With almost 70 percent of the U.S. population overweight or obese, it’s no surprise that the number one New Year’s resolution each year is to lose weight. Now that you or someone you know has made this resolution, what are you going to do about it?
Roughly 50 percent of people make New Year’s resolutions, and 71 percent of people maintain their resolve for the first two weeks. In six months, about half are still working toward their goals, at least to some degree. So about half of us make resolutions and about half of us stick to them at least halfway through the year (1). The good news is that people who make resolutions are about 10 times more likely to reach their objectives than those who don’t (2). So don’t give up!
Wouldn’t it be nice if we had a silver bullet that would help us lose weight without much thought? Are diet pills at least part of the answer? Diet pills, both medications and supplements, have a checkered past. But don’t despair, the armament of diet pills is beginning to grow. Two drugs were approved in 1999: Xenical (orlistat) and Meridia (sibutramine). Meridia was subsequently withdrawn due to side effects. Since then, the options have expanded with the 2012 approval of two additional drugs: Qsymia (phentermine-topiramate combination) and Belviq (lorcaserin). And finally, we have two new medications, approved in the latter half of 2014: Contrave (naltrexone-buproprion) and Saxenda (liraglutide). At this point, you need a playbook to keep them straight.
How do we evaluate weight-loss drugs? There are two important parameters: effectiveness in weight loss and impact on health. Drugs considered modestly effective cause at least 5 percent weight loss. Those that cause 10 percent weight loss are considered very good. Those that cause over 15 percent weight loss are considered excellent.
Let’s look at the history of diet drugs, along with evidence on the two newest entrants.
DIET PILL’S BLACK EYE
Unfortunately, diet pills’ track records have made both the medical community and the population at large leery. One of the most notorious medications was Fen-phen (fenfluramine-phentermine combination). While this drug combination helped people lose weight, it also had some serious side effects, pulmonary hypertension and heart valve defects resulting in serious adverse events and even mortality in some patients who took the drug. It was withdrawn from the market in 1997 by the FDA (3). Fenfluramine was blamed for causing these side effects, not phentermine. The reason I highlight this is that another more recent combination uses phentermine.
In terms of supplements, green coffee bean extract had been touted for its weight-loss capabilities based on a small 2012 study funded by the manufacturer (4). However, the FTC took this study to task, noting that the lead investigator changed the weights of patients, altered the length of the trial and could not determine which patients actually took supplement or placebo. In 2014, the journal responsible for publishing the research retracted the results (5).
This brings up another point. Green coffee bean supplements were promoted on a TV medical talk show. A recent study looked at the validity of advice given on these shows. Research evidence that supported the shows’ claims was found only half the time, and it was usually only from small studies or case studies. Unfortunately, the magnitude of benefit, the side effects, conflicts of interest and costs were highlighted on the shows no more than 20 percent of the time (6). So caveat emptor or, as “The Doctors” show says many times, consult your physician.
DRUGS WITH LONGER
TRACK RECORDS
There have been two established drugs since 1999: Xenical (orlistat) and Meridia (sibutramine). In a meta-analysis (a group of 14 randomized controlled trials, 11 with orlistat and 3 with sibutramine), results showed that there was a mean reduction in weight of 2.9 percent with orlistat and 4.6 percent with sibutramine (7). Also, there were only 12 percent of patients on orlistat and 15 percent of patients on sibutramine who achieved greater than 10 percent body weight reduction when compared to placebo. To boot, both drugs have side effects. Orlistat is known for causing gastrointestinal (GI) side effects.
Another smaller trial with Alli (orlistat over the counter) found that those who followed diet and exercise regimens while taking the drug saw a median 5 percent reduction in weight over a two-month period. The patients were satisfied or very satisfied with the results, despite GI side effects after three months of study duration (8).
Orlistat assessment: modest efficacy and mild-to-moderate side effect profile.
Sibutramine was taken off the market in 2010 due to increased risk of cardiovascular events (3).
NEWLY APPROVED DRUGS BETTER?
Two drugs are recent enough that they don’t have track records in the marketplace. In September 2014, Contrave (naltrexone-bupropion) was approved by the FDA (3). In a large randomized controlled phase 3 trial, naltrexone-bupropion demonstrated significant effectiveness over placebo (9). The mean weight lost was 5.0 percent in the low-dose drug and 6.1 percent in the high-dose drug, whereas the placebo demonstrated a 1.6 percent reduction. These results were seen over 56 weeks. Nausea was the most common side effect, occurring in 30 percent of patients. The drug did also raise blood pressure 1.5 mmHg initially. There is an ongoing study intended to demonstrate no increased risk of heart attack, and interim results have been good.
There is a black box warning that patients may have suicidal thoughts because of bupropion, an antidepressant. Ultimately, Contrave reduces weight by an additional 4.1 percent over placebo (3). This medication can be used for those who are obese (BMI>30 kg/m2) or who have a BMI>27 kg/m2 with an additional weight-related disease, such as diabetes or high blood pressure.
Naltrexone-bupropion assessment: modest effectiveness and mild-moderate potential side effect profile. If the drug does not reduce the weight when using maintenance dose by at least 5 percent in 12 weeks, it should be discontinued according to the FDA (3).
The latest drug, Saxenda (liraglutide), was approved in December 2014. In a randomized controlled trial with a 56-week duration, liraglutide resulted in a 6.2 percent reduction in weight, whereas the placebo had 0.2 percent reduction in weight (10). Interestingly, the researchers required that all participants have a pre-trial period of lifestyle modifications, which resulted in a 6 percent weight loss prior to the trial. The treatment population is the same as for naltrexone-bupropion, either obese (BMI>30 kg/m2) or a BMI>27 kg/m2 with an additional weight-related disease, such as diabetes or high blood pressure. Liraglutide is an injectable diabetes drug in the class referred to as GLP-1 agonists. The dose is higher for weight-loss patients. The side effect profile was mainly associated with GI distress.
Liraglutide assessment: modest effectiveness and mild side effect profile.
Interestingly, metformin has been used as an off-label weight-loss drug as well, meaning not approved by the FDA for that use, but at the discretion of the physician.
Your best recourse is always lifestyle changes, but a diet drug could help jump start your resolution to lose weight. The medications have very similar modest effectiveness and mild-to-moderate side effect profiles. However, the newer drugs do not have post-marketing safety data yet. Even if you start a diet medication, diet and exercise are highly recommended or else the results may not be achieved with medication alone. I can’t stress it enough: always consult your doctor before starting a weight-loss drug.
REFERENCES:
(1) statisticbrain.com. (2) J Clin Psychol. 2002 Apr;58(4):397-405. (3) FDA.gov. (4) Diabetes Metab Syndr Obes. 2012;5:21-7. (5) Diabetes Metab Syndr Obes. 2014;7:467. (6) BMJ. 2014;349:g7346. (7) Int J Obes Relat Metab Disord. 2003;27:1437-1446. (8) Obesity (Silver Spring). 2008;16:623-629. (9) Lancet. 2010;376:595-605. (10) Int J Obes (Lond). 2013;37:1443-1451.

