Monthly Archives: February 2012

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Studying both brain and bone cells to defeat two mountains: Alzheimer’s, osteoporosis

Lisa Miller lives a life of extremes. At work, she looks inside brain and bone cells through some of the highest-tech equipment in the country, checking the chemistry of diseases like Alzheimer’s and osteoporosis. In her free time, the Brookhaven National Laboratory’s Associate Division Director climbs mountains, looking out at the world from the planet’s highest peaks.

Using mid-infrared light, Miller, who is in BNL’s Photon Sciences Directorate, has shown that some areas of the brains of people afflicted with Alzheimer’s disease have high amounts of metals like copper and zinc.

“Metals in our body are tightly regulated and are bound to proteins,” Miller explained. On their own, the metals could be “toxic and can kill cells.”

The brains of people who suffer from Alzheimer’s have amyloid plaques, where brain cells are folded over and clumped together. These plaques have high amounts of these metals.
Using the National Synchrotron Light Source (one of only four such Department of Energy funded tools in the country), Miller wanted to examine how the metals might build up in the brains of those with Alzheimer’s.

Because the concentration of iron in the amyloid plaques is ten times higher than normal, the presence of this metal could be an important diagnostic tool.

MRIs and other tools in doctors’ offices can measure the concentration of iron in a person’s brain.

“It’s possible to image patients who don’t have symptoms yet for high iron content,” Miller offered. Miller cautioned that it’s unclear whether there is a direct connection between the presence of these metals and the onset or course of Alzheimer’s disease.

Indeed, the BNL faculty plans to examine the link between copper in the plaques with disease severity. If the presence of metal is an important part of the progression of the disease, it shouldn’t show up in people who have amyloid plaques but don’t have symptoms. Miller is helping to hire scientists and engineers at BNL to build the next generation light source that uses x-ray, ultraviolet and infrared light. The NSLS-ii, which will be complete in March of 2014, will produce x-rays that are more than 10,000 times brighter than the ones from the current NSLS.

“She’s taken an active role in managing the facility,” said Antonio Lanzirotti, a senior research associate at the University of Chicago who collaborated with Miller on her Alzheimer’s studies. “She’s incredibly impressive in terms of her breadth of knowledge. People respect her opinion at the highest level of management.”

In addition to Alzheimer’s, Miller has also used the NSLS to study osteoporosis.
Partnering with biomedical engineer Stefan Judex at Stony Brook University, Miller and her lab have looked at how osteoporosis drugs affect the chemistry and strength of bones.
Fosamax and Actonel “work really well, not only in slowing down the resorption of bone,” she said, but also in helping the body produce “good, quality bone.”

When she’s not studying the chemistry of bones, brains and other tissues, Miller is an enthusiastic backpacker. She has climbed to highest point in 48 of the 50 U.S. states. Last year, she trekked to the top of Mt. Kilimanjaro.

A native of Cleveland, Miller took her first hike when her father “dragged us to the top of Mount St. Helens” when she was in graduate school at the Albert Einstein College of Medicine. Once she got the climbing bug, she couldn’t stop.

Miller believes in helping the next generation of researchers reach its own scientific peaks.
She helped start a new BNL program called Introducing Synchrotrons into the Classroom (called InSynC) that allows high school students to design research studies that use BNL’s synchrotron.

The projects, which go through a competitive review process, give students and teachers a chance to test their ideas using the NSLS. Miller credits her advisors with guiding her career and wants to pass that long.

“I always had good mentors,” she recalls. “If you’re excited about something, you want others to be as well.”

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The numbers of patients on proton pump inhibitors has grown precipitously

Last week I wrote that proton pump inhibitors and H2 blockers are two mainstays of medical treatment for gastroesophageal reflux disease. Since GERD affects so many people, these are two of the most widely prescribed classes of medications. Here, I will focus on PPIs, for which more than 113 million prescriptions are written every year in the U.S. (JW Gen Med. Jun. 8, 2011).

PPIs include Nexium (esomeprazole), Prilosec (omeprazole), Protonix (pantoprazole) and Prevacid (lansoprazole) Many come in two forms — over-the-counter and prescription strength. PPIs have demonstrated efficacy for short-term use in the treatment of H. pylori-induced (bacteria overgrowth in the gut) peptic ulcers, GERD symptoms and complication prevention, and gastric ulcer prophylaxis associated with NSAID use (aspirin, ibuprofen, etc.) as well as upper gastrointestinal bleeds.

