Antibiotic Use and Your Risk for Diabetes

For years, epidemiologists have been warning about the overuse of antibiotics. The greatest danger is that bacteria and viruses can (and do) develop resistance to the drugs. For instance, there are drug-resistant strains of TB, staph, malaria, HIV, and gonorrhea.

Certain classes of antibiotics have their own problems. As an example, the fluoroquinolones (Cipro, Levaquin, and their cousins) can weaken tendons. I know several people who have torn an Achilles tendon during or shortly after a course of one of these drugs. And Levaquin makes my knees hurt so badly I can barely get out of a chair. (And what’s with all the football players who are out for this season with tendon damage? Achilles, ACL, MCL, it seems like any tendon in the lower body is a target. Knowing how cavalierly trainers treat other drugs, I wouldn’t be surprised to hear about tubs of antibiotics in the trainer’s room.) Now there’s evidence that connects antibiotic use with diabetes.

Want a Danish With That Antibiotic?

Denmark has a nationalized medical care system, so it’s possible to gather very complete records on populations. A recent review looked at the records of every person in Denmark who had been diagnosed with type 2 diabetes during the period 2000–2012. They then case-matched each of these records with another person who did not have diabetes. When the results of the 2 groups were compared, it turned out that any antibiotic use within the previous 15 years raised the risk of developing diabetes by about 30%. The risk was higher the more recent the use had been, and rose with the number of prescriptions for antibiotics.

We don’t know what the cause is here. It’s possible that as diabetes is developing you’re more susceptible to infections, or that somehow antibiotics interfere with blood sugar metabolism. The only theory the researchers could reject was that gut bacteria are somehow involved. They came to that conclusion because all types of antibiotics created the effect. Different types of drugs affect gut bacteria differently, so if that were the source of the problem you would expect there to have been more of a difference between drug classes. At any rate, the connection is there.

Antibiotics in Your Life

You can control your antibiotic intake. Obviously if you have pneumonia an antibiotic could save your life. But people go to their doc asking for an antibiotic for almost any upset, and it’s been this way for many years. Antibiotics don’t help colds or flu, so don’t you be that person. And be careful about the meat you eat. Conventionally raised meat of all types has had antibiotics used in the process to support the animal’s growth.

You may not be able to eliminate the use of all antibiotics, but if you do need a course or if you’ve been on a regimen in the past keep in mind your increased risk of diabetes. Pay more attention to your food intake and activity level. Do the things we should all be doing already to maintain good health.

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The Drug of a Lifetime

After yesterday’s post about the overuse of statin drugs in the elderly, this morning I came across the results of a recent study investigating medications for high blood pressure.

Stop, I Say!

Actually, the study looked at patients who stop taking meds for high blood pressure. Several recent studies have noted that higher blood pressure in the elderly is associated with better brain function, so the investigators wondered whether taking patients off their medication would help those who had some degree of cognitive impairment.

After 16 weeks, those patients who had stopped their medication didn’t do any better on cognitive tests than those who continued on the drugs. There was also no difference in other aspects of mental function, such as mood, memory, and quality of life. The researchers were somewhat surprised, and guessed that they hadn’t tracked the two groups for long enough to notice a difference.

The premise is that brain function depends on adequate blood flow, so maintaining a higher volume and pressure of blood through the brain might improve things, or at least keep function from deteriorating. But other trials had shown that lowering blood pressure in the elderly didn’t change brain function either, so it’s possible that BP doesn’t affect the brain in either direction. The flip side of this is that stopping medication for high blood pressure won’t cause harm to the brain, either.

We’re All Lab Rats Now

As it happens, I’m especially interested in meds for blood pressure, because I have a family history of the condition—in both parents and my younger sister—and it’s the only medical condition I have. My doctor prescribed a relatively benign medication for me, a beta blocker. Still, I’m not happy about the idea of a lifetime of morning pills. For one thing, it’s a pain. And for another, our generation is part of a giant on-going experiment—and we’re the lab rats.

Drug trials are considered long-term if they go beyond 6 months or so, and new drug approvals are based on the risk/benefit ratio that appears in that short time. (See my recent post about Addyi/flibanserin, for example.) That’s simply not enough time to get the full assessment of truly long-term risks and benefits.

Since 1995, 26 drugs have been withdrawn* from the US market after having been approved by the FDA. Some of these had been around for more than 20 years; it took that long for reports and observational studies to pick up the pattern of adverse effect from these drugs. And granted that this is an outlier, but one drug, DES, is currently under review for adverse effects in the grandchildren of women who took it in the ‘50s and ’60s to prevent complications in pregnancy.

