Archive for the ‘Women Health’ Category

New study dispels belief that increasing the hormone level improves the sexual function

Bethesda, Md.— The American Journal of Physiology: Endocrinology and Metabolism, one of the 14 peer-reviewed journals published by the American Physiological Society (APS), spotlights recent research findings designed to improve and understand human well-being and health. A study in the December edition examines how different doses of testosterone affect body composition, muscle size, strength, and sexual functions.

Background

Testosterone regulates many physiological processes, including muscle protein metabolism, some aspects of sexual and cognitive functions, secondary sex characteristics, erythropoiesis, plasma lipids, and bone metabolism. However, testosterone dose dependency of various hormonal dependent functions has not been well understood in the scientific community. Previous studies reveal that administration of replacement doses of testosterone to hypogonadal men and of supraphysiological doses to eugonadal men increases fat-free mass, muscle size, and strength. Conversely, suppression of endogenous testosterone concentrations is associated with loss of fat-free mass and a decrease in fractional muscle protein synthesis.

What is not known is whether testosterone effects on the muscle are dose dependent, or the nature of the testosterone dose-response relationships. Animal studies suggest that different androgen-dependent processes have different androgen dose-response relationships. Sexual function in male mammals is maintained at serum testosterone concentrations that are at the lower end of the male range. However, it is not known whether the low normal testosterone levels that normalize sexual function are sufficient to maintain muscle mass and strength, or whether the higher testosterone concentrations required to maintain muscle mass and strength might adversely affect plasma lipids, hemoglobin levels, and the prostate.

The Study

The primary objective of this study was to determine the dose dependency of testosterone’s effects on fat-free mass and muscle performance. The authors hypothesized that changes in circulating testosterone concentrations would be associated with dose-dependent changes in fat-free mass, muscle strength, and power in conformity with a single linear dose-response relationship, and that the dose requirements for maintaining other androgen-dependent processes would be different.

Young men were treated with a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion, and concomitantly also with one of five testosterone-dose regimens to create different levels of serum testosterone concentrations extending from subphysiological to the supraphysiological range. The lowest testosterone dose, 25 mg weekly, was selected because this dose had been shown to maintain sexual function in GnRH antagonist-treated men. The selection of the 600-mg weekly dose was based on the consideration that this was the highest dose that had been safely administered to men in controlled studies.

The authors of the study, “Testosterone Dose-Response Relationships in Healthy Young Men” are Shalender Bhasin, Linda Woodhouse, Connie Dzekov, Jeanne Dzekov, Indrani Sinha-Hikim, Ruoquing Shen, and Atam B. Singh, all from the Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA; Richard Casaburi, Dimple Bhasin, Nancy Berman, Rachelle Bross and Jeffrey Phillips, from the Harbor-University of California Los Angeles Medical Center, Torrance, CA; Xianghong Chen and Kevin E. Yarasheski at the Biomedical Mass Spectrometric Research Resource, Department of Internal Medicine, Washington University, School of Medicine, St. Louis, Missouri, Lynne Magliano and Thomas W. Storer, from the Laboratory for Exercise Sciences, El Camino College, El Camino, CA.

Protocol

This was a double-blind, randomized study consisting of a four-week control period, a 20-week treatment period, and a 16-week recovery period. The participants were healthy men, 18-35 years of age, with prior weight-lifting experience and normal testosterone levels. These men had not used any anabolic agents and had not participated in competitive sports events in the preceding year, and they were not planning to participate in competitive events in the following year. The participants were asked not to undertake strength training or moderate-to-heavy endurance exercise during the study. These instructions were reinforced every four weeks.

Sixty-one eligible men were randomly assigned to one of five groups. All received monthly injections of a long-acting GnRH agonist to suppress endogenous testosterone production. In addition, group 1 received 25 mg of testosterone enanthate intramuscularly weekly; group 2, 50 mg testosterone enanthate; group 3, 125 mg testosterone enanthate; group 4, 300 mg testosterone enanthate; and group 5, 600 mg testosterone enanthate. Twelve men were assigned to group 1, 12 to group 2, 12 to group 3, 12 to group 4, and 13 to group 5.