However, they are often used long-term as maintenance therapy for GERD. PPIs used to be considered to have mild side effects. Unfortunately, recent evidence is showing that this may not be true. Most of the data in the package inserts is based on short-term studies lasting weeks, not years. The landmark study supporting long-term use approval was only one year, not ten years. Maintenance therapy usually continues over multiple years.

The side effects that have occurred after years of use are increased risk of bone fractures and calcium malabsorption; Clostridium difficile, a bacterial infection in the intestines; potential B12 deficiencies and weight gain (World J Gastroenterol. 2009;15(38):4794–4798).

Fracture risks

There has been a debate about whether PPIs contribute to fracture risk. The Nurses’ Health Study, a prospective (forward-looking) study involving approximately 80,000 postmenopausal women, showed a 40 percent overall increased risk of hip fracture in long-term users (more than two years duration) compared to nonusers (BMJ 2012;344:e372). Risk was especially high in women who also smoked or had a history of smoking, with a 50 percent increased risk. Those who never smoked did not experience significant increased fracture risk. The reason for the increased risk may be due partially to malabsorption of calcium, since stomach acid is needed to effectively metabolize calcium.

In the Women’s Health Initiative, a prospective study that followed 130,000 postmenopausal women between the ages of 50 and 79, hip fracture risk did not increase among PPI users, but the risks for wrist, forearm and spine were significantly increased (Arch Intern Med. 2010;170(9):765-771). The study duration was approximately eight years.

Bacterial infection
The FDA warned that patients who use PPIs may be at increased risk of a bacterial infection called C. difficile. This is a serious infection that occurs in the intestines and requires treatment with antibiotics. Unfortunately, it only responds to a few antibiotics and that number is dwindling.

In the FDA’s meta-analysis, 23 of 28 studies showed increased risk of infection. Patients need to contact their physicians if they develop diarrhea when taking PPIs and the diarrhea doesn’t improve (www.FDA.gov/safety/medwatch/safetyinformation). In one study, there was a 96 percent increased risk of C. difficile with PPIs, compared to a 40 percent increased risk with H2 blockers (Am J Gastroenterol. 2007;102(9):2047-2056).

B12 deficiencies

Suppressing hydrochloric acid produced in the stomach may result in malabsorption issues if turned off for long periods of time. In a study where PPIs were associated with B12 malabsorption, it usually took at least three years duration to cause this effect. B12 was not absorbed properly from food, but the PPIs did not affect B12 levels from supplementation (Linus Pauling Institute; lpi.oregonstate.edu). Therefore, if you are taking a PPI chronically, it is worth getting your B12 and methylmalonic acid (a metabolite of B12) levels checked and discussing possible supplementation with your physician if you have a deficiency (Aliment Pharmacol Ther. 2000;14(6):651-668).

Package insert of the PPIs

Interestingly, the package inserts of PPIs recommend the lowest dose possible for maintenance therapy. While prescription PPIs warn that fractures of the wrist, back and hip may occur, suggesting that it may be appropriate to use vitamin D and calcium supplementation to reduce fracture risk, OTC PPIs are not required to include the fracture risk warning.

The problem with PPIs is that patients taking the medications for more than a year are mostly unwitting participants in long-term, anecdotal, postmarketing study on efficacy and tolerability.

My recommendations would be to use PPIs for the short term, except with careful monitoring by your physician.  If you choose medications for GERD management, H2 blockers might be a better choice, since they only partially block acid. Lifestyle modifications may also be appropriate in some of the disorders, with or without PPIs. Consult your physician before stopping PPIs since there may be rebound hyperacidity (high acid produced) if they are stopped abruptly.

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.

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Some people like slamming things together, whether it’s a young child sitting on a floor crashing two matchbox cars into each other or an adult behind the wheel of a bumper car at a fairground.

Gene Van Buren gets to do the same thing, although he’s not using cars. He’s propelling a gold nucleus along a 2.4-mile track at speeds approaching that of light and slamming it into another gold nucleus.

The effects of the collision are more spectacular, albeit on a miniature scale, than watching the bumper pop off a matchbox car. The temperatures in these crashes climb to 4 trillion degrees Celsius. That’s 250,000 times hotter than the temperature in the center of the sun.

“The day when we get to see what [such a collision] looks like on a computer screen, we are all like a bunch of kids,” said Van Buren, an experimental nuclear physicist at Brookhaven National Lab. “It’s so cool. It’s what we’ve been working for for the past decade to do. We remember how exciting this is.”

