STUDY: FDA hopes to cut down on unnecessary prescriptions

JOURNAL: Food and Drug Administration

AUTHORS: Mark McClellan

ABSTRACT: Antibiotics will soon need to carry warnings advising doctors to avoid unnecessary prescriptions, which have become a major contributor to the problem of drug-resistant infections.

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COMMENTARY: The new requirement, announced by the Food and Drug Administration on Wednesday, aims to reduce inappropriate prescribing of antibiotics for common ailments such as ear infections and chronic coughs, which often are caused by viruses that do not respond to antibiotics.

Antibiotics only kill bacteria, but patients often request them for treating a variety of infections.

Starting next year, antibiotic labels will be required to include instructions for doctors to prescribe them only when an infection is proven or strongly suspected to be caused by bacteria.

The labels also will encourage physicians to counsel patients about what types of infections require antibiotic treatment, as well as remind them to take all of their medication, even if they feel better in a few days.

Not completing a full course of treatment can give microbes the chance to mutate to resist antibiotics, causing infections that are harder to treat.

According to the Center for Disease Control and Prevention, half of the 100 million prescriptions a year written by office-based physicians in the United States are unnecessary because they are prescribed for the common cold and other viral infections.



“Antibiotic resistance is a serious and growing public health problem, not only in this country but worldwide,” FDA Commissioner Mark McClellan said, noting that the growth of resistant germs is outpacing development of new antibiotics.

“We may end up in a situation where we don’t have effective antibiotic drugs for common infections that were once easily treated.”

The agency plans to try and publicize the warnings through medical journals and professional medical societies.

STUDY: Progesterone could help stem growing problem

JOURNAL: Society for Maternal-Fetal Medicine

AUTHORS: Dr. Paul Meis

ABSTRACT: Obstetricians say they may have discovered a powerful new solution to the dramatic rise in premature births in the last two decades.

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The hormone progesterone prevented premature births in a surprisingly high number of high-risk pregnancies, according to a groundbreaking study.

COMMENTARY: “The evidence of this treatment’s effectiveness was so dramatic, the research was stopped early,” said the study’s lead researcher, Dr. Paul Meis of Wake Forest University Baptist Medical Center.

Progesterone is naturally produced by the ovaries. It softens the uterus lining into a spongy bed that holds a fertilized egg.

Weekly injections of the hormone reduced the chance of premature births by 34 percent in the 306 high-risk women who received the therapy, the study reported. Another 153 women were injected with a placebo. All the women had previously given birth prematurely, the single biggest indication of risk.

“The results are so good that it’s surprising,” said Dr. Fredric Frigoletto, chief of obstetrics at Massachusetts General Hospital in Boston. “No intervention that we have ever applied has had any measurable effect. This is very good news.”

Doctors have prescribed progesterone for years to help infertile and menopausal women.

STUDY: Cutting 100 calories a day could prevent annual weight gain

JOURNAL:

AUTHORS: Dr. James Hill

ABSTRACT: The average adult slips on about 2 extra pounds a year, a weight creep that some researchers argue could be prevented merely by eating one less cookie a day.

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That treat or even three fewer bites of a fast-food hamburger — the equivalent of 100 calories daily — can keep the pounds off in the first place so people do not face the harder battle of losing weight.

COMMENTARY: Scientists are searching for different approaches to what is fast becoming a national epidemic. Sixty percent of U.S. adults are overweight, and the government blames 300,000 deaths a year on weight-related diseases.

“The biggest problem we face in America is not terrorism. The biggest health problem we’re facing is obesity,” Dr. Julie Gerberding, head of the Centers for Disease Control and Prevention.

It is just a theory, and Hill acknowledges he has not proved yet that such a simple step works. But scientists are searching for different approaches to what is fast becoming a national epidemic.

Sixty percent of U.S. adults are overweight, and the government blames 300,000 deaths a year on weight-related diseases.

“The biggest problem we face in America is not terrorism. The biggest health problem we’re facing is obesity,” Dr. Julie Gerberding, head of the Centers for Disease Control and Prevention, said last week.

Fixing the problem will require changing societal norms starting with children, she added, such as doing more and eating less in a society that encourages more driving than walking and provides unfettered access to calorie-laden foods.

To focus attention on the problem, the journal Science, turned to some well-known obesity researchers for opinions on what it will take to lower the scales.

Hill’s response was to examine government figures showing about 40 million adults are obese and how steadily Americans have put on weight in recent years.



“The future is not hopeful unless we act now,” he concluded. Hill estimated that if current trends continue, 39 percent of adults will be obese by 2008, compared with 31 percent in 2000.



