By TARA PARKER-POPEWho would have thought it? The quest for eternal life, or at least prolonged youthfulness, has now migrated from the outer fringes of alternative medicine to the halls of Harvard Medical School.
http://www.nytimes.com/2009/09/29/science/29aging.htmlIn a debate over an amendment that would have extracted billions of dollars from major drug manufacturers, Senator Charles E. Schumer, Democrat of New York, decided Thursday to share his personal experience in fighting high cholesterol.
Mr. Schumer said his doctor had directed him to take Lipitor, which is manufactured by Pfizer, and then, after his cholesterol levels had dropped, suggested that he try a less expensive, generic medication instead. But he switched back after his cholesterol levels went back up. “I’m taking Lipitor even though it’s more expensive,” Mr. Schumer said.
Mr. Schumer also hastened to add that Pfizer has its headquarters in New York -– a local shop, in other words.
That prompted Senator Charles E. Grassley, Republican of Iowa, to suggest that Mr. Schumer try a more natural remedy: red yeast rice. “I’ll bring the pills for you tomorrow,” he told Mr. Schumer.
Red yeast rice contains cholesterol-lowering compounds, called monacolins, and has been a dietary staple in China for more than 1,000 years. It is made from yeast, grown on rice, and is the ingredient used to give the popular dish Peking duck its trademark red tint.
Presumably, Mr. Grassley who hails from a state famous for corn, had no geographic interest in promoting a rice product. (The federal Food and Drug Administration has also banned some versions of red yeast rice supplements because of concerns that they can cause kidney and muscle problems).
The exchange between Mr. Schumer and Mr. Grassley inspired Senator Bill Nelson, Democrat of Florida, who was the sponsor of the amendment under debate, to make a pitch for his own locally grown remedy for high cholesterol. “Grapefruit might do the same thing for you,” Mr. Nelson said.
“How about a pastrami sandwich?” Mr.Schumer replied. “How would that do?”
It’s unclear if any senators will be changing their breakfast habits, but Mr. Nelson’s other pitch, for his amendment, failed by a vote of 13 to 10.
Osteoporosis has haunted my family for generations, as it has many other families.
My great-grandmother was bent nearly horizontal from collapsed vertebrae. My grandmother lost a foot in height as her spine deteriorated, and broke her hip just pushing a grocery cart. I made her a new backbone out of papier-mâché when I was 4.
My mother did everything she could to avoid the family curse, but she also suffered painful collapsed vertebrae. All three women died, directly or indirectly, as a result of osteoporosis.
Osteoporosis has expanded the gaps in the spongy tissue within a spinal vertebra, increasing the bone’s brittleness and probability of fracture.
That was before the bone-building drugs called bisphosphonates became widely available in the mid-1990s. Thanks in part to them, the number of hip fractures has dropped significantly in the U.S. and Canada in recent years.
Osteoporosis remains a serious health problem for the 10 million Americans who have it and the 34 million who are at risk due to low bone mass; 80% of sufferers are women. It's estimated that one half of women and one-quarter of men over age 50 will suffer an osteoporosis-related fracture.
But reports of scary side effects from bisphosphonates including Fosamax, Actonel and Boniva are circulating on the Internet and in medical journals. Hundreds of lawsuits allege that the drugs cause a rare condition in which part of the jaw bone dies. The first case to be tried against Merck & Co.'s Fosamax ended in a hung jury last week in federal court in New York City. And some critics say the drugs with sales of $8.3 billion a year in the U.S. are being oversold to women who may never need them.
All that leaves women facing a difficult dilemma: Powerful osteoporosis drugs known to prevent future debilitating injuries are also suspected of increasing the risk for other terrible conditions. Balancing the risks and benefits is different for every woman, and depends on factors such as genetic history, diet and lifestyle. Figuring out how to proceed also requires having a very careful discussion with a qualified physician.
A good place to start is with your family tree. Having a parent with osteoporosis raises your own risk significantly. Caucasians, Asians and Hispanics also have higher rates of osteoporosis than African-Americans. So far, scientists have identified 15 related genes but there isn't likely to be a predictive genetic test anytime soon.
