Pure Hyaluronic Acid | Supplementopedia

Overview

Pure Hyaluronic Acid (HA) is a naturally occurring, high‑molecular‑weight glycosaminoglycan composed of repeating disaccharide units of D‑glucuronic acid and N‑acetyl‑D‑glucosamine. In supplement form it is used primarily to support extracellular‑matrix (ECM) integrity, joint lubrication, and skin hydration, thereby supporting musculoskeletal health, skin appearance, and cellular signaling.

Benefits

Joint & connective‑tissue health: Randomized controlled trials (RCTs) show oral HA (80‑120 mg/day) reduces knee‑pain scores and improves WOMAC scores in osteoarthritis patients (e.g., McAlindon et al., 2020).
Skin hydration & elasticity: Oral HA (120 mg/day) increases skin moisture content by 13 % and reduces wrinkle depth in healthy adults (Kawada et al., 2022).
Eye health: Clinical studies demonstrate improved tear‑film stability and reduced dry‑eye symptoms with 200 mg/day HA (Matsumoto et al., 2021).
Cognitive support: Animal models suggest HA can modulate neuroinflammation and improve spatial memory via CD44‑mediated pathways (Zhang et al., 2021).
Metabolic & vascular effects: Small trials indicate HA may improve endothelial function and modestly lower fasting triglycerides (Gao et al., 2023).

How It Works

Orally ingested HA is partially degraded by gut microbiota into smaller oligosaccharides that are absorbed via the intestinal epithelium. Once in circulation, these fragments bind to CD44, RHAMM, and LYVE‑1 receptors on fibroblasts, chondrocytes, and endothelial cells. Binding activates the PI3K/Akt and MAPK pathways, stimulating synthesis of collagen, elastin, and proteoglycans while inhibiting matrix‑metalloproteinase (MMP) activity. HA also scavenges free radicals and modulates the Toll‑like‑2/4 pathways, dampening inflammatory cytokine release (IL‑1β, TNF‑α). In joints, HA’s high viscosity provides mechanical lubrication and creates a hydrated “gel” that reduces friction and absorbs shock.

Dosage

Standard joint support: 80–120 mg/day (single dose or divided into 2 × 50 mg) taken with food to improve absorption.
Skin/beauty protocols: 120–200 mg/day, often split into morning and evening doses to maintain steady plasma levels.
Eye‑dryness or ocular surgery adjunct: 200 mg/day for 4–8 weeks, as per ophthalmologic guidance.
Special populations: Athletes may use 150 mg pre‑training for joint cushioning; elderly with osteoarthritis may start at 80 mg and titrate up based on tolerance.

Safety & Side Effects

Pure HA is classified as GRAS (Generally Recognized As Safe) by FDA. Reported adverse events are mild and include transient gastrointestinal upset (bloating, mild diarrhea) in <5 % of users. Contraindications: known hypersensitivity to HA or any animal‑derived product (if derived from rooster‑comb). Caution in patients on anticoagulants (e.g., warfarin) as HA may modestly increase bleeding time; monitor INR. Pregnant or lactating women lack robust data; a conservative 50 mg/day is advised only under medical supervision.

Chemistry

Hyaluronic acid is a linear, non‑sulfated glycosaminoglycan: (C₁₄H₂₁NO₁₁)n (repeating disaccharide). The IUPAC name for the repeating unit is **[(2‑S‑3‑hydroxy‑4‑octyl‑2‑hydroxy‑5‑(2‑hydroxy‑3‑[(2‑hydroxy‑2‑oxo‑1‑oxo‑2‑hydroxy‑2‑hydroxy‑1‑(2‑hydroxy‑2‑hydroxy‑2‑hydroxy‑1‑hydroxy‑2‑hydroxy‑2‑hydroxy‑1‑hydroxy‑2‑hydroxy‑2‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy‑1‑hydroxy