Losing weight and keeping it off can be hard. The possibly easier short-term goal would be to get no fatter. So Hill and colleagues calculated what he calls the energy gap — how many calories are eaten but not burned off.

Using that same government data, he estimates that on average people gain 2 pounds a year, which equals 50 extra calories stored each day. Because the body can store half of calories consumed, he said preventing that 2-pound weight gain might simply require eating 100 fewer calories a day.

There are problems with that simple approach, says Dr. Jeffrey Friedman of Rockefeller University, who discovered the obesity hormone leptin in 1995. Some people gain 10 pounds in a year while others gain none. Few people actually know how many calories they consume, a key difficulty in cutting them.

Scientists have discovered a number of hormones and genes that generate a basic biological drive to eat that can be difficult to fight, he explains.

Genetics aside, scientists also know that the more volume and variety of food people are offered — think super-sized restaurant portions and buffets — the more they’ll overeat, adds CDC nutrition chief Dr. Willian Dietz.

“Portion size is an issue. How one goes about controlling it is not so simple,” he cautions.

For people reluctant to eat less, Colorado’s Hill points to a current experiment in which Colorado is encouraging people to buy $20 battery-operated step-counters and take an extra 2,000 steps a day, enough to walk a mile and burn 100 calories.

Hill is studying 500 participants to see if that extra little bit helps their weight; results are not due for another year or two. He plans to add his theory on eating 100 fewer calories to the study, too.

STUDY: Testosterone Replacement: Good or Bad

JOURNAL: National Institutes of Health

AUTHORS: Marc Blackman

ABSTRACT: Federal advisers began the first of several meetings that will result in recommendations later this year on how to best determine if testosterone replacement therapy is good or bad for aging men.

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COMMENTARY: An unknown, but significant number of older men have begun using patches, gels or other forms of testosterone in the hopes of reversing the aging process and a flagging sex drive, but there is no scientific evidence that hormone supplements can help.

And, there may even be some dangerous side effects, including an increased risk of prostate cancer.

"The chasms of our ignorance here are vast," Marc Blackman, an endocrinologist with the National Institutes of Health, told a 17-member Institute of Medicine (IOM) advisory committee.

The panel has been asked to make recommendations on how to answer questions on the pros and cons of testosterone replacement, and its mechanism of action.

They are also weighing how to properly inform potential study participants when the benefits and the risks of therapy are very unclear.

Over the last few decades, studies on relatively young men with testosterone deficiencies have shown that replacement can counter increased body fat and cholesterol levels, decreased skeletal strength and decline in immune function associated with lower testosterone levels, said Blackman.

Four to five million relatively young American men have below-normal testosterone levels, and 5% are receiving replacement therapy, he said.

The few studies in older men with naturally declining testosterone levels has shown that replacement therapy decreases fat and increases lean muscle mass. But only one, a small 15-person study in very frail elderly men, has shown any improvement in muscle strength or function. So it is unclear if increased muscle mass leads to better physical functioning, Blackman said.

It's also not known if testosterone replacement reduces the risk of disability, falls, or fractures, or otherwise improves health outcomes. And it's unclear if supplementation would have similar effects in healthy older men and physically impaired older men.

A big concern is whether testosterone supplementation will increase the risk of prostate cancer. Increased levels of male hormones can enlarge the gland, and most researchers believe that increased prostate volume eventually leads to cancer.

Scientists at Baylor College of Medicine have drawn up plans to carry out a large, long-term study of testosterone replacement therapy in older men. The trial has been put on hold while the IOM panel considers its merits.

Lead investigator Glenn Cunningham said the study aims to enroll 6,000 men over age 65. They would be in the study for four years, and then followed for five years more. The main goal is to see if testosterone replacement reduces fractures, since men, just like women, are at risk for osteoporosis as they age, primarily due to declining hormone levels.

Researchers will also measure testosterone replacement's ability to reduce heart attacks and strokes, and to improve mood, energy levels, cognition and sexual function.

Finally, they will assess whether replacement therapy increases the incidence of prostate cancer or leads to more procedures to reduce prostate size.

STUDY:

JOURNAL: Journal of Nutrition

AUTHORS: Donald K. Layman

ABSTRACT: A relatively high-protein diet improves body composition, enhances weight loss, and improves glucose and insulin homeostasis.

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COMMENTARY: "Amino acids interact with glucose metabolism both as carbon substrates and by recycling glucose carbon via alanine and glutamine; however, the effect of protein intake on glucose homeostasis during weight loss remains unknown," write Donald K. Layman and colleagues from the University of Illinois at Urbana-Champaign.