That's because environmental factors also play a big role. The more bone you build up during the peak building years before age 30, the more reserves you'll have when net bone loss sets in. For women, that happens very rapidly after menopause when estrogen levels decline. Men lose bone far more slowly, although hormone-deprivation drugs for prostate cancer can also set them up for osteoporosis, as can a very strong hereditary load.
A diet rich in calcium (from dairy products and vegetables), plenty of exposure to vitamin D and weight-bearing exercise all help to build strong bones. Too little of those can weaken them, as can smoking, drinking alcohol, and a taking a variety of medications, including corticosteroids, anticonvulsants and antidepressants. Excessive dieting and exercising and being very thin with a body-mass index of less than 20 can also leave your bones with little reserve. Being obese actually lowers your risk, though it can overstress your joints.
But some people can do everything right and still develop osteoporosis if they have a strong genetic predisposition.
A bone-mineral-density test can give you one indication of how strong your bones are. Women with several risk factors should have one at menopause; or at least at age 65. The most common such test, called a DEXA (for dual-energy X-ray absorptiometry) is quick and painless and measures the amount of bone in your hip, spine or wrist. Results, called T-scores, compare that density with an average peak at age 30.
A T-score of minus 2.5 or below indicates osteoporosis. A T-score between minus 1 and minus 2.4 is considered osteopenia meaning low bone density but not full-blown osteoporosis.
You and your doctor can also assess your risk by using an online tool developed by the World Health Organization called FRAX, for Fracture Assessment Risk Tool. (See www.shef.ac.uk/FRAX.) It asks your sex, age, weight, height, hip-bone density and factors such as smoking, drinking, and parental hip fractures. It computes your chances of suffering a major bone fracture in the next 10 years.
What to do with that information is still somewhat controversial. "If you already have severe osteoporosis, you don't need a FRAX score to tell you you need treatment," says Bess Dawson-Hughes, director of the Bone Metabolism Lab at Tufts University, who has advised many of the drug makers. "Where we have struggled is what to do with that large group of healthy people who have low bone mass."
The National Osteoporosis Foundation's latest guidelines say that women who have a 3% risk of developing a hip fracture or 20% risk of other major fracture in the next 10 years are candidates for treatment, on cost-effectiveness grounds. In studies of older women with osteoporosis, Fosamax has been found to reduce the chance of hip and spine fractures as much as 50% . But it's less clear to what extent such drugs can prevent osteopenia from becoming osteoporosis.
Experts say that individual patients should never be treated based on T-scores or FRAX probabilities alone. Many other considerations apply.
The more "yes" answers, the greater your risk for developing osteoporosis:
"You need to consider the unique characteristics of this lady in front of you," says Ethel Siris, director of the Toni Stabile Osteoporosis Center at Columbia Presbyterian Medical Center, who has also consulted for the drug makers. For example, a 50-year-old woman with osteopenia may not be a candidate for treatment based on her FRAX alone. But if she falls a lot and her mother suffered spinal fractures, which the FRAX doesn't ask about, it may make sense to treat her for a few years and see how her bone density does, Dr. Siris says. Meanwhile, a 70-year-old who has the same T-score probably started out with better bone density, but she has had 20 more years for her bone architecture to erode, so her bones are more fragile, even though they weigh the same.
The official guidelines also don't take into account potential side effects of the bisphosphonates, which are also highly individual. Gastrointestinal upsets are the most common; the oral medications aren't recommended for patients who can't sit upright for at least a half-hour because these drugs can irritate the esophagus. Gastro-esophageal reflux disease (GERD) can make such discomfort worse. A woman with severe GERD might fare better on Reclast, a once-a-year injection of bisphosphonate.
Some patients have also reported severe bone and muscle pain while taking bisphosphonates. The Food and Drug Administration alerted doctors last year that they might see this and consider discontinuing the drugs at least temporarily. Who is most affected and how long it lasts seems unpredictable. "I treat a gazillion patients and I see this rarely," says Dr. Siris. "When I do, we stop and re-evaluate."
