October 10, 2024
Home » Urolithin A vs. Osteoarthritis

Degenerative diseases, specifically those that affect joints and muscle, produce detrimental effects on movement, agility, strength, and quality of life. Numerous nutritional and strength exercise therapies focus on the regeneration of these tissues, mostly slowing the disease progression by modulating inflammatory response. Nowadays, osteoarthritis (OA) affects tens of millions worldwide and associates with joint degradation, loss of articular cartilage, and synovial inflammation. Indeed, OA is a multifactorial condition coinciding with aging, obesity, injury, and joint malformation. Urolithin A, a microbiome-derived metabolite, is associated with powerful anti-inflammatory effects and anti-aging benefits. Let’s find out what the studies say about reversing and preventing OA with UA supplementation. 

OA physiopathology:

Inflammation plays a central part in OA physiopathology. Indeed, studies suggest that elevated levels of pro-inflammatory mediators IL-1b, IL-6, and tumor necrosis factor-alpha (TNF-a) are found in OA cartilage. In addition, extensive research proves that IL-1b is a potent inflammatory response initiator and acts as a master regulator of the inflammatory cascade. 

Furthermore, an IL-1b upregulation stimulated the production of metalloproteinases (MMPs) by chondrocytes. In this pro-inflammatory environment, the combination of MMPs and thrombospondin type 1 motifs (ADAMTS), along with the presence of cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS). Combining these factors results in cartilage alteration, promotes tissue catabolism, and promotes extracellular matrix (ECM) degradation.

UA vs. inflamm-aging

Low-grade inflammation is the continuous exposure of chronic inflammation. This factor is consistent with chronic degenerative diseases and age-related cellular decline resulting in organ and tissue dysfunction.

Several studies using animal models report consistent inflammatory modulatory effects of UA and its metabolic responses. Firstly, UA supplementation can reduce the expression of mRNA and circulatory levels of pro-inflammatory marker cyclooxygenase- 2 in rat models with acute colitis. Following studies in rat models associated UA with reduced inflammatory response inducer IL-1b, resulting in decreased concentration of IL-6 and TNF-A. On the contrary, an elevation of the anti-inflammatory cytokine IL-10 was observed in UA- treated diabetic mice.  

UA mechanism of action in joint disorders 

Between the anti-inflammatory mechanisms mediated by UA, the inhibition of TNF-a at a nuclear level of pulpous cells and the reduction of intervertebral disc degradation have been demonstrated in vivo.

A recent study performed in human chondrocytes intervened with UA demonstrated the anti-inflammatory orchestra of this microbiome-derived metabolite. Some of the mechanisms of action were:

  • UA reduced the levels of MMP3 and MMP13 in previously IL-1b-treated chondrocytes. This effect was associated with an attenuation of the expression of iNOS and COX-2.
  • The decrease of MMP3 resulted in an increase in Collagen II and proteoglycan synthesis.
  • Another crucial benefit associated with UA was the upregulation of Sox-9. Furthermore, Sox-9 is a transcription factor that modulated Collagen II synthesis, the cornerstone of chondrocyte differentiation.
  • In conclusion, this study reported that UA could be used as a therapeutic agent due to its capacity to restore the balance between the cartilage matrix anabolism and catabolism.

 UA modulates MAPK and NF-kb pathways.

Mitogen-activated protein kinase (MAPK) and NF-kb pathways function as master regulators in the process of OA pathology. In a healthy environment, MAPK transmits cellular stimulation signals that induce cell proliferation, differentiation, transformation, and apoptosis. However, in a pro-inflammatory environment, three key members of this pathway can act as potent initiators of a pro-inflammatory cascade. Indeed, elevated concentrations of the extracellular regulated kinase (ERK), N-terminal kinase (JNK), and p38 are found in synovial tissue and cartilage lesion. This upregulation reflects in articular damage caused by a higher concentration of MMPs-induced by activating these three factors and IL-1b inflammatory milieu.

Furthermore, IL-1b can stimulate NF-kB activation and nuclear translocation, resulting in an elevated expression of iNOS and COX-2. Consequently, this cascade reaction catalyzes the NO, increasing MMPs, which attenuates collagen II and proteoglycan synthesis. 

Concurrently, the study performed by Shen-long et al. reported that UA intervention could potentially reduce lipopolysaccharide-induced inflammation. Ultimately, this mechanism would decrease the MAPK and NF-kB pathways and promote an anabolic environment in the joint tissues. However, the same authors report that more information is still to be elucidated on this topic, and further research is needed. 

The inflammatory mechanism that promotes osteoarthritis can be prevented, reversed, and treated. Although, we have to consider that inflammation can be enabled by excessive fat mass, elevated concentration on ROS, and dietary components. Therefore, treating this age-related condition can be supported by weight reduction therapy, proper physical exercise, and nutritional advice. Furthermore, nutritional treatment should include an anti-inflammatory diet that enables a beneficial microbiome that can promote the formation of UA.- Ana Paola Rodríguez Arciniega, MS.

