individuality when it comes to whole grains and starchy vegetables, though those with diabetes, heart disease, obesity and hyperinsulinemia would be advised to minimize their intake. Of course, all of us should minimize our intake of refined grains, sugars and processed foods.

References: (1) FDA.gov. (2) Uptodate.com. (3) JAMA Intern Med. online Sept. 12, 2016. (4) NYTimes.com. (5) PLoS One. 2013 Oct 9;8(10):e76632. (6) Diabetes Care. 2016;39(3):376-384. (7) PLoS Med. 2015;12(9):e1001878.

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

Fruits and vegetables may protect the kidneys. Stock photo

By David Dunaief

Chronic kidney disease is on the rise in this country. In a study that looked at data from the National Health and Nutrition Examination Survey, prevalence of chronic kidney disease (CKD) increased more than 30 percent from 1988 to 2004 (1). Earlier-stage (moderate) CKD is no exception and may not be getting enough attention. In this article, we will look beyond the more obvious causes of moderate chronic kidney disease, like diabetes, smoking, aging, obesity and high blood pressure (2).

Why is earlier-stage CKD so important? It is associated with a 40 percent increased risk of developing cardiovascular events, such as heart attacks (3). It also significantly increases the risk of peripheral artery disease (PAD). Those with decreased kidney function have a 24 percent prevalence of PAD, compared to 3.7 percent in those with normal kidney function (4). Of course, it can lead ultimately to end-stage renal (kidney) disease, requiring dialysis and potentially a kidney transplant.

One of the problems with earlier-stage CKD is that it tends to be asymptomatic. However, there are simple tests, such as a basic metabolic panel and a urinalysis, that will indicate whether a patient may have moderate chronic kidney disease.

These indices for kidney function include an estimated glomerular filtration rate (eGFR), creatinine level and protein in the urine. While the other two indices have varying ranges depending on the laboratory used, a patient with an eGFR of 30 to 59 mL/minute/1.73 m2 is considered to have moderate disease. The eGFR and the kidney function are inversely related, meaning as eGFR declines, the more severe the chronic kidney disease.

What can be done to stem earlier-stage CKD, before complications occur? There are several studies that have looked at medications and lifestyle modifications and their impacts on its prevention, treatment and reversal. Let’s look at the evidence.

Medications

Allopurinol is usually thought of as a medication for the prevention of gout. However, in a randomized controlled trial, the gold standard of studies, the results show that allopurinol may help to slow the progression of CKD, defined in this study as an eGFR less than 60 mL/min/1.73 m2 (5).

The group using 100 mg of allopurinol showed significant improvement in eGFR levels (a 1.3 mL/minute per 1.73 m2 increase) compared to the control group (a 3.3 mL/minute per 1.73 m2 decrease) over a two-year period. There were 113 patients involved in this study. The researchers concluded that there was a slow progression of CKD with allopurinol. Allopurinol also decreased cardiovascular risk by 71 percent.

Fibrates are a class of drug usually used to boost HDL (“good”) cholesterol levels and reduce triglyceride levels, another cholesterol marker. Fibrates have gotten negative press for not showing improvement in cardiovascular outcomes.

However, in patients with moderate CKD, a meta-analysis (a group of 10 studies) showed a 30 percent reduction in major cardiovascular events and a 40 percent reduction in the risk of cardiovascular mortality with the use of fibrates (6). This is important, since patients with CKD are mostly likely to die of cardiovascular disease. The authors concluded that fibrates seem to have a much more powerful beneficial effect in CKD patients, as opposed to the general population. So, there may be a role for fibrates after all.

Lifestyle modifications

Fruits and vegetables may play a role in helping patients with CKD. In one study, the results showed that fruits and vegetables work as well as sodium bicarbonate in improving kidney function by reducing metabolic acidosis levels (7). What is the significance of metabolic acidosis? It means that body fluids become acidic and it is associated with chronic kidney disease. The authors concluded that both sodium bicarbonate and a diet including fruits and vegetables were renoprotective, helping to protect the kidneys from further damage in patients with CKD.