One review of the study above said that it represented a “paradigm shift” in the way we conduct trials on lifetime medications. Hooray for that.

* “Market withdrawal” means that the FDA pushed the maker to stop manufacturing and distributing the drug in the US permanently, mostly for reasons of safety. A “recall” occurs when the FDA requires a maker to pull something from the market. This is usually over a temporary issue, such as a manufacturing glitch or labeling problems. Recalls most often apply to specific lots or batches of a drug, and seldom affect its long-term future.

Statin Use in the Elderly

Statin drugs, prescribed to lower cholesterol levels, are among the most widely prescribed drugs. Ads for the various brands used to be inescapable, but now that most of them have come off patent protection Crestor is the only one you’ll still see promotions for.

There’s no doubt that statin drugs do what they are intended to do: lower blood levels of cholesterol. The question ever since the first of these drugs was introduced, though (Mevacor/lovastatin in 1987) has been, “So what?” That is, what’s the benefit to the patient? The claim was that, because high cholesterol was associated with heart disease and heart attacks, lowering a person’s cholesterol level ought to reduce their risk of heart trouble. Except that, well, it didn’t work out that way. Patients on cholesterol-lowering medications tend to have roughly the same risk of heart disease as patients not taking the drug.

Overuse of Statins Is a Chronic Problem

Given that statins in general don’t seem to have much of an effect on their main endpoint (reduction of heart disease), there’s been lots of concern about their overuse. There’s extra concern about use of the drugs in populations that typically haven’t been included in clinical trials, namely the very young and the very old.

Now the use of drugs to lower cholesterol in children is shocking in itself, and a topic for another time. But a report published this week in the online version of JAMA Internal Medicine says that statin use among the very elderly—those age 80 and above—has increased significantly between 1999 and 2012, rising from 8.8% in 1999–2000 to 34.1% in 2011–12. As I said, there’s been little research into the benefits and—especially—the risks of statin use in this age group. (By the way, both my parents turned 81 this year. They finally consider themselves elderly. I’m not so sure about very elderly.)

For those of you in this age group, or who are caring for someone who is, it may be time to ask the doctor if this drug is necessary. As we age our bodies process drugs differently. In addition, we begin to lose our ability to cope with stresses, such as the effects of drugs. And data from the CDC shows that more than a third of all people over age 60 are taking 5 or more prescription drugs. That’s quite a load on a body.

If I had to guess, I’d say that the increase in use among this age group has more to do with inertia than anything else. They were given a script for a statin 20 years ago, and they’re still on it because nobody has said, “That’s enough.”

Treatments for Allergies That, Well, Don’t Work So Well

Yesterday I told you about some non-drug therapies that work well for some people in reliving seasonal allergies (and year-round ones, too). Here are two that have plenty of word-of-mouth support, but not much in the way of research to back them up.

Honey

Honey seems like the perfect solution for seasonal allergies. After all, the standard “cure” for allergies is regular injections of tiny amounts of known triggers, a process known as desensitization. And for many people who have seasonal allergies, the biggest culprit is pollen. What’s in honey? Pollen, of course.

Unfortunately, clinical trials using raw local honey have not found any benefit for common allergy symptoms. In one trial, 12 people received one teaspoon of local, unfiltered, unpasteurized honey a day. Another 12 received grocery store honey, and another 12 honey-flavored sugar syrup. There was no difference in symptoms among the groups after several months of daily use.

One study from 2011 showed that birch pollen honey was effective in reducing symptoms in people who were allergic to birch pollen. It’s important to note though, that this was regular honey that had birch pollen added to it by the researchers, not straight-from-the-hive honey. The people in the study who used regular local honey didn’t see any benefit.

So why doesn’t honey measure up? Pollens that trigger allergic symptoms tend to have small grains that are easily blown around. The pollen in honey is generally from plants with larger pollen grains that are more easily collected by bees and other insects.

If you happen to be allergic to the pollen from clover, or orange blossoms, or sourwood (my favorite!), then you may see some benefit from regular consumption of a teaspoon a day. Otherwise, it’s not likely. If you do decide to give honey a try, check around for a local beekeeper.

Apple Cider Vinegar

This is the mother of all folk cures. Apple cider vinegar is supposed to be the remedy for everything from arthritis to high cholesterol.