Nutritional Intake

Energy and protein intakes were standardized at 36 kcal/kg. The standardized diet was initiated two weeks before treatment started; dietary instructions were reinforced every four weeks. The nutritional intake was verified by analysis of three-day food records and 24-hour food recalls every four weeks.

Outcome Measures

Body composition and muscle performance were assessed at baseline and during week 20. Fat-free mass and fat mass were measured by underwater weighing and dual-energy X-ray absorptiometry. Total thigh muscle and quadriceps muscle volumes were measured by MRI scanning.

For estimation of total body water, the men ingested 10 g of 2H2O, and plasma samples were drawn at 0, 120, 180, and 240 min. A measurement of 2H abundance in plasma was made by nuclear magnetic resonance spectroscopy, with a correction factor of 0.985 for exchangeable hydrogen. Another measure of bilateral leg press strength was taken by use of the one-repetition maximum (1-RM) method. A seated leg press exercise with pneumatic resistance was used for this purpose. Subjects performed 5-10 min of leg cycling and stretching warm-up and received instruction and practice in lifting mechanics before performing progressive warm-up lifts leading to the 1-RM. Seat position and the ensuing knee and hip angles, as well as foot placement, were measured and recorded for use in subsequent testing. To ensure reliability in this highly effort-dependent test, the 1-RM score was reassessed within seven days, but not sooner than two days, after the first evaluation. If duplicate scores were within five percent, the higher of the two values was accepted as the strength score. If the two tests differed by greater than five percent, additional studies were conducted.

Sexual function was assessed by daily logs of sexual activity and desire that were maintained for seven consecutive days at baseline and during treatment by use of a published instrument. Spatial cognition was assessed by a computerized checkerboard test and mood by Hamilton’s depression and Young’s mania scales.

Adverse experiences, blood counts and chemistries, prostate-specific antigen (PSA), plasma lipids, total and free testosterone, luteinizing hormone (LH), sex steroid-binding globulin (SHBG), and insulin-like growth factor I (IGF-I) levels were measured periodically during control and treatment periods. Serum total testosterone was measured by an immunoassay.

Results

Of 61 men enrolled, 54 completed the study: 12 in group 1, 8 in group 2, 11 in group 3, 10 in group 4, and 13 in group 5. One man discontinued treatment because of acne; other subjects were unable to meet the demands of the protocol. The five groups did not significantly differ with respect to their baseline characteristics. Key findings included:

– Compliance: All evaluable subjects received 100percent of their GnRH agonist injections, and only one man in the 125-mg group missed one testosterone injection.

– Nutritional intake: Daily energy intake and proportion of calories derived from protein, carbohydrate, and fat were not significantly different among the five groups at baseline. There was no significant change in daily caloric, protein, carbohydrate, or fat intake in any group during treatment.

– Hormone levels: Serum total and free testosterone levels, measured during week 16, one week after the previous injection, were linearly dependent on the testosterone dose (P = 0.0001). Serum total and free testosterone concentrations decreased from baseline in men receiving the 25- and 50-mg doses and increased at 300- and 600-mg doses. Serum LH levels were suppressed in all groups. Serum SHBG levels decreased dose dependently at the 300- and 600-mg doses but did not change in other groups. Serum IGF-I concentrations increased dose dependently at the 300- and 600-mg doses.

– Body composition: Fat-free mass, measured by underwater weighing, did not change significantly in men receiving the 25- or 50-mg testosterone dose, but it increased dose dependently at higher doses. The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log total testosterone concentrations during treatment (r = 0.73, P = 0.0001). Fat mass, measured by underwater weighing, increased significantly in men receiving the 25- and 50-mg doses, but did not change in men receiving the higher doses of testosterone. There was an inverse correlation between change in fat mass by underwater weighing and log testosterone concentrations.

– Muscle size: The thigh muscle volume and quadriceps muscle volume did not significantly change in men receiving the 25- or 50-mg doses but increased dose-dependently at higher doses of testosterone. The changes in thigh muscle and quadriceps muscle volumes correlated with log testosterone levels during treatment.

– Muscle performance: The leg press strength did not change significantly in the 25- and 125-mg-dose groups but increased significantly in those receiving the 50-, 300-, and 600-mg doses. Leg power did not change significantly in men receiving the 25-, 50-, and 125-mg doses of testosterone weekly, but it increased significantly in those receiving the 300- and 600-mg doses. The increase in leg power correlated with log testosterone concentrations and changes in fat-free mass and muscle strength.