Alkali diets are primarily plant-based, although not necessarily vegetarian or vegan-based diets. Animal products tend to cause an acidic environment. The study was one year in duration. However, though the results were impressive, the study was small, with 77 patients.

Sodium rears its ugly head yet again. Red meat is not thought of positively, and animal fat is not far behind. In the Nurses’ Health Study, the results show that animal fat, red meat and salt all negatively impact kidney function (8). The risk of protein in the urine, a potential indicator of CKD, increased by 72 percent in those participants who consumed the highest amounts of animal fat compared to the lowest, and by 51 percent in those who ate red meat at least twice a week. With higher amounts of sodium, there was a 52 percent increased risk of having lower levels of eGFR.

The most interesting part with sodium was that the difference between higher mean consumption and the lower mean consumption was not that large, 2.4 grams compared to 1.7 grams. In other words, the difference between approximately a teaspoon of sodium and three quarters of a teaspoon was responsible for the decrease in kidney function.

In my practice, when CKD patients follow a vegetable-rich, nutrient-dense diet, there are substantial improvements in kidney functioning. For instance, for one patient, his baseline eGFR was 54 mL/min/1.73 m2. After one month of lifestyle modifications, his eGFR improved by 9 points to 63 mL/min/1.73 m2, which is a return to “normal” functioning of the kidney. His kidney functioning after 6 months actually exceeded 90 mL/min/1.73 m2 for eGFR. However, this is an anecdotal story and not a study.

Therefore, it is important to have your kidney function checked with mainstream tests. If the levels are low, you should address the issue through medications and/or lifestyle modifications to manage and reverse earlier-stage CKD. However, lifestyle modifications don’t have the negative side effects of medications. Don’t wait until symptoms and complications occur. In my experience, it is much easier to treat and reverse a disease in its earlier stages, and CKD is no exception.

References:

(1) JAMA. 2007;298:2038-2047. (2) JAMA. 2004;291:844-850. (3) N Engl J Med. 2004;351:1296-1305. (4) Circulation. 2004;109:320–323. (5) Clin J Am Soc Nephrol. 2010 Aug;5:1388-1393. (6) J Am Coll Cardiol. 2012 Nov. 13;60:2061-2071. (7) Clin J Am Soc Nephrol. 2013;8:371-381. (8) Clin J Am Soc Nephrol. 2010; 5:836-843.

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

Eat a banana! We take in far too much sodium and not enough potassium.

By David Dunaief, M.D.

One of the most popular food additives is also one of the most dangerous: salt. We need salt, but not in excess. On the other hand, potassium is beneficial in our diet. However, we have the opposite problem with potassium: It is underconsumed.

More than 90 percent of people consume far too much sodium, with salt being the primary culprit (1). Sodium is found in foods that don’t even taste salty. Bread and rolls are the primary offenders, since we eat so much of them. Other foods with substantial amounts of sodium are cold cuts and cured meats, cheeses, pizza (which has both bread and cheese), fresh and processed poultry, soups, meat dishes, pastas and snack foods. Foods that are processed and those prepared by restaurants are where most of our consumption occurs (2).

By contrast, only about 2 percent of people get enough potassium from their diets (3). According to the authors of the study, we would need to consume about eight sweet potatoes or 10 bananas each day to reach appropriate levels. Why is it important to reduce sodium and increase potassium? A high sodium-to-potassium ratio increases the risk of cardiovascular disease by 46 percent, according to a study looking at more than 12,000 Americans over almost 15 years (4). In addition, both may have significant impacts on blood pressure and cardiovascular disease, while sodium may also impact multiple sclerosis and potentially other autoimmune diseases.

To improve our overall health, we need to tip the sodium-to-potassium scales, consuming less sodium and more potassium. Let’s look at the evidence.

Reduced sodium

There are two studies that illustrate the benefits of reducing sodium in high blood pressure and normotensive (normal blood pressure) patients, ultimately preventing cardiovascular disease: heart disease and stroke.