References:

Ding, Sheng-Long et al. “Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes.” Journal of inflammation (London, England) vol. 17 13. 24 Mar. 2020, doi:10.1186/s12950-020-00242-8

D’Amico, Davide et al. “Impact of the Natural Compound Urolithin A on Health, Disease, and Aging.” Trends in molecular medicine vol. 27,7 (2021): 687-699. doi:10.1016/j.molmed.2021.04.009

Additional Online Links & Resources (Available 24/7)

 

Online Appointments or Consultations: bit.ly/Book-Online-Appointment

 

Online Physical Injury / Accident Intake Form: bit.ly/Fill-Out-Your-Online-History 

 

Online Functional Medicine Assessment: bit.ly/functionmed

General Disclaimer

Professional Scope of Practice *

The information herein on "Urolithin A vs. Osteoarthritis" is not intended to replace a one-on-one relationship with a qualified health care professional or licensed physician and is not medical advice. We encourage you to make healthcare decisions based on your research and partnership with a qualified healthcare professional.

Blog Information & Scope Discussions

Our information scope is limited to Chiropractic, musculoskeletal, physical medicines, wellness, contributing etiological viscerosomatic disturbances within clinical presentations, associated somatovisceral reflex clinical dynamics, subluxation complexes, sensitive health issues, and/or functional medicine articles, topics, and discussions.

We provide and present clinical collaboration with specialists from various disciplines. Each specialist is governed by their professional scope of practice and their jurisdiction of licensure. We use functional health & wellness protocols to treat and support care for the injuries or disorders of the musculoskeletal system.

Our videos, posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate to and directly or indirectly support our clinical scope of practice.*

Our office has reasonably attempted to provide supportive citations and has identified the relevant research study or studies supporting our posts. We provide copies of supporting research studies available to regulatory boards and the public upon request.

We understand that we cover matters that require an additional explanation of how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez, DC, or contact us at 915-850-0900.

We are here to help you and your family.

Blessings

Dr. Alex Jimenez DC, MSACP, RN*, CCST, IFMCP*, CIFM*, ATN*

email: coach@elpasofunctionalmedicine.com

Licensed as a Doctor of Chiropractic (DC) in Texas & New Mexico*
Texas DC License # TX5807, New Mexico DC License # NM-DC2182

Licensed as a Registered Nurse (RN*) in Florida
Florida License RN License # RN9617241 (Control No. 3558029)
Compact Status: Multi-State License: Authorized to Practice in 40 States*
Presently Matriculated: ICHS: MSN* FNP (Family Nurse Practitioner Program)

Dr. Alex Jimenez DC, MSACP, RN* CIFM*, IFMCP*, ATN*, CCST
My Digital Business Card

Dr. Alex Jimenez

Specialties: Stopping the PAIN! We Specialize in Treating Severe Sciatica, Neck-Back Pain, Whiplash, Headaches, Knee Injuries, Sports Injuries, Dizziness, Poor Sleep, Arthritis. We use advanced proven therapies focused on optimal Mobility, Posture Control, Deep Health Instruction, Integrative & Functional Medicine, Functional Fitness, Chronic Degenerative Disorder Treatment Protocols, and Structural Conditioning. We also integrate Wellness Nutrition, Wellness Detoxification Protocols, and Functional Medicine for chronic musculoskeletal disorders. In addition, we use effective "Patient Focused Diet Plans," Specialized Chiropractic Techniques, Mobility-Agility Training, Cross-Fit Protocols, and the Premier "PUSH Functional Fitness System" to treat patients suffering from various injuries and health problems.
Ultimately, I am here to serve my patients and community as a Chiropractor, passionately restoring functional life and facilitating living through increased mobility.

Purpose & Passions:
I am a Doctor of Chiropractic specializing in progressive, cutting-edge therapies and functional rehabilitation procedures focused on clinical physiology, total health, functional strength training, functional medicine, and complete conditioning. In addition, we focus on restoring normal body functions after neck, back, spinal and soft tissue injuries.

We use Specialized Chiropractic Protocols, Wellness Programs, Functional & Integrative Nutrition, Agility & Mobility Fitness Training, and Cross-Fit Rehabilitation Systems for all ages.

As an extension to dynamic rehabilitation, we offer our patients, disabled veterans, athletes, young and elder a diverse portfolio of strength equipment, high-performance exercises, and advanced agility treatment options. In addition, we have teamed up with the cities premier doctors, therapists, and trainers to provide high-level competitive athletes the options to push themselves to their highest abilities within our facilities.

We've been blessed to use our methods with thousands of El Pasoans over the last 3 decades allowing us to restore our patients' health and fitness while implementing researched non-surgical methods and functional wellness programs.

Our programs are natural and use the body's ability to achieve specific measured goals, rather than introducing harmful chemicals, controversial hormone replacement, unwanted surgeries, or addictive drugs. As a result, please live a functional life that is fulfilled with more energy, a positive attitude, better sleep, and less pain. Our goal is to ultimately empower our patients to maintain the healthiest way of living.

With a bit of work, we can achieve optimal health together, regardless of age, ability, or disability.

View all posts
Certified Functional Medicine Doctor El Paso