Meta Information
ID:hyaluronic-acid
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/active-cancer
Target name:
Active Cancer
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some cancer cells have receptors (like CD44) that use hyaluronic acid for growth, proliferation, and metastasis. Oral supplementation could theoretically provide fuel for cancer progression.
Actionable advice:
Oral hyaluronic acid supplements should not be used by those with an active cancer diagnosis.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
certain cancer cells, like pancreatic cancer cells, are fueled by hyaluronic acid; others express excessive amounts of hyaluronic acid and its receptors. Other studies have shown that hyaluronic acid injection can promote tumor growth
Label source:
Primary literature: https://lifespan.io/topic/hyaluronic-acid-benefits-side-effects/
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of oral hyaluronic acid supplementation during pregnancy has not been established through rigorous clinical trials.
Actionable advice:
Oral hyaluronic acid supplements should be avoided during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
There isn't enough reliable information to know if hyaluronic acid is safe to use when pregnant.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown if hyaluronic acid or its metabolites are excreted in breast milk or what effects they might have on a nursing infant; safety has not been established.
Actionable advice:
Oral hyaluronic acid supplements should be avoided while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
It's not clear if it's excreted in breast milk and what effect that might have on an infant.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/procedure/hyaluronic-acid-injection
Target name:
Hyaluronic Acid Injections (Fillers, Joints)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A known allergy or hypersensitivity to hyaluronic acid products or to lidocaine (which is often mixed in) is an absolute contraindication for receiving injections.
Actionable advice:
HA injections should not be received with a known allergy to the product components.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Local infection, fractures, and allergy to injection substrates are contraindications to joint and soft tissue injections.
Label source:
PubMed: American family physician (2023)
Source url:
Exact phrase from label:
Rare complications with HA fillers and those associated with constituents of the product, contaminants, and lidocaine are reviewed.
Label source:
PubMed: Patient preference and adherence (2011)
Source url:
Exact phrase from label:
Delayed-type hypersensitivity (DTH) reaction is one of these delayed inflammatory reactions, which is preventable by performing a pretreatment skin test.
Label source:
PubMed: Aesthetic surgery journal (2020)
Action type:
informational_none
Target id:
/condition/active-skin-infection
Target name:
Active Skin Infection at Injection Site
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Injecting hyaluronic acid into an area with an active bacterial, viral (e.g., herpes simplex), or fungal infection can spread the infection and cause severe complications.
Actionable advice:
Postpone any hyaluronic acid injections until the skin infection is fully resolved.
Validation status:
validated_via_clinical_guidance
Evidence tier:
tier_b
Evidence basis:
clinical_guidance_verbatim
Evidence anchors:
Exact phrase from label:
Skin or knee joint infections or other problems at the place where the injection is to be given—Should not be given in patients with these conditions
Label source:
Clinical guidance: Mayo Clinic — Hyaluronic Acid Injection Route contraindications
Action type:
informational_none
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
For injections, these drugs significantly increase the risk of bleeding, hematoma, and extensive bruising. For oral HA, there is a minor, theoretical antiplatelet effect.
Actionable advice:
It is important to talk to a doctor before taking oral HA, and use should be discontinued 5-7 days before any planned HA injection procedure.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Local injection of HA at 0.8% prolonged the bleeding time, and increased hemorrhage and swelling in the early postoperative period after third molar extractions.
Label source:
PubMed: Journal of applied oral science : revista FOB (2017)
Source url:
Exact phrase from label:
Immediate injection-related reactions such as erythema, edema, and bruising/hematoma were the most reported complications, followed by early contour irregularities and blue discoloration.
Label source:
PubMed: Turkish journal of ophthalmology (2025)
Source url:
Exact phrase from label:
Adverse events associated with these products are typically transient and mild to moderate in severity. Serious adverse events, such as infection and intravascular occlusion, are rare.
Label source:
PubMed: The Australasian journal of dermatology (2020)
Action type:
avoid
Target id:
/condition/history-of-cancer
Target name:
History of Cancer
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to the role of hyaluronic acid in cell proliferation, there is a theoretical, though unproven, risk of promoting recurrence. This warrants caution.
