Supplementary Materials

References.

A
Alcântara, et al., (2018) Hyaluronic Acid Accelerates Bone Repair in Human Dental Sockets:
A Randomized Triple-Blind Clinical Trial. Braz Oral Res. 32: e84. https://pubmed.ncbi.nlm.nih.gov/30231173/.

Amin, et al., (2014) Trends in Fracture Incidence: A Population-Based Study Over 20Years.
J Bone Miner Res. 29: 581. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929546/.

Asari, et al., (2010) Oral Administration of High Molecular Weight Hyaluronan (900 kDa)
Controls Immune System via Toll-like Receptor 4 in the Intestinal Epithelium. J Biol
Chem. 285: 2475. /.

Asparuhova, et al., (2019) Activity of Two Hyaluronan Preparations on Primary Human
Oral FIbroblasts. J Periodontal Res. 54: 33.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586051/.

Ayars, et al., (2013) Sputum Hyaluronan and Versican in Severe Eosinophilic Asthma. Int
Arch Allergy Immunol. 161: 65.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059000/.

B
Bell, et al., (2019) Defective lung function following influenza virus is due to prolonged,
reversible hyaluronan synthesis. Matrix Biol. 80: 14.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548309/.

Bellar, et al., (2019) Safety of Hyaluronan 35 in Healthy Human Subjects: A Pilot Study.
Nutrients. 11: 1135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566413/.

Bijelc, et al, (2017) Risk Factors for Osteoporosis in Postmenopausal Women. Med Arch 71:
25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364787/.

Braga, et al., (2015) Antioxidant Activity of Hyaluronic Acid Investigated by Means of
Chemiluminescence of Equine Neutrophil Bursts and Electron Paramagnetic
Resonance Spectroscopy. J Vet Pharmacol Ther. 38: 48.
https://pubmed.ncbi.nlm.nih.gov/25066541/.

Brauer, et al., (2009) Incidence and Mortality of Hip Fractures in the United States. JAMA.
302: 1573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410861/.

Boulos & Geraghty, (2020) Geographical tracking and mapping of coronavirus disease
COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic
and associated events around the world: how 21st century GIS technologies are
supporting the global fight against outbreaks and epidemics. Int J Health Geogr. 19: 8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065369/.

C
Calve, et al., (2012) Hyaluronic Acid, HAS1, and HAS2 Are Significantly Upregulated During
Muscle Hypertrophy. Am J Physiol Cell Physiol. 303: C577.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468343/.

Cantor, (2007) Potential Therapeutic Applications of Hyaluronan in the Lung. Int J Chron
Obstruct Pulmon Dis. 2: 283.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695200/.

Cantor, et al., (2017) A Pilot Clinical Trial to Determine the Safety and Efficacy of
Aerosolized Hyaluronan as a Treatment for COPD. Int J Chron Obstruct Pulmon Dis 12:
2747. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609793/.

Casale, et al., (2016) Hyaluronic acid: Perspectives in dentistry. A systematic review. Int J
immunopathol Pharmacol. 29: 572.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806851/.

Ceccarelli, et al., (2017) Emerging Perspectives in Scaffold for Tissue Engineering in Oral
Surgery. Stem Cells Int. 2017: Article ID 4585401.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346390/.

Cermelli et al. (2011) In Vitro Evaluation of Antiviral and Virucidal Activity of a High
Molecular Weight Hyaluronic Acid. Virology Journal 8: 141
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073889/.

Chang, et al., (2016) Bone Healing Improvements Using Hyaluronic Acid and
Hydroxyapatite/Beta-Tricalcium Phosphate in Combination: An Animal Study. Biomed
Res Int. 2016: Article ID 301624.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192297/.

Chang, et al., (2019) The Development of Gelatin/Hyaluronate Copolymer Mixed with
Calcium Sulfate, Hydroxyapatite, and Stromal-Cell-Derived Factor-1 for Bone
Regeneration Enhancement. Polymers (Basel). 11: 1454.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780272/.

