Botox: A Closer Look at Its Use, Emerging Risks, and the Importance of Patient Screening
Botox (botulinum toxin) is widely marketed as a solution for aesthetic enhancements and medical issues like migraines and hyperhidrosis. However, emerging evidence suggests that Botox may have systemic effects, potentially influencing muscle metabolism, joint stability, and overall musculoskeletal health. While Botox has provided benefits for millions, it’s crucial to explore its less-discussed effects and the need for careful patient screening—especially in populations at higher risk for joint instability, sarcopenia, or osteopenia.
Case Update: Exploring Systemic Effects of Botox in Ehlers-Danlos Syndrome
A Personal Exploration: Botox and Muscle Recovery
At TOBI 2024, Dr. Rowan Paul and I presented our case report, Orthobiologics in Ehlers-Danlos Syndrome: A Transformative Case Report. While previous discussions focused on connective tissue vulnerabilities and Orthobiologic approaches, this year’s update introduces a new variable: Botox use. For the first time, we explore how long-term Botox use may contribute to systemic muscle suppression, metabolic disruption, and broader implications for patient management. Physicians can review all 2024 presentations in detail via the TOBI Access Plus library here.
The patient (myself), a 36-year-old woman with hEDS, multiple mutations of unknown significance within collagen related genes [COL5A2: c.1633C>T, COL4A4: c.3979G>A, COL17A1: c.4304C>T (p.A1435V)], genetic variants in transcobalamin, methionine synthase, MTHFR (compound heterozygous), and glutathione synthase, had a 15-year history of receiving approximately 20 units of Botox in the forehead and glabellar lines every 4-6 months. Initially prescribed for tension headaches during medical school exams and later for aesthetic purposes, Botox use was discontinued during the recovery period for a recent rotator cuff tear (sustained the day prior to TOBI 2024). The results were transformative, revealing unexpected changes in facial muscle tone and significant strength gains upon resuming heavier weightlifting. Hip abduction strength nearly doubled from 90-100 lbs to 180 lbs, and for the first time in adult memory, I was able to perform unassisted pull-ups. I also observed increased quadriceps mass and notable lat prominence, improvements that are underscored by the inverse correlation between leg strength and all-cause mortality BMJ. Additionally, my facial structure changed as the masseter muscle—never directly injected—regained prominence, suggesting systemic diffusion of Botox may have suppressed muscle activation beyond the injection site and could have even potentially contributed to atlantoaxial instability.
These findings, never previously discussed in this case, indicate that Botox may have systemic effects, compounding joint instability and metabolic suppression over time. Emerging literature supports this hypothesis, with studies documenting tendon atrophy and stem cell senescence following botulinum toxin exposure, even in areas distant from injection sites PMC3563356. This aligns with the substantial strength recovery and increased exercise capacity observed post-cessation, findings relevant to all patients, but especially relevant for EDS patients, who already experience connective tissue fragility. These observations highlight the need for further exploration into the systemic implications of Botox use.
This new evidence underscores the importance of caution when prescribing Botox to patients, and especially those with musculoskeletal vulnerabilities, as well as those with risk for sarcopenia or osteopenia, and those taking or considering easily accessible GLP-1 agonists for metabolic decline. By sharing this update, we aim to enhance awareness of Botox’s potential systemic effects and the implications for healthy aging, advocating for comprehensive patient screening and vigilant follow-up. For additional details and prior insights, please refer to the TOBI Access Plus 2024 archive here.
Systemic Absorption and Metabolic Effects:
A Growing Hypothesis
Although Botox is marketed as a localized treatment, studies suggest it can be absorbed systemically with cumulative effects, some of which may be permanent.
Research published in the Journal of Neuroscience (PMID: PMC3563356) highlights how botulinum toxin may impact distant muscles, raising concerns about its broader effects. For instance, even light Botox use—such as my 20 units in the forehead—might influence muscle tone, metabolism, and stem cell activity in tendons, yet patients are being marketed everything from Botox use for hyperhidrosis, to lip flips, forehead wrinkle prevention, headache treatment, masseter slimming (“V-Line Tox”), and trap tox (“Barbie Tox”), including regions and dosages which may be larger than those mentioned in various studies cited herein. More recently, approximately 25 units of hyperdilute Botox had been incorporated into my last 3 cycles of bilateral Stellate ganglion blocks. The blocks were immensely and undeniably helpful, and I would still consider that intermittent use in this manner, when considered with responsible informed consent and as part of a holistic picture, can remain deeply valuable. Due to overall stability and health, and the lack of a strong indication for further use, I would omit the hyperdilute Botox from further Stellate blocks in my personal case, but still value its prior use and could consider intermittent use in the future if warranted.