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

Holidays are when many people add pounds. With that in mind, let’s start off with a quiz to test your knowledge of obesity-related issues. The answers and research are provided below. Regardless of your quiz score, it is important to understand the research.

Obesity reduces lifespan by up to:

A) Not at all

B) 4 years

C) 8 years

D) 10 years

Obesity shortens healthy years of life by:

A) 8 years

B) 12 years

C) 15 years

D) 20 years

Food cravings can be reduced for the short term by:

A) Counting to 20

B) Tapping your finger against your head

C) Watching TV

D) Texting on your cellphone

Obesity can lead to the following complication(s):

A) High blood pressure

B) Diabetes

C) Cancer

D) All of the above

Are you eager to find out the answers? I hope so, because there are some very salient points I am trying make by providing multiple choice questions. The answers are: 1. D; 2. D; 3. B; 4. D.

So how did you do? One of the questions was actually similar to a question on a medical website for doctors, so don’t be too hard on yourself if you did not get them all right. Let’s look at the research.

Mortality & effect

on healthy lifespan

Many of you know that obesity would have an impact on development of other chronic diseases and a decrease in quality of life, but to what extent? A 2013 study indicated that almost as many as one in five deaths in the U.S. are associated with obesity (1).

In a recent computer modelling study, the results showed that those who are obese may lose up to eight years, almost a decade, of their lifespan (2). But that is only part of the results. The other, more compelling result is that patients who are very obese, defined as a BMI >35 kg/m2, could lose almost two decades of healthy living. According to the researchers, this means you may have diseases such as diabetes and cardiovascular disease. However, even those patients who were obese and those who were overweight also could have reductions in lifespan, up to 6 years and 3 years respectively.

There were 3,992 adults between the ages of 20 and 79 evaluated in this study. The data was taken from an NHANES database from 2003 to 2010, which looked at participants who went on to develop diabetes and cardiovascular disease. Though this is not a clinical trial, and there is a need for more study, the results are eye-opening, with the youngest and very obese negatively impacted the most.

Cancer impact

Since it is very difficult to “cure” cancer, although hopefully someday soon we will, it is important to reduce modifiable risk factors. Obesity may be one of these contributing factors, although it is hotly debatable how much of an impact obesity has on cancer development.  The American Society of Clinical Oncologists, in a position paper, supported the idea that it is important to treat obesity in the fight against cancer (3). The authors indicate obesity may make the prognosis worse, may hinder the delivery of therapies to treat cancer, and may increase the risk of malignancy.

Also, possibly reinforcing ASCO’s stance, a recent study suggested that upwards of a half-million cases of cancer worldwide were related to being overweight or obese, with the overwhelming concentration in North American and Europe (4).

Possible solutions

A potential counterweight to both the reductions in life quality and life expectancy may be the Mediterranean diet. In a newly published analysis of the Nurses’ Health Study, results show that the Mediterranean diet helped slow shortening of the telomeres (5). Repeat sequences of DNA found at the end of chromosomes, telomeres shorten with age; the shorter the telomere, the shorter life expectancy. Thus, the Mediterranean diet may decrease occurrence of chronic diseases, increase lifespan and decrease premature mortality. Hence, the opposite effect of obesity. In fact, it may help treat obesity, though this was not mentioned in the study.

Interestingly, the effects of the Mediterranean diet were on a dose-response curve. The greater the adherence to the diet, rated on a scale of 0 to 9, the better the effect. Those who had an increase in adherence by three points saw a corresponding decrease in telomere aging by 4.5 years. There were 4,676 middle-aged women involved in this analysis. The researchers believe that the anti-inflammatory and antioxidant effects could be responsible for the diet’s effects.

According to an accompanying editorial, no individual component of the diet was identified as having beneficial effects by itself, so it may be the diet as a whole that is important (6).

Short-term solution

There are easy-to-use distraction tactics that involve physical and mental techniques to reduce food cravings. These include tapping your foot on the floor, staring at a blank wall and, yes, alternating tapping your index finger against your forehead and your ear (7). The forehead and ear tapping was most effective, although probably most embarrassing in public. Among mental techniques, seeing pictures of foods that were unhealthy and focusing on their long-term detriments to health had the most impact (8). All of these short-term distractors were done for 30 seconds at a time. The results showed that in obese patients they indeed decreased food cravings.

Exercise impact

I recently wrote about exercise and that it does not lead to fat percentage loss in adults. Well, before you write off exercise for fat loss, it seems that adolescents may benefit from exercise. In a randomized controlled trial, the gold standard of studies, results show that those in the resistance training group alone and those in a combined resistance and aerobic training group had significantly greater percentages of fat loss compared to a control group (9).

However, the aerobic group alone did not show a significant change in fat percent versus the control. There were 304 study participants, ages 14 to 18, followed for a six-month duration, and results were measured with MRI. The reason that resistance training was effective in reducing fat percentage may have to do with an increase in muscle mass rather than a decrease in actual fat. Still, exercise is important. It doesn’t matter if it decreases the fat percentage; it is still getting you to the goal.

Obesity can have devastating effects, from potentially inducing cancer or worsening it, to shortening life expectancy and substantially decreasing quality of life. Fortunately, there may be ways to help treat obesity with specific lifestyle modifications. The Mediterranean diet as a whole may be an effective step toward decreasing the burden of obesity and reducing its complications. Kids, teenagers specifically, should be encouraged to “Play 60,” as the NFL has encouraged, but also to do some resistance training. As we mentioned, there are simple techniques that may help reduce short-term food cravings.

References

(1) Am J Public Health. 2013;103:1895-1901. (2) The Lancet Diabetes & Endocrinology, online December 5, 2014. (3) J Clin Oncol. 2014;32(31):3568-74. (4) The Lancet Oncology. online November 26, 2014. (5) BMJ. online December 2, 2014. (6) BMJ 2014;349:g6843. (7) Obesity Week 2014 abstract T-2658-P. (8) Obesity Week 2014 abstract T-3023-OR. (9) JAMA Pediatr. 2014;168(11):1006-1014.

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

The prevalence of osteoporosis is increasing especially as the population ages. Why is this important? Osteoporosis may lead to increased risk of fracture due to a decrease in bone strength (1).

That is what we do know. But what about what we think we know?

For decades we have been told that if we want strong bones, we need to drink milk. Advertising slogans have morphed from “Milk does a body good” to “Got Milk?” to this year’s “Milk Life.” Celebrities have worn milk mustaches to show how important it is to our diet. This has been drilled into our brains since we were toddlers. Milk has calcium and is fortified with vitamin D, so milk could only be helpful, right?

Not necessarily.

The data is mixed, but studies indicate that milk may not be as beneficial as we have been led to believe and, even worse, it may be harmful. The operative word here is “may.” We will investigate this further.

Vitamin D and calcium are good for us. But do supplements help prevent osteoporosis and subsequent fractures? Again the data is mixed, but supplements may not be the answer for those who are not deficient.