– Behavioral measures: The scores for sexual activity and sexual desire measured by daily logs did not change significantly at any dose. Similarly, visual-spatial cognition and did not change significantly in any group.

– Adverse experiences and safety measures: Hemoglobin levels decreased significantly in men receiving the 50-mg dose but increased at the 600-mg dose; the changes in hemoglobin were positively correlated with testosterone concentrations. Changes in plasma HDL cholesterol, in contrast, were negatively dependent on testosterone dose and correlated with testosterone concentrations. Total cholesterol, plasma low-density lipoprotein cholesterol, and triglyceride levels did not change significantly at any dose. Serum PSA, creatinine, bilirubin, alanine aminotransferase, and alkaline phosphatase did not change significantly in any group, but aspartate aminotransferase decreased significantly in the 25-mg group. Two men in the 25-mg group, five in the 50-mg group, three in the 125-mg group, seven in the 300-mg group, and two in the 600-mg group developed acne. One man receiving the 50-mg dose reported decreased ability to achieve erections.

Discussion

The researchers found that GnRH agonist administration suppressed endogenous LH and testosterone secretion. Therefore, circulating testosterone concentrations during treatment were proportional to the administered dose of testosterone enanthate. This strategy of combined administration of GnRH agonist and graded doses of testosterone enanthate was effective in establishing different levels of serum testosterone concentrations among the five treatment groups. The different levels of circulating testosterone concentrations created by this regimen were associated with dose- and concentration-dependent changes in fat-free mass, fat mass, thigh and quadriceps muscle volume, muscle strength, leg power, hemoglobin, circulating IGF-I, and plasma HDL cholesterol.

Serum PSA levels, sexual desire and activity, and spatial cognition did not change significantly at any dose. The changes in fat-free mass, muscle volume, leg press strength and power, hemoglobin, and IGF-I were positively correlated, whereas changes in plasma HDL cholesterol and fat mass were negatively correlated with testosterone dose and total and free testosterone concentrations during treatment.

There were no significant changes in overall sexual activity or sexual desire in any group, including those receiving the 25-mg dose. Testosterone replacement of hypogonadal men improves frequency of sexual acts and fantasies, sexual desire, and response to visual erotic stimuli. The data demonstrate that serum testosterone concentrations at the lower end of male range can maintain some aspects of sexual function.

Conclusions

This study demonstrates that an increase in circulating testosterone concentrations results in dose-dependent increases in fat-free mass, muscle size, strength, and power. The relationships between circulating testosterone concentrations and changes in fat-free mass and muscle size conform to a single log-linear dose-response curve. The data do not support the notion of two separate dose-response curves reflecting two independent mechanisms of testosterone action on the muscle.

In addition, the study could not determine if responsiveness to testosterone is attenuated in older men. Testosterone dose-response relationships might be modulated by other muscle growth regulators, such as nutritional status, exercise and activity level, glucocorticoids, thyroid hormones, and endogenous growth hormone secretory status. Serum PSA levels decrease after androgen withdrawal, and testosterone replacement of hypogonadal men increases PSA levels into the normal range.

The data demonstrate that different androgen-dependent body functions respond differently to different testosterone dose-response relationships. Some aspects of sexual function and spatial cognition, and PSA levels, were maintained by relatively low doses of testosterone in GnRH agonist-treated men and did not increase further with administration of higher doses of testosterone. In contrast, graded doses of testosterone were associated with dose and testosterone concentration-dependent changes in fat-free mass, fat mass, muscle volume, leg press strength and power, hemoglobin, IGF-I, and plasma HDL cholesterol.

Testosterone doses associated with significant gains in fat-free mass, muscle size, and strength were associated with significant reductions in plasma HDL concentrations. Further studies are needed to determine whether clinically significant anabolic effects of testosterone can be achieved without adversely affecting cardiovascular risk. Selective androgen receptor modulators that preferentially augment muscle mass and strength, but only minimally affect prostate and cardiovascular risk factors, are desirable.

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Article adapted by MD Sports from original press release.
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Contact: Donna Krupa
American Physiological Society

Source: American Journal of Physiology: Endocrinology and Metabolism, December 2001

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

Genetic research into athletic ability should be encouraged for its potential benefits in both sport and public health, a leading group of scientists meeting at the University of Bath said today.

