What are the benefits of oral hyaluronic acid for joint health and skin hydration in otherwise healthy adults or those with mild‑to‑moderate knee osteoarthritis?

Oral Hyaluronic Acid: Limited Evidence for Joint Health, Modest Support for Skin Hydration

The evidence for oral hyaluronic acid is weak and should not be recommended for knee osteoarthritis, as current guidelines focus exclusively on intra-articular (injected) hyaluronic acid—which itself is conditionally recommended against—and there is minimal high-quality data supporting oral supplementation for joint health.

Key Distinction: Oral vs. Intra-articular Hyaluronic Acid

The critical issue is that all major clinical guidelines address only intra-articular (injected) hyaluronic acid, not oral supplementation 1. The 2019 American College of Rheumatology/Arthritis Foundation guidelines conditionally recommend against even intra-articular hyaluronic acid for knee osteoarthritis, noting that when limited to low-risk-of-bias trials, the effect size compared to saline injections approaches zero 1. If injected hyaluronic acid directly into the joint shows minimal benefit, the rationale for oral supplementation—which must survive digestion, absorption, and systemic distribution—is even weaker.

Evidence for Oral Hyaluronic Acid in Joint Health

• One small trial (n=60) showed modest improvement in knee osteoarthritis symptoms with 200mg daily oral hyaluronic acid over 12 months, but only in patients aged 70 years or younger, and only when combined with quadriceps strengthening exercises 2
• The effect was statistically significant only at 2 and 4 months, not sustained throughout the study period 2
• This single study is insufficient to overcome the guideline-level evidence against hyaluronic acid for osteoarthritis management 1

Clinical pitfall: Do not substitute oral hyaluronic acid for evidence-based osteoarthritis treatments including weight loss, land-based exercise, physical therapy, topical or oral NSAIDs, and acetaminophen up to 3g daily 3.

Evidence for Oral Hyaluronic Acid in Skin Hydration

• One randomized, double-blind trial (n=40) demonstrated that 120mg daily oral hyaluronic acid for 12 weeks significantly improved wrinkles, stratum corneum water content, transepidermal water loss, and skin elasticity compared to placebo 4
• Improvements were statistically significant at 8 and 12 weeks of supplementation 4
• This represents the strongest evidence for oral hyaluronic acid, though limited to cosmetic outcomes rather than morbidity or mortality

Why Intra-articular Hyaluronic Acid Guidelines Matter Here

The 2019 ACR/Arthritis Foundation guidelines found that apparent benefits of intra-articular hyaluronic acid were restricted to studies with higher risk of bias 1. When meta-analysis was limited to high-quality trials, the effect size approached zero 1. Earlier meta-analyses from 2003-2004 showed small effect sizes (0.19-0.32) with significant publication bias 5, 6. The number needed to treat for intra-articular hyaluronic acid is 17 patients, meaning 16 patients receive no benefit for every 1 who does 3.

If direct intra-articular injection—bypassing all absorption barriers—shows minimal to no benefit in high-quality studies, oral supplementation faces an even higher burden of proof that current evidence does not meet.

Appropriate Treatment Algorithm for Osteoarthritis

For patients seeking joint health benefits:

• First-line: Land-based exercise, weight loss if overweight, physical therapy 3
• Second-line: Topical NSAIDs, oral NSAIDs, or acetaminophen up to 3g daily in divided doses 3
• Third-line: Intra-articular corticosteroid injections for acute flares (Level 1B evidence, supported by 19 high-quality studies) 3
• Avoid: Oral hyaluronic acid for osteoarthritis (insufficient evidence), intra-articular hyaluronic acid (conditionally recommended against) 1, 3, and arthroscopic debridement (strongly recommended against) 7, 3

Bottom Line

Oral hyaluronic acid lacks sufficient evidence for joint health benefits and should not be recommended for osteoarthritis management. The single positive trial is small, limited to younger patients, and requires concurrent exercise 2. For skin hydration and cosmetic benefits, there is modest evidence supporting 120mg daily supplementation 4, though this does not impact morbidity, mortality, or quality of life in meaningful ways. Patients seeking osteoarthritis treatment should pursue evidence-based therapies including exercise, weight management, NSAIDs, and corticosteroid injections when appropriate 3.