Chaplin, (2010) Overview of the Immune Response. J Allergy Clin Immunol. 125: S3.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923430/.

Chiou, et al., 2018 Mechanistic insight into hyaluronic acid and platelet-rich plasma
mediated anti-inflammatory and anti-apoptotic activities in osteoarthritic mice.
Aging. 2018 10 4152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326674/.

Ciofalo, et al., (2017) Pathological and Cytological Changes of the Nasal Mucosa in Acute
Rhinosinusitis: The Role of Hyaluronic Acid as Supportive Therapy. Eur Rev Med
Pharmacol Sci. 21:4411. https://pubmed.ncbi.nlm.nih.gov/29077152/.

Colgan (2013) Swimming through the gut: Implications of fluid transport on the
microbiome. Dig Dis Sci. 58: 602.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075287/.

Cronkite & Strutt (2018) The Regulation of Inflammation by Innate and Adaptive
Lymphocytes. J Immunol Res. 2018:1467538.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016164/.

Cyphert, et al., (2015) Size Matters: Molecular Weight Specificity of Hyaluronan Effects in
Cell Biology. Int J Cell Biol. 2015: 563818.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581549/.

D
Deed, et al., (1997) Early-response Gene Signalling Is Induced by Angiogenic
Oligosaccharides of Hyaluronan in Endothelial Cells. Inhibition by Non-Angiogenic,
High-Molecular-Weight Hyaluronan. Int J Cancer. 71: 251.
https://pubmed.ncbi.nlm.nih.gov/9139851/.

de la Motte, (2011) Hyaluronan in Intestinal Homeostasis and Inflammation: Implications
for Fibrosis. Am J Physiol. 301: G945.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233788/.

de la Motte & Kessler, (2015) The Role of Hyaluronan in Innate Defense Responses of the
Intestine. Int J Cell Biol. 2015: Article ID 481301.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397497/.

Dini, et al., (2006) New polyphenol derivative in Ipomoea batatas tubers and its
antioxidant activity. J. Agric. Food. Chem. 54: 8733.
https://pubmed.ncbi.nlm.nih.gov/17090114/.

Drago, et al., (2014) Antiadhesive and Antibiofilm Activity of Hyaluronic Acid Against
Bacteria Responsible for Respiratory Tract Infections. APMIS. 122: 1013.
https://pubmed.ncbi.nlm.nih.gov/24698341/.

Drewnowski & Rehm, (2013) Vegetable Cost Metrics Show That Potatoes and Beans
Provide Most Nutrients Per Penny. PLOS ONE 8: e63277).
https://pubmed.ncbi.nlm.nih.gov/23691007/.

E
Eliezer, et al., (2019) Hyaluronic Acid as Adjunctive to Non-Surgical and Surgical
Periodontal Therapy: A Systematic Review and Meta-Analysis. Clin Oral Investig. 23:
3423. https://pubmed.ncbi.nlm.nih.gov/31338632/.

Engering, et al., (2013) Pathogen–host–environment interplay and disease emergence.
Emerg Microbes Infect. 2: e5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630490/.

Esposito, et al., (2017) Hyaluronic acid is associated with organ dysfunction in acute
respiratory distress syndrome. Crit Care. 21: 304.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729515/.

F
Fanfair, et al., (2012) Necrotizing Cutaneous Mucormycosis After a Tornado in Joplin,
Missouri, in 2011. N Engl J Med. 367: 2214.
https://pubmed.ncbi.nlm.nih.gov/23215557/.

Fisher, et al., (2015) Cancer resistance, high molecular weight hyaluronic acid, and
longevity. J Cell Commun Signal. 9: 91.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414831/.

Fujioka-Kobayashi, et al., (2016) Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier
for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential. J Clin Med. 5: 112.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5184785/.

G
Galland, (2014) The Gut Microbiome and the Brain. J Med Food. 17: 1261.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259177/.

Gannotta, et al., (2018) Integrative Medicine as a Vital Component of Patient Care. Cureus.
10: e3098. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173273/.