Besides doing it because they can, nuclear physicists like Van Buren who work at the Relativistic Heavy Ion Collider (RHIC) study the results of those nuclear mash ups to gain a better understanding of the way nature works at very small scales.

When they’ve jammed these tiny particles together, they’ve been able to examine the way smaller ones, like quarks and gluons, interact. Quarks are the building blocks for protons (matter with a positive charge) and neutrons (those with a neutral charge). Gluons, which don’t have mass, serve as the “glue” that holds quarks together.

“From a theoretical calculation, we expected that once you got these gluons and quarks really hot, they wouldn’t want to interact with each other,” he said. Their collisions, however, showed the opposite, that these subatomic particles “still want to stick to each other.”

What that means is that the parts of the nucleus of an atom behave much more like a liquid than a gas. In a gas like air, Van Buren explained, molecules tend to flow freely away from each other. Liquids like water, on the other hand, tend to bind together. That is why water forms droplets when it is spilled.

“For us, this is very exciting because it has implications for the nature” of how these particles behave, “under normal, everyday conditions that we don’t necessarily observe from our perspective of everyday life,” Van Buren said.

At the same time, these experiments may simulate the kinds of conditions that existed during the beginning of the universe, at least according to the big bang theory. At RHIC, colliding these nuclei at such high speeds is similar to making a “little bang.”

The biggest difference, however, is that RHIC doesn’t collide matter with as much “stuff.”
“In the big bang, the universe started out dense and hot with a lot of material and energy. In our case, we have two out of those three” conditions, Van Buren said. “We have the density and heat.”

Still, by examining high temperatures and density, the scientists at RHIC may be able to see “how the universe evolved during that particular epoch.”

Van Buren said down the road, maybe decades of even a hundred years from now, other scientists can use the knowledge he and others are generating at RHIC to engineer new products.

“It was like that with electricity,” he said. “The first people studying it had no idea how this would affect their everyday life. Over 100 years later, look what electricity does. We can learn to engineer things with the knowledge we gain about the universe.”
Physicists like Van Buren are inspired by the first dozen years that RHIC has been operating (its first experiment was in the summer of 2000).

The scientists “have the pioneering spirit of climbing to the top of Mount Everest,” offered Jim Thomas, a visiting physicist from Lawrence Berkeley Lab in California who has worked closely with Van Buren for several years.

In addition to designing collision experiments, Van Buren has helped create computer programs that analyze the results of the collisions.

Van Buren “understands a lot about computers and a ton about physics,” said Thomas. “He’s able to make the physics/ computer connection very nicely.”

If Van Buren ever needs to consult with a computer-programming expert, he doesn’t have to look far. His wife Marie Van Buren, whom he met when he was at graduate school at the Massachusetts Institute of Technology, is a computer programmer at BNL.

The couple met when they joined a volleyball league at MIT. Marie, who is around 5 feet tall, sometimes sets up her 5-foot-10-inch nuclear physicist husband to spike the ball when they are on the same team.

Sports have always been an important part of Van Buren’s life, whether it was soccer in high school, track and racquetball in college or volleyball and, in summer, ultimate frisbee.
Residents of Middle Island, the Van Burens have lived on Long Island since 1998, when Gene did his post-doctoral work for UCLA at Brookhaven National Lab.

As for his research, Van Buren said his primary goal is “pure research,” in which the end result is knowledge, not a product. The basic knowledge of nuclear physics may one day pave “the way for new developments that perhaps no one today can dream.”

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Research shows eating prior to bed increases risk by 700 percent

It seems like almost everyone is diagnosed with gastroesophageal reflux disease, or at least it did in the last few weeks in my practice. I exaggerate, of course, but the pharmaceutical companies do an excellent job of making it appear that way with advertising. Wherever you look there is an advertisement for the treatment of heartburn or indigestion, both of which are related to reflux disease.

GERD affects as much as 40 percent of the U.S. population (Gut 2005;54(5):710; Gut 2011 Dec 21). Its incidence is on the rise, with an increase of nearly one-third over the last decade (Gut 2011 Dec 21).

Reflux disease typically results in symptoms of heartburn and regurgitation brought on by stomach contents going backward up the esophagus, according to the definition by PubMed Health. For one reason or another, the lower esophageal sphincter, the valve between the stomach and esophagus, inappropriately relaxes. No one is quite sure why it happens with some people and not others. Of course there is a portion of reflux that is physiologic (normal functioning), especially postprandial, that is, after a meal (Gastroenterol Clin North Am. 1996;25(1):75).