A quick search of the web provides dozens, maybe hundreds of anecdotes about how apple cider vinegar (ACV) relieved someone’s allergy symptoms after just a few days. Unfortunately, there are no studies—not one—looking at the use of apple cider vinegar for allergy symptoms.

Still, people swear by ACV. They have their own way to take it: how much, what time of day, what to mix it with. There’s certainly no harm in taking a couple tablespoons of ACV daily. You’ll want to water it down, and probably add a sweetener or other flavoring to cut the sour taste.

One consistent recommendation for ACV is that you want it raw and unfiltered. Look for a product such as Bragg’s at health food stores or on the web.

Treatments for Allergies that Work Well

(Part 2 of 3)

In yesterday’s post I gave you some background on allergies: what’s going on in your body and some common drugs used as treatment. As I said, drugs either mask symptoms or interfere with your immune system. What you really want is something that will help your immune system tell the difference between true danger and benign visitors. So here are a couple things that appear to work well for many people.

Acupuncture

According to Chinese medicine, energy travels through your body in pathways called meridians. A disruption in energy flow can create illness, sometimes far away from the place of disruption. Acupuncture is the science of restoring energy flow. An acupuncturist most often uses needles to stimulate one or more specific points, but may also use heat or the pressure of fingers or stones.

More than 50 studies over the last couple decades have shown how effective acupuncture can be for relieving the symptoms of seasonal allergies. For example, in a 2013 trial patients were asked about their symptoms and their use of rescue medication. After 12 treatments over the course of eight weeks, patients reported a better quality of life and less use of allergy drugs. They were asked again after 16 weeks and one year about their quality of life and medication use, and the benefits had continued long after the treatments had stopped. It appears that acupuncture treatment actually corrects the immune problem rather than just interrupting the chemical pathway.

If you’re not a fan of needles, there’s no need to worry. The needles are very thin, and you can barely feel them as they go into your skin. Most acupuncturists use disposable needles, so there’s no concern about infection. And the treatment itself is relaxing; some patients even report sleeping through the session. My wife and I have both had acupuncture treatments for various conditions, and we’re big fans.

You do need a professional for acupuncture. A licensed practitioner will have the designation L.Ac. Acupuncture has become much more widely available over the last 20 years, so you should be able to find a practitioner near you.

Stinging Nettles

The name alone is enough to keep some people away from this therapy, but stinging nettle is a remarkably effective therapy for seasonal allergy symptoms.

Research into stinging nettle for allergies is rather thin, but herbalists and naturopathic physicians who have done their own studies with patients swear by its benefits. One study of 69 people showed that just one week’s use of stinging nettle improved people’s overall assessment of their symptoms compared to placebo. In this study, people took 300 mg of freeze-dried nettle leaf twice a day.

Research in 2009 showed that stinging nettle affects two links in the chemical pathway of allergic rhinitis. An extract of stinging nettle blocked histamine receptors, and it reduced the amount of histamine released by mast cells. As a side benefit, the extract blocked enzymes responsible for inflammation. This study wasn’t done in humans, but it does give us an idea of how stinging nettles provide their benefit.

When using stinging nettle, look for a freeze-dried extract of the leaf. You may see the product shown under its plant name, Urtica dioica.

Tomorrow I’ll let you know about a couple therapies that have lots of support in folk medicine, but little research support.

Here Come Those Seasonal Allergies

(Part 1 of 3)

It’s hard to believe that fall is almost here. School starts today where I live, and evenings are getting cool (thank goodness). And with the fall comes another bout of seasonal allergies for those who are sensitive. (Though really, any season is allergy season. While most people think of blooming flowers and trees in the spring and ragweed in the fall as the worst culprits when it comes to allergens, we’re always surrounded by things that can make us sneeze, itch and, wheeze. Dust, mold, pet dander, and tobacco smoke know no season. )

Watery eyes, runny nose, and sneezing are the body’s way of trying to get rid of whatever is bothering you at the moment. Together, these symptoms are called allergic rhinitis (that’s hay fever to you and me), and they’re a gold mine for the medical industry. The top-selling prescription drug for nasal allergies, Nasonex, brought in more than a billion dollars in 2013 for its manufacturer.

But for most people, drugs are not the best solution. Depending on their category, prescription drugs either provide symptom relief or interfere with the function of your immune system. Whichever kind you use, the benefits are overwhelmed by the adverse effects.