Garantziotis & Matalon, (2019) Sugarcoating Lung Injury: A Novel Role for HighMolecular-Weight Hyaluronan in Pneumonia. Am J Respir Crit Care Med. 200: 1197.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857491/.

Garantziotis, et al., (2016a) The Role of Hyaluronan in the Pathobiology and Treatment of
Respiratory Disease. Am J Physiol Lung Cell Mol Physiol. 310: L785.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867348/.

Garantziotis, et al., (2016b) Hyaluronan mediates ozone-induced airway
hyperresponsiveness in mice. J Biol Chem. 291: 19257.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016665/.

Gollner, et al., (2017) Ingestion of an Oral Hyaluronan Solution Improves Skin Hydration,
Wrinkle Reduction, Elasticity, and Skin Roughness: Results of a Clinical Study. J Evid
Based Complementary Altern Med. 22: 816.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871318/.

Groß, et al., (2018) Comparative Study of 0.1% Hyaluronic Acid Versus 0.5%
Carboxymethylcellulose in Ppatients with Dry Eye Associated with Moderate
Keratitis or Keratoconjunctivitis. Clin Ophthalmol 12: 1081.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001744/.

Guaitolini, et al., (2019) Randomized, Placebo-controlled Study of a Nutraceutical Based
on Hyaluronic Acid, L-carnosine, and Methylsulfonylmethane in Facial Skin
Aesthetics and Well-being. J Clin Aesthet Dermatol. 12: 40-45.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508480/.

Gupta, et al, (2019) Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory.
Front Vet Med. 6: Article 192.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603175/.

I

J
Jensen, et al., (2015) Oral Intake of a Liquid High-Molecular-Weight Hyaluronan
Associated with Relief of Chronic Pain and Reduced Use of Pain Medication: Results
of a Randomized, Placebo-Controlled Double-Blind Pilot Study. J Med Food. 18: 95.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281855/.

Jiang, et al., (2011) Hyaluronan as an Immune Regulator in Human Diseases. Physiol Rev.
91: 221. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051404/.

K
Kalman, et al., (2008) Effect of a Natural Extract of Chicken Combs with a High Content of
Hyaluronic Acid (Hyal-Joint) on Pain Relief and Quality of Life in Subjects with Knee
Osteoarthritis: A Pilot Randomized Double-Blind Placebo-Controlled Trial. Nutr J. 7:
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2245974/.

Kaux, et al., (2016) Hyaluronic Acid and Tendon Lesions. Muscles Ligaments Tendons J. 5:
264. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762636/.

Kawada, et al., (2014) Ingested hyaluronan moisturizes dry skin. Nutr J. 13: 70.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110621/.

Kawada, et al., (2015) Ingestion of Hyaluronans (Molecular Weights 800 K and 300 K)
Improves Dry Skin Conditions: A Randomized, Double Blind, Controlled Study. J Clin
Biochem Nutr. 13: 70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306664/.

Kessler, et al., (2018) Multifunctional Role of 35 Kilodalton Hyaluronan in Promoting
Defense of the Intestinal Epithelium. J Histochem Cytochem. 66: 273–287.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958379/.

Kim, et al., (2007) Bone Regeneration Using Hyaluronic Acid-Based Hydrogel with Bone
Morphogenic protein-2 and Human Mesenchymal Stem Cells. Biomaterial. 28: 1830.
https://pubmed.ncbi.nlm.nih.gov/17208295/.

Kim, et al., (2018) Layilin Is Critical for Mediating Hyaluronan 35kDa-induced Intestinal
Epithelial Tight Junction Protein ZO-1 in Vitro and in Vivo. Matrix Biol. 66: 93.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845474/.

Kim, et al., (2019) Oral Hyaluronic Acid Supplementation for the Treatment of Dry Eye
Disease: A Pilot Study. J Opthalmol. 2019: Article ID 5491626.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778932/.

Kim & de la Motte (2020) The Role of Hyaluronan Treatment in Intestinal Innate Host
Defense. Front Immun 11: 569.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201044/.