Of course, we know which drugs are potentially beneficial for osteoporosis, however, which one works the best for whom may be unclear. There are minimal head-to-head trials comparing different drugs (2). They all have beneficial reductions in fracture risk in patients with osteoporosis, but also have side-effects.

What do the guidelines tell us about those who are at potential risk for osteoporosis and fracture? Recently a study looked at the predictability, or reliability, of the United States Preventive Services Task Force (USPSTF) recommendations for screening patients for osteoporosis. Unfortunately, the study showed that USPSTF guidelines were a nominal improvement over chance (3). In other words, the guidelines were able to predict only 24 percent of patients who ended up developing osteoporosis between the ages of 50 and 64.

Milk – it’s not what you think

The new slogan for milk is, “Milk Life.” It’s a catchy phrase. However, is it appropriate?

The results of a newly published large observational study involving men and women in Sweden showed that milk may be harmful (4). When comparing those who consumed three or more cups of milk daily to those who consumed less than one, there was a 93 percent increased risk of mortality in women between the ages of 39 and 74. There was also an indication of increased mortality based on dosage. For every one glass of milk consumed there was a 15 percent increased risk of death in these women. There was a much smaller, but significant, 3 percent per glass increased risk of death in men. Women experienced a small, but significant, increased risk of hip fracture, but no increased risk in overall fracture risk. There was no increased risk of fracture in men, but there was no benefit either. There were higher levels of biomarkers that indicate oxidative stress and inflammation found in the urine.

This study was 20 years in duration and is eye-opening. We cannot make any decisive conclusions, only associations, since it is not a randomized controlled trial. But it does get you thinking. The researchers surmise that milk has high levels of D-galactose, a simple sugar that may increase inflammation and ultimately contribute to this potentially negative effect, whereas other foods have many-fold lower levels of this substance.

Ironically, the USDA recommends that, from nine years of age through adulthood, we consume three cups of dairy per day (5). This is interesting, since the results from the previous study showed the negative effects at this recommended level of milk consumption. The USDA may want to rethink these guidelines.

Prior studies show milk may not be beneficial for preventing osteoporotic fractures. Specifically, in a meta-analysis that used data from the Nurses’ Health Study for women and the Health Professionals Follow-up Study for men, for each additional glass of milk per day during the teenage years there was a nine percent increased risk of hip fracture in men only (6). However, this effect was negated when height was taken into account. Neither men nor women saw any benefit from milk consumption in preventing hip fractures. In other words, the milk you drank during your teenage years might not reduce hip fractures later in life.

Calcium disappointments

Unfortunately, it is not only milk that may not be beneficial. There was a meta-analysis that included observational studies and clinical trials. In the meta-analysis involving a group of observational studies, there was no statistically significant improvement in hip fracture risk in those men or women ingesting at least 300 mg of calcium from supplements and/or food on a daily basis (7). The researchers did not differentiate the types of foods containing calcium. In a group of randomized controlled trials analyzed in the same study, those taking 800 to 1600 mg of calcium supplements per day also saw no increased benefit in reducing nonvertebral fractures. In fact, in four clinical trials the researchers actually saw an increase in hip fractures among those who took calcium supplements. A weakness of the large multi-varied meta-analyses is that vitamin D baseline levels, exercise and phosphate levels were not taken into account.

Vitamin D benefit

Finally, though the data is not always consistent for vitamin D, when it comes to fracture prevention, it appears it may be valuable. In a meta-analysis (involving 11 randomized controlled trials), vitamin D supplementation resulted in a reduction in fractures (8). When patients were given a median dose of 800 IUs (ranging from 792 to 2000 IUs) of vitamin D daily, there was a significant 14 percent reduction in nonvertebral fractures and an even greater 30 percent reduction in hip fractures in those 65 years and over. However, vitamin D in lower levels showed no significant ability to reduce fracture risk.

Just because something in medicine is a paradigm does not mean it’s correct. Milk may be an example of this. Also, ironically, the new “Milk Life” slogan may need an overhaul, especially in women between the ages of 39 and 74 years old, where there is a potential increased risk of mortality. No definitive statement can be made about calcium, although even in randomized controlled trials with supplements there seemed to be no significant benefit. Of course, the patients in these trials were not necessarily deficient in calcium or vitamin D.

In order to get benefit from vitamin D supplementation to prevent fracture, patients may need at least 800 IUs per day, which is the Institute of Medicine’s recommended amount for a relatively similar population as in the study. Also, different drugs have different benefits and side-effect profiles.

Remember that studies, though imperfect, are better than tradition alone. Prevention and treatment therefore should be individualized, and deficiency in vitamin D or calcium should usually be treated, of course. Please, talk to your doctor before adding or changing any supplements.

References

(1) JAMA. 2001;285:785-95. (2) Ann Intern Med. 2014;161(10):711-723. (3) NAMS 2014 Meeting: Abstract S-13. October 16, 2014. (4) BMJ 2014;349:g6015. (5) choosemyplate.gov. (6) JAMA Pediatr. 2014;168(1):54-60. (7) Am J Clin Nutr. 2007 Dec;86(6):1780-90. (8) N Engl J Med. 2012 Aug 2;367(5):481.

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

With the holiday dinners right around the corner, what would be better topic to discuss than exercise? To quell our guilt about Thanksgiving-dinner indiscretions, many of us will resolve to exercise to burn off the calories from this seismic meal and the smaller, calorically dense aftershock meals, whether with a vigorous family football game or with a more modest walk.

Before I go on, let’s take a little quiz. A little knowledge goes a long way in feeling good about your plans to potentially exercise.

Question #1: I can offset potential weight gain from a calorically dense meal by doing which of the following?

a) Exercising intensely for a short   

    duration

b) Exercising moderately for a long

    duration

c) Exercising lightly for a long
        duration

d) Exercise is unlikely to offset a       

     calorically dense meal

Question #2: Exercise is beneficial for which of the following? Choose all that apply.

a) Chronic kidney disease

b) Rheumatoid arthritis

c) Cognitive decline

d) Risk of falls

Unfortunately, the answer to question one is “d.” Exercise without dietary changes may not actually help many people to lose weight, no matter what the intensity or the duration (1). If it does help, it may only modestly reduce fat mass and weight for the majority of people. However, it may be helpful with weight maintenance. Therefore, it may be more important to think about what you are eating than to succumb to the rationalization that you can eat with abandon during the holidays and work it off later.

Don’t give up on exercise just yet, though. There is very good news: the answer to question two is that exercise has beneficial effects on all of the choices plus many others, including diabetes, cardiovascular disease, osteoporosis, fatigue, insomnia, and depression.

Let’s look at the evidence.

Weight loss attenuated

The well-known weight-loss paradigm in medicine is that when more calories are burned than consumed, we will tip the scale in favor of weight loss. The greater the negative balance with exercise, the greater the loss. However, the results of a recent study say otherwise. They show that in premenopausal women there was neither weight nor fat loss from exercise (2). This involved 81 women over a short duration, twelve weeks. All of the women were overweight to obese, although there was great variability in weight.