In this study, 24 adult women who were more than 15% above ideal body weight were assigned to either a predominantly protein diet or a predominantly carbohydrate diet. The protein diet included 1.6 g/kg/day protein, with less than 40% of energy coming from carbohydrate, while the carbohydrate diet included 0.8 g/kg/day protein, with more than 55% of energy coming from carbohydrate. Both diets were equal in calories (7100 kJ/day) and in fat (50 g/day).



After 10 weeks, weight loss was 7.53 ± 1.44 kg in the protein group and 6.96 ± 1.36 kg in the carbohydrate group. Subjects in the carbohydrate group had lower fasting (4.34 ± 0.10 vs. 4.89 ± 0.11 mmol/L) and postprandial blood glucose (3.77 ± 0.14 vs. 4.33 ± 0.15 mmol/L) and an elevated insulin response to meals (207 ± 21 vs. 75 ± 18 pmol/L).

"This study demonstrates that consumption of a diet with increased protein and a reduced carbohydrate/protein ratio stabilizes blood glucose during nonabsorptive periods and reduces the postprandial insulin response," the authors write.

According to a second report from the same study group, "claims about the merits or risks of carbohydrate vs. protein for weight loss diets are extensive, yet the ideal ratio of dietary carbohydrate to protein for adult health and weight management remains unknown."

In this study, 24 women were assigned to either a predominantly carbohydrate diet containing 68 g/day protein with a carbohydrate/protein ratio of 3.5, or to a predominantly protein diet containing 125 g/day protein with a ratio of 1.4. Each diet provided 7100 kJ/day and approximately 50 g/day of fat. Age range was 45 to 56 years and body mass indices were greater than 26 kg/m2.

After 10 weeks, weight loss was 6.96 ± 1.36 kg in the carbohydrate group and 7.53 ± 1.44 kg in the protein group.

Compared with the carbohydrate group, weight loss in the protein group had an increased ratio of fat to muscle loss (6.3 ± 1.2 g/g vs. 3.8 ± 0.9 g/g). Serum cholesterol reduction was approximately 10% in both groups, but only the protein group had significant reductions in triacylglycerols (TAG; 21%) and in the ratio of TAG to high-density lipoprotein cholesterol (23%).



"This study demonstrates that increasing the proportion of protein to carbohydrate in the diet of adult women has positive effects on body composition, blood lipids, glucose homeostasis and satiety during weight loss.

Although it is unlikely that any one diet will be ideal for all individuals, these results indicate that changes in the ratio of protein to carbohydrate toward a higher protein diet can be effective in the control of body weight with parallel improvements in blood lipids.

The National Cattlemen's Beef Association and Kraft Foods helped support this study.

STUDY: Women with rheumatoid disease have increased risk

JOURNAL: Circulation: Journal of the American Heart Association

AUTHORS: Daniel Solomon

ABSTRACT: Women suffering from rheumatoid arthritis may face up to double the heart attack risks of women without the condition.

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COMMENTARY: Researchers at the Brigham and Women’s Hospital analyzed health conditions of more than 114,000 people in a 20-year study, including 527 arthritis sufferers.

Their findings, point to a possible correlation between rates of arthritis and heart attack risks in women.

The Brigham and Women’s study found women with rheumatoid arthritis had twice the risk of heart attack compared to those without it. Those who had the joint condition for at least 10 years faced triple the heart attack risks of non-sufferers.

“Both physicians and patients should recognize rheumatoid arthritis as a marker for increased heart attack risk,” said Daniel Solomon, a rheumatologist and epidemiologist at Brigham and Women’s in Boston.

“Our study, the largest of its kind to date, illustrates the importance of considering more aggressive cardiac preventive measures in arthritic patients,” he said.

Rheumatoid arthritis, or RA, involves inflammation in the lining of the joints and/or other internal organs. RA typically affects many different joints. It can be chronic or can be a disease of flares and remissions.

STUDY: Synthetic vitamin prevents retina damage in rats, study finds

JOURNAL: Nature Medicine

AUTHORS: Dr. Michael Brownlee

ABSTRACT: New hope for people with a diabetes-related eye disease may be found in a synthetic form of vitamin B1 used to treat nerve problems. Benfotiamine has been shown to prevent the most common form of diabetes-related eye disease in rats.

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COMMENTARY: Diabetic rats treated with this form of Vitamin B1 for 36 weeks did not develop any of the retina damage found in a similar group of untreated rats.

In diabetics, excess sugar in the blood can damage some cells, especially those lining blood vessels, that are unable to block the sugar from entering. That sugar is burned for fuel by mitochondria, the energy engines of cells.

