Toguchi A, Noguchi N, Kanno T, Yamada A. Methylsulfonylmethane improves knee quality of life in participants with mild knee pain: a randomized, double-blind, placebo-controlled trial. Nutrients. 2023;15(13):2995.
To assess the effects of oral consumption of methylsulfonylmethane (MSM) on mild knee pain in healthy Japanese participants
Oral consumption of MSM led to significant improvements in knee and systemic health conditions, as demonstrated by the total scores of the Japanese Knee Osteoarthritis Measure (JKOM) and health assessments in a randomized, double-blind, placebo-controlled trial involving 88 healthy participants with mild knee joint pain.
Randomized, double-blind, placebo-controlled trial
In this study, conducted between May 25, 2021, and August 21, 2021, investigators screened for enrollment a total of 163 healthy Japanese individuals experiencing mild knee joint pain. Ultimately, 88 participants were enrolled and randomly assigned, with 44 individuals in the MSM consumption group and 44 in the placebo control group.
One participant from the MSM group withdrew during the study, and a few others were excluded due to low compliance with test-food consumption. Investigators analyzed data from 80 participants for efficacy and 88 for safety. Notably, the baseline demographics between the MSM and placebo groups were well-balanced, with no significant differences at week 0.
To be eligible, participants had to meet inclusion criteria, which included being Japanese, aged 20 years or more, healthy, and experiencing mild knee joint pain. Exclusion criteria encompassed factors such as a history of certain medical conditions, use of specific medications or supplements, allergies, and participation in other clinical trials within the past 28 days. Additionally, participants had to have a Kellgren-Lawrence grade of 0 or 1 on x-ray, and they were prioritized based on their total score on the JKOM.
In this randomized, double-blind, placebo-controlled trial, participants were divided into 2 groups: an MSM consumption group and a placebo control group, in a 1:1 ratio. Both groups took 10 tablets per day, with 200 mg of MSM (OptiMSM®) per tablet in the MSM group and an equivalent amount of lactose in the placebo group, for a duration of 12 weeks. The tablets were manufactured to be indistinguishable in appearance and smell.
Participants were monitored at 4 clinic visits over the course of the intervention, which was conducted from September 11, 2021, to December 25, 2021.
OptiMSM® is a brand of methylsulfonylmethane, which is an organic, sulfur-containing compound. The exact composition of OptiMSM® typically consists of at least 99.9% pure MSM.
Study Parameters Assessed
For primary and secondary outcomes, the parameters assessed included:
- Japanese Knee Osteoarthritis Measure (JKOM)
- Visual Analog Scale (VAS) for pain and stiffness scores
- Japanese Orthopedic Association (JOA)
- Plasma levels of inflammatory markers: interleukin 1 (IL-1) beta, IL-6, and high-sensitivity C-reactive protein (Hs-CRP)
- Procollagen II C-terminal propeptide (PIICP) and collagen type II cleavage (C2C), which are biomarkers related to type II collagen
Primary Outcome Measure
The primary outcome of the study was the “total score of JKOM (Japanese Knee Osteoarthritis Measure)” at 12 weeks.
Secondary Outcomes: The study also included several secondary outcomes, which were measured at various time points:
- The total score of JKOM at 4 and 8 weeks after test sample consumption
- The differences in the total score of JKOM between the initial screening (0 weeks) and 4, 8, or 12 weeks after consumption
- The measured values and amounts of changes in the VAS scores, pain and stiffness in knees, conditions in daily life, general activities, and health conditions of JKOM
- JOA scores at 4, 8, and 12 weeks
- Scores related to pain on walking, pain on ascending or descending stairs, range of motion, and joint effusion of JOA at 4, 8, and 12 weeks
- Plasma levels of inflammatory markers: IL-1 beta, IL-6, and high-sensitivity C-reactive protein (Hs-CRP)
- Procollagen II C-terminal propeptide (PIICP) and collagen Type II cleavage (C2C)
- The values of individual items in the JKOM questionnaire and JOA score at 4, 8, and 12 weeks
Additionally, the study included safety evaluations, which consisted of physical examinations, urine analysis, peripheral blood tests, and medical interviews.
It’s worth noting that the measurement marker for collagen Type I and II cleavage was unavailable due to the Covid-19 pandemic, and therefore, the marker was changed to C2C.
Results revealed that the JKOM total scores at 12 weeks were 8.1 for the MSM group and 10.9 for the placebo group. This difference was statistically significant (P=0.046), indicating an improvement in the MSM group. Interestingly, these scores were not significantly different from the baseline scores within each group (18.2 and 19.9, respectively). Moreover, health condition scores at 12 weeks in the MSM group were notably lower than those in the placebo group (P=0.027), indicating an improvement in health conditions.