However, more than two-thirds of the women (55) gained a mean of 1 kilogram, or 2.2 pounds, of fat mass by the end of the study. There were a few who gained 10 pounds of predominantly fat. Significant variability was seen among the participants, ranging from significant weight loss to substantial weight gain. These women were told to exercise at the American College of Sports Medicine’s optimal level of intensity (3). This is to walk 30 minutes on a treadmill three times a week at 70 percent VO2max — maximum oxygen consumption during exercise— or, in other words, a moderately intense pace. The good news is that the women were in better aerobic shape by the end of the study and that women who had lost weight at the four-week mark were more likely to continue to do so by the end of the study. This was a preliminary study, so no definitive conclusions can be made.

Other studies have shown modest weight loss. For instance, in a meta-analysis involving 14 randomized controlled trials — the gold standard of studies — results showed that there was a disappointing amount of weight loss with exercise alone (4). In six months, patients lost a mean of 1.6 kilograms, or 3.5 pounds, and at 12 months, participants lost 1.7 kilograms, or about 3.75 pounds.

Weight maintenance

However, exercise may be valuable in weight maintenance, according to observational studies. Premenopausal women who exercised at least 30 minutes a day were significantly less likely to regain lost weight (5). When exercise was added to diet, women were able to maintain 30 percent more weight loss than with diet alone after a year in a prospective study (6).

Chronic kidney disease

Chronic kidney disease affects about 1 in 10 people in the United States, according to the Centers for Disease Control and Prevention (7). The U.S. Preventive Services Task Force has indicated that there is insufficient evidence to treat asymptomatic CKD. In fact, the American College of Physicians has said that asymptomatic CKD, which includes stages 3a and 3b, or moderate disease levels, should not be screened for, since the treatment risks outweigh the benefits, and lead to false positive results and unnecessary treatments (8).

However, in a recent trial, the results showed that walking regularly could reduce the risk of kidney replacement therapy and death in patients who have moderate to severe CKD, stages 3-5 (9). Yes, this includes stage 3, which most likely is asymptomatic. There was a 21 percent reduction in the risk of kidney replacement therapy and a 33 percent reduction in the risk of death when walkers were compared to non-walkers.

Walking had such an impressive impact, results were based on a dose-response curve. In other words, the more frequently patients walked in the week, the better the probability of preventing complications. Those who walked between one and two times per week had 17 and 19 percent reductions in death and kidney replacement therapy, respectively, while those who walked at least seven times per week saw 44 and 59 percent reductions in death and kidney replacement. These are substantial results. The authors concluded that the effectiveness of walking on CKD was independent of kidney function, age or other diseases.

Rheumatoid arthritis

Unfortunately, more than three quarters of patients with rheumatoid arthritis are affected with varying degrees of hand dysfunction. Well, it turns out that in a randomized controlled trial that included supervised (physiotherapist or occupational therapist) exercise for six sessions and exercise at home showed more than twice the improvement in hand function than those in the usual care group over a 12-month period (10). There were no changes in drug therapies or pain.

Therefore, while it is important to enjoy the holidays, it is food choices that will have the greatest impact on our weight and body composition. Exercise will not be the solution for most of us to overcome holiday weight gain. However, exercise is extremely beneficial for preventing progression of chronic disorders, such as CKD. Improved functioning of the hand with exercise in rheumatoid arthritis patients reduces disability.

So, by all means, exercise during the holidays, but also focus on more nutrient-dense foods. At the least, strike a balance rather than eating purely calorically dense foods. They are unlikely to be rationalized with exercise.

References

(1) update.com. (2) J Strength Cond Res. Online Oct. 28, 2014. (3) ACSM.org. (4) Am J Med. 2011;124(8):747. (5) Obesity (Silver Spring). 2010;18(1):167. (6) Int J Obes Relat Metab Disord. 1997;21(10):941. (7) cdc.gov. (8) Ann Intern Med. online October 21, 2013. (9) Clin J Am Soc Nephrol. 2014 Jul;9(7):1183-9. (10) Lancet. online Oct. 9, 2014.

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

With winter’s icy conditions around the corner, our risk for falls is about to go up. When we were younger, falls usually did not result in significant consequences. However, when we reach middle age and chronic diseases become more prevalent, falls become more substantial. And, unfortunately, falls are a serious concern for older patients, where consequences can be devastating. They can include brain injuries, hip fractures, a decrease in functional ability, and a decline in physical and social activities (1). Ultimately, falls can lead to loss of independence (2).

Of those over the age of 65, between 30 and 40 percent will fall annually (3). Most of the injuries that involve emergency room visits are due to falls in this older demographic (4).

What can increase the

risk of falls?

A multitude of factors contribute to fall risk. A personal history of falling in the recent past is the most prevalent. But there are many other significant factors, such as age; female gender; drugs like antihypertensive medications used to treat high blood pressure; and psychotropic medications used to treat anxiety, depression, and insomnia. Chronic diseases, including arthritis, as an umbrella term; history of stroke; cognitive impairment and Parkinson’s disease can also contribute. Circumstances that predispose us to falls also involve weakness in upper and lower body strength, decreased vision, hearing disorders and psychological issues, such as anxiety and depression (5).

How do we prevent falls?

Fortunately, there are ways to modify many risk factors and ultimately reduce the risk of falls. Of the utmost importance is exercise. But what do we mean by “exercise?” Exercises involving balance, strength, movement, flexibility and endurance, whether home-based or in groups, all play significant roles in fall prevention (6). We will go into more detail below.

Many of us in the northeast suffer from low vitamin D, which strengthens muscle and bone. This is an easy fix with supplementation. Obviously, footwear needs to be addressed. Non-slip shoes, if last year is any indication, are of the utmost concern because of ice, especially black ice. Inexpensive changes in the home can also make a big difference.

Medications that exacerbate fall risk

There are a number of medications that may heighten fall risk. As I mentioned earlier, psychotropic drugs top the list. Ironically, they also top the list of the best-selling drugs. But what other drugs might have an impact?

High blood pressure medications have recently been investigated. A recent propensity-matched sample study (a notch below an RCT in terms of quality) showed an increase in fall risk in those who were taking high blood pressure medication (7). Surprisingly, those who were on moderate doses of blood pressure medication had the greatest risk of serious injuries from falls, a 40 percent increase. One would have expected those on the highest levels of BP medication to have the greatest increase in risk, but this was not the case.

While blood pressure medications may contribute to fall risk, they have significant benefits in reducing the risks of cardiovascular disease and events. Thus, we need to tread lightly before considering stopping a medication; we need to weigh the risk-benefit ratio, specifically in older patients. When it comes to treating high blood pressure, lifestyle modifications may also play a significant role in treating this disease (8).

Where does arthritis fit into this paradigm?

In those with arthritis, compared to those without, there is an approximately two-times increased risk of two or more falls and, additionally, a two-times increased risk of injury resulting from falls, according to the CDC (1). This survey encompassed a significantly large demographic; arthritis was an umbrella term including those with osteoarthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia. Therefore, the amount of participants with arthritis was 40 percent. Of these, about 13 percent had one fall and, interestingly, 13 percent experienced two or more falls in the previous year. Unfortunately, almost 10 percent of the participants sustained an injury from a fall. Patients 45 and older were as likely to fall as those 65 and older.