The risk factors for GERD are diverse. They range from lifestyle, as in obesity, smoking cigarettes and diet; to medications, such as calcium channel blockers and antihistamines; to other medical conditions, like hiatal hernia and pregnancy (emedicinehealth.com). Diet issues include triggers like spicy foods, peppermint, fried foods, chocolate, etc.

Smoking and salt’s role

A recent study showed that both smoking and salt consumption added to the risk of GERD significantly (Gut 2004 Dec; 53:1730-5). The risk increased 70 percent in people who smoked. Surprisingly, people who used table salt regularly saw the same increased risk as seen with smokers.

Treatments vary, from lifestyle modifications for the “mild” to medications or surgery for the severe, noticeable esophagitis. The goal is to relieve symptoms and prevent complications, such as Barrett’s esophagus, which could lead to esophageal adenocarcinoma. Fortunately, Barrett’s esophagus is not common and adenocarcinoma is even rarer.

Medications

The most common and effective medications for the treatment of GERD are H2 receptor blockers (e.g., Zantac and Tagamet), which partially block acid production; and proton pump inhibitors (e.g., Nexium and Prevacid), which almost completely block acid production (Gastroenterology. 2008;135(4):1392). Both classes of medicines have two levels: over the counter and prescription strength. You need to tell your doctor if you have taken these medications, even those that are OTC. There are potential side effects with these drugs, especially proton pump inhibitors.

Lifestyle modifications

There are a number of modifications that can improve the situation, such as raising the head of the bed about 6 inches, not eating prior to bedtime and obesity treatment, to name a few (Arch Intern Med. 2006;166:965-971).

In the same study already mentioned with smoking and salt, both fiber and exercise had the opposite effect, that is reducing the risk of GERD (Gut 2004 Dec; 53:1730-5; Gut 2005;54:11-17). This was a prospective (forward looking) trial. The analysis by Journal Watch suggests that the fiber effect may be due to its ability to reduce nitric oxide production, a relaxant for the lower esophageal sphincter (JWatch Gastro. Feb. 16, 2005).

Obesity
In one study, obesity exacerbated GERD. What was interesting about the study is that researchers used manometry, which measures pressure, to show that obesity increases the pressure on the lower esophageal sphincter significantly (Gastroenterology 2006 Mar; 130:639-49). Intragastric (within the stomach) pressures were higher in both overweight and obese patients on inspiration and on expiration, compared to those with normal BMI. This is yet another reason to lose weight.

Eating prior to bed, myth or reality?

We have all heard that it’s better to avoid eating late. But is this a myth?
Though it may be simple, it is one of the most powerful modifications we can make to avoid GERD. There was a study that showed a 700 percent increased risk of GERD for those who ate within three hours of bedtime, compared to those who ate four hours or more prior to bedtime.

Of note, this is 10 times the increased risk of the smoking effect (Am J Gastroenterol. 2005 Dec;100(12):2633-6). Therefore, it is best to not eat right before bed and to avoid “midnight snacks.”

Although, there are number of ways to treat GERD, the most comprehensive have to do with modifiable risk factors. Drugs have their place in the arsenal of choices, but lifestyle changes are the first and most effective approach in many instances.

Next week, I will discuss the pros and cons of proton pump inhibitors, as more and more studies are published on the role of these drugs.

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 www.medicalcompassmd.com and/or consult your personal physician.

 

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When their son Dylan was under a year old, Debbie and Ron Cuevas noticed he couldn’t support his head and had trouble rolling over. They brought him to a pediatrician, who diagnosed Dylan with spinal muscular atrophy.

The doctor said he likely had two years to live. Determined to make every day count, the Cuevas family of Rockville Centre has rallied around their son, who is now 8 and in third grade.

A genetic disease with varying severity that weakens muscles in the central nervous system, spinal muscular atrophy (or SMA) has no current cure. Some with the disease die because they can’t breathe or swallow. SMA is the leading genetic cause of death among infants and affects about 1 in 6,000 newborns.

Researchers, including Dr. Adrian Krainer at Cold Spring Harbor Laboratory, however, have been working to find a treatment. Krainer has unlocked a potential solution. His work with antisense oligonucleotides (or ASOs) has been impressive enough in the lab and on mice that California-based Isis Pharmaceuticals started using his treatment in the first phase of clinical trials in December. It’s too early to determine the effectiveness of this approach.

SMA is a genetic disorder and is caused by a defective SMN1 gene, which is on the fifth chromosome. That gene produces the survival of motor neuron protein. Without enough of that protein, the motor neurons in the spinal chord gradually die and the muscles they control cease to function.

