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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

What Your Doctor Is Reading What Your Doctor Is Reading

Update From the Medical Journals: March 2014

March 31, 2014

By Mary Pickett M.D.

Harvard Medical School

What's the latest news in the medical journals this month? Find out what your doctor is reading.

  • Obesity Might Not Look Good in "Genes"
  • Guidelines Would Add Statin Drug for 13 Million Americans
  • More News in Brief: Fewer Americans are Dying from Colon Cancer; Vegetarian Diets Help Lower Blood Pressure; Glucosamine Doesn't Help Knee Pain; ACOG Advises Against Water Births; Tylenol in Pregnancy May Be Associated with (A Few) Additional Cases of Childhood ADHD

Obesity Might Not Look Good in "Genes"

Researchers have discovered something extraordinary about obesity. It might cause a variety of health problems by affecting genes. The journal Lancet published the work of these researchers online on March 12. If future research confirms this thinking, it could help explain why obesity-associated health problems appear to run in families. 

Anyone who has studied biology in school is familiar with the idea that genes can be passed down from one generation to the next. And (when health is concerned) there are certain "good genes" and "bad genes" a person can inherit. Some genes contribute to diseases, and some genes protect against health problems. But there is a new aspect to the genetics story that we are just beginning to understand. It's called  "epigenetics." Epigenetics is a way that a person's health or environmental exposures — and now, perhaps a person's body weight, too — can turn genes on or off. How does it work? A gene can be turned "off" when molecule fragments, such as methyl groups, attach to the gene.

During reproduction, methyl groups or other molecule fragments appear to be copied along with genes from mom and dad. This means an active gene (with no methyl groups) is inherited by a new generation as an active gene and an "off" gene (made inactive by methyl groups) is inherited in the form of an "off" gene (the baby’s gene, too, carries methyl groups). This means you didn't only inherit your genes from your parents, you also inherited a genetic "memory" of sorts, built from your parents' life experiences. We don’t know much about what it takes for methyl groups or other genetic "clutter" to be removed, once these molecule fragments become part of the genetic message. 

An example of epigenetics is the effect of smoking on genes. Smoking was recently found to add methyl groups to certain genes. Experts think the genes affected are the ones that protect against cancer.

What's new is the discovery that being obese appears to add methyl groups to a particular gene. Researchers analyzed the DNA of 459 people. The higher the body mass index (BMI) of a person, the more methyl groups were present in the area of HIF3A. This gene is familiar in genetic research. When it is active, this gene triggers a large number of other genes to function and build proteins. Researchers wonder if lower activity of this gene might be one reason that certain problems, such as diabetes, high cholesterol and high blood pressure, are so common in obese people. 

This research is so new that it involves a fair amount of speculation. But it could create a tremendous opportunity for us. Eventually, we may be able to create treatments that can "remove" methyl groups from specific gene areas. Someday this could limit the health impact of obesity. Or it might even help the biology and health of the next generation.

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Guidelines Would Add Statin Drug for 13 Million Americans

The American Heart Association and the American College of Cardiology issued new cholesterol treatment guidelines in November 2013. The guidelines recommended that more people take statins. Now, an analysis has applied the guidelines to a group of typical Americans to see whether a statin drug would be recommended to prevent heart disease and stroke. The analysis was published in the New England Journal of Medicine's online edition March 19.

According to the results, following the guideline means that almost 13 million more Americans will be eligible to take statins. Almost all of the increase was among adults who did not have heart disease, but were at risk to develop it.

Most adults with heart disease already take a statin. But the guidelines recommend statins for most adults between ages 60 and 75, even when heart disease is not present. This would mean that 87.4% of healthy men ages 60 to 75 who don't currently take a statin would be eligible for one. For healthy women, 53.6% ages 60 to 75 who are not already on statin would now be eligible to take a statin. If patients go along with the guideline, this added statin use may prevent as many as 475,000 heart attack and stroke events (counting both fatal and non-fatal events) over 10 years.

Many doctors and patients are hesitating to adopt these new guidelines fully, because they represent such a large change in our threshold to begin statin drugs. Statin use, like any drug, has trade-offs. In this case, statins can prevent heart disease, but they are a daily pill, have potential side effects, and they add to health care costs.