Why is exercise critical?

All exercise has value. A meta-analysis of a group of 17 trials showed that exercise significantly reduced the risk of a fall (9). If their categories are broken down, exercise had a 37 percent reduction in falls that resulted in injury and a 30 percent reduction in those falls requiring medical attention. But even more impressive was a 61 percent reduction in fracture risk. Remember, the lower the fracture risk, the more likely you are to remain physically independent. Thus, the author summarized that exercise not only helps to prevent falls, but also fall injuries. The weakness of this study was that there was no consistency in design of the trials included in the meta-analysis. Nonetheless, the results were impressive.

What specific types of exercise are useful?

Many times exercise is presented as a word that defines itself. In other words: just do any exercise and you will get results. But some exercises may be more valuable or have more research behind them. Tai chi, yoga and aquatic exercise have been shown to have benefits in preventing falls and injuries from falls.

A randomized controlled trial (RCT), the gold standard of studies, showed that those who did an aquatic exercise program (HydrOS) had a significant improvement in the risk of falls (10). Results showed a reduction in the number of falls from a mean of 2.00 to a fraction of this level — a mean of 0.29. There was no change in the control group.

Both groups were given equal amounts of vitamin D and calcium supplements. The aim of the aquatic exercise was to improve balance, strength and mobility. Also, there was a 44 percent decline in the number of patients who fell. This study’s duration was six months and involved 108 post-menopausal women with an average age of 58. This is a group that is more susceptible to bone and muscle weakness. The good news is that many patients really like aquatic exercise.

Thus, our best line of defense against fall risk is prevention. Does this mean stopping medications? Not necessarily. But for those 65 and older, or for those who have “arthritis” and are at least 45 years old, it may mean reviewing your medication list with your doctor. Before considering changing your BP medications, review the risk-to-benefit ratio with your physician. The most productive and least dangerous way to prevent falls is through lifestyle modifications.

References

(1) MMWR. 2014;63(17):379-83. (2) J Gerontol A Biol Sci Med Sci. 1998;53(2):M112. (3) J Gerontol. 1991;46(5):M16. (4) MMWR Morb Mortal Wkly Rep. 2003;52(42):1019. (5) JAMA. 1995;273(17):1348. (6) Cochrane Database Syst Rev. 2012;9:CD007146. (7) JAMA Intern Med. 2014 Apr;174(4):588-95. (8) JAMA Intern Med. 2014;174(4):577-87. (9) BMJ. 2013;347:f6234. (10) Menopause. 2013;20(10):1012-1019.

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

I recently watched “The Caine Mutiny,” a wonderful 1954 film starring Humphrey Bogart. I encourage those who have not seen the movie to watch it, but this is not a film review. Sadly, Humphrey Bogart died at 57 from esophageal cancer. It got me thinking: what might prevent this cancer? I thought of proton pump inhibitors. This class of medication includes Nexium (omeprazole), Prilosec (pantoprazole), and Prevacid (lansoprazole). As I am sure you know, PPIs can be found in both prescription and over-the-counter forms.

What are PPIs?

PPIs are acid-reducing medications that work by blocking the gastric proton pump (H+/K+ ATPase) of parietal cells in the lining of the stomach. They are used to treat GERD reflux; Barrett’s esophagus, a potential consequence of reflux; esophagitis (inflammation of the esophagus); and ulcers in the stomach and small intestines (1). Barrett’s can potentially lead to esophageal cancer.

Are PPIs effective?

The prevailing thought is that, by treating reflux disease with PPIs, you reduce the risk of esophageal cancer in those who have Barrett’s esophagus. However, the effectiveness has been called into question by a Danish study, which I will explain in more detail below.

How common are PPIs?

According to the FDA, there were 21 million prescriptions filled in 2009 for this class of medication (2). PPIs were the fifth most common drugs prescribed in the U.S. in 2011 (3). The median length of use is six months.

Do PPIs have significant

side effects?

Unfortunately, PPIs have side effects, and with chronic use, we seem to be seeing more side effects. The FDA warns of infections, both community-acquired pneumonia and Clostridium difficile, a bacterial infection that causes watery diarrhea and substantial discomfort; potential absorption issues with vitamins and minerals such as magnesium, calcium and B12; drug interactions with Plavix (clopidegril); increased bone fracture risk; and negative effects in older patients in general (2). Note that none of these side effects has been definitively tied to this class of drugs, but it should make you think twice.

Let’s look at the evidence.

Do PPIs prevent esophageal cancer?

The answer is probably not, and they may even increase risk. In a newly published Danish study, the surprising results showed that PPIs did not decrease the risk of esophageal cancer or high-grade dysplasia (abnormal growth of tissue) in patients who had Barrett’s esophagus (4). One precursor of cancer of the esophagus is Barrett’s esophagus, which can develop from chronic reflux disease. The risk of esophageal cancer in long-term users was greater in those who were more adherent than in those who had lower adherence with PPI use, but both had significantly increased risk of cancer development, 3.4 times and 2.2 times, respectively. This study involved 9,883 patients over a 10-year duration.

This study was observational, so the results are suggestive and require further studies to confirm these results. The authors surmise that the reason for this increased risk is that reflux disease involves other factors besides stomach acid production, and PPIs may increase the proportion of bile acids that are prone to cause cancer. Another reason may be that gastrin (which initiates secretion of stomach juices) production increases with the use of PPIs and may be responsible for the increased risk.

Do PPIs really increase
the risk of infection?

There are two scary diseases that are a potential result of PPIs: pneumonia and Clostridium difficile.

Pneumonia risk

PPIs may increase our risk of the most common type of bacterial pneumonia, Streptococcus pneumoniae. In an observational prospective (forward-looking) study, those who used PPIs were at two times the increased risk of developing this type of pneumonia compared to those not using these drugs (5). There were 463 patients involved in this study.

Fortunately, the severity of pneumonia was the same whether it was potentially caused by PPIs or not. In other words, PPIs did not make the pneumonia worse. The researchers surmise that PPIs may increase the risk of pneumonia because of potential bacterial overgrowth in esophagus due to a decrease in gut acid production and from modulation of the immune system.

In a meta-analysis (a group of nine studies), results showed that PPIs increased the risk of developing pneumonia (6). The most interesting part of this study was that those at higher risk were patients who used PPIs for less than 30 days. These patients had a 65 percent increased risk. Those who used high doses of the therapies were at a 50 percent increased risk. Interestingly, patients who had been using the PPIs for over six months did not show an increased risk of pneumonia. So it may not always relate to just long-term or chronic use.

Clostridium difficile risk

The infection by a bacterium Clostridium difficile may cause mild to severe watery diarrhea and abdominal pain. It is typically precipitated by antibiotic use. However, PPIs might also be implicated. In a meta-analysis (a group of 42 observational studies), results showed that PPIs increased the risk of Clostridium difficile infection by 74 percent compared to those who did not use these medications (7). And those who used both PPIs and antibiotics were at an even greater risk of 96 percent. There were 313,000 patients involved in this meta-analysis. No definitive conclusions can be made, though, since these results were based on observational trials; however, it makes you ponder the use of these drugs.