Kisiel, et al., (2013) Improving the Osteogenic Potential of BMP-2 With Hyaluronic Acid
Hydrogel Modified With Integrin-Specific Fibronectin Fragment. Biomaterials. 34: 704.
https://pubmed.ncbi.nlm.nih.gov/23103154/.

Koca, et al., (2020) Comparison of Efficiency of Hyaluronic Acid and/or Bone Grafts in
Healing of Bone Defects. Niger J Clin Pract. 22: 754.
https://pubmed.ncbi.nlm.nih.gov/31187758/.

Kouvidi, et al., (2011) Role of Receptor for Hyaluronic Acid-Mediated Motility (RHAMM)
in Low Molecular Weight Hyaluronan (LMWHA)-mediated Fibrosarcoma Cell
Adhesion. J Biol Chem. 286:38509. https://pubmed.ncbi.nlm.nih.gov/21914806/.

L
Labetoulle, et al., (2018) Efficacy and safety of dual-polymer hydroxypropyl guar- and
hyaluronic acid-containing lubricant eyedrops for the management of dry-eye
disease: A randomized double-masked clinical study. Clin Ophthalmol. 5: 2499.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287663/.

Lazrak, et al., (2015) Hyaluronan mediates airway hyperresponsiveness in oxidative lung
injury. Am J Physiol Lung Cell Mol Physiol. 308: L891.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421785/.

Leng, et al., (2019) Hyaluronic Acid, CD44 and RHAMM Regulate Myoblast Behavior During
Embryogenesis. Matrix Biol. 78-79: 236.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379145/.

Lee, et al., (2014) Potential Anti-Osteoporotic Activity of Low-Molecular Weight
Hyaluronan by Attenuation of Osteoclast Cell Differentiation and Function in Vitro.
Biochem Biophys Res Commun. 449: 438.
https://pubmed.ncbi.nlm.nih.gov/24853804/.

Lee, et al., (2020) Hyaluronic acid-bilirubin nanomedicine for targeted modulation of
dysregulated intestinal barrier, microbiome, and immune responses in colitis. Nat
Mater. 19: 118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923573/.

Lewis, et al., (2013) The Naked Mole-Rat Response to Oxidative Stress: Just Deal with It.
Antioxid Redox Signal. 19: 138.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791056/.

Lim, et al., (2013) Role of Anthocyanin-enriched Purple-fleshed Sweet Potato P40 in
Colorectal Cancer Prevention. Mol Nutr Food Res. 57: 1908.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980565/.

Liu, et al., (2019) Therapeutic Effects of Hyaluronic Acid in Bacterial Pneumonia in Ex Vivo
Perfused Human Lungs. Am J Respir Crit Care Med. 200 1234.
https://pubmed.ncbi.nlm.nih.gov/31390880/.

Lubart, et al., (2019) Topical Hyaluronic Acid Facial Cream with New Micronized
Molecule Technology Effectively Penetrates and Improves Facial Skin Quality:
Results from In-vitro, Ex-vivo, and In-vivo (Open-label) Studies. Antioxid Redox
Signal. 19: 138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937149/.

M
Ma, et al., (2013) Oral Administration of Hyaluronan Reduces Bone Turnover in
Ovariectomized Rats. J Agric Food Chem. 61: 339.
https://pubmed.ncbi.nlm.nih.gov/23256527/.

Macchi, et al., (2013) Hyaluronan Plus Saline Nasal Washes in the Treatment of RhinoSinusal Symptoms in Patients Undergoing Functional Endoscopic Sinus Surgery for
Rhino-Sinusal Remodeling. Int J Immunopathol Pharmacol. 26:137.
https://pubmed.ncbi.nlm.nih.gov/23527716/.

Maia, et al., (2019) Viscosupplementation Improves Pain, Function and Muscle Strength,
but Not Proprioception, in Patients with Knee Osteoarthritis: A Prospective
Randomized Trial. Clinics Sao Paulo. 74: e1207.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844143/.

