Boswellia Leads Knee Osteoarthritis Supplement: Network Meta-Analysis of 39 Studies Ranks Priorities

Nutrients published a network meta-analysis of 39 randomized trials (42 comparisons; 4,599 participants) on which nutraceuticals actually help with knee osteoarthritis (knee OA). The comparison included 7 popular supplements: boswellia, curcumin, collagen, krill oil (ω - 3), ginger, vitamin D, and eggshell membrane. The result: boswellia confidently outperformed the others in pain and stiffness; in terms of function, the top three were boswellia, krill oil, and curcumin. None of the supplements increased the frequency of side effects compared to placebo.

Background

Knee osteoarthritis is one of the leading causes of chronic pain and disability worldwide, with a prevalence estimated by GBD to exceed 5.5% of the population in 2020 across all regions.

• What the core guidelines say. OARSI and ACR agree: the mainstay of treatment is patient education, exercise, weight loss, topical/oral NSAIDs; there is little evidence for supplements and they are not included in strong recommendations. Against this background, patients still want “gentle” remedies for pain/stiffness.
• Why network meta-analysis? There are almost no direct “duels” between supplements — basically, each was compared with a placebo. Network meta-analysis allows you to indirectly rank options (via the SUCRA indicator) and understand which has a greater chance of being “the best”, even without head-to-head trials. This approach is exactly what was used in the new work.
• Heterogeneity of extracts is a sore subject. “Natural” products differ in their raw materials, standardization, and dosages (e.g., boswellia has a profile of boswellic acids; curcumin has bioavailable forms and piperine additives; collagen has a type/degree of hydrolysis; egg membrane has a purification technology). This explains the spread of results in RCTs and the need for aggregation at the level of network models.
• High 'placebo noise' in OA - why it's important to consider. In OA trials, up to half or more of the pain reduction can be attributed to the placebo response, and it is predictably related to baseline symptom intensity and variability; therefore, individual small RCTs are easily 'whipped'. Network meta-analysis helps smooth out this noise. j
• What the new paper adds: Using a pool of 39 RCTs, the authors compared seven popular supplements (boswellia, curcumin, collagen, krill oil, ginger, vitamin D, egg membrane) and came up with a general hierarchy of effectiveness for pain, stiffness, and function—a useful “radar” for practice and for planning future head-to-head trials.

What was known before the review (strokes on key positions)

1. Boswellia: Meta-analyses and recent RCTs have shown reduction in pain/stiffness with good tolerability - a consistent signal but dependent on extract standardization.
2. Curcumin: Overall, moderate symptom improvement with good safety profile; efficacy varies by formulation and dose.
3. Krill oil (omega-3): individual studies have given positive signals, but a large RCT JAMA 2024 in patients with severe pain and synovitis did not confirm benefits over placebo at 24 weeks.
4. Collagen peptides: meta-analyses report pain reduction compared with placebo, although the quality of evidence is mixed.
5. Eggshell membrane: Systematic reviews suggest reduction in pain/stiffness, but trials are limited.
6. Vitamin D: Poorly effective as an analgesic for OA in the absence of deficiency; use is justified for other indications (bones). Guidelines do not recommend it for OA symptoms.

How they searched and compared

The authors selected RCTs from PubMed/Embase/Cochrane up to December 2024 using PRISMA; they included adults with a diagnosis of knee OA, where one of the supplements was compared with placebo. The primary outcomes were WOMAC (pain/stiffness/function) and VAS (pain), and the secondary outcome was adverse events. Bayesian network meta-analysis and the SUCRA (probability of being the “best”) score were used for ranking. The network was “star-studded” (almost all against placebo, few direct “head-to-head” results).

Main results

• Pain (WOMAC): only boswellia significantly improved: mean difference (MD) -10.58 (95% CI -14.78…-6.45) versus placebo. Curcumin, ginger, vit. D, krill oil, egg membrane and collagen were visually “better” than placebo, but without strict significance. According to SUCRA: boswellia 0.981 → curcumin 0.663 → ginger 0.503… (below - vit. D, krill, egg membrane, collagen).
• Stiffness (WOMAC): Boswellia was again in the clear lead: MD -9.47 (-12.74…-6.39); according to SUCRA - 0.997, then krill oil (0.553) and ginger (0.537).
• Function (WOMAC): significant improvements were shown by krill oil (MD -14.01), boswellia (-14.00) and curcumin (-9.96); according to SUCRA, the leaders were boswellia 0.842 and krill 0.808.
• Pain according to VAS: significant decreases in boswellia (MD -17.26), collagen (-16.65), curcumin (-12.34) and ginger (-11.89). VAS is often measured in mm (0-100); such changes correspond to approximately -1.2…-1.7 points on a scale of 0-10, i.e. clinically noticeable. According to SUCRA, the leaders were: boswellia (0.803) and collagen (0.766).

Translation into practice: if we were to choose one supplement with the best balance of evidence, it would be Boswellia ( Boswellia resin extracts ). For function, krill oil and curcumin also look convincing; for VAS pain, collagen also made a significant contribution.

What about security?

In 41 articles that reported adverse events, no supplement increased their incidence versus placebo. Reporting was mixed, with only 5 studies directly linking specific complaints to the intervention. Examples: rare hypercalcemia with high-dose vitamin D; isolated dyspepsia/heartburn with ginger; rash/itching in the egg membrane control. The authors' conclusion: overall safety was OK, but standardized reporting was desperately needed.

Why Boswellia Comes First

Boswellic acids have an anti-inflammatory effect (inhibition of 5-lipoxygenase, reduction of cytokines), which logically "hits" the pain and inflammatory component of OA. The network model showed that it is in pain and stiffness that Boswellia has the highest probability of being the best.

Important Disclaimers

• Different extracts and doses. Formulas and doses varied greatly (from 4 weeks to 36 months of therapy), making it difficult to say "how many mg and what brand" is optimal.
• Few "direct duels". Network is mostly "additive versus placebo", which is why ranking relies on indirect comparisons. Need "head-to-head" RCTs.
• The risk of bias is moderate. Some domains (allocation, blinded assessment, selective reporting) are marked as "unclear". Funding was often not specified in publications.

What does this change for the patient?

• Consider boswellia as an adjunct to basic non-drug therapy (weight control, exercise, physical therapy); for function, consider krill oil; for pain, consider curcumin/collagen. Discuss with physician, taking into account medications (e.g., anticoagulants, NSAIDs) and co-morbidities.
• Don't expect a "miracle": the effects are moderate, but clinically noticeable, especially in terms of pain (equivalent to -1–2 points on a 0–10 scale).
• Vitamin D: It has not been a great pain reliever for OA; indications for its use are deficiency and bone health, not arthritic pain.

Source: Zhang Y. et al. Comparative Effectiveness of Nutritional Supplements in the Treatment of Knee Osteoarthritis: A Network Meta-Analysis. Nutrients 17(15):2547, 2025. https://doi.org/10.3390/nu17152547