Aspirin and PPIs

Many people take daily low-dose (75 to 325 mg) aspirin to prevent a heart attack, stroke or even potentially cancer. Well, when it comes to taking two of the most common drugs together, aspirin and PPIs, this may not be a good combination. In a recent observational study, the results showed that PPI use in those patients who take low-dose aspirin prompted a more than twofold greater risk of causing a break in the mucosa, or lining of the small bowel (8). This study involved 198 patients. The researchers used video capsule endoscopy to confirm the rupture of the mucosa.

Bone Fracture and PPIs

While the results with bone fracture are mixed, it seems that the longer the use and the higher the dose, the greater the risk (9).

Does the lack of efficacy with preventing serious consequences of esophageal cancer mean that the drugs are ineffective? The answer is no. This class of drugs is still valuable for treating heartburn symptoms. In addition, there needs to be randomized controlled trials before we can even consider making a definitive statement about the risks. The problem is that most of the trials are post-marketing studies and there is a lower probability of funding for side effect trials that will be large enough to be useful.

Therefore, be cautious with the use of PPIs. Just because they are over the counter does not mean they are harmless. GI doctors have the most experience with the drugs. Do not change your use of the medications without talking to your doctor.

References

(1) uptodate.com. (2) FDA.gov. (3) imshealth.com. (4) Aliment Pharmacol Ther. 2014 May;39(9):984-91. (5) Aliment Pharmacol Ther. 2012;36(10):941-49. (6) Expert Rev Clin Pharmacol. 2012 May;5(3):337-44. (7) Am J Gastroenterol. 2012;107(7):1011. (8) Gastrointest Endosc online May 13, 2014. (9) JAMA. 2006;296(24):2947.

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

Last week, I wrote about factors that increase the risk of gallstones, an all-too-common GI problem. Many of these are modifiable. A logical extension of this discussion is complications and prevention techniques. Let’s look at the evidence.

What are the complications?

Complications include cardiovascular disease, psoriasis and pancreatitis. I wrote about how gallstones are the major risk factor for acute pancreatitis in my Oct. 16, 2014 article, entitled “How much do you know about pancreatitis?” Here, we will touch on some of these additional complications.

Cardiovascular complications

Cardiovascular disease, comprised of heart disease and stroke, is responsible for about 45 percent of deaths in the United States. In a recent observational, prospective (forward-looking) study, the results show an overall 32 percent increased risk of cardiovascular disease in patients with gallstones (1). When these results are further broken out, there was a 42 percent increased risk of heart disease, 15 percent increased risk of stroke, and a 31 percent increased risk of heart failure. These results are scary, and it is not even Halloween yet.

Interestingly, those who were younger, 18 to 40 years old, were at the highest risk of developing cardiovascular disease. And those who had mild gallstone disease were at higher risk, as well. This study was six years in duration and involved more than 34,000 patients. The authors hypothesized that the possible reason for this association, between gallstones and cardiovascular disease, may have to do with an abundance of cholesterol, inflammation and oxidative stress.

Psoriasis & Psoriatic Arthritis

In the Nurses’ Health Study II, a prospective observational trial, results show that there is a 70 percent increased risk of developing psoriasis and an 196 percent increased risk of developing psoriatic arthritis in women who have a personal history of gallstone disease (2). These results were segregated from obesity. In fact, this association between gallstones and psoriasis was greatest in those who were <30 BMI — a threefold increased risk.

This is not an excuse to be obese, however, because there was still a significantly increased risk, 1.71-fold, in this group. There were 89,234 women involved in this study over a 14-year follow-up period. As with cardiovascular disease’s association with gallstones, inflammation also may play a role with gallstones and psoriasis and psoriatic arthritis. Therefore, it may be important to reduce inflammation in the body to prevent gallstones and their complications.

prevention 

Fortunately, there are several ways to reduce the occurrence of gallstones, including lifestyle changes with exercise and diet, such as coffee, more fiber, statins and unsaturated non-trans fats (3).

physical activity

In last week’s article on risk factors for gallstones, low physical activity increased the risk of this disease. It turns out that the opposite is also true. In the Physicians’ Health Study, results showed a significant reduction in the risk of gallstones in those in the highest quintile of activity compared to those in the lowest quintile (4). In fact, men who were in the highest quintile and under 64 years old saw the greatest reduction — 42 percent — in the risk of gallstones. However, those over the age of 65 and in the highest quintile of activity also had substantial reductions in risk — 25 percent. There were 45,813 men involved in this study over an eight-year duration. The authors concluded that, overall, 34 percent of symptomatic gallstones could be avoided if men did aerobic training for an average of 30 minutes per day, five days a week.

Fruits and vegetables

If you ever needed another reason to consume more fruits and vegetables, reducing the risk of gallstones may motivate you.

In the Nurses’ Health Study, the results showed that those in the highest quintile of fruit and vegetable intake had a 21 percent reduction in the need for a cholecystectomy (surgery to remove the gallbladder, usually due to symptomatic gallstones) compared to those in the lowest quintile (5). Interestingly, fruits and vegetables looked at separately had the same significant reduction as fruits and vegetables taken together. There were 77,090 women involved in the study with a duration of 16 years.

The fruits and vegetables consumed in the study were common; they included citrus fruits, green leafy vegetables, cruciferous vegetables, and other vitamin C-rich fruits and vegetables. The authors surmise that the effect may be due to antioxidants, vitamin C, dietary fiber, and minerals like magnesium – and to the interactions among these different components.

This was not just a reduction in gallstones, but a reduction in the actual number of surgical procedures. This makes it a very powerful study. To give perspective, there are around 800,000 cholecystectomies done each year in the U.S. (6).

rapid weight-loss diets

I mentioned in last week’s article that rapid weight loss increases the risk of gallstone formation. However, if you were going to attempt a rapid weight-loss diet, which is better: high-fiber or high-animal-protein? Well, in a small, randomized controlled study, the gold standard of studies, results show that a high-fiber, very low-calorie diet had one-third the number of patients with gallstone formation compared to a high-protein, very low-calorie diet (7).

Although it is better not to lose weight rapidly, as far as gallstones are concerned, there may be lower risk with a high-fiber diet rather than with an animal-protein-dominant diet. It is important to note that this study considered rapid weight loss to be more than 20 pounds. in a month. Both groups lost about the same amount of weight. However, the high-fiber diet resulted in less biliary sludge. The study included 68 patients with a mean BMI of 35 kg/m2, severely obese, at the start of the trial.

Coffee effect

Coffee must be one of the more controversial beverages. Using the Swedish Mammography Cohort and the Cohort of Swedish Men studies, a meta-analysis of two studies, the results show that only women, not men, had a significantly reduced risk of undergoing cholecystectomies in those who drank at least six cups of coffee a day, versus those who drank fewer than two cups (8). And this effect was not seen in all women, but only in those women who were premenopausal or on hormone replacement therapy. A cup was considered eight ounces. Does this mean these specific women should drink more coffee? Not necessarily, for it seems as if every good result is balanced out with a bad result when it comes to coffee and gallstones.