The first study used the prestigious Cochrane review to demonstrate that blood pressure is reduced by a significant mean of −4.18 mm Hg systolic (top number) and −2.06 mm Hg diastolic (bottom number) involving both normotensive and hypertensive participants (5). When looking solely at hypertensive patients, the reduction was even greater, with a systolic blood pressure reduction of −5.39 mm Hg and a diastolic blood pressure reduction of −2.82 mm Hg.

This study was a meta-analysis (a group of studies) that evaluated data from randomized clinical trials, the gold standard of studies. There were 34 trials reviewed with more than 3,200 participants. Salt was reduced from 9 to 12 grams per day to 5 to 6 grams per day. These levels were determined using 24-hour urine tests. The researchers believe there is a direct linear effect with salt reduction. In other words, the more we reduce the salt intake, the greater the effect of reducing blood pressure. The authors concluded that these effects on blood pressure will most likely result in a decrease in cardiovascular disease.

In the second study, a meta-analysis of 42 clinical trials, there was a similarly significant reduction in both systolic and diastolic blood pressures (6). This meta-analysis included adults and children. Both demographics saw a reduction in blood pressure, though the effect, not surprisingly, was greater in adults. Interestingly, an increase in sodium caused a 24 percent increased risk of stroke incidence but, more importantly, a 63 percent increased risk of stroke mortality. The risk of mortality from heart disease was increased as well, by 32 percent.

In an epidemiology modeling study, the researchers projected that either a gradual or instantaneous reduction in sodium would save lives (7). For instance, a modest 40 percent reduction over 10 years in sodium consumed could prevent 280,000 premature deaths. These are only projections, but in combination with the above studies may be telling. The bottom line is decrease sodium intake by almost half and increase potassium intake from foods.

Potassium’s positive effects

When we think of blood pressure, sodium comes to mind, but not enough attention is given to potassium. The typical American diet is lacking in enough of this mineral.

In a meta-analysis involving 32 studies, results showed that, as the amount of potassium was increased, systolic blood pressure decreased significantly (8). When foods containing 3.5 to 4.7 grams of potassium were consumed, there was an impressive −7.16 mm Hg reduction in systolic blood pressure with high blood pressure patients. Anything more than this amount of potassium did not have any additional benefit. Increased potassium intake also reduced the risk of stroke by 24 percent. If this does not sound like a large reduction, consider that, by comparison, aspirin has been shown to reduce the risk of stroke by 20 percent.

This effect was important: The reduction in blood pressure was greater with increased potassium consumption than with sodium restriction, although there was no head-to-head comparison done. The good news is that potassium is easily attainable in the diet. Foods that are potassium rich include bananas, sweet potatoes, almonds, raisins and green leafy vegetables such as Swiss chard.

Multiple sclerosis

There are several very preliminary studies that suggest higher levels of salt may increase the risk of multiple sclerosis. One study showed that salt seems to increase the levels of interleukin-17-producing CD4 helper T cells (Th17), which are potentially implicated in autoimmune diseases such as multiple sclerosis (9). The researchers used mice to show feeding them high levels of salt resulted in high levels of Th17 cells and, as a result, a severe form of multiple sclerosis.

Lowering sodium intake may have far-reaching benefits, and it is certainly achievable. We need to reduce our intake and give ourselves a brief period to adapt — it takes about six weeks to retrain our taste buds, once we reduce our sodium intake. We can also improve our odds by increasing our dietary potassium intake, which also has a substantial beneficial effect, striking a better sodium-to-potassium balance.

References: (1) Am J Clin Nutr. 2012 Sep;96(3):647-657. (2) www.cdc.gov. (3) Am J Clin Nutr. 2012 Sep;96(3):647-657. (4) Arch Intern Med. 2011;171(13):1183-1191. (5) BMJ. 2013 Apr 3;346:f1325. (6) BMJ. 2013 Apr 3;346:f1326. (7) Hypertension. 2013; 61: 564-570. (8) BMJ. 2013; 346:f1378. (9) Nature. 2013 Mar 6.

