ʟ-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background Multisite pain, including low-back and knee pain, is a major health issue that greatly decreases quality of life. Objectives This study analyzed the effects of l-serine, which provides necessary components for nerve function, and EPA, which exerts anti-inflammatory properties, on pain scores of adults with pain in at least the low back and knee for ≥3 mo. Methods This was a randomized, double-blind, placebo-controlled, parallel-group study. The Japan Low Back Pain Evaluation Questionnaire (JLEQ) and Japanese Knee Osteoarthritis Measure (JKOM) were applied as primary outcomes. The Brief Pain Inventory (BPI) and safety evaluation were secondary outcomes. We enrolled 120 participants aged ≥20 y (36 men and 84 women: mean ± SD age = 40.8 ± 10.9 y). The participants were randomly allocated to either the active group (daily ingestion of 594 mg l-serine and 149 mg EPA) or placebo group. The study period consisted of 8-wk dosing and 4-wk posttreatment observation. ANCOVA between groups for each time point was conducted using the baseline scores as covariates. Results The JLEQ scores (active compared with placebo: 14.2 ± 11.2 compared with 19.0 ± 10.2) at week 8 were lower in the active group (P < 0.001). The JKOM scores at week 4 (11.7 ± 9.0 compared with 13.9 ± 7.9), week 8 (10.4 ± 7.9 compared with 13.1 ± 7.1), and week 12 (10.3 ± 7.4 compared with 13.8 ± 7.5) were lower in the active group (P ≤ 0.04). Additionally, the active group had 11–27% better scores compared with the placebo group for BPI1 (worst pain), BPI3 (average pain), and BPI5D (pain during moving) at week 4 (P ≤ 0.028) and week 8 (P ≤ 0.019), respectively, and BPI5D was 23% better in the active group at week 12 (P = 0.007). No adverse events were observed. Conclusions l-Serine and EPA were effective for pain relief in adults with low-back and knee pain after multiplicity adjustment. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000035056.

Mendelian Randomization Study on the Putative Causal Effects of Omega-3 Fatty Acids on Low Back Pain

“…Previous observational studies have suggested an important role of omega-3 in low back pain ( 4 – 6 ). In the present two-sample MR study, we established a putative causal link between plasma omega-3 levels and low back pain in the European population.…”

“…Critically, a randomized controlled trial (RCT) demonstrated omega-3 dietary supplementation using fish oil significantly reduced low back pain ( 5 ). A recent RCT showed that eicosapentaenoic acid (EPA), one important omega-3 member, was effective for pain relief in adults with lower back pain ( 6 ). Although these results suggest an important role of omega-3 in the treatment of low back pain, the putative causal link between omega-3 and low back pain is still unclear.…”

The Role of Serum Metabolomics in Distinguishing Chronic Rhinosinusitis With Nasal Polyp Phenotypes

“…Accordingly, serine is one of the crucial amino acids in the synthesis of human proteins, and L-serine, another isoform of serine, was proven to be pivotal in suppressing the production of reactive oxygen species and reducing oxidative stress in several inflammatory diseases (Rodriguez et al, 2019 ). A previous study reported that L-serine provided components for nerve function and exerted anti-inflammatory properties, it could relieve chronic pain in low-back and knee pain patients (Sasahara et al, 2020 ). Glycine has been previously demonstrated to be critical in controlling the levels of oxygen species, and it exhibits anti-inflammatory and immunomodulatory effects in several disorders (Yang et al, 2020 ).…”

The Role of Nutraceuticals in Osteoarthritis Prevention and Treatment: Focus on n‐3 PUFAs

“…EPA, L-Serine, and Pain. Additionally, a randomized, double-blind, placebo-controlled, parallel group study was recently conducted to evaluate the effect of EPA and L-Serine on lower-back and knee pain [59]. The study was conducted on 120 adult participants with lower-back and knee pain for at least three months, divided into a placebo group and a group given 594 mg of L-Serine and 149 mg of EPA daily for eight weeks.…”