Doctors are well aware that daily intake of prednisone promotes obesity and a host of other side effects. Still, researchers from Northwestern Medicine have found in a new study that intermittent, once-weekly prednisone has different results, stimulating nutrient absorption into muscles and enhancing lean body mass.
Taking prednisone once per week while on a high-fat diet improved exercise endurance in obese mice, strengthened them, helped them lose weight, and increased their lean body mass.
The treated mice also displayed increased muscle metabolism and adiponectin levels (a hormone derived from fat that has beneficial effects against obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease, as well as suppressing glucose production in the liver and enhancing fatty acid oxidation in skeletal muscles)
Long-term, chronic prednisone intake leads to obesity and metabolic syndrome (an obesity-related disorder that involves elevated blood lipids and blood sugar).
Intermittent Dosing Of Prednisone May Be Beneficial For Health
Thus, the results of this study, where the scientists intermittently pulsed the mice with prednisone once a week, are rather different. A once-weekly prednisone dose may be a novel approach to treating obesity since it could facilitate nutrient uptake into muscle.
The researchers explained that fat and muscle communicate to regulate metabolism using circulating signals, including adiponectin. Exercise tolerance and muscle bioenergetics could both be improved by controlling this cross-talk.
Chronic use of glucocorticoids like prednisone promotes metabolic stress and obesity. Various immune conditions require the everyday use of prednisone, such as people who have arthritis, blood disorders, breathing problems, severe allergies, skin diseases, and cancer, to name a few.
Some of the known side effects of daily prednisone include:
- weight gain
- increased risk of infections
- thinning bones
- suppressed adrenal gland hormone production
- muscle weakness
- mood swings
- slower healing
The researchers wanted to know whether patients could get the same immune benefit with intermittent prednisone dosing, which could benefit the muscle more. In one of their earlier studies, these same researchers uncovered that intermittent dosing of prednisone helped with muscular dystrophy, and they demonstrated that once-weekly prednisone enhanced strength.
Furthermore, they recently reported findings from a clinical trial involving individuals with muscular dystrophy, in which prednisone was found to improve lean mass.
This new research study found that once-weekly intermittent prednisone effectively increased adiponectin levels, improved exercise tolerance, and increased energy expenditure in mice with dietary obesity.
In mice with pre-established obesity, intermittent prednisone decreased weight gain and improved strength, treadmill endurance, and glucose homeostasis compared to daily dosing.
Similarly, treatment with once-weekly prednisone also resulted in increased strength and running capacity in mice already obese from eating a high-fat diet. Even in obese mice, prednisone had a favorable effect on metabolic outcomes only when administered intermittently.
Most of what we previously knew about steroids, such as prednisone, was derived from studies investigating the effects of daily dosages of prednisone. The researchers plan to optimize dosing to determine the correct dose in humans, but knowing adiponectin is one marker might provide a hint. If taken once a week, it has a very different result.
Prednisone Increases Nutrients Absorption
The weekly dose of prednisone was characterized as a spike in nutrients going into the muscles in the study. In their opinion, releasing these spikes of nutrients intermittently may be a particularly efficient way to enhance lean body mass.
An important finding in this study is that glucocorticoids like prednisone can be transformed from obesity inducers to obesity preventers by changing the frequency of their dosage. Once-daily chronic consumption of these drugs promotes obesity. As shown here, intermittent dosing of the same type of drug (in this case, once weekly) has the opposite effect, boosting muscle metabolism and reducing metabolic stress caused by a high-fat diet.
As different people respond differently to prednisone, the researchers are trying to determine which biomarkers are crucial for having a positive reaction to prednisone. Their goal is to find a dose of prednisone that minimizes atrophy factors and maximizes positive markers like adiponectin, so they can customize prednisone dosing to meet the needs of each patient.
In another recently published study, the research team recently showed that male versus female mice utilizes different molecular pathways for muscle strengthening when given weekly prednisone.
In general, the team of researchers continues to be cautious about making clinical conclusions regarding the application of intermittent prednisone. The studies were performed on mice. Yet, once-weekly prednisone could benefit obesity if these same pathways hold in humans.
Despite their motivation from a pilot study on humans with muscular dystrophy, mouse muscles contain more fast-twitch fibers than humans, and slow-twitch muscles may differ. To fully understand how these mechanisms work in human muscles, more studies are needed.
In any case, the study showed that intermittent prednisone stimulates fat-muscle communication through adiponectin. Researchers may be able to develop adjuvant drug strategies to restore adiponectin sensitivity and exercise tolerance in metabolic stress conditions based on the results of this study.