In conclusion, it is important to prevent gallstones, since this disorder can lead to significant complications, including cardiovascular disease and death. Lifestyle modifications and even some medications may reduce the risk of gallstones, which in turn could have a beneficial impact on reducing heart disease and strokes, as well as autoimmune diseases, such as psoriasis and psoriatic arthritis. Inflammation seems to be the common denominator when it comes to gallstones, their complications and the ways to prevent them.

References

(1) PLoS One. 2013 Oct 3;8(10):e76448. (2) Br J Dermatol. online Oct 11, 2014. (3) uptodate.com. (4) Ann Intern Med. 1998;128(6):417. (5) Am J Med. 2006;119(9):760. (6) AdvData. 2002;(329):1-19. (7) Georgian Med News. 2014;(231):95-9. (8) Clin Gastroenterol Hepatol. online Sep 19, 2014.

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

A good follow-up to last week’s acute pancreatitis article is one on gallstones. As I wrote, gallstones are the most significant contributing factor to the development of acute pancreatitis. Like pancreatitis, gallstones are a very common gastrointestinal disease; they affect up to 20 million Americans between the ages 20 of and 74, with a more than two-times increased occurrence in women than in men, according to the NHANES III survey (1). There are two types of gallstones, the majority of which are cholesterol stones — 80 percent occurrence — with pigment stones — 20 percent occurrence — making up the remainder.

Common symptoms

Gallstones may be asymptomatic; however, when gallstones block either the cystic or common bile ducts, symptoms occur. Symptoms include abdominal pain, exacerbated by meals, that is dull or crampy and lasts one to five hours; jaundice, which includes yellowing of skin and eyes; nausea and vomiting; rapid heart rate; hypotension — low blood pressure — and fever (2).

Tests used for diagnosis

Blood tests include complete blood count where there may be a rise in white blood cells; liver enzymes; and pancreatic enzymes — lipase and amylase. In general, diagnostic tests that have more accuracy are the endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). However, these are invasive tests. Less accurate but non-invasive tests include abdominal x-ray, ultrasound and CAT Scan (CT). The tests used also depend on where the stone may be located. Hepatobiliary (HIDA) scans are accurate if the stone is located in the cystic duct. And magnetic resonance retrograde cholangiopancreatography (MRCP) is used if the stone is thought to be located in the common bile duct (2).

What are the risk factors?

There are a multitude of risk factors. Some of these are modifiable, whereas others are not. The modifiable ones include obesity, measured by body mass index (BMI); rapid weight loss; fat consumption; hormone replacement therapy (HRT); oral contraceptives; decreased physical activity; Crohn’s disease and certain drugs. One non-modifiable risk factor is age; the older we get, the higher the risk, with 40 years of age being the demarcation line (3). Other risk factors are gender — females are more predisposed — pregnancy; and family history (4).

Let’s look at the evidence.

Obesity

Again, as with acute pancreatitis, obesity may play an important role. Obesity is not age-discriminant; it can impact both adults and children. The reason obesity is implicated is potentially due to bile becoming supersaturated (5). Bile is a substance produced in the liver and stored in the gallbladder. Bile aids in the digestion or breakdown of fats in the small intestines. Crystals may form, creating cholesterol gallstones from the bile.

Body Mass Index

A body mass index of greater than 30 kg/m2 is considered obese. In a meta-analysis of two prospective, forward-looking observational trials — Copenhagen General Population Study and the Copenhagen City Heart Study — those in the highest quintile of BMI were almost three times as likely to experience symptomatic gallstones compared to those who were in the lowest quintile (6). The highest quintile was those who had a mean BMI of 32.5 kg/m2 and thus were obese, whereas those in the lowest quintile had a mean BMI of 20.9 kg/m2. This is a comparison of ideal to obese BMI. Not surprisingly, since women in general have a higher risk of gallstones, they also have a higher risk when their BMI is in the obese range compared to men, a 3.36-fold increase and 1.51-fold increase, respectively.

Also, the research showed that for every 1 kg/m2 increase in BMI, there was a 7 percent increase in the risk of gallstones. Those who had genetic variants that increased their likelihood of an elevated BMI had an even greater increase in gallstone risk —17 percent —  per 1 kg/m2. In the study population of approximately 77,000, more than 4,000 participants became symptomatic for gallstones.

Gallstones in children

Sadly, obese children are not immune to gallstones, even though they are young. In a prospective observational study based on Kaiser Permanente data from Southern California, children who were overweight had a twofold increased risk of gallstones (7). But if that is not enough, girls who were extremely obese had a higher propensity for gallstones, similar to women in the previous study, with a  greater than sevenfold increase compared to a still very substantial greater-than-threefold increase for obese boys. Hispanic children were affected the most. The age range in this study was between 10 and 19 years old. Obesity is a disease that is blind to age.

Physical activity

We know physical activity is very important to stave off many diseases, but in this case, the lack of physical activity can be detrimental. In the Physicians’ Health Study, a prospective observational trial, those in the lowest quintile of activity between the ages of 40 and 64 had a 72 percent increased risk of gallstone formation, and those 65 and older had a 33 percent increased risk. (8). Also, men who were 65 and older and watched television more than six hours a week were at least three times as likely to have gallstones as those who watched fewer hours. There was a substantial increased risk for those under 65, as well, though to a slightly lesser degree.

Diabetes rears its ugly head

Just like with obesity, diabetes is almost always a culprit for complications. In a prospective observational study, those with diabetes were at a significant 2.55-times greater risk of developing gallstones than those without (9). Again, women had a higher propensity than men, but both had significant increases in the risk of gallstone formation, 3.85-times and 2.03-times, respectively. There were almost 700 participants in this study. The researchers believe that an alteration in glucose — sugar — metabolism may create this disease risk.

Hormone Replacement Therapy

If you needed another reason to be leery of hormone replacement therapy (HRT), then gallstones might be it. In a prospective observational trial, women who used HRT, compared to those who did not, had a 10 percent increased risk in cholecystectomy — removal of the gallbladder — to treat gallstones (10). Though this may not sound like a large increase, oral HRT increased the risk 16 percent, and oral estrogen-only therapy without progestogens increased the risk the most — 38 percent. Transdermal HRT did not have a significantly increased risk.

It is never too early or too late to treat obesity before it causes, in this case, gallstones. With a lack of exercise, obesity is exacerbated and, not surprisingly, so is symptomatic gallstone formation. Diabetes needs to be controlled to prevent complications. HRT, unless menopausal symptoms are unbearable, continues to show why it may not be a good choice. Next week, we will look at the complications of gallstones and how to prevent them.