Genetic research into athletic ability should be encouraged for its potential benefits in both sport and public health, a leading group of scientists meeting at the University of Bath said today.

However, ethical concerns, such as whether seeking information about differences between ethnic groups could be perceived as racist research, need to be properly addressed, they warn.

Their recommendations are published in a ‘position stand’ on genetic research and testing launched at the British Association of Sport & Exercise Sciences annual meeting today.

They call for more genetic research in the sport and exercise sciences because of the anticipated benefits for public health, but want researchers to take a more active role in debating the implications of their work with the public.

“If a powerful muscle growth gene was identified, on the one hand this could help develop training programmes that increase muscle size and strength in athletes, but even more importantly the knowledge could be used to develop exercise programmes or drugs to combat muscle wasting in old age,” said Dr Alun Williams from Manchester Metropolitan University, one of the report’s authors.

“We, as scientists investigating genetics, acknowledge a public concern about some genetic research and we believe scientists need to engage in public in debates about the potential benefits of their research.

“Research into the athletic success of East African distance runners or sprinters of West African ancestry might be perceived as unethical.

“But understanding the limits of human exercise capacity in sport could lead to the development of treatments for a range of diseases like cancer and cardiovascular disease.”

The potential applications of genetic testing in sport and exercise also raise some ethical concerns, for example in identifying potential athletic ability before birth.

An Australian company already offers the first genetic performance test (for the ACTN3 gene) which has been linked to sprint and power performance.

The report authors are sceptical about whether this test is useful but anticipate that more advanced versions of these tests will be available in future.

“We are not yet at a point where we can identify a potential future Olympic champion from genetic tests but we may not be very far away,” said Dr Williams, who wrote the report with Drs Henning Wackerhage (Aberdeen University), Andy Miah (University of Paisley), Roger Harris (University of Chichester) and Hugh Montgomery (University College London).

They highlight two dangers of genetic performance tests. Firstly, genetic performance tests might later be linked to disease. For example, a muscle growth gene may later be linked to cancer growth.

“Not all people may want to know, while young that they are at increased risk of cancer by early middle age, but they might inadvertently become aware of that just because they had a ‘sport gene’ test,” said Dr Williams.

Secondly, genetic performance tests can be performed even before birth and this may lead to the selection of foetuses or to abortions based on athletic potential.

The report recommends genetic counselling and that the testing should be confined to mature individuals who fully understand the relevant issues.

Genetic tests might also be used to screen for health risks during sport such as genes that are linked to sudden cardiac death.

Genetic tests for sudden cardiac death are already available but the report recommends that such testing should not be enforced on athletes.

Problems with mandatory testing are highlighted by the case of the basketball player Eddy Curry, who had an irregular heart beat.

Curry was asked by his club, the Chicago Bulls, to perform a predictive genetic test for a heart condition. The athlete refused and was traded to the New York Knicks who did not make such a demand.

In future, genetic tests might be used to identify those that respond with the biggest drop in cholesterol, blood pressure or glucose to exercise.

In a personalised medicine approach, such tests could be used to select subjects for therapeutic exercise programmes but scientists are concerned that this might undermine the ‘exercise for all’ message that already seems difficult to get across to the public.

The authors say that genetic testing might also be used to detect gene doping, which may be a real threat by the time of the London Olympics in 2012, or to show that positive doping tests are the result of a genetic mutation in an athlete.

The report recommends that genetic testing should be used for anti-doping testing as long as the genetic samples are destroyed after testing.

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Article adapted by MD Sports from original press release.
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Contact: Andrew McLaughlin
University of Bath

Investigators in The Research Institute at Nationwide Children’s Hospital have identified the role of a protein that could potentially lead to new clinical treatments to combat musculoskeletal diseases, including Duchenne muscular dystrophy (DMD).

Results of these studies appear in the March 11, 2008 issue of the Proceedings of the National Academy of Sciences.

These studies, led by Brian Kaspar, PhD, a principal investigator in the Center for Gene Therapy at The Research Institute and an assistant professor of Pediatrics at The Ohio State University, focus on a protein called follistatin (FS). Using a single injection, gene-delivery strategy involving FS, investigators treated the hind leg muscles of mice. Results showed increased muscle size and strength, quadruple that of mice treated with proteins other than FS. The muscle enhancements were shown to be well-tolerated for more than two years.

