Global Ingredient Risk Index Joint Health

Hyaluronic Acid

Sodium hyaluronate

Also known as: Hyaluronic acid, Sodium hyaluronate, Hyaluronan, Hyaluronate sodium, HA

04 მარ 2026

LOW RISK 1.5/10 How?

Evidence Strength: MODERATE

This ingredient is classified as unclassified risk (GIRI score: 1.5/10). The classification is based on mechanistic and clinical evidence: hyaluronic acid functions by binding to water molecules, thereby increasing the viscosity….

Common Adverse Effects

Nausea
headache
diarrhea
abdominal pain
bloating

Serious Adverse Effects

Allergic reactions
anaphylaxis
severe skin rash

Contraindications

Severe liver disease
avian protein allergy
active infection
People taking Anticoagulants

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Drug / Nutrient	Interaction Mechanism	Warning
Anticoagulants	potential increased bleeding risk — monitor closely. NSAIDs: additive effects on joint pain relief — use with caution. Corticosteroids: no significant interaction — safe to use concurrently.	Monitor

Hyaluronic acid, also known as sodium hyaluronate, is a naturally occurring glycosaminoglycan found in connective tissues throughout the body. It is commonly used in dietary supplements for joint health due to its role in maintaining synovial fluid viscosity and cartilage health. Hyaluronic acid supplements are often derived from bacterial fermentation or rooster combs and are popular for their potential to alleviate joint pain and improve mobility.

Chemical Class: Glycosaminoglycan
Biological Class: Polysaccharide
Natural Source: Endogenous in human connective tissues, rooster combs
Scientific Name: Sodium hyaluronate
Chemical Formula: C14H21NO11
CAS Number: 9004-61-9

Hyaluronic acid functions by binding to water molecules, thereby increasing the viscosity of synovial fluid in joints, which helps to lubricate and cushion them. It interacts with CD44 receptors on chondrocytes and synovial cells, promoting cartilage repair and reducing inflammation. Additionally, it may inhibit the expression of inflammatory cytokines and enzymes that degrade cartilage.

Indication	Evidence Level	Summary
General	Moderate	Clinical studies have shown that oral hyaluronic acid can improve symptoms of osteoarthritis, particularly in the knee. Randomized controlled trials indicate a moderate reduction in pain and improvement in joint function. However, the bioavailability of oral hyaluronic acid is a subject of debate, with some studies suggesting limited systemic absorption. Overall, evidence supports its use as an adjunctive therapy for joint health.

Evidence levels: Strong Moderate Limited Experimental

Absorption

Oral absorption of hyaluronic acid is relatively low, with bioavailability estimated to be less than 10%. Peak plasma concentrations are typically reached within 2 to 6 hours after ingestion. The half-life of hyaluronic acid in the bloodstream is short, necessitating regular dosing to maintain therapeutic levels.

Distribution

Hyaluronic acid is distributed primarily to connective tissues, including joints and skin. It has a high affinity for synovial fluid and cartilage. The volume of distribution is not well-defined due to its rapid uptake by tissues.

Metabolism

Hyaluronic acid is primarily metabolized in the liver and by synovial cells. It is broken down into smaller polysaccharide fragments by hyaluronidase enzymes. These fragments can be further metabolized or excreted.

Excretion

Excretion of hyaluronic acid occurs mainly through the kidneys, with urinary excretion of its metabolites. A small amount may also be excreted via bile.

Bioavailability

10%

Condition / Use	Typical Dose
Osteoarthritis	200-240 mg daily. Joint pain: 100-200 mg daily. Skin health: 120-240 mg daily.

Dosage ranges are based on clinical studies and commonly used supplement formulations. Individual requirements may vary.

SETI Score 73/100

Risk Level Moderate risk

Scientific Confidence Moderate

Evidence Strength Limited

Key Benefit Hyaluronic acid, also known as sodium hyaluronate, is a naturally occurring glycosaminoglycan found in connective tissues throughout the…

Key Safety Concern Hyaluronic acid is generally considered safe for most populations, including older adults and those with osteoarthritis. However, caution is advised in individuals with known allergies to hyaluronic acid sources, such as avian proteins. Pregnant and breastfeeding women should consult a healthcare provider before use. There are no significant regulatory warnings associated with its use.

Evidence Reviewed 10 PubMed studies

Scientific Confidence Moderate

Based on study quality, consistency, and recency

Executive Summary — Ingredient Assessment

SETI Score 73/100

Risk Level Moderate risk

Evidence Strength Limited

Main Benefit Hyaluronic acid, also known as sodium hyaluronate, is a naturally occurring glycosaminoglycan found in connective tissues throughout the…

Main Safety Concern Hyaluronic acid is generally considered safe for most populations, including older adults and those with osteoarthritis. However, caution is advised in individuals with known allergies to hyaluronic acid sources, such as avian proteins. Pregnant and breastfeeding women should consult a healthcare provider before use. There are no significant regulatory warnings associated with its use.