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

We should dedicate 33 percent of our lives to sleep to improve brain health. Stock photo

By David Dunaief, M.D.

The brain is the most important and complex organ, yet what we know about the brain is inverse to its prominence. In other words, our knowledge only scratches the surface. While other organs can be transplanted readily, it is the one organ that can’t, at least not yet.

The brain also has something called the blood-brain barrier. This is an added layer of small, densely packed cells, or capillaries, that filter what substances from the blood they allow to pass through from the rest of the body (1). This is good, since it protects the brain from foreign substances; however, on the downside, it also makes it harder to treat, because many drugs and procedures have difficulty penetrating the blood-brain barrier.

Unfortunately, there are many things that negatively impact the brain, including certain drugs, head injuries and lifestyle choices. There are also numerous disorders and diseases that affect the brain, including neurological (dementia, Parkinson’s, stroke), infectious (meningitis), rheumatologic (lupus and rheumatoid arthritis), cancer (primary and secondary tumors), psychiatric mood disorders (depression, anxiety, schizophrenia), diabetes and heart disease.

These varied diseases tend to have three signs and symptoms in common: they either cause an alteration in mental status — cognitive decline, weakness or change in mood – or a combination of these.

Probably our greatest fear regarding the brain is cognitive decline. We have to ask ourselves if we are predestined to this decline, either because of the aging process alone or because of a family history, or if there is a third option, a way to alter this course. Dementia, whether mild or full-blown Alzheimer’s, is cruel; it robs us of functioning. We should be concerned about Alzheimer’s because 5.2 million Americans have the disease, and it is on the rise, especially since the population is aging (2).

Fortunately, there are several studies that show we may be able to choose the third option and prevent cognitive decline by altering modifiable risk factors. They involve rather simple lifestyle changes: sleep, exercise and possibly omega-3s. Let’s look at the evidence.

The impact of clutter

The lack of control over our mental capabilities as we age is what frightens us the most since we see friends, colleagues and relatives negatively affected by it. Those who are in their 20s seem to be much sharper and quicker. But are they really?

In a recent study, German researchers found that educated older people tend to have a larger mental database of words and phrases to pull from since they have been around longer and have more experience (3). When this is factored into the equation, the difference in terms of age-related cognitive decline becomes negligible. This study involved data mining and creating simulations. It showed that mental slowing may be at least partially related to the amount of clutter or data that we accumulate over the years. The more you know, the harder it becomes to come up with a simple answer to something. We may need a reboot just like a computer. This may be possible through sleep and exercise and omega-3s.

Sleep

I have heard people argue that sleep gets in the way of life. Why should we have to dedicate 33 percent of our lives to sleep? There are several good reasons. One involves clearing the mind, and another involves improving our economic outlook.

For the former, a study shows that sleep may help the brain remove waste, such as those all-too-dangerous beta-amyloid plaques (4). When we have excessive plaque buildup in the brain, it may be a sign of Alzheimer’s. This study was done in mice. When mice were sleeping, the interstitial space (the space between brain gyri, or structures) would increase by as much as 60 percent.

This allowed the lymphatic system, with its cerebrospinal fluid, to clear out plaques, toxins and other waste that had developed during waking hours. With the enlargement of the interstitial space during sleep, waste removal was quicker and more thorough because cerebrospinal fluid could reach much further into the spaces. When the mice were anesthetized, a similar effect was seen as with sleeping.

In a published follow-up study, the authors found that sleep position had an impact on glymphatic transport in rodents. Sleeping in a lateral position, or on their sides, was more effective at clearing waste than prone or supine positions. Of course, the authors note that for rodents a prone position is similar to their awake positions. It would be most like a human sleeping while sitting upright (5).