According to Dr. Kaspar, increased muscle mass and strength were also evident when this strategy was tested using a model of DMD. Apart from the injected hind leg muscles, strengthening effects were also shown in the triceps. In addition, fibrosis, abnormal formation of scar tissue and a hallmark of muscular dystrophy, was decreased in FS-treated animals.

“We believe this new FS strategy may be more powerful than other strategies due to its additional effects, including its ability to reduce inflammation,” said Dr. Kaspar.

The strategy showed no negative effects on the heart or reproductive ability of either males or females. The results were also replicated in older animals, suggesting that this strategy could be useful in developing clinical treatments for older DMD patients.

“This research provides evidence of multiple potential treatment applications for muscle diseases including, but not limited to, muscular dystrophy,” said Jerry Mendell, MD, director of the Center for Gene Therapy at The Research Institute, a co-author on the study, and professor of Pediatrics in Neurology and Pathology at The Ohio State University. “These results offer promise for treatment of potentially any muscle-wasting disease, including muscle weakness due to other illnesses, aging, and inflammatory diseases such as polymyositis. Our next step is to pursue clinical trials.”

The Research Institute at Nationwide Children’s Hospital has a patent pending on the FS technique due to the major role it may play for muscular dystrophy treatment and other muscle-wasting diseases.

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Article adapted by MD Sports from original press release.
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Contact: Pam Barber/Mary Ellen Fiorino
Nationwide Children’s Hospital

USC study finds combining resistance training and androgens gives more muscular bang for the buck

PHILADELPHIA (June 19, 2003)-Men who take supplemental androgens-the male hormone testosterone or similar medications-increase their strength by adding muscle mass, but androgens alone do not pack more might into the muscles, according to studies presented today by University of Southern California researchers.

Treatment with androgens increases lean body mass-which encompasses everything in the body but bone and fat-and strength increases proportionately with the amount of muscle added, says E. Todd Schroeder, Ph.D., postdoctoral fellow in the Department of Medicine at the Keck School of Medicine of USC and adjunct assistant professor in the USC Department of Biokinesiology and Physical Therapy. Schroeder presented his findings at the Endocrine Society’s 85th Annual Meeting.

However, when men use androgen therapy combined with resistance training, such as weightlifting, their gains in strength may far outpace the amount of muscle that can be added with androgens alone. Each muscle cell packs a bigger punch, a concept known as improved muscle quality.

“The results of androgen therapy alone on muscle and strength are not necessarily bad, but they are not optimal,” Schroeder says. “The men did improve their strength, but it was proportional to the muscle mass they added.”

The findings wield health implications beyond the stereotypes of muscle-bound bodybuilders. Schroeder and his colleagues are studying the usefulness of androgens and exercise in helping maintain muscle strength, muscle power and physical function among seniors, for example. They also have studied androgen therapy’s effectiveness in battling wasting among HIV-positive patients.

In their recent study, Schroeder and USC colleagues Michael Terk, M.D., and Fred R. Sattler, M.D., looked at both young men and seniors. They followed two groups: 33 seniors ranging from their mid-60s to late 70s, and 23 HIV-positive men ranging from their early 30s to late 40s.

The younger men were randomly assigned to get 600 milligrams (mg) each week of nandrolone alone or in combination with resistance training. The older men were randomly assigned to receive 20 mg a day of oxandrolone or a placebo. These pharmacologic androgen doses were given over 12 weeks.

Researchers determined maximal strength-the most weight a participant could safely lift or push-using leg press, leg extension and leg flexion machines.

The researchers also measured the cross-sectional area of participants’ thighs and the lean body mass of their lower extremities by magnetic resonance imaging, or MRI. They then determined the strength that participants exerted for each unit of muscle (muscle quality) and how muscle quality changed over time.

Androgens alone increased lean body mass and maximum strength in both groups of men, but “gains were modest,” Schroeder says, and muscle quality did not change, since the muscle size and strength both increased proportionately. However, among those using nandrolone and undergoing resistance training, muscle quality improved significantly: Gains in strength were much greater than the gains that could occur from muscle-mass increase alone.