The hypothesized effects of BTX are particularly important to consider for individuals with pre-existing conditions, such as Ehlers-Danlos Syndrome (EDS) and may be a contributing factor in the observed increased severity of hEDS within America. One hypothesis could be that patients with connective tissue disorders, such as Ehlers-Danlos Syndrome (EDS), might have an increased susceptibility to Botox diffusion due to altered extracellular matrix composition, vascular permeability, or neuromuscular signaling, potentially making them more prone to systemic effects, unintended muscle weakening, or prolonged impact beyond the injection site.
Potential Side Effects:
Emerging Research Findings:
Studies indicate that botulinum toxin (Botox) injections can lead to tendon atrophy by inducing senescence in tendon-derived stem cells (TDSCs). This process may result in long-term musculoskeletal effects, including reduced tendon strength and impaired healing. Stem Cell Research
Botulinum toxin (BTX) injections can lead to muscle atrophy and subsequent bone loss, particularly in populations already at risk, such as postmenopausal women or individuals with chronic illnesses. Animal studies have demonstrated that BTX-induced muscle paralysis results in significant reductions in muscle mass and bone strength. For instance, a study involving rats reported a 61% decrease in rectus femoris muscle mass and a 31% reduction in femoral neck bone strength following BTX injection. Springer
Additionally, research has demonstrated that BTX-induced muscle atrophy can contribute to bone loss in both the injected and contralateral limbs, even at dosages commonly used in masseter and trapezius injections. A study in mice found that BTX injections led to significant muscle atrophy and bone loss not only in the treated limb but also in the untreated contralateral limb, suggesting systemic effects. Springer This phenomenon is particularly evident in patients treated for spasticity, where the proposed mechanisms include systemic spread of the toxin or neural adaptations that result in bilateral muscle weakening. For instance, a study on post-stroke spasticity management reported contralateral weakness and fatigue following high-dose BoNT-A injections. J Neurology
These findings highlight the potential widespread impact of BoNT-A injections beyond the targeted muscles, raising considerations for both therapeutic and aesthetic applications where muscle integrity and joint stability are crucial.
Implications for Joint Stability:
The weakening of both targeted and contralateral muscles can have significant implications for joint stability. Muscles play a crucial role in maintaining joint integrity; thus, their atrophy may predispose individuals to joint instability and associated complications. This is particularly relevant for now commonly injected muscles like the trapezius and masseter, which are often targeted in aesthetic procedures (“traptox,” “v-line tox,” and “barbietox”). Weakening of these muscles could potentially affect the stability of the shoulder girdle, craniocervical junction, and temporomandibular joint.
Botox and Potential Metabolic Suppression
Botox’s ability to suppress muscle activity also may suppress metabolism. Over time, this may contribute to the development of “skinny-fat” body types—patients with low muscle mass but normal or slightly elevated body fat percentages and metabolic dysfunction, restricting due to perceived “slowed metabolism” and sometimes presenting with osteopenia. This phenomenon is particularly concerning as it coincides with the rising popularity of GLP-1 agonists, such as semaglutide. These drugs, now widely marketed off-label, slow digestion and may further reduce metabolism, potentially compounding the risk of sarcopenia and osteopenia in aging populations.