The solution to this recessive genetic disease may be in the genes themselves. There is a backup gene, called SMN2, that produces the same protein. The problem in children with the disease is that the backup often doesn’t produce enough protein or the protein isn’t complete or breaks apart.

Krainer’s lab has aimed one of its efforts at improving the function of SMN2. The problem with SMN2 is in something called splicing, a process where important pieces of genetic information (exons) are linked together while white noise (introns) is spliced or cut away. The exons are like the proverbial wheat and the introns are the chaff.

As DNA and its cousin RNA go from the genetic blueprint stage to the protein-building stage, there are signposts along the way that indicate whether the next set of genetic instructions is an exon or an intron. A repressor sits on SMN2 at exon 7 that mistakenly sends the cell’s RNA machinery away. The repressor acts like a “Do Not Enter” sign, making it hard for the cell’s machinery to recognize an exon.

Krainer’s lab has created a synthetic molecule called antisense oligonucleotide that replaces that “Do Not Enter” sign and encourages the gene splicing tools to include the information from exon 7 when it builds the survival of motor neuron protein.

In the lab, ASO has done its job, making SMN2 act like its much more effective SMN1 cousin. When Krainer injected ASO into mice with severe SMA, he found that they not only lived longer, but they also were able to grow and develop the same way as mice without the genetic defect.

Krainer’s lab is “changing how the splicing machinery” works, he offered. “We took the repressor out of the picture.”

Krainer has been working on SMA for over a decade. The Uruguay-native who has been at Cold Spring Harbor Lab since 1986 is on the advisory board for two SMA foundations.

He said he quickly moved from understanding SMA as an abstract cell mechanism problem to the urgent need to “do something about it. When [a disease] affects children and very young infants in particular, it is something even more touching.”
Residents of Huntington Station, Krainer and his family have made the Cold Spring Harbor Lab a family affair over the years.

Krainer’s wife Denise Roberts (who met Adrian when they were Ph.D. students at Harvard in the 1980s) is the deputy administrative director of the cancer center at Cold Spring Harbor.
All three of their children — Emily, 22, Andrew, 19 and Brian, 18 — have pitched in at different labs over the years. After she graduates from Brandeis this year, Emily plans to attend medical school and has shown an interest in pediatric neurology. Some day, if her father’s treatment proves effective, Emily may be able to do more for children like Dylan Cuevas than doctors have been able to do up until now.

“I definitely hope [Krainer’s treatment] leads to an improvement,” said Debbie Cuevas, who runs the Families of SMA Greater New York Chapter. “I’m happy to see that it’s going into clinical trials.”

A full-time mom to Dylan and Heather, 5, Debbie Cuevas gave up her job at AIG to take care of her children. Cuevas and her husband, Ron, who works for Chips Technology Group in Syosset, have been through some harrowing times. Dylan has had respiratory failure several times and breathes with the assistance of a respirator.

Still, Cuevas remains positive. “Every day we’re on this Earth is a gift,” she said.

Even if Krainer’s research doesn’t provide the single, definitive solution to SMA, Cuevas believes his research, and that of others, can move science and medicine in the right direction.

Some day, for all the families who pray for a cure, she hopes “someone won’t have to utter the words SMA as a diagnosis.”

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Reducing the risk is 90 percent of the battle in dealing with this debilitating condition

In last week’s article, I talked about treatment of the acute (sudden or rapid onset) migraine. Treatment, however, is only one part of the puzzle. The other is 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 (Headache. 2006;46 Suppl 4:S202).

Beyond treating the acute migraine episode, what should a patient do? 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 antiseizure medications, botulinum toxin (botox) and antidepressants (uptodate.com).

Blood pressure control itself reduces the occurrence of headaches (Circulation. 2005;112(15):2301). 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 (Cochrane Database Syst Rev. 2004). However, it showed only short-term effects. Also, there were a substantial number of dropouts from the studies.

Topiramate, an antiseizure medication, showed a significant effect compared to placebo in reducing migraine frequency (JAMA. 2004;291(8):965-973). In a randomized control trial 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. Due to a 30 percent withdrawal rate at the 200 mg dose due to side effects, the highest recommended dose is 100 mg (CMAJ. 2010;182(7):E269).

Botulinum toxin type A injection has not been shown to be beneficial for preventive treatment of episodic migraines, but has recently 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 effects (Prescrire Int. 2011 Dec;20(122):287-90).