Many people turn to over-the-counter medications for relief. Older antihistamines, such as diphenhydramine (Benadryl) and chlorpheniramine (Chlor-Trimeton), are infamous for their adverse effects—especially drowsiness, but also rapid heartbeat, dry mouth, and problems emptying the bladder.

The second-generation antihistamines, including cetirizine (Zyrtec) and loratadine (Claritin), are less likely to have negative side effects, but users still report dry mouth, headache, and occasional rapid heartbeat. The newest antihistamines available aren’t really new at all; they’re just modifications of older drugs. While there does seem to be a slightly smaller risk of side effects, the drugs aren’t any more effective than their older brothers.

What’s Going On Inside

The human body is set up to reject unfamiliar invaders. Your immune system is constantly on the alert for bacteria and viruses that can cause infection if left unchallenged. A well-tuned immune system will know the difference between non-threatening newcomers and true stranger danger. But if something goes awry, in either genes or experience, your immune system goes after harmless substances such as dust and pollen.

The first time your immune system encounters something new, it creates specific antibodies that then attach themselves to specialized cells known as mast cells. When the newcomer shows up again, the mast cells release histamine—the chemical that causes the classic allergy symptoms.

Most drugs for allergy relief, including all the ones available over the counter, address the receptors for histamine—meaning that your immune response is still going haywire but the desired result, getting rid of the offenders, is blocked. A smaller class of drugs works to stabilize mast cells, so they don’t release so much histamine. Drugs in a third class disrupt the immune response entirely. Almost all of the drugs in this group are steroids, and are prescription-only.

That’s the background on allergies. Over the next couple days I’ll give you the rundown on allergy treatments that work—and ones that don’t.

The Travels of a Prescription Drug

Prescription drugs can take a winding path to market. It takes much investigation and pre-clinical work before the first molecule enters a human subject’s body. After that there are still years of clinical trials ahead before a new drug makes it to market. Many candidates fail at some stage along the way.

Drugmakers invest huge amounts of money to get that new wonder drug into patients’ hands. Our patent system gives the maker 17 years to sell as much of the drug as they can for as much money as they can before other makers are allowed to produce their own generic version. The generics have to undergo their own testing and approval before coming on the market, but initial costs are much lower and the price of a brand-name drug tends to come down significantly once generics are available.

Unfortunately for the makers of the original drug, the patent clock starts as soon as they’ve identified their molecule, and keeps running while the trials are underway. This means that the competition-free time for a new drug is significantly less than 17 years. But sometimes the maker has a backup strategy.

Extending the Life of a Drug

If you’ll recall your dusty high-school chemistry, molecules are three-dimensional objects. And many molecules come in 2 mirror-image versions of each other—left- and right-handed versions if you will. As it turns out, for many of these molecules only one of the -handed versions has an effect in the body.

So when a manufacturer finds a molecule that will work as a new drug, the first introduction might be a mixture of both the left and right versions. This is a natural result of the manufacturing process, so it’s not like the maker is adulterating their product in any way. But it does mean that only half of the molecules of product X are doing you any good.

Here’s where the backup comes in. The patent was originally granted on the left-and-right mixture. The 17-year limit is coming up, and voila! here’s a “new” version that’s really only the active half of the original. There’s still patient trials to conduct, but no investigative work to be done, and the trials can typically be shorter and smaller (and so cheaper) because the original drug has already been shown to be safe and effective.

When Drugs Do the Splits

Here’s an example of how that works. In 1989 the FDA approved the drug Prilosec for the treatment of frequent heartburn and GERD (gastroesophageal reflux disease). Prilosec is the molecule omeprazole. In 2002 the FDA approved generic omeprazole. It’s no coincidence that in February of 2001 the FDA had approved Nexium to treat the same conditions—Nexium’s molecule is esomeprazole, the left-handed version of omeprazole.

While Prilosec had market exclusivity for 13 years, for Nexium it was 14 years (generic esomeprazole was approved earlier this year). One more year of protection might not seem like much, but in 2013 Nexium was the #2-selling prescription drug in the US, with sales of more than $6 billion.

I want to emphasize that there’s nothing underhanded about this process. The manufacturer simply adds a step to separate the two -handed versions, and packages the one that’s effective. And I’m not picking on Nexium, it just happens to be one I have data for at hand. But keep in mind that, in this example if Nexium works for you at whatever it’s costing you for your prescription, then the drugstore’s generic OTC version of Prilosec will probably work just as well.