In another study, done in Australia, results showed that sleep deprivation may have been responsible for an almost 1 percent decline in gross domestic product for the country (6). The reason is obvious: People are not as productive at work when they don’t get enough sleep. Their attitude tends to be more irritable, and concentration may be affected. We may be able to turn on and off sleepiness on an acute, or short-term, basis, depending on the environment, but it’s not as if we can do this continually.

According to the Centers for Disease Control and Prevention, an average of 4 percent of Americans report having fallen asleep in the past month behind the wheel of a car (7). I hope this hammers home the importance of sleep.

Exercise

How can I exercise, when I can’t even get enough sleep? Well there is a study that just may inspire you to exercise.

In the study, which involved rats, those that were not allowed to exercise were found to have rewired neurons in the area of their medulla, the part of the brain involved in breathing and other involuntary activities. There was more sympathetic (excitatory) stimulus that could lead to increased risk of heart disease (8). In those rats that were allowed to exercise regularly, there was no unusual wiring, and sympathetic stimuli remained constant. This may imply that being sedentary has negative effects on both the brain and the heart.

This is intriguing since we used to think that our brain’s plasticity, or ability to grow and connect neurons, was finite and stopped after adolescence. This study’s implication is that a lack of exercise causes unwanted new connections. Of course, these results were done in rats and need to be studied in humans before we can make any definitive suggestions.

Omega-3 fatty acids

In the Women’s Health Initiative Memory Study of Magnetic Resonance Imaging Study, results showed that those postmenopausal women who were in the highest quartile of omega-3 fatty acids had significantly greater brain volume and hippocampal volume than those in the lowest quartile (9). The hippocampus is involved in memory and cognitive function.

Specifically, the researchers looked at the level of omega-3 fatty acids, called eicosapentaenoic acid and docosahexaenoic acid, in red blood cell membranes. The source of the omega-3 fatty acids could either have been from fish or supplementation. This was not delineated. The researchers suggest eating fish high in these substances, such as salmon and sardines, since it may not even be the omega-3s that are playing a role but some other substances in the fish. It’s never too late to improve brain function. You can still be sharp at a ripe old age. Although we have a lot to learn about the functioning of the brain, we know that there are relatively simple ways we can positively influence it.

References: (1) medicinenet.com. (2) alz.org. (3) Top Cogn Sci. 2014 Jan.;6:5-42. (4) Science. 2013 Oct. 18;342:373-377. (5) J Neurosci. 2015 Aug 5;35(31):11034-11044. (6) Sleep. 2006 Mar.;29:299-305. (7) cdc.gov. (8)J Comp Neurol. 2014 Feb. 15;522:499-513. (9) Neurology. 2014;82:435-442. Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management.

Hormone replacement can have serious consequences. Stock photo

By David Dunaief, M.D.

We are bombarded continually with ads suggesting that men should talk to their doctors about “Low T.” This refers to low testosterone. Is this all hype, or is this a serious malady that needs medical attention? The short answer is it depends on the candidate. The best candidates have deficient testosterone levels and are symptomatic.

Men do go through andropause or have unusually low testosterone (hypogonadism). The formal name for treatment is androgen replacement therapy.

The greatest risk factor for lower testosterone is age. As men age, the level of testosterone decreases. Respectively, 20, 30 and 50 percent of those who are in their 60s, 70s and 80s have total testosterone levels of less than 320 ng/dL (1). However, some of the pharmaceutical ads would have you think that most men over 40 should seek treatment. Treatments offered include gels, transdermal patches and injections.

While real estate is all about “location, location, location,” with testosterone “caution, caution, caution” should be used.

Who are the most appropriate candidates for therapy? Those who have symptoms including lack of sexual desire, fatigue and lack of energy. However, what is scary is that around 25 percent of patients are getting scripts for testosterone without first testing their blood levels to determine if they have a deficiency (2). A simple blood test can measure total testosterone, as well as free and weakly bound levels at mainstream labs.

The number of testosterone scripts increased threefold from 2001 to 2011 for men more than 40 years old (3). Either we have discovered vast numbers of men with low levels or, more likely, marketing has caused the number of scripts to outstrip the need.