Ingredient Hyaluronic Acid

Scientific name Sodium hyaluronate

Scientific Evidence Overview

10 studies reviewed
1 high-quality study (meta-analysis or RCT)
Main clinical benefit observed: Hyaluronic acid, also known as sodium hyaluronate, is a naturally occurring glycosaminoglycan found in connective tissues throughout the…
Evidence consistency: High consistency across studies (100%)

Safety Signals

Hyaluronic acid is generally considered safe for most populations, including older adults and those with osteoarthritis. However, caution is advised in individuals with known allergies to hyaluronic acid sources, such as avian proteins. Pregnant and breastfeeding women should consult a healthcare provider before use. There are no significant regulatory warnings associated with its use.

Evidence Strength Limited

Regulatory Status

USA/FDA — Approved

Final Scientific Assessment

Current scientific evidence suggests potential clinical benefits for Hyaluronic Acid; however, some safety concerns have been reported in the literature. Additional large-scale randomized clinical trials are needed to confirm long-term safety and effectiveness.

Ingredient Hyaluronic Acid

Evidence reviewed 10 peer-reviewed studies (last 10 years)

Scientific name Sodium hyaluronate

73 /100

Total SETI Score

Moderate risk

Evidence quality	33/40
Evidence consistency	20/20
Safety signals	0/20
Study recency	10/10
Evidence transparency	10/10

Evidence Summary

10 studies reviewed
1 high-quality study (meta-analysis or systematic review)
0 studies identified benefits or no safety concern (GREEN)
10 studies reported limited or advisory safety evidence (YELLOW)

Evidence Policy

Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.

Last updated: 06 მარ 2026, 12:00

Evidence Distribution

1 Meta-analyses

4 Randomized clinical trials

1 Animal studies

4 Other / unclassified

Meta-analysis HIGH evidence YELLOW
A Network Meta-Analysis Comparing the Efficacy Differences of Different Acupuncture and Sodium Hyaluronate Eye Drops in the Treatment of Dry Eye Disease. ↗

PMID 41768110 ↗

Journal J Pain Res

Year 2026

Study type Meta-analysis

Evidence strength HIGH evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41768110/

Yan X et al.. A Network Meta-Analysis Comparing the Efficacy Differences of Different Acupuncture and Sodium Hyaluronate Eye Drops in the Treatment of Dry Eye Disease.. J Pain Res. 2026. PMID:41768110.
Randomized clinical trial MEDIUM evidence YELLOW
Acupuncture combined with auricular acupressure for dry eye: a SPIRIT-guided protocol for a multicenter randomized controlled trial. ↗

PMID 41767509 ↗

Journal Front Med (Lausanne)

Year 2026

Study type Randomized clinical trial

Evidence strength MEDIUM evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41767509/

Li Z et al.. Acupuncture combined with auricular acupressure for dry eye: a SPIRIT-guided protocol for a multicenter randomized controlled trial.. Front Med (Lausanne). 2026. PMID:41767509.
Randomized clinical trial MEDIUM evidence YELLOW
Single-injection hyaluronic acid treatment demonstrates non-inferiority in the relief of symptomatic knee osteoarthritis: A randomized double-blind, multi-center controlled study. ↗

PMID 41756523 ↗

Journal Osteoarthr Cartil Open

Year 2026

Study type Randomized clinical trial

Evidence strength MEDIUM evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41756523/

Ruosi C et al.. Single-injection hyaluronic acid treatment demonstrates non-inferiority in the relief of symptomatic knee osteoarthritis: A randomized double-blind, multi-center controlled study.. Osteoarthr Cartil Open. 2026. PMID:41756523.
Animal study LOW evidence YELLOW
An In Vitro Evaluation of the Effect and Protection of Artificial Tear Formulations on Human Corneal Epithelial Cells in Normal and Dry… ↗

PMID 41754944 ↗

Journal Pharmaceutics

Year 2026

Study type Animal study

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41754944/

Wong KY et al.. An In Vitro Evaluation of the Effect and Protection of Artificial Tear Formulations on Human Corneal Epithelial Cells in Normal and Dry Eye Disease States.. Pharmaceutics. 2026. PMID:41754944.
Randomized clinical trial MEDIUM evidence YELLOW
Concentrated growth factor as treatment for temporomandibular joint osteoarthritis: A randomized controlled clinical trial. ↗

PMID 41747664 ↗

Journal J Craniomaxillofac Surg

Year 2026

Study type Randomized clinical trial

Evidence strength MEDIUM evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41747664/

Zheng XJ et al.. Concentrated growth factor as treatment for temporomandibular joint osteoarthritis: A randomized controlled clinical trial.. J Craniomaxillofac Surg. 2026. PMID:41747664.
Observational / other LOW evidence YELLOW
A Natural Antioxidant-Rich Hydrogel Formulation with Laurus nobilis Hydrosol: Physicochemical and Cosmeceutical Evaluation. ↗