Maizes, et al., (2009) Integrative Medicine and Patient-Centered Care. Explore (NY). 5:
277. https://pubmed.ncbi.nlm.nih.gov/19733814/.

Mao & Kapur, (2010) Acupuncture in Primary Care. Prim Care. 37: 105.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830903/.

Marin, et al., (2020) Hyaluronic acid treatment outcome on the post-extraction wound
healing in patients with poorly controlled type 2 diabetes: A randomized controlled
split-mouth study. Med Oral Patol Oral Circ Bucal. 25: e154.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103456/.

McCall-Perez, et al., (2011) Efficacy and Tolerability of a Facial Serum for Fine Lines,
Wrinkles, and Photodamaged Skin. J Clin Aesthet Dermatol. 4: 51.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140905/.

Missinato, et al., (2015) Extracellular Component Hyaluronic Acid and Its Receptor Hmmr
Are Required for Epicardial EMT During Heart Regeneration. Cardiovasc Res. 107:
487. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540147/.

Molina-Solana, et al., (2020) Improved Tear Film Stability in Patients with Dry Eye After
Hyaluronic Acid and Galactoxyloglucan Use. Clin Ophthalmol. 14: 1153.,
https://pubmed.ncbi.nlm.nih.gov/32425501/.

Mong, et al., (2020) Accelerated Hyaluronan Concentration as the Primary Driver of
Morbidity and Mortality in High-Risk COVID-19 Patients: With Therapeutic
Introduction of an Oral Hyaluronan Inhibitor in the Prevention of “Induced
Hyaluronan Storm” Syndrome. Non-peer-reviewed, pre-publication reprint.
https://www.medrxiv.org/content/10.1101/2020.04.19.20071647v3

Moriña, et al., (2018) Effectiveness of a Low-Fat Yoghurt Supplemented with Rooster
Comb Extract on Muscle Strength in Adults with Mild Knee Pain and Mechanisms of
Action on Muscle Regeneration. Food Funct. 9: 3244.
https://pubmed.ncbi.nlm.nih.gov/29888778/.

N
Nagaoka, et al., (2010) Evaluation of the Effects of a Supplementary Diet Containing
Chicken Comb Extract on Symptoms and Cartilage Metabolism in Patients with Knee
Osteoarthritis. Exp Ther Med. 1: 817. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445888/.

Nanashima, et al., (2018) Black Currant Anthocyanins Increase the Levels of Collagen,
Elastin, and Hyaluronic Acid in Human Skin Fibroblasts and Ovariectomized Rats.
Nutrients. 10: 495. https://pubmed.ncbi.nlm.nih.gov/29659549/.

Nenna, et al., (2014) Seven Percent Hypertonic saline–0.1% Hyaluronic Acid in Infants
with Mild-To-Moderate Bronchiolitis. Pediatr Pulmonol. 49: 919.
https://pubmed.ncbi.nlm.nih.gov/24574431/.

O
Oe, et al., (2017) Oral Hyaluronan Relieves Wrinkles: A Double-Blinded, Placebo-Controlled
Study Over a 12-Week Period. Clin Cosmet Investig Dermatol. 10: 267.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522662/.

P
Papakonstantinou, et al., (2012) Hyaluronic Acid: A Key Molecule in Skin Aging.
Dermatoendocrinol. 4: 255 https://pubmed.ncbi.nlm.nih.gov/23467280/.

Papakonstantinou, et al., (2019) Serum Levels of Hyaluronic Acid Are Associated with
COPD Severity and Predict Survival. Eur Respir J. 53: 1801183.
https://pubmed.ncbi.nlm.nih.gov/30705130/.

Penna, et al., (2019) Cytoprotective, Anti-Inflammatory, and Antioxidant Properties of
High-Molecular-Weight Hyaluronan Enriched with Red Orange Extract in Human
Fibroblasts Exposed to Ultraviolet Light B Irradiation. Biotechnol Appl Biochem. 66:
273. https://pubmed.ncbi.nlm.nih.gov/30588719/.