Secondary outcomes included analyzing various aspects of JKOM and JOA scores, with both groups exhibiting lower JKOM scores at 12 weeks compared to their baseline values. The difference between the groups was –0.5 (P=0.032), implying improvements in both groups. However, there were no significant differences in the amount of change in JOA total scores among different time periods between the 2 groups.
Further analysis of type II collagen biomarkers showed a significant increase in procollagen II C-terminal propeptide (PIICP) at 8 weeks in the MSM group compared to the placebo group, suggesting an impact from MSM consumption. Nevertheless, PIICP values at 12 weeks in both groups decreased from their baseline levels, and no significant differences were observed in other blood markers. Additionally, inflammatory markers like IL-1 beta, IL-6, and Hs-CRP showed no significant differences in the amount of change between the MSM and placebo groups during any week of comparison.
Upon exploration of specific items within the JKOM questionnaire, only 4 exhibited significant score changes during the study period. Morning pain, pain while standing, nocturnal pain, and health condition improved notably in the MSM group compared to the placebo group. However, there were no significant changes observed in the scores of other JKOM questionnaire items.
Finally, dietary intake surveys conducted 3 days before measurements revealed no factors associated with the study results.
Safety evaluations through physical examinations, urine analyses, peripheral blood tests, and medical interviews detected no health problems or adverse events during the study period.
The authors declare no conflict of interest. The study was funded by the Chlorella Industry. The Chlorella Industry Co Ltd is a Japanese-based company specializing in the cultivation, production, and distribution of Chlorella-based products.
Practice Implications & Limitations
In this study, the researchers conducted the first clinical trial of methylsulfonylmethane oral consumption in healthy participants with mild knee pain, as opposed to patients with osteoarthritis (OA). The study aimed to assess the effects of MSM consumption on knee quality of life and associated health conditions.
The findings indicate that after 12 weeks of MSM consumption, the participants in the MSM group experienced significant improvements compared to the placebo group. Specifically, the study observed significant reductions in the Japanese Knee Osteoarthritis Measure total scores, which reflect knee quality of life and health conditions. These improvements were noted in various aspects, including morning pain, pain while standing, and overall health condition, as assessed by JKOM questionnaires. The study suggests that MSM supplementation alleviated morning and standing pain and improved the general health and quality of life of healthy individuals with mild knee pain in their daily lives.
While the study observed improvements in pain-related questions and the potential antioxidant effects of MSM, it did not find significant changes in certain markers related to inflammation and cartilage metabolism. The researchers suggest that further investigation using alternative markers and urine samples might be necessary to better assess the effects of MSM on these aspects.
Knee pain is often a chronic condition, and the short-term nature of the study may not capture the long-term effects of MSM supplementation on knee pain over time.
The study acknowledges its limitations, including the use of healthy participants with low Kellgren-Lawrence (K-L) grades and low levels of inflammatory markers, which may have affected the assessment of MSM’s anti-inflammatory effects. Further research is needed to explore the impact of MSM consumption in different populations and its potential benefits on various aspects of knee health. The study had a relatively short intervention period, which lasted 12 weeks. Knee pain is often a chronic condition, and the short-term nature of the study may not capture the long-term effects of MSM supplementation on knee pain over time. The study included a relatively small number of participants (44 in each group). Small sample sizes can increase the risk of type 2 errors, limiting the ability to detect significant differences between groups. The study population may not adequately represent the diversity seen in clinical practice. A more diverse sample would help determine whether MSM supplementation is equally effective across different demographic groups. The study relied on self-reported measures of knee quality of life, which can introduce subjectivity and potential bias in the assessment of outcomes. Objective measures, such as radiographic imaging or functional tests, could provide more robust data.
While the study has limitations, it suggests that MSM supplementation may have a positive impact on quality of life in individuals with mild knee pain. Healthcare practitioners should consider MSM as an adjunctive therapy for such patients, especially when conventional treatments alone do not provide sufficient relief. Practitioners should assess the severity of knee pain in each patient and tailor treatment plans accordingly. For patients with mild knee pain, MSM supplementation may be a viable option, but for those with moderate-to-severe pain, it may be more appropriate as part of a multimodal approach.
Overall, the study presented promising findings regarding the potential benefits of MSM supplementation in improving mild knee pain. However, it is vital for healthcare practitioners to recognize the study’s limitations, including its short duration, restricted participant selection, and small sample size. Despite these limitations, the study suggests that MSM may have a role in improving knee quality of life, particularly in patients with mild knee pain. Practitioners should consider MSM as an adjunctive therapy and tailor treatment plans based on individual patient needs, while also advocating for further research to strengthen the evidence.