“It is clear from our studies and others that resistance training is critical for increasing muscle quality, but the effects can probably be augmented with androgens,” Schroeder says. “In addition, not everyone can do resistance training, and a short course of androgens can help get people stronger and more functional.”

Finally, results provide researchers insight into how to better design future studies to test strategies to best preserve and even improve muscle strength and physical function among seniors. Similar studies will be important for other types of patients who experience muscle loss and frailty, such as those with cancer, chronic lung disease, chronic renal failure and other conditions.

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Article adapted by MD Sports from original press release.
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Contact: Jon Weiner
University of Southern California

Grants by the National Institute of Diabetes & Digestive & Kidney Diseases and the National Center for Research Resources (General Clinical Research Center) supported the research. Bio Technology General Corp., which makes Oxandrin (oxandrolone), also supported part of the research.

Edward T. Schroeder, Michael Terk and Fred R. Sattler, “Pharmacological Doses of Androgen Do Not Improve Muscle Quality in Young or Older Men: Results from Two Studies,” Endocrine Society’s 85th Annual Meeting, poster P3-212, presentation 11 a.m., June 21. Findings released at news conference 1:30 p.m., June 19.

Molecular switch found in mice could lead to future obesity treatments, scientists say

A surprise discovery — that calorie-burning brown fat can be produced experimentally from muscle precursor cells in mice — raises the prospect of new ways to fight obesity and overweight, say scientists from Dana-Farber Cancer Institute.

Reporting in the Aug. 21 issue of the journal Nature, the researchers demonstrated that brown fat, which is known as the “good” form of fat — so called because it burns calories and releases energy, unlike “bad” white fat that simply stores extra calories — can be generated from unspecialized precursors that routinely spawn skeletal muscle.

The team led by Dana-Farber’s Bruce Spiegelman, PhD, showed that a previously known molecular switch, PRDM16, regulates the creation of brown fat from immature muscle cells. They also determined that the process is a two-way street: Knocking out PRDM16 in brown fat cells can convert them into muscle cells. However, Spiegelman called the latter an “experimental lab trick” for which he currently envisions no practical applications.

The “huge surprise” of the study results, he said, was that muscle precursor cells known as “satellite cells” are able to give birth to brown fat cells under the control of PRDM16.

Spiegelman said the finding confirms that PRDM16 is the “master regulator” of brown fat development. The confirmation will spur ongoing research in his laboratory, he said, to see if drugs that rev up PRDM16 in mice — and potentially, in people — could convert white fat into brown fat and thereby treat obesity. Another strategy, he said, might be to transplant brown fat cells into an overweight person to turn on the calorie-burning process.

“I think we now have very convincing evidence that PRDM16 can turn cells into brown fat cells, with the possibility of combating obesity,” said Spiegelman, the senior author of the paper. The lead author is Patrick Seale, PhD, a postdoctoral fellow in the Spiegelman lab.

Another paper in the same issue of Nature described a different trigger of brown fat production, a molecule called BMP7. A commentary in the journal by Barbara Cannon, an internationally recognized researcher in the biology of fat cells at the University of Stockholm, said that the two reports “take us a step closer to the ultimate goal of promoting the brown fat lineage as a potential way of counteracting obesity.”

The Spiegelman group has long studied fat cells both as a model for normal and abnormal cell development, which relates to cancer, and also because fat cells play such a key role in the growing epidemics of obesity and diabetes.

There is much interest in brown fat’s role in regulating metabolism. Rodents and human infants have abundant brown fat that dissipates food energy as heat to protect against the cold. Though human adults have little brown fat, it apparently does have a metabolic function, including the potential to be amplified in some way to combat obesity.

In 2007, Spiegelman and colleagues reported they had inserted PRDM16 genes into white fat precursors, which they implanted under the skin of mice. The PRDM16 switch coaxed the white fat precursors to produce brown fat cells instead of white. To Spiegelman, this suggested the possibility of transplanting PRDM16-equipped white fat precursors into people who are at high risk of becoming obese, to shift their metabolism slightly into a calorie-burning mode.