Pérez-Sánchez, et al., (2018) Nutraceuticals for Skin Care: A Comprehensive Review of
Human Clinical Studies. Nutrients. 10: 403.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946188/.

Pignataro, et al., (2018) Topically Administered Hyaluronic Acid in the Upper Airway: A
Narrative Review. Int J Immunopathol Pharmacol. 32: 2058738418766739.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871036/.

Q

R
Rammal, et al., (2018) Combining Calcium Phosphates with Polysaccharides: A BoneInspired Material Modulating Monocyte/Macrophage Early Inflammatory Response.
Int J Mol Sci. 19: 3458. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274876/.

Rayahin, et al., (2015) High and Low Molecular Weight Hyaluronic Acid Differentially
Influence Macrophage Activation. ACS Biomater Sci Eng. 1: 481.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533115/.

Rothan, et al. (2020) The Epidemiology and Pathogenesis of Coronavirus Disease (COVID19) Outbreak. J Autoimmun. 109: 102433.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127067/.

S
Safrankova, et al., (2010) The Potency of Hyaluronan of Different Molecular Weights in the
Stimulation of Blood Phagocytes. Mediators of Inflammation. 2010: Article ID 380948.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042665/.

Salem, et al., (2018) The Gut Microbiome as a Major Regulator of the Gut-Skin Axis. Front
Microbiol. 9: 1459. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048199/.

Sánchez, et al., (2014) Blood Cells Transcriptomics as Source of Potential Biomarkers of
Articular Health Improvement: Effects of Oral Intake of a Rooster Combs Extract Rich
in Hyaluronic Acid. Genes Nutr. 9: 417.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172652/.

Schwartz & Park, (2012) Ingestion of BioCell Collagen (®), a Novel Hydrolyzed Chicken
Sternal Cartilage Extract; Enhanced Blood Microcirculation and Reduced Facial Aging
Signs. Clin Interv Aging. 7: 267.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426261/.

Shi, et al., (2020) COVID-19 Infection: The Perspectives on Immune Responses. Cell Death
Differ. 27:1451. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091918/.

Song, et al., (2020) Cytokine Storm Induced by SARS-CoV-2. Clin Chim Acta. Epub ahead of
print. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283076/.

Soriano-Lerma, et al., (2019) Short-term Effects of Hyaluronic Acid on the Subgingival
Microbiome in Peri-Implantitis: A Randomized Controlled Clinical Trial. J Periodontol.
Epub ahead of print. https://pubmed.ncbi.nlm.nih.gov/31577041/.

Soroosh, et al., (2016) Crohn’s Disease Fibroblasts Overproduce the Novel Protein
KIAA1199 to Create Proinflammatory Hyaluronan Fragments. Cell Mol Gastroenterol
Hepatol. 2: 358. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042354/.

Stephens, et al., (2016) A Randomized, Double-blind, Placebo-controlled Clinical Trial
Evaluating an Oral Anti-aging Skin Care Supplement for Treating Photodamaged Skin.
J Clin Aesthet Dermatol. 9: 25.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898581/.

Sugata, et al., (2015) Anti-Inflammatory and Anticancer Activities of Taiwanese PurpleFleshed Sweet Potatoes (Ipomoea Batatas L. Lam) Extracts. Biomed Res Int. 2015:
768093. https://pubmed.ncbi.nlm.nih.gov/26509161/.

Sun, et al., (2020) Cytokine Storm Intervention in the Early Stages of COVID-19 Pneumonia.
Cytokine Growth Factor Rev. Epub ahead of print.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182527/.

T
Takasugi, et al., (2020) Naked Mole-Rat Very-High-Molecular-Mass Hyaluronan Exhibits
Superior Cytoprotective Properties. Nature Communications. 11: Article number 2376.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217962/.