What are the risks and benefits of treating testosterone levels? Is testosterone treatment really the fountain of youth? There are benefits reported for those who actually have significantly deficient levels. Benefits may include improvements in muscle mass, strength, mood and sexual desire (4). However, several studies have suggested that testosterone therapy may increase the risk of cardiovascular disease, including stroke, heart disease and even death. These are obviously serious side effects. It also may cause acquired hypogonadism by shrinking the testes, resulting in a dependency on exogenous, or outside, testosterone therapy.

When testosterone is given, it may be important to also test PSA levels (5). If they increase by more than 1.4 ng/ml over a three-month period, then it may be wise to have a discussion with your physician about considering discontinuing the medication. You should not stop the medication without first talking to your doctor, and then a consult with a urologist may be appropriate. If the PSA is greater than 4.0 ng/ml initially, treatment should probably not be started without a urology consult.

How can you raise testosterone levels and improve symptoms without hormone therapy? Lifestyle changes, including losing weight, exercising and altering dietary habits, have shown promising results. Let’s look at the evidence.

Cardiovascular risk

One study’s results showed that men were at significantly increased risk of experiencing a heart attack within the first three months of testosterone use (6). There was an overall 36 percent increased risk. When stratified by age, this was especially true of men who were 65 and older. This population had a greater than twofold risk of having a heart attack. This risk may have to do with an increased number of red blood cells with testosterone therapy. Those who were younger showed a trend toward increased risk but did not meet statistical significance.

When the patient was younger than 65 and had heart disease, there was a significant twofold greater risk of a heart attack; however, those without heart disease did not show risk. This does not mean there is no risk for those who are “healthy” and younger; it just means the study did not show it. This observational study compared over 50,000 men who received new testosterone scripts with over 150,000 men who received scripts for erectile dysfunction drugs: phosphodiesterase type 5 (PDE5) inhibitors, including tadalafil (Cialis) and sildenafil (Viagra). PDE5 inhibitors have not demonstrated this cardiovascular risk.

Unfortunately, this is not the only study that showed potential cardiovascular risks. A 2013 study reinforced these results, showing that there was an increased risk of stroke, heart attack and death after three years of testosterone use (7). Ultimately, it found a 30 percent greater chance of cardiovascular events. What is worse is that risk was significant in both those with a history of heart disease and those without. This was a retrospective study involving 1,200 men with a mean age of 60.

We need randomized controlled trials to make a more definitive association. Still, these are two large studies that suggest increased risk. If you already have heart disease, be especially careful when considering testosterone therapy.

FDA response

The FDA, which approved testosterone therapy originally, is now investigating the possible cardiovascular risk profile based on the above two studies (8). The FDA doesn’t suggest stopping medication if you are taking it presently, but it should be monitored closely. The agency, in the meantime, has issued an alert to doctors about the potential dangerous side effects of androgen replacement therapy. The FDA says that the use of testosterone therapy is for those with low levels and other medical issues, such as hypogonadism from either primary or secondary causes.

Conflicting data

Two newer studies contradict the previous findings and suggest that testosterone supplementation for those who are deficient may not increase the risk of cardiovascular events or death. However, both studies have their weaknesses. One found that, although the cardiovascular events and death increased over the first two months, over the medium (9 months) and long terms (35 months), the risks actually decreased (9). Weaknesses: There was an initial detrimental cardiovascular effect; the study was observational; and the population was not well-defined as to participants’ history of cardiovascular disease or not. The second study was retrospective or backward-looking in time (10). These studies may not change the FDA warnings. What we need is a large randomized controlled trial.

Obesity and weight loss

Not surprisingly, obesity is an important factor in testosterone levels. In a study that involved 900 men with metabolic syndrome — borderline or increased cholesterol levels, sugar levels and a waist circumference greater than 40 inches — those who lost weight were 50 percent less likely to develop testosterone deficiencies. Those who participated in lifestyle modification had a highly statistically significant 15 percent increase in testosterone (11). Also, when men increased their physical activity and made dietary changes, there was an almost 50 percent risk reduction one year out, compared to their baseline at the start of the trial.