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More News In Brief

  • Fewer Americans are Dying from Colon Cancer. In the 1940s and 1950s, colon cancer was the leading cause of cancer deaths for Americans. Now, it is the third leading cause of cancer death. According to an update published March 17 by the American Cancer Society, we are beating colon cancer. The update was published in CA: A Cancer Journal for Clinicians. Colon cancer rates fell 30% for Americans age 50 and older between 2000 and 2010. Deaths from colon cancer also dropped, by a similar amount during that same decade.  Researchers said the main reason is clear. Rates of colonoscopy rose during the same period. This screening test can find and remove colon polyps before they turn into cancer. In 2000, 19% of adults ages 50 through 75 had been screened with colonoscopy. That jumped to 55% in 2010. Treatments have improved as well, so more colon cancers that are discovered are cured with treatment. Colon cancer screening is recommended for all adults over the age of 50.
  • Vegetarian Diets Help Lower Blood Pressure. Researchers combined data from 39 studies. The results show that a vegetarian diet can lead to modestly lower, healthier blood pressure, compared with diets that include meat. The authors published their findings in JAMA Internal Medicine on February 24. There are other diets that have previously been proven to lower blood pressure, including the low-salt DASH diet. When counseling patients, doctors can include a vegetarian diet as one suggested way to lower blood pressure.

  • Glucosamine No Help for Knee Pain. As recently as 2007, 1 out of every 5 American adults surveyed reported taking the supplement glucosamine to relieve their aching joints. Several years ago a combined analysis of small studies failed to show a benefit from glucosamine and chondroitin. This month a new small study has again failed to show benefit. The study included 201 adults with chronic knee pain. The participants were randomly assigned to either receive glucosamine in a daily lemonade drink or to receive lemonade with placebo. The study continued for 24 weeks. MRI images showed no differences between the two groups, and pain scores were the same. The journal Arthritis & Rheumatology published the study on March 11. Glucosamine may be a harmless product, but it is not helpful for arthritis.

  • ACOG Advises Against Water Births. In some hospitals, offering a warm water "birthing pool" has become popular. Some women say immersion in the tub is relaxing and might help to reduce labor pain. On March 24, after a review of hospitals' experiences with the tubs, the American College of Obstetricians and Gynecologists (ACOG) released recommendations for this practice. According to ACOG there may be some positive effects of water immersion in the early stages of labor. However, underwater delivery has risks. Potential risks include infections in the newborn, unsafe body temperature changes in the baby, umbilical cord injury, seizures, infant drownings and respiratory distress from water entering the lungs. AGOC recommends that hospitals wishing to offer water immersion offer it only during the first stage of labor.
  • Tylenol in Pregnancy May Be Associated with (a Few) Additional Cases of Childhood ADHD. Acetaminophen (Tylenol) has been considered safe for pregnant women. But a study released online February 24 by JAMA Pediatricsmakes this less certain. The study authors used data from extensive surveys that came from a project known as the Danish National Birth Cohort. That project collected information about 64,322 children and mothers, for births between 1996 and 2002. More than half of the mothers reported taking acetaminophen at least once during pregnancy. We can assume this was to treat pain or fever. When the researchers looked at the health of the children at age 7, they found that a somewhat higher number of children had a diagnosis of attention deficit hyperactivity disorder (ADHD) in the group whose moms had reported taking acetaminophen. The difference was not large — for every 10 children being treated for ADHD in the group with no prenatal exposure, there were about 12 children being treated for ADHD in the families of mom's who had taken acetaminophen during pregnancy.

    This data are not strong enough to make doctors or drug safety experts change their advice about Tylenol.  The difference between groups was so small that it barely met criteria of "statistical significance." Even if the difference between the exposed and unexposed groups had been larger, this might have been caused by harm from fever, pain or infection that led to Tylenol use. In other words, Tylenol may have been present as a coincidence, not a cause. Based on this study, I will continue to tell patients that it's OK to use Tylenol in pregnancy if you have a high fever or a bad headache. Even though drug safety experts will give Tylenol a closer look after this study, Tylenol is still considered one of our safest medicines to use in pregnancy. 

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Mary Pickett, M.D., is an associate professor at Oregon Health Science University where she is a primary care doctor for adults. She supervises and educates residents in the field of Internal Medicine, for outpatient and hospital care. She is a lecturer for Harvard Medical School and a senior medical editor for Harvard Health Publications.

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