Actionable advice:
It is important to talk to an oncologist before using oral hyaluronic acid supplements.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
The Hyaluronan/CD44 Axis: A Double-Edged Sword in Cancer
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC10649834/
Action type:
informational_none
Target id:
/condition/scleroderma
Target name:
Scleroderma
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Scleroderma is characterized by excessive deposition of extracellular matrix components, including hyaluronic acid. Supplementation could theoretically exacerbate this process.
Actionable advice:
It is important to consult a rheumatologist before using hyaluronic acid supplements.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Skin fibrosis in SSc is characterized by the progressive accumulation of extracellular matrix components, including collagen, in the dermis, and is associated with adipocyte atrophy in the hypodermis.
Label source:
PubMed: Systemic sclerosis: pathogenic mechanisms and their implications for treatment. (PMID 41217519)
Action type:
informational_none
Target id:
/class/nsaids
Target name:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
24
Description:
When receiving HA injections, NSAIDs inhibit platelet function and increase the risk of bleeding and significant bruising at the injection site.
Actionable advice:
NSAIDs should be discontinued 3-7 days before a planned HA injection and for 24 hours after, per a practitioner's advice.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Other factors that increase the risk of GI bleeding in patients treated with NSAIDs
include longer duration of NSAID therapy; concomitant use of oral corticosteroids, antiplatelet
drugs (such as aspirin), anticoagulants; or selective serotonin reuptake inhibitors (SSRIs);
smoking; use of alcohol; older age; and poor general health status.
Label source:
Action type:
separate
Target id:
/class/herbal-anticoagulants
Target name:
Herbal Anticoagulants (Fish Oil, Ginkgo, Garlic)
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
168
Hours after target:
24
Description:
Supplements like fish oil, ginkgo biloba, garlic, and high-dose vitamin E can thin the blood, increasing the risk of bruising and bleeding from HA injections.
Actionable advice:
Supplements with blood-thinning effects should be discontinued 1 week prior to HA injections, as directed by a practitioner.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Facial aesthetic treatment with injectable neuromodulators and hyaluronic acid fillers is well established, with favourable safety profiles and consistent outcomes. As with any medical treatment, adverse events and complications may occur.
Label source:
PubMed: The Australasian journal of dermatology (2020)
Source url:
Exact phrase from label:
Subjects treated with needles had a statistically significant greater incidence rate of ecchymosis, compared to those treated with cannula.
Label source:
PubMed: Journal of cosmetic dermatology (2023)
Source url:
Exact phrase from label:
No local reaction to the HA dermal filler or any other complications other than minor skin bleeding at the injection sites were noted in all patients.
Label source:
PubMed: Veterinary ophthalmology (2019)
Action type:
avoid
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
2
Description:
As a large molecule (polysaccharide), oral hyaluronic acid absorption may be slightly improved when taken on an empty stomach, though evidence for this is not strong.
Actionable advice:
For potentially better absorption, it is best taken 30 minutes before a meal or at least 2 hours after eating.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Hyaluronic acid (HA) is key to the stability of the internal environment of tissues. HA content in tissues gradually decreases with age, causing age-related health problems. Exogenous HA supplements are used to prevent or treat these problems including skin dryness and wrinkles, intestinal imbalance, xerophthalmia, and arthritis after absorption.
Label source:
PubMed: Carbohydrate polymers (2023)
Source url:
Exact phrase from label:
Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered (14)C-hyaluronic acid was found in the blood. Approximately 90% of (14)C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week) after administration.
Label source:
PubMed: TheScientificWorldJournal (2014)
Source url:
Exact phrase from label:
In vivo results showed that, except for high MM f-HA, there is an inverse relationship between rheological changes in the intestinal membrane macerates resulting from mucoadhesion and the effective intestinal permeability that led to blood clearance of the structures.
Label source:
PubMed: Biomolecules (2020)
Action type:
separate
Target id:
/intervention/collagen-peptides
Target name:
Collagen Peptides
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Hyaluronic acid helps bind water to collagen, enhancing skin hydration and joint lubrication, while collagen provides the structural framework for these tissues.