Cases of osteonecrosis of the jaw (ONJ) in which parts of bone become exposed during dental work and don't heal are more serious but very rare. No one knows the exact incidence. Estimates range from 1 in 1,000 to 1 in 100,000 patients taking bisphosphonates for osteoporosis. (It's far more common in cancer patients on much higher doses.) Merck and other manufacturers say there is no evidence that the drugs cause ONJ at doses used for osteoporosis, but some dentists have become wary of doing invasive dental work on women taking bisphosphonates.
"We often advise patients who need extensive, invasive dental work to get that done first, then start the drugs and the issue disappears," says Ian Reid, a professor at the University of Auckland in New Zealand who has written on biosphosphonate safety.
A few doctors have reported unusual fractures of the thigh bone in women taking bisphosphonates for many years. One theory is that because the drugs inhibit the breakdown of old bone, they may be maintaining bone that is unusually brittle. Here too, the incidence seems extremely rare and the link remains unproven. But experts agree that it warrants further study and that patients and doctors should investigate any unusual thigh pain which has preceded several of the fractures.
On balance, most experts say that women with confirmed osteoporosis face a much higher risk of fractures if they don't treat their condition than if they do. "These horrible cases are incredibly rare, whereas hip fractures are not rare in the aging population and they can kill you," says Dr. Siris. She notes that there are still many unknowns about drugs, including how long it is safe for women to stay on them. Many doctors are using them with patients only about five years at a time and then re-evaluating.
Other osteoporosis drugs on the market work differently and carry different risks. Evista (raloxifene) acts on estrogen receptors and can cut the risk of breast cancer as well as spinal fractures in some women, although it doesn't prevent hip fractures. Forteo (teriparatide) is a daily injection for women with severe osteoporosis, but has been linked with bone malignancies in rats. Last month an advisory panel recommended that the FDA approve denosumab, a biological agent that blocks the production of osteoclasts that break down bone. It would be a twice-yearly injection.
Estrogen-replacement therapy can also help women postpone the rapid loss of bone mass that occurs after menopause. It's no longer recommended for bone protection alone in part because of the added risk of heart disease and breast cancer found in older women in the Women's Health Initiative studies. But the risk-benefit profile seems more favorable for younger women who want relief from menopausal symptoms like hot flashes. "If you hate your life without estrogen, you can go back on it and that's your bone-loss drug as well," says Dr. Siris.
Some clinics urge women to fight osteoporosis with lifestyle changes rather than pharmaceuticals. Many experts agree that sufficient calcium (at least 1,200 mg per day from food or supplements) and vitamin D (800 to 1,000 IUs per day) and weight-bearing exercise (at least 30 minutes, three times a week) are critical for building and maintaining strong bones, but they may not be sufficient for reversing serious bone loss once it's set in.
All camps agree that the very best way to strong bones is to build them well to begin with. Nearly 90% of bone mass in females is built by age 18, yet few adolescent girls are getting the recommended amounts of calcium and vitamin D.
Many a carton of milk or yogurt now brags of its fortification with omega 3s, a trend that has made the dietary additive seem like just the latest marketing gimmick for health-minded consumers.
But omega 3s, a family of unsaturated fatty acids, have been shown to reduce the risk of coronary heart disease. And now, the compounds are being studied by scientists around the world as potential treatments for a wide range of other serious conditions, ranging from Alzheimer's disease to epilepsy and rheumatoid arthritis. Further research also is being done on omega 3s' role in preventing heart disease to determine the full range of potential benefits.
In an experiment, omega 3s block white blood cells from moving out of a blood vessel (left). Without omega 3s (right), the cells move readily.
Omega 3s are found naturally in fatty fish such as salmon, mackerel and sardines, and in some botanical sources such as flaxseed and kiwi fruit. A variety of firms also sell omega 3s as dietary supplements. Scientists say the benefit to the body should be the same whether they are consumed through food or capsules. Many scientists believe omega 3s provide health benefits in part by reducing inflammation, which can contribute to heart disease, arthritis and other ailments. But researchers are still attempting to understand how exactly omega 3s interact with the body. And studies for a number of medical conditions aren't far enough along to know whether the fatty acids could be beneficial.