Interestingly, metformin had no effect in preventing lower testosterone levels in patients with abnormal sugar levels, but lifestyle modifications did. These patients were relatively similar to the average American biometrics with prediabetes: HbA1c of 6 percent and glucose of 108 mg/dL; a mean of 42-inch waists; and a BMI that was obese at 32 kg/m2. The mean age was between 53 and 54.

If there is one thing that you get from this article, I hope it’s that testosterone is not something to be taken lightly. You can improve testosterone levels if you’re overweight by losing fat pounds. If you think you have symptoms and you might need testosterone, talk to your doctor about getting a blood test before you do anything. It may be preferable to try alternate medications that improve erections such as sildenafil and tadalafil.

References: (1) J Clin Endocrinol Metab. 2001 Feb;86(2):724. (2) J Clin Endocrinol Metab. Online 2014; Jan 1. (3) JAMA Intern Med. 2013 Aug 12;173(15):1465-1466. (4) J Clin Endocrinol Metab. 2000 Aug;85(8):2839. (5) UpToDate.com. (6) PLoS One. 2014 Jan 29; 9(1):e85805. (7) JAMA. 2013;310:1829-1836. (8) FDA.gov. (9) Lancet Diabetes Endocrinol. 2016;4(6):498-506. (10) Eur Heart J. 2015;36(40):2706-2715. (11) ENDO 2012; Abstract OR28-3.

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

Trying to avoid triggers for migraines can be worse than navigating a minefield. Stock photo

By David Dunaief, M.D.

Migraines are a debilitating disorder. Symptoms typically include nausea, photophobia and phonophobia — sensitivity to light and to sound, respectively. The corresponding headache usually is unilateral and has a throbbing or pulsating feeling.

Migraines typically last anywhere from four to 72 hours, which is hard to imagine. Then, there is a postdrome recovery period, when the symptoms of fatigue can dog a patient for 24 hours after the original symptoms subside. Migraines are among the top reasons patients see a neurologist (1).

According to the American Migraine Foundation, there are approximately 36 million migraineurs, the medical community’s term for migraine sufferers. This has increased from 23.6 million in 1989. Women are three times more likely to be affected than men (2), and the most common age range for migraine attacks is 30 to 50 (3), although I have seen them in patients who are older.

What causes a migraine?

The theory was once simple: It was caused by vasodilation (enlargement) of the blood vessels. However, this may only be a symptom, and there are now other theories, such as inflammation of the meninges (membrane coverings of the brain and spinal cord). As one author commented, “Migraine continues to be an elephant in the room of medicine: massively common and a heavy burden on patients and their healthcare providers, yet the recipient of relatively little attention for research, education, and clinical resources” (4). There are many potential triggers for migraines, and trying to avoid them all can be worse than navigating a minefield. Triggers include stress, hormones, alcohol, caffeine, diet, exercise, weather, odor, etc. (5).

Focusing on prevention

There are many problems with treating acute migraine attacks beyond the obvious patient suffering. Eventually, patients may increase tolerance to drugs, needing more and more medication until they reach the maximum allowed. There are also rebound migraines that occur from using medication too frequently — more than 10 days in the month — including with acetaminophen (Tylenol) and NSAIDs (6). There are several options for preventive paradigms, some of which include medication, supplements, alternative therapies and dietary approaches.

Medication’s role

There are several classes of medications that act as a prophylaxis for episodic (less than 15 days per month) migraines. These include blood pressure and anti-seizure medications, botulinum toxin (botox) and antidepressants (7).

Blood pressure control itself reduces the occurrence of headaches (8). The data is strongest for beta blockers. Propranolol, a beta blocker, has shown significant results as a prophylaxis in a meta-analysis (group of studies) involving 58 studies where propranolol was compared to placebo or compared to other drugs (9). However, it showed only short-term effects. Also, there were a substantial number of dropouts from the studies.