The new research adds another potential source of brown fat — the muscle cell progenitors, or myoblasts, that exist in the body to replace mature muscle cells as needed. The progenitors, which can be thought of as “adult stem cells,” are committed to becoming specialized muscle cells when activated by appropriate signals, or, as the study revealed, brown fat cells when PDRM16 is turned on. The PRDM16 trigger “is very powerful at what it does,” said Spiegelman, who is also a professor of cell biology at Harvard Medical School.

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Article adapted by MD Sports from original press release.
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Contact: Bill Schaller
Dana-Farber Cancer Institute 

Other authors of the paper include Bryan Bjork, PhD, and David R. Beier, PhD, MD, of Brigham and Women’s Hospital; Michael Rudnicki, PhD, of the Ottawa Health Research Institute; and Hediye Erdjument-Bromage, PhD, and Paul Tempst, PhD, of Memorial Sloan-Kettering Cancer Center.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

    Creatine, a popular nutritional supplement used by weightlifters and sprinters to improve athletic performance, could lend muscle strength to people with muscular dystrophies.

    Muscle strength increased by an average of 8.5 percent among patients taking creatine, compared to those who did not use the supplement, according to a recent review of studies. Creatine users also gained an average of 1.4 pounds more lean body mass than nonusers.

    The evidence from the studies “shows that short- and medium-term creatine treatment improves muscle strength in people with muscular dystrophies and is well-tolerated,” said lead reviewer Dr. Rudolf Kley of Ruhr University Bochum in Germany.

    The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

    Creatine is found naturally in the body, where it helps supply energy to muscle cells. Athletes looking for short bursts of intense strength have used creatine in powders or pills for decades, but the supplement became more popular after the 1992 Barcelona Olympics, when sprinters, rowers and cyclists went public with their creatine regimens.

    Although creatine has been widely studied as a performance enhancer, it’s still not clear if the supplement makes a difference, according to Roger Fielding, Ph.D., of Tufts University, who has also recently written a review of creatine treatments for neuromuscular diseases.

    People with muscular dystrophies can have lower-than-normal levels of creatine, along with increasing muscle weakness as their disease progresses. Since some studies suggest that creatine improves muscle performance in healthy people, many researchers have reasoned that it might be helpful in treating muscle disease.

    The Cochrane researchers reviewed 12 studies that included 266 people with different types of muscular dystrophy. People in the studies who took creatine supplements used them for three weeks to six months.

    In muscular dystrophies, the proteins that make up the muscles themselves are either missing or damaged. In a related group of disorders called metabolic myopathies, the chemicals that help muscles operate go awry.

    Although creatine seemed to help many patients with muscular dystrophies, those with metabolic myopathies gained no more muscle strength or lean body mass than patients who did not use the supplement.

    The reason for the contrasting results — creatine’s “fairly consistent” effects in muscular dystrophy and lack of effectiveness in metabolic diseases — is “not entirely clear,” Kley said, calling for more research on treatment for metabolic disorders.

    The review was supported by the Neuromuscular Center Ruhrgebiet/Kliniken Bergmannsheil, at Ruhr-University Bochum and the Hamilton Health Sciences Corporation, in Canada. Kley and colleagues have each participated in trials of creatine treatment for muscle disorders, although none of the studies was sponsored by a maker of creatine.

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    Article adapted by MD Sports from original press release.
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    FOR MORE INFORMATION
    Health Behavior News Service: hbns-editor@cfah.org

    Kley RA, Vorgerd M, Tarnopolsky MA. Creatine for treating muscle disorders. Cochrane Database of Systematic Reviews 2007, Issue 1.

    The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

Recipe to recover more quickly from exercise: Finish workout, eat pasta, and wash down with five or six cups of strong coffee.

Glycogen, the muscle’s primary fuel source during exercise, is replenished more rapidly when athletes ingest both carbohydrate and caffeine following exhaustive exercise, new research from the online edition of the Journal of Applied Physiology shows. Athletes who ingested caffeine with carbohydrate had 66% more glycogen in their muscles four hours after finishing intense, glycogen-depleting exercise, compared to when they consumed carbohydrate alone, according to the study, published by The American Physiological Society.