Tashiro, et al., (2012) Oral Administration of Polymer Hyaluronic Acid Alleviates
Symptoms of Knee Osteoarthritis: A Double-Blind, Placebo-Controlled Study Over a
12-month Period. Sci World J. 2012: Article ID 167928.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512263/.

Tian, et al., (2013) High Molecular Weight Hyaluronan Mediates the Cancer Resistance of
the Naked Mole-Rat. Nature. 499: 436.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720720/.

Todd, et al., (2014) Hyaluronan Contributes to Bronchiolitis Obliterans Syndrome and
Stimulates Lung Allograft Rejection through Activation of Innate Immunity. Am J
Respir Crit Care Med. 189: 556.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977710/.

Turino, et al., (2017) The Therapeutic Potential of Hyaluronan in COPD. Chest. 153: 792.
https://pubmed.ncbi.nlm.nih.gov/29289686/.

U

V
VanderPloeg & Yi (2009) Acupuncture in Modern Society. J Acupunct Meridian Stud. 2:26.
https://pubmed.ncbi.nlm.nih.gov/20633471/.

Venge, et al., (1996) Subcutaneous Administration of Hyaluronan Reduces the Number of
Infectious Exacerbations in Patients with Chronic Bronchitis. Am J Respir Crit Care
Med. 153: 312. https://pubmed.ncbi.nlm.nih.gov/8542136/.

W
Wang, et al., (2019) Hyaluronic Acid Oligosaccharides Improve Myocardial Function
Reconstruction and Angiogenesis Against Myocardial Infarction by Regulation of
Macrophages. Theranostics. 9: 1980.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485288/.

Wiig, et al., (2014) PXL01 in Sodium Hyaluronate for Improvement of Hand Recovery After
Flexor Tendon Repair Surgery: Randomized Controlled Trial. PLoS One.9: e110735.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207831/.

Willcox, et al., (2014) Healthy Aging Diets Other than the Mediterranean: A Focus on the
Okinawan Diet. Mech Ageing Dev. 136-137: 148.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403516/.

X

Y
Yeom, et al., (2014) Effect of Osteoconductive Hyaluronate Hydrogels on Calvarial Bone
Regeneration. Biomater Res. 18: 8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549130/.

Yoshimura, et al., (2012) Evaluation of the Effect of a Chicken Comb Extract-Containing
Supplement on Cartilage and Bone Metabolism in Athletes. Exp Ther Med. 4: 577.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501371/.

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Certificate of Analysis.

Certificate of Analysis

Acknowlegments.

The authors would like to thank Dr. Lawrence Dahners for his careful and thoughtful critique of this manuscript and for his cogent suggestions to improve its quality and completeness.


Disclosures.

Douglas W. Kiburz, M.D. is co-owner of HA-TOPSHELF and profits from sales of the product. Dr. Kiburz collaborated with partners, Don Grove, Jr. and Don Jessup, to develop, produce, and market HA-TOPSHELF over the counter supplement. Dr. Kiburz identified the content, illustrations, and writing style of this manuscript and critically reviewed the entire document prior to publication. Dr. Kiburz is a practicing orthopedic surgeon at Bothwell Orthopedics & Sports Medicine, Bothwell Regional Health Center in Sedalia, MO.

Linda A. Landon, Ph.D. is a basic biomedical research scientist, molecular pharmacologist, data scientist, and medical writer. Dr. Landon was responsible for all background basic science and clinical literature research, review, and analysis; for writing, copy editing, and proofreading the text; for identifying, designing, and/or producing all figures; and for managing production of the print and digital versions of the book. Dr. Landon was paid for her work on this book. Dr. Landon is the founder and president of Research Communiqué, a research and communication firm, and is cofounder, co-CEO, and COO/CFO of Velocity DataTech, a data science firm.

Dalton Hermanson is a medical student in the accelerated sixyear medical program at the University of Missouri – Kansas City School of Medicine. Mr. Hermanson is augmenting his medical education by completing an unpaid internship with Dr. Kiburz and Dr. Landon. Mr. Hermanson contributed to the extensive background literature research and analysis of clinical trials and participated in writing