Topiramate, an anti-seizure medication, showed a significant effect compared to placebo in reducing migraine frequency (10). In a randomized control trial (RCT) that lasted six months, there was a dose-response curve; the higher the dose, the greater the effect of the drug as a prophylaxis. However, drugs come with side effects: fatigue, nausea, numbness and tingling. The highest recommended dose is 100 mg because of side effects. As a result, almost one-third or 30 percent of patients cease therapy at the 200-mg dose because of side effects (11).

Botulinum toxin type A injection has not been shown to be beneficial for preventive treatment of episodic migraines but has been approved for use as a prophylaxis in chronic (greater than 15 days per month) migraines. However propranolol, mentioned already, has shown better results with fewer adverse reactions (12).

Alternative approaches

Butterbur, an herb from the butterbur (Petasites hybridus) root, was beneficial in a four-month RCT for the prevention of migraine (13). The 150-mg dose, given in two 75-mg increments, reduced the frequency of migraine attacks by almost twofold compared to placebo. This herb was well tolerated, with burping the most frequent side effect. Only Petasites’ commercial form should be ingested; the plant contains pyrrolizidine alkaloids, which may be a carcinogen and seriously damage the liver.

Feverfew, another herb, but this time the leaves are used for medicinal purposes, unfortunately, had mixed prophylaxis results. In a meta-analysis, study authors concluded that feverfew was not more beneficial than placebo (9). And, the most significant caveat with herbal medications is that their safety is not regulated by the FDA nor by any officially sanctioned regulatory body.

What about supplements?

High-dose riboflavin, also known as vitamin B2, may be an effective preventive measure. In a small RCT, 400 mg of riboflavin decreased the frequency of migraine attacks significantly more than placebo (14). The number of days patients had migraines also decreased. The side effects were mild for both placebo and riboflavin. Thus, this has potential as a prophylaxis, though the trial, like most of those mentioned above, was relatively short.

How about diet and exercise?

From my experience and those of other physicians, such as Dr. Joel Fuhrman and Dr. Neal Bernard, nutrient-dense foods are potentially important in substantially reducing the risk of migraine recurrence. I have seen many patients, both in my practice and in the three years I worked with Dr. Fuhrman, do much better, if not recover. There are a number of foods that are unlikely to cause migraine and reduce their occurrence, such as cooked green, orange and yellow vegetables, some fruits — though not citrus fruits — certain nuts, beans and brown rice. The number of foods can be expanded over time.

Interestingly, endogenous (from within the body) and exogenous (from outside the body, such as preservatives) toxins cause high levels of free fatty acids and blood lipids that are triggers for migraine (15). Higher fat diets and high levels of animal protein have been associated with more migraines. In addition, obesity may increase the frequency and severity of migraines (16).

Also, there was a small randomized controlled trial that showed exercise with 40 minutes of cycling three times a week may be comparable to medication for migraine prevention (17). Thus, there are several options for preventing migraines. The most well studied are medications; however, the most effective may be dietary changes and exercise, which don’t precipitate the rebound migraines that medication overuse may cause. And the herb butterbur may be an option as well.

References: (1) uptodate.com Sept. 2011. (2) Headache. 2001;41(7):646. (3) Medscape.com. (4) Annals of Neurology 2009;65(5):491. (5) Cephalalgia. 2007;27(5):394. (6) Headache. 2006;46 Suppl 4:S202. (7) uptodate.com. (8) Circulation. 2005;112(15):2301. (9) Cochrane Database Syst Rev. 2004. (10) JAMA. 2004;291(8):965-973. (11) CMAJ. 2010;182(7):E269. (12) Prescrire Int. 2011;20(122):287-290. (13) Neurology. 2004;63(12):2240. (14) Neurology. 1998;50(2):466-470. (15) J Women’s Health Gend Based Med. 1999;8(5):623-630. (16) Obes Rev. 2011;12(5):e362-371. (17) Cephalalgia. 2011;31(14):1428-1438.

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