Furthermore, it should be considered that metabolic health, particularly muscle mass, plays a crucial role in mitigating the risk of Alzheimer’s disease, often referred to as “type 3 diabetes” due to its strong association with insulin resistance. U.S. News Health. Additionally, Alzheimer's disease has been called "type 3 diabetes" because of shared molecular and cellular features among diabetes and Alzheimer's. Harvard Health. Therefore, a global and prolonged reduction in muscle mass during key muscle mass and bone mass developmental and maintenance years could theoretically provoke an increased risk of Alzheimer’s by impairing systemic metabolic regulation:
Research has demonstrated that insulin sensitivity is critical for regulating glucose uptake in the hippocampus, a brain region essential for memory and cognitive function. Studies indicate that impaired insulin signaling in the hippocampus can lead to decreased neuroplasticity and cognitive deficits. Diabetes Journals Additionally, insulin plays a vital role in memory formation processes in the hippocampus, and systemic insulin resistance can interfere with hippocampal metabolism and cognitive function. Oxford Academic
Chronic disruptions to this process, potentially exacerbated by reduced muscle mass and suppressed metabolism, could create a pathway for neurodegenerative disease development, which is even more concerning for patients with family history, individuals carrying the APOE ε4 allele, and patients with comorbidities such as MCAS who may require essential antihistamine medications for quality of life and safety. Research indicates that the use of certain antihistamines, particularly those with anticholinergic properties like diphenhydramine, is associated with an increased risk of dementia, including Alzheimer's disease Harvard. Therefore, for patients with comorbidities such as Mast Cell Activation Syndrome (MCAS) who may require such antihistamine treatment, it is crucial to consider these potential risks when screening for long-term use of Botox.
Importantly, the Botox generation has not yet reached old age, and the long-term effects of widespread and sustained use of botulinum toxin on metabolic and cognitive health remain unknown, warranting further investigation into these potential risks.
Updated Recommendations for Screening
Given the potential systemic effects of Botox, patient evaluations should routinely incorporate Botox history, particularly for individuals at higher risk for musculoskeletal or metabolic complications.
Key Screening Considerations:
Joint Instability & Connective Tissue Disorders:
Patients with Ehlers-Danlos Syndrome (EDS), generalized hypermobility, or other connective tissue disorders should be assessed for Botox use, as it may exacerbate existing muscle weaknesses and contribute to joint instability.
Muscle Mass & Metabolic Health:
Routine screening for sarcopenia and osteopenia is recommended in patients with a history of regular, multi-site, high dose, and/or long-term Botox use, especially those also using metabolic suppressors like GLP-1 agonists (e.g., semaglutide, liraglutide).
Patients with low muscle mass or chronic illness should be evaluated for potential compounded risks, including accelerated muscle loss, metabolic slowdown, and reduced functional strength.
Rehabilitation & Injury Recovery:
Patients recovering from orthopedic injuries should be informed of potential systemic Botox effects, which may impair muscle recovery, slow strength gains, or exacerbate instability.
Potentially increased risk of accelerated arthritis due to muscle weakening and joint instability should also be considered and investigated.
Potential neurological effects have been suggested and warrant further investigation.
Neurodegenerative Disease Risk & Fall Prevention:
Patients with a family history of Alzheimer’s disease or those at increased risk of neurodegeneration should be screened for long-term Botox use, as emerging research suggests potential links between Botox, metabolic dysfunction, and cognitive decline which are not yet clear.
Patients at risk for falls should be evaluated for Botox-related muscle weakening that could impact balance and mobility.
Regulatory and Safety Considerations:
The CDC is actively investigating Botox safety concerns, including reports of neurological side effects, some of which may not be solely due to counterfeit products (CDC Botox Safety Inquiry).
Given the growing body of evidence, clinicians should prioritize informed consent, patient education, and proactive screening to ensure safe and responsible Botox administration, particularly for high-risk populations.
Conclusion:
A More Cautious Approach to Botox Use
While Botox has undeniable benefits, and times where the benefit may outweigh the risk (such as intermittent or low-frequency use during focused rehabilitation for cerebral palsy and in the off label use in Stellate ganglion blocks for highly effective CPSD treatment) its systemic and long-term effects warrant greater scrutiny. For patients with musculoskeletal concerns, injuries, or those with risk for sarcopenia, osteopenia, or metabolic dysfunction, the risks may outweigh the benefits. More research is needed to fully understand the long-term implications of Botox on metabolism, muscle strength, and overall health, as well as the risks when combined with glp-1 agonists. Until then, clinicians should prioritize patient education, thorough screening, and informed consent to ensure safe and effective use.
- Lonnie Rae Kurlander
