As functional medicine providers, we are continually assessing the benefits and drawbacks of various therapeutic options for our patients. One such therapy that has gained considerable attention is glucagon-like peptide-1 (GLP-1) receptor agonists. While these medications have demonstrated useful roles in managing type 2 diabetes, promoting weight loss and reducing future risks of dementia and others, we also must consider the potential downsides, particularly myosteatosis.
What is Myosteatosis?
Myosteatosis, the accumulation of fat within muscle tissue, poses a significant ongoing risk factor for worsening metabolic dysfunction, insulin resistance, and decreased physical performance. Fortunately, a full 360-degree functional medicine and lifestyle optimization approach can mitigate such risks. Additionally, we can consider alternatives to initiating GLP-1 agonist therapy prematurely in favor of lifestyle and nutraceutical therapies that can mimic the same physiology without increasing sarcopenia or myosteatosis risks.
For context, you have likely seen lot of excitement and progress in the medical literature around liver steatosis, so much so that we have new nomenclature. Conditions like MASH (metabolic-associated steatotic hepatitis) and MASLD (metabolic-associated steatotic liver disease) demonstrate our improved understanding of the primary system imbalances that result in the liver organ disease. Although this advancement has been necessary, it is vital that we, as systems biology thinkers, remember that there are other organs downstream of the same metabolic imbalances. Myosteatosis is considered a significant pathological change in the process of sarcopenia development. Similar to the process in which MASLD (fatty liver) can advance to cirrhosis (liver cell death), myosteatosis (fatty muscle) can advance to sarcopenia (muscle cell death). Therefore, developing effective muscle retention strategies is essential with use of GLP-1 agonists to not only enhance short-term outcomes, but also to promote healthy aging long-term.
Mechanisms Behind Myosteatosis
The underlying mechanisms linking GLP-1 therapy to myosteatosis are still being investigated. One theory posits that the caloric deficit induced by appetite suppression may lead to muscle catabolism, particularly when dietary protein intake is inadequate. Additionally, GLP-1 can also lead to alterations in lipid metabolism within muscle tissues, potentially exacerbating fat infiltration. Another consideration is the impact of GLP-1 on physical activity levels. Patients may experience gastrointestinal side effects such as nausea and vomiting, which can lead to reduced physical activity. Reduced physical activity not only contributes to further muscle loss but also promotes fat accumulation in muscle tissue, compounding the issue of myosteatosis.
Clinical Implications
For functional medicine practitioners, the implications of these findings are significant. While GLP-1 therapies can provide short-term benefits in glycemic control and weight loss, they may inadvertently contribute to long-term muscle health issues. It is crucial to consider the following:
- Comprehensive Assessments: Before initiating GLP-1 therapy, conduct thorough assessments of body composition, including evaluations of intramuscular fat and overall muscle mass. This baseline data will be essential for monitoring changes throughout treatment. Be sure to emphasize caloric targets so patients don’t inadvertently “starve” themselves into muscle catabolism.
- Nutritional Guidance: Ensure that patients are receiving adequate protein intake to support muscle maintenance during weight loss. Educating patients about the importance of a balanced diet, rich in high-quality protein sources, can mitigate some risks associated with myosteatosis.
- Encourage Physical Activity: Actively promote resistance training and aerobic exercise as part of a holistic treatment plan. Incorporating regular physical activity can help preserve muscle mass and counteract the adverse effects of GLP-1 therapy on muscle composition.
- Enhancement/Alternative Therapies: As we continue to understand how GLP-1s exert their beneficial effects, we can mindfully amplify supportive pathways like AMPK, GLP-1 production, and others with lifestyle and nutraceuticals. These can be used to reduce the dose and/or side effects of GLP-1 or to be a substitute altogether for some.
The Bottom Line
While GLP-1 receptor agonists offer promising benefits for managing type 2 diabetes and promoting weight loss, their potential impact on myosteatosis cannot be overlooked. As functional medicine providers, it is our responsibility to weigh these risks against the benefits and to adopt a comprehensive approach to patient care. By understanding the complexities of GLP-1 therapy and its effects on muscle composition, we can better support our patients in achieving optimal health outcomes.
In addition to over 20 years of progressive patient care, Shilpa P. Saxena, MD, IFMCP serves as Chief Medical Officer of Forum Health and Medical Director of their Tampa location. She is Faculty with the Institute for Functional Medicine and has served in various contributing physician educator roles with the Andrew Weil Center for Integrative Medicine, George Washington University’s Metabolic Medicine Institute, University of Miami Miller School of Medicine’s Department of Family Medicine and Community Health, and Universidad San Ignacio de Loyola (Lima, Perú). She joined Lifestyle Matrix Resource Center team over 10 years ago to help providers, patients and practices around the world deliver effective functional medicine through her Group Visit Toolkits. She also continues to serve as the Clinical Expert for the CM Vitals Program.