References:

(1) Gastroenterology. 1999;117:632. (2) emedicine.medscape.com. (3) J Hepatol. 1993;18 Suppl 1:S43. (4) uptodate.com. (5) Best Pract Res Clin Gastroenterol. 2014 Aug;28:623-635. (6) Hepatology. 2013 Dec;58:2133-41. (7) J Pediatr Gastroenterol Nutr. 2012;55:328-333. (8) Ann Intern Med. 1998;128:417. (9) Hepatology. 1997;2:787. (10) CMAJ. 2013;16;185:549-50.

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

Everyone has heard of pancreatic cancer, but pancreatitis is a significantly more common disease in gastroenterology and seems to be on an upward projection. Ironically, this disease gets almost no coverage in the general press. In the United States, it is among the top reasons for patients to be admitted to the hospital (1).

Now that I have your attention, let’s define pancreatitis. A rudimentary definition is an inflammation of the pancreas. There are both acute and chronic forms. We are going to address the acute – abrupt and of short duration – form. There are three acute types: mild, moderate and severe. Those with the mild type don’t have organ failure, whereas those with moderate acute pancreatitis experience short-term or transient (less than 48 hours) organ failure. Those with the severe type have persistent organ failure. One in five patients present with moderate or severe levels (2).

What are the symptoms?

In order to diagnosis this disease, the American College of Gastroenterology guidelines suggests that two of three symptoms be present. The three symptoms include severe abdominal pain; increased enzymes, amylase or lipase, that are at least three times greater than normal; and radiologic imaging (ultrasound, CT, MRI, abdominal and chest X-rays) that shows characteristic findings for this disease (3). Most of the time, the abdominal pain is epigastric, and it may also present with pain in the right upper quadrant of the abdomen (4). Approximately 90 percent of patients may also experience nausea and vomiting (5). In half of patients, there may also be pain that radiates to the back.

What are the risk factors?

There is a multitude of risk factors for acute pancreatitis. These include gallstones, alcohol, obesity and, to much lesser degree, drugs. Gallstones and alcohol may cause up to 75 percent of the cases (2). Many of the other cases of acute pancreatitis are considered idiopathic (of unknown causes). Although medications are potentially responsible for between 1.4 percent and 5.3 percent of cases, making it rare, the number of medications implicated is diverse (6) (7). These include certain classes of diabetes therapies, some antibiotics – Flagyl (metronidazole) and tetracycline – and immunosuppressive drugs used to treat ailments like autoimmune diseases. Even calcium may potentially increase the risk.

Obesity effects

When given a multiple-choice question for risk factors that includes obesity as one of the answers, it’s a safe bet to choose that answer. Pancreatitis is no exception. However, in a recent study, using the Swedish Mammography Cohort and the Cohort of Swedish Men, results showed that central obesity is an important risk factor, not body mass index or obesity overall (8). In other words, it is fat in the belly that is very important, since this may increase risk more than twofold for the occurrence of a first-time acute pancreatitis episode.

Those who had a waist circumference of greater than 105 cm (41 inches) experienced this significantly increased risk compared to those who had a waist circumference of 75 to 85 cm (29.5 to 33.5 inches). The association between central obesity and acute pancreatitis occurred in both gallbladder-induced and nongallbladder-induced disease. There were 68,158 patients involved in the study with a median duration of 12 years. Remember that waistline is measured not from the hips, but rather from the navel. This may be surprising wake-up call for some.

Mortality risks

What makes acute pancreatitis so noteworthy and potentially dangerous is that the rate of organ failure and mortality is surprisingly high. One study found that the risk of mortality was 5 percent overall. This statistic broke out into a smaller percentage for mild acute pancreatitis and a greater percentage for severe acute pancreatitis, 1.5 percent and 17 percent respectively (9). This was a prospective (forward-looking) observational trial involving 1,005 patients.

However, in another study, when patients were hospitalized for this disease, the mortality rate was even higher at 10 percent overall (10).

Diabetes risks

The pancreas is a critical organ for balancing glucose (sugar) in the body. In a recent meta-analysis (involving 24 observational trials), the results showed that more than one-third of patients diagnosed with acute pancreatitis went on to develop pre-diabetes or diabetes (11). Within the first year, 15 percent of patients were newly diagnosed with diabetes. After five years, it was even worse; the risk of diabetes increased by 2.7-fold. This is scary, considering that diabetes has become a pandemic. If we can reduce the risk of pancreatitis, we may also help to reduce the risk of diabetes.

Surgical treatments

Gallstones and gallbladder sludge are major risk factors, accounting for 35 to 40 percent of acute pancreatitis incidence (12). Gallstones are thought to cause pancreatitis by temporarily blocking the duct shared by the pancreas and gallbladder that leads into the small intestine. When the liver enzyme ALT is elevated threefold (measured through a simple blood test), it has a positive predictive value of 95 percent that it is indeed gallstone-induced pancreatitis (13).

If it is gallstone-induced, surgery plays an important role in helping to resolve pancreatitis and prevent recurrence of acute pancreatitis. In a recent study, results showed that surgery to remove the gallbladder was better than medical treatment when comparing hospitalized patients with this disease (14). Surgery trumped medical treatment in terms of outcomes, complication rates, length of stay in the hospital and overall cost for patients with mild acute pancreatitis. This was a retrospective (backward-looking) study with 102 patients.

Can diet have an impact?

The short answer is: yes. What foods specifically? In a large, prospective observational study, results showed that there was a direct linear relationship between those who consumed vegetables and a decreased risk of nongallstone acute pancreatitis (15). For every two serving of vegetables, there was 17 percent drop in the risk of pancreatitis. Those who consumed the most vegetables – the highest quintile (4.6 servings per day) – had a 44 percent reduction in disease risk, compared to those who were in the lowest quintile (0.8 servings per day). There were 80,000 participants involved in the study with an 11-year follow-up. The authors surmise that the reason for this effect with vegetables may have to do with their antioxidant properties, since acute pancreatitis increases oxidative stress on the pancreas.

References:

(1) Gastroenterology. 2012;143:1179-1187. (2) www.uptodate.com. (3) Am J Gastroenterol. 2013;108:1400-1415. (4) JAMA. 2004;291:2865-2868. (5) Am J Gastroenterol. 2006;101:2379-2400. (6) Gut. 1995;37:565-567. (7) Dig Dis Sci. 2010;55:2977-2981. (8) Am J Gastroenterol. 2013;108:133-139. (9) Dig Liver Dis. 2004;36:205-211. (10) Dig Dis Sci. 1985;30:573-574. (11) Gut. 2014;63:818-831. (12) Gastroenterology. 2007;132:2022-2044. (13) Am J Gastroenterol. 1994;89:1863-1866. (14) Am J Surg online. 2014 Sept. 20. (15) Gut. 2013;62:1187-1192.

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

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 breast cancer incidence in the U.S. is 230,000 cases, with approximately 40,000 patients, or 17 percent, 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 or 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 a recent 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, 5 to 9 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 its “Play 60” campaign.

Soy intake

Contrary to popular belief, soy may be beneficial in reducing breast cancer risk. In a recent 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 versus Mediterranean diets

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 self-breast 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) CA Cancer J Clin. 2013;63:11-30. (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 and/or consult your personal physician.