The study, “High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is co-ingested with caffeine,” is by David J. Pedersen, Sarah J. Lessard, Vernon G. Coffey, Emmanuel G. Churchley, Andrew M. Wootton, They Ng, Matthew J. Watt and John A. Hawley. Dr. Pedersen is with the Garvan Institute of Medical Research in Sydney, Australia, Dr. Watt is from St. Vincent’s Institute of Medical Research, Fitzroy, Victoria, Australia. All others are with the Royal Melbourne Institute of Technology University (RMIT) in Bundoora, Victoria, Australia.

A fuller audio interview with Dr. Hawley is available in Episode 11 of the APS podcast, Life Lines, at www.lifelines.tv. The show also includes an interview with Dr. Stanley Schultz, whose physiological discovery of how sugar is transported in the gut led to the development of oral rehydration therapy and sports drinks such as Gatorade and Hi-5.

Caffeine aids carbohydrate uptake  

It is already established that consuming carbohydrate and caffeine prior to and during exercise improves a variety of athletic performances. This is the first study to show that caffeine combined with carbohydrates following exercise can help refuel the muscle faster.

“If you have 66% more fuel for the next day’s training or competition, there is absolutely no question you will go farther or faster,” said Dr. Hawley, the study’s senior author. Caffeine is present in common foods and beverages, including coffee, tea, chocolate and cola drinks.

The study was conducted on seven well-trained endurance cyclists who participated in four sessions. The participants first rode a cycle ergometer until exhaustion, and then consumed a low-carbohydrate dinner before going home. This exercise bout was designed to reduce the athletes’ muscle glycogen stores prior to the experimental trial the next day.

The athletes did not eat again until they returned to the lab the next day for the second session when they again cycled until exhaustion. They then ingested a drink that contained carbohydrate alone or carbohydrate plus caffeine and rested in the laboratory for four hours. During this post-exercise rest time, the researchers took several muscle biopsies and multiple blood samples to measure the amount of glycogen being replenished in the muscle, along with the concentrations of glucose-regulating metabolites and hormones in the blood, including glucose and insulin.

The entire two-session process was repeated 7-10 days later. The only difference was that this time, the athletes drank the beverage that they had not consumed in the previous trial. (That is, if they drank the carbohydrate alone in the first trial, they drank the carbohydrate plus caffeine in the second trial, and vice versa.)

The drinks looked, smelled and tasted the same and both contained the same amount of carbohydrate. Neither the researchers nor the cyclists knew which regimen they were receiving, making it a double-blind, placebo-controlled experiment.

Glucose and insulin levels higher with caffeine ingestion
The researchers found the following:  
  • one hour after exercise, muscle glycogen levels had replenished to the same extent whether or not the athlete had the drink containing carbohydrate and caffeine or carbohydrate only
  • four hours after exercise, the drink containing caffeine resulted in 66% higher glycogen levels compared to the carbohydrate-only drink
  • throughout the four-hour recovery period, the caffeinated drink resulted in higher levels of blood glucose and plasma insulin
  • several signaling proteins believed to play a role in glucose transport into the muscle were elevated to a greater extent after the athletes ingested the carbohydrate-plus-caffeine drink, compared to the carbohydrate-only drink

 Dr. Hawley said it is not yet clear how caffeine aids in facilitating glucose uptake from the blood into the muscles. However, the higher circulating blood glucose and plasma insulin levels were likely to be a factor. In addition, caffeine may increase the activity of several signaling enzymes, including the calcium-dependent protein kinase and protein kinase B (also called Akt), which have roles in muscle glucose uptake during and after exercise.

Lower dose is next step  

In this study, the researchers used a high dose of caffeine to establish that it could help the muscles convert ingested carbohydrates to glycogen more rapidly. However, because caffeine can have potentially negative effects, such as disturbing sleep or causing jitteriness, the next step is to determine whether smaller doses could accomplish the same goal.

Hawley pointed out that the responses to caffeine ingestion vary widely between individuals. Indeed, while several of the athletes in the study said they had a difficult time sleeping the night after the trial in which they ingested caffeine (8 mg per kilogram of body weight, the equivalent of drinking 5-6 cups of strong coffee), several others fell asleep during the recovery period and reported no adverse effects.

Athletes who want to incorporate caffeine into their workouts should experiment during training sessions well in advance of an important competition to find out what works for them.

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Article adapted by MD Sports from original press release.
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Contact: Christine Guilfoy
American Physiological Society

Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society (APS) has been an integral part of this scientific discovery process since it was established in 1887.