PMID 41745037 ↗

Journal Gels

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41745037/

Juretiu0107 L et al.. A Natural Antioxidant-Rich Hydrogel Formulation with Laurus nobilis Hydrosol: Physicochemical and Cosmeceutical Evaluation.. Gels. 2026. PMID:41745037.
Randomized clinical trial MEDIUM evidence YELLOW
Combining Hyaluronic Acid and Amino Acids for Improved Healing of Post-Extraction Tooth Socket in Type 2 Diabetes Mellitus Subjects: A Randomized Clinical… ↗

PMID 41744941 ↗

Journal Dent J (Basel)

Year 2026

Study type Randomized clinical trial

Evidence strength MEDIUM evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41744941/

Ruggiero T et al.. Combining Hyaluronic Acid and Amino Acids for Improved Healing of Post-Extraction Tooth Socket in Type 2 Diabetes Mellitus Subjects: A Randomized Clinical Trial.. Dent J (Basel). 2026. PMID:41744941.
Observational / other LOW evidence YELLOW
Fabrication and characterization evaluation of sustained-release dissolving microneedles with skin soothing function. ↗

PMID 41721023 ↗

Journal Drug Deliv Transl Res

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41721023/

Yang Y et al.. Fabrication and characterization evaluation of sustained-release dissolving microneedles with skin soothing function.. Drug Deliv Transl Res. 2026. PMID:41721023.
Observational / other LOW evidence YELLOW
An SH-BDDE crosslinked hydrogel for sustained paeonol delivery: enabling long-lasting dual antibacterial and antiinflammatory action. ↗

PMID 41702053 ↗

Journal Biomed Mater

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41702053/

Yue Y et al.. An SH-BDDE crosslinked hydrogel for sustained paeonol delivery: enabling long-lasting dual antibacterial and antiinflammatory action.. Biomed Mater. 2026. PMID:41702053.
Observational / other LOW evidence YELLOW
Folate-functionalized core-shell nanocarrier System for sustained and targeted delivery of Saraca Indica for breast cancer treatment. ↗

PMID 41686450 ↗

Journal Drug Dev Ind Pharm

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41686450/

Ragheb Y et al.. Folate-functionalized core-shell nanocarrier System for sustained and targeted delivery of Saraca Indica for breast cancer treatment.. Drug Dev Ind Pharm. 2026. PMID:41686450.

Q × L × D × S × 10 = 1.5 / 10

The GIRI Score is the product of four independently computed evidence components, each normalised to 0–1, then scaled to 0–10. Every component is derived exclusively from peer-reviewed references and regulatory data — no editorial judgement is applied.

0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.

Method: Q = number of approved references ÷ 10 (capped at 1.0)

50%

Limited — mostly case reports or animal studies

Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.

Benefit

Risk

50%

Mixed or neutral — roughly equal benefit and risk signals

Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.

50%

One or more monitoring-level safety signals active

Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.

0Q × 5L × 5D × 5S = 1.5 / 10

Final GIRI Score for Hyaluronic Acid. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.

Full methodology & data sources

The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.

References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.

LOW RISK 1.5/10

Based on available regulatory signals and scientific evidence, this ingredient presents a low safety concern under normal conditions of use.

LOW
0–3.0

MODERATE
3.0–5.5

HIGH
5.5–7.5

CRITICAL
7.5–10

1.5

The score pin shows exactly where this ingredient falls on the fixed risk scale.

What drove the Low classification for Hyaluronic Acid

A score of 1.5 places this ingredient in the Low band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.

0 approved references.

Limited — mostly case reports or animal studies (Level 4–5).

Neutral or mixed — benefit and risk signals roughly balanced.

No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.

1 jurisdiction has active restrictions or advisories. Regulatory signals are recorded as Safety Signals and raise the S component.

How are the Low / Moderate / High / Critical thresholds defined?

The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:

Level	Score	Meaning
LOW	0.0 – 2.9	Sparse or predominantly beneficial evidence. No active safety alerts.
MODERATE	3.0 – 5.4	Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups.
HIGH	5.5 – 7.4	Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended.
CRITICAL	7.5 – 10	Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision.

Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.

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Hyaluronic Acid

Safety Profile

Common Adverse Effects

Serious Adverse Effects

Contraindications

Interactions

Evidence and Scientific Findings

Ingredient Overview

Biological and Chemical Classification

Mechanism of Action

Clinical Evidence of Effectiveness

Pharmacokinetics

Recommended Dosage

SETI — Scientific Evidence Transparency Index

Executive Summary — Ingredient Assessment

Evidence Summary

Evidence Policy

Evidence Distribution

Score Transparency

Risk Level Classification

What drove the Low classification for Hyaluronic Acid

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