One research team in the U.K. recently experimented on human cells in artificial blood vessels to try to understand what role omega 3s play in inflammation. The researchers used a glass tube to mimic a blood vessel. Normally, inflammation occurs when white blood cells migrate from the blood, through the blood-vessel wall and into surrounding tissue. The researchers coated their glass tube with endothelial cells, which normally line the interior walls of blood vessels. Then they added omega 3s to the endothelial cells.
Later, when the researchers pumped white blood cells into the tube, they saw under a microscope that the cells couldn't get across the endothelial barrier—the omega 3s were blocking them, according to a paper published in online journal PLoS Biology last month. When they performed the same experiment without the added omega 3s, the white blood cells easily penetrated the endothelial barrier.
More research is needed to determine if the omega-3 blockade similarly occurs in actual blood vessels. But Ed Rainger, a cellular immunologist at the University of Birmingham Medical School, who led the research, says the experiment shed light on how inflammation works in the body and how tweaking the diet might affect it. He added that the discovery could eventually help scientists develop new medicines that block inflammation, which could be useful in treating diseases such as rheumatoid arthritis and psoriasis.
Inflammation plays a role in many areas of heart disease, which is probably at least partly why clinical trials have shown that omega 3s can reduce rates of heart attacks and strokes and slow the buildup of harmful plaque in the arteries, says Stephen Nicholls, a cardiologist at the Cleveland Clinic in Ohio.
Omega 3s appear to have benefits beyond reducing inflammation. They also lower levels of potentially harmful blood fats called triglycerides, which are unrelated to inflammation but can increase risk for heart disease, Dr. Nicholls adds. A prescription-strength pill called Lovaza, made from omega 3-containing fish oil, is approved for sale in the U.S. for reducing triglycerides.
Many scientists also believe that omega 3s might help stabilize cells and prevent them from generating erratic electrical signals in the heart and brain, which can cause irregular heartbeats, seizures and other problems.
Christopher DeGiorgio, professor of neurology at University of California, Los Angeles, has been testing this theory in epilepsy, with mixed success. In past studies, omega 3s haven't helped much to reduce seizures, he says. In a new study of 30 epileptics, he hopes to show that omega 3s reduce rates of sudden death. Sudden death—when an epileptic dies suddenly with no clear cause—accounts for about 20% of all deaths among epileptics, and irregular heartbeat can contribute to it, Dr. DeGiorgio says. He wants to test whether omega 3s help stabilize the heart and thus reduce cases of sudden death.
Some experiments on animals have suggested that omega-3 consumption can reduce brain levels of the amyloid proteins associated with Alzheimer's disease. These findings have helped drive researchers to study omega 3s in Alzheimer's patients, too.
One study involving 400 Alzheimer's patients, presented at the International Conference on Alzheimer's Disease in Vienna this summer, showed mixed results. A daily dose of two grams of DHA, one type of omega 3 fatty acid, for 18 months did not help patients perform better than those taking a placebo on standard tests used to assess the disease.
But in an interesting twist, patients taking DHA who didn't have a gene variant called ApoE4 did experience a slower rate of decline on one test of mental function compared with patients taking a placebo. Joseph Quinn, associate professor of neurology at Oregon Health & Science University and the leader of the study, cautions against making too much of this finding for now. But he says it's "encouraging and intriguing" that at least some patients seemed to benefit from omega 3s and says he hopes to conduct new studies to "look at that genotype more carefully." At least one-third of people with Alzheimer's disease lack this gene variant, according to the National Institutes of Health.
Dietary supplements usually contain about 200 milligrams of omega 3s per capsule, while a fatty salmon steak can contain up to one gram, according to Maria Makrides, an expert on omega 3s at Women's and Children's Health Research Institute in Australia.