In cells that cannot regulate their amount of sugar, byproducts accumulate that can activate three different pathways of cell damage that can lead to blindness and other complications.

Brownlee’s group focused on two compounds involved in this damage. Those compounds are affected by an enzyme called transketolase, which depends on thiamine — also known as vitamin B1 — for its activity.

The researchers sought to block the cell damage by using thiamine to boost the activity of transketolase, but this increased the enzyme activity only about 20 percent.

German researchers on the team suggested trying the synthetic thiamine form, benfotiamine, and it increased the enzyme activity by 300 percent to 400 percent.

While benfotiamine is a synthetic derivative of thiamine, it is different from that vitamin, Brownlee said. He cautioned diabetics that “going out to a health food store and buying a lot of thiamine is not going to help.”

STUDY: Antihyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic mice and their lean littermates.

JOURNAL: Diabetes 51:1851-1858, 2002

AUTHORS: Anoja S. Attele, Yun-Ping Zhou, Jing-Tian Xie, Ji An Wu

ABSTRACT: We evaluated antihyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On day 12, 150 mg/kg extract–treated ob/ob mice became normoglycemic (137 ± 6.7 mg/dl) and had significantly improved glucose tolerance.

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COMMENTARY: IT’S ONE of those cases when you shrug your shoulders and ask, “Why didn’t anyone think of this sooner?” For more than 2,000 years, Chinese practitioners have prescribed ginseng root to restore energy to patients suffering from everything from cancer to heart failure. In the United States, extracts made from the ginseng root are the fifth best-selling herbal supplement.

But only now, for the first time, have Chicago researchers studied the berry of the ginseng and found that it — not the root — may hold the key to wellness for millions. Previously, there had been no study of the ginseng berry’s biological activity, People believed that nutrients accumulated in the root and thus shied away from testing the berry for medicinal effects. A new study, which appears in the June issue of the journal Diabetes, suggests they should have broadened their view long ago. Antidiabetic Effects of Panax ginseng Berry Extract and the Identification of an Effective Component

It is stunning how different the berry is from the root in terms of its chemical profile and by how effective it is in correcting the multiple metabolic abnormalities associated with diabetes. In fact, the berry is more effective than the root in multiple ways, with an extract made from its pulp normalizing blood sugar and lowering cholesterol levels in fat mice. Additionally, obese mice given the extract ate less and exercised more — the payoff being weight loss. There’s some anti-diabetes effect with the root, but the effect of the berry is much stronger. Additionally ginseng root doesn’t change body weight at all.



The Key Ingredient

So what makes the ginseng berry so unique? In terms of its weight-loss effects, that remains to be seen. But when it comes to fighting diabetes, the key ingredient appears to be a substance known as ginsenoside Re. “This is very interesting,” says Dr. Nathaniel Clark, national vice president for clinical affairs at the American Diabetes Association (ADA). “The results are quite dramatic both in helping blood sugar levels to normalize and in causing weight loss, which is extremely important in type 2 diabetes.”



Study Details

For the study, Yuan and colleagues used genetic engineering to breed mice predisposed to weight gain and type 2 diabetes, which is linked to obesity.

Among the findings of the 12-day study:

Daily injections of an extract of the ginseng berry extract restored normal blood sugar in mice who had suffered “quite high” levels. Treated mice also had better scores on a glucose tolerance test, which measures how quickly the mice could remove excess sugar from the blood.

The obese diabetic mice shed more than 10 percent of their bodyweight, while untreated mice gained 5 percent of their weight. The reason: The treated mice ate 15 percent less and were 35 percent more active than untreated mice. Once the injections stopped, weight gain gradually resumed.

The extract improved insulin sensitivity, a risk factor for type 2 diabetes, in mice with diabetes.

Cholesterol levels dropped 30 percent in the treated mice, while the extract had no detectable effect on normal mice.

Tests using ginsenoside Re alone found that it had all of the anti-diabetic but none of the obesity-fighting activities of the extract. The scientists hypothesize that ginsenoside Re may speed up sugar transport from the blood to the muscle, thereby lowering blood sugar and reducing the risk of diabetes.

The extract appears to be safe though only tests in humans can bear that out. The next steps: Finding the right dose, isolating other obesity-fighting compounds in the berry and learning more about how the compounds exert their beneficial effects.

Ginsenoside Re could serve as the basis for a whole new class of anti-diabetic medications. Once they identify all the obesity-fighting compounds contained in this plant they can develop better compounds to combat obesity and diabetes.