Actionable advice:
Consider taking with collagen peptides for enhanced skin and joint benefits.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Furthermore, the topical application of hyaluronic acid is discussed as a mechanism to increase collagen production and skin moisture, contributing to the anti-aging effects of collagen supplementation.
Label source:
PubMed: Unlocking the Therapeutic Potential of Marine Collagen: A Scientific Exploration for Delaying Skin Aging. (PMID 38667776)
Action type:
informational_none
Target id:
/intervention/glucosamine
Target name:
Glucosamine
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Glucosamine is a building block for cartilage and hyaluronic acid itself. Together, they provide both structural components and lubrication for joint health.
Actionable advice:
Consider taking with glucosamine for comprehensive joint support.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The synthesis of HA requires GlcN as one of its main building blocks. We therefore hypothesized that addition of GlcN might increase HA production by synovium tissue.
Label source:
PubMed: BMC musculoskeletal disorders (2008)
Source url:
Exact phrase from label:
An alternative or additional possibility is that glucosamine stimulates synovial production of hyaluronic acid (HA), which is primarily responsible for the lubricating and shock-absorbing properties of synovial fluid.
Label source:
PubMed: Medical hypotheses (1998)
Source url:
Exact phrase from label:
Hyaluronic acid is a linear, non-sulfated glycosaminoglycan that is widely distributed in nature and is mainly composed of repeating units of N-acetylglucosamine and glucuronic acid. It has a wide and unique range of properties such as viscoelasticity, lubrication, and hydration, which makes it an attractive material for several industrial applications such as cosmetics, pharmaceuticals, and medical devices.
Label source:
PubMed: Molecules (Basel, Switzerland) (2023)
Action type:
informational_none
Target id:
/intervention/chondroitin-sulfate
Target name:
Chondroitin Sulfate
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chondroitin provides cartilage with resistance to compression, while hyaluronic acid lubricates the joint, offering a combined and complementary benefit for joint function.
Actionable advice:
Consider taking with chondroitin sulfate for comprehensive joint support.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The case we present demonstrates the effectiveness of this Col II-CS-HA cartilage biomimetic matrix gel, which is expected to become a new effective solution for huge cartilage defects in future clinical practice.
Label source:
PubMed: Col II-CS-HA cartilage biomimetic matrix gel provides a new treatment option for huge cartilage defects - a case report. (PMID 41837055)
Action type:
informational_none
Target id:
/intervention/vitamin-c
Target name:
Vitamin C
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin C is an essential cofactor for the synthesis of collagen, which works in concert with hyaluronic acid to maintain the structure and integrity of skin and connective tissues.
Actionable advice:
Adequate Vitamin C intake may help support the structural benefits of hyaluronic acid.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Vitamin C is an essential part of skin health both as a small molecular weight antioxidant and as a critical factor for collagen synthesis
Label source:
Primary literature: https://lpi.oregonstate.edu/mic/health-disease/skin-health/vitamin-C
Action type:
informational_none
Target id:
/intervention/magnesium
Target name:
Magnesium
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium is a required cofactor for the enzymes (hyaluronan synthases) involved in the body's natural production of hyaluronic acid.
Actionable advice:
Adequate magnesium intake may help support both endogenous and supplemental hyaluronic acid function.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We found that the expressions of hyaluronan synthase (HAS), HAS2 and HAS3 are influenced by MgCl2 concentration in human keratinocyte-derived HaCaT cells. The exposure of cells to a high concentration (5.8 mM) of MgCl2 induced the elevation of HAS2/3 expression, which was inhibited by mRNA knockdown of nonimprinted in Prader-Willi/Angelman syndrome-like domain containing 4 (NIPAL4).
Label source:
PubMed: International journal of molecular sciences (2021)
Source url:
Exact phrase from label:
The enzyme utilized UDP-sugar precursors of HA in the presence of Mg2+ or Mn2+ at neutral pH.
Label source:
PubMed: Biochemistry (1996)
Source url:
Exact phrase from label:
The only attribute that appears to be absolutely required for binding is a nucleotide containing two phosphates complexed with magnesium ion.
Label source:
PubMed: The Journal of biological chemistry (2002)
Action type:
informational_none