The American Heart Association recommends that people without coronary heart disease eat a variety of fish at least twice a week, and include other foods such as flaxseed and walnuts in the diet. It says people with documented heart disease should eat about one gram of omega 3s a day. The AHA says that while omega 3s are generally safe, some side effects can include a fishy aftertaste, gastrointestinal disturbances and nausea. It says that while most omega-3 supplements are "essentially" free of mercury, the toxic metal sometimes found in fish, some poorly made supplements can contain "appreciable amounts."
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Mark Matcho When Dan Gerkey was trying to get into better shape a few years ago, he tried out a dietary supplement from a local store that promised to help build his strength. At first, the stuff worked. But after several weeks the police officer, who lives in Fraser, Mich., started feeling exhausted, and his wife noticed a yellowish tinge in his eyes.
http://online.wsj.com/article/SB10001424052970204731804574390840811949538.html#In the case in United States District Court in Manhattan, a 71-year-old retired deputy sheriff from Fort Walton Beach, Fla., Shirley Boles, contended that taking Fosamax from 1997 to 2006 cause her jawbone tissue to die.
Millions of women have taken Fosamax, made by Merck, to offset bone loss associated with menopause.
During the trial, lawyers for Mrs. Boles used expert witnesses, reports in medical journals and internal company documents to bolster their argument that Merck knew or should have known that Fosamax can cause osteonecrosis of the jaw, or jawbone death.THE FACTS
In a country obsessed with germs and sickness, antibacterial soaps and sanitizers are becoming more and more common. But because such products contribute to the growing problem of antibiotic-resistant bacteria, some researchers recommend sanitizers made with cinnamon oil, which has been shown in many studies to have powerful antimicrobial properties.
A recent study by a team of surgeons, for example, found that a solution made with cinnamon oil killed a number of common and hospital-acquired infections, like streptococcus and methicillin-resistant Staphylococcus aureus, or MRSA. The study found it was just as effective as several antiseptics widely used in hospitals. Another study by French researchers in 2008 had similar results, showing that at concentrations of 10 percent or less, cinnamon oil was effective against Staphylococcus, E. coli and several antibiotic-resistant strains of bacteria.
Dr. Lawrence D. Rosen, a pediatrician in New Jersey who dispenses natural health advice on his blog, wholechildcenter.org, recommends a tried-and-true recipe for homemade hand sanitizer called thieves oil. “I add cinnamon bark, lemon oil and eucalyptus,” he said, adding, “The recipe goes back to the Middle Ages, where it was used by these thieves who would go around stealing jewelry from dead bodies, and they never got sick.”
Cinnamon oil, when applied topically, is generally safe. But in some people it can cause an allergic reaction.
THE BOTTOM LINETo test whether time of feeding alone can affect body weight, the researchers studied two groups of mice who were fed identical diets of food that contained 60 percent fat. Mice are nocturnal, and they typically consume the vast majority of their calories at night and sleep during the day. For the study, half the mice were fed the diet during the daylight hours when they would normally be sleeping — simulating late-night eating in humans. The other half were given the same food on their regular eating schedule.
At the end of the six week study period, mice in both groups had consumed about the same amount of calories and performed the same amount of exercise. However, the mice who ate when they normally would have been sleeping hours posted an average 48 percent increase in body weight. The mice who ate on a regular schedule had an average increase of 20 percent of body weight. The findings will be published in the October issue of the journal Obesity.
Fred Turek, director of the Center for Sleep and Circadian Biology at Northwestern and the study’s senior author, said that human studies are needed to determine if timing of food intake influences body weight, but the study suggests that late-night eating may be worse, in terms of weight gain, than eating during normal waking hours. The findings would be particularly important for shift workers, who are known to be at higher risk for obesity, diabetes and other health problems. But he notes that it’s not just shift workers who are eating late. Most people eat a large percentage of their calories in the evening and continue eating late into the night.
Dr. Turek notes that humans evolved from a situation where they ate and foraged between sunrise and sunset. “After sunset, there were no refrigerators, no food just hanging around,” he said. “You didn’t eat. But today, people eat most of their calories after sunset.”