Alternative approaches

Butterbur, a herb from the Butterbur (Petasites hybridus) root, was beneficial in a four-month RCT for the prevention of migraine (Neurology. 2004;63(12):2240). 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, which I mentioned previously for migraine treatment, had mixed prophylaxis results. In a meta-analysis, the authors concluded that feverfew was not more beneficial than placebo (Cochrane Database Syst Rev. 2004)

The caveat with herbal medications is that their safety is not regulated by the FDA.

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 (Neurology. 1998 Feb;50(2):466-70). 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.

Dietary approach

From my experience and those of my esteemed colleagues, such as Joel Fuhrman, M.D., and Neal Bernard, M.D., 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 (J Women’s Health Gend Based Med. 1999;8(5): 623-630). Higher fat diets and high levels of animal protein have been associated with more migraines. Obesity may also increase the frequency and severity of migraines (Obes Rev. 2011 May;12(5):e362-71).

Thus, there are several options for preventing migraines. The most well studied are medications, however, the most effective may be dietary changes, which don’t precipitate the rebound migraines that medication overuse may cause.

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.

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Migraine triggers have a lot in common with a minefield — hard to avoid

Migraines are a debilitating disorder. Symptoms typically include nausea, photophobia and phonophobia — sensitivity to light and 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 among the top reasons patients see a neurologist (uptodate.com September 2011).

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 (Headache. 2001;41(7):646), and the most common age range for migraine attacks is 30 to 50 (Medscape.com), 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 (Annals of Neurology 2009;65(5):491).”

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, diet, exercise, weather, odor, etc. (Cephalalgia. 2007;27(5):394).

What is done to treat migraine sufferers?

For those who want to avoid traditional medicines, a feverfew-ginger combination pill — an oil-based herbal supplement — as a first-line treatment showed promising results for those suffering from mild migraine prior to the onset of moderate to severe migraine(Headache 2011;51:1078-1086). A sublingual preparation was the most beneficial. In this small, double-blind, placebo-controlled (well-designed) study, patients were aged 13 to 60 and suffered migraines from two to six times a month.

Sixty-four percent of patients in the treatment group rated the symptoms as mild to no pain, compared to 39 percent of those in the placebo group. The side-effect profile of the herbal remedy was similar to placebo. The challenge is, if it doesn’t work, you may have lost your window to take traditional medications. There is a caution: Women who are pregnant should not take feverfew.

Mild treatments for migraines include aspirin, Tylenol (acetaminophen) and NSAIDs, such as ibuprofen. In a randomized controlled trial, 1000 mg of acetaminophen reduced intensity of symptoms in episodic (occasional) and moderate migraine sufferers significantly more than placebo at the two-hour and six-hour marks (Headache. 2010;50(5):819-833). It also reduced the nausea, sensitivity to light and sound, and the functional disability. However, if you have more intense migraines this may not be effective.

In a Cochrane Database review (a meta-analysis of RCTs), ibuprofen 400 mg provided at least partial relief to migraine patients, though complete relief to relatively few (Cochrane Database Syst Rev. Oct. 6, 2010). There was statistical significance compared to placebo.
One of the most powerful and common treatments is the use of triptans which include Imitrex (sumatriptan), Zomig (zolmitriptan) and Relpax (eletriptan). These drugs are 5HT-1 receptor agonists. They stimulate a metabolite of serotonin to vasoconstrict (narrow) the blood vessels. These are more specific than NSAIDs and acetaminophen. Sumatriptan, which is generic, was more effective in a 6 mg subcutaneous (under the skin) injection than as a 100 mg oral formulation in an RCT (Cephalalgia. 1998;18(8):532).

In another study, sumatriptan in combination with naproxen sodium (an NSAID) was more effective than either drug alone in treating acute migraine attacks at the two-hour and 24-hour marks, according to two randomized clinical trials (JAMA. 2007;297(13):1443). These studies involved approximately 3,000 patients. While these results are inspiring, they are far from completely effective. In other words, the sumatriptan-naproxen sodium at its best showed a complete reduction in nausea in 71 percent of patients, but only 25 percent of patients were pain free overall with this combination.

Be cautious of drug overuse, which can cause rebound headaches, and thus increase the frequency of migraine (CNS Drugs. 2005; 19(6):483-497).

What happens to patients who don’t respond to therapy?

I recently encountered a patient who did not respond to therapy and it was difficult for both the patient and physician during the acute attack. Thus, the most effective treatment of migraine is prevention, but how do you prevent a migraine? Stay tuned to next week’s article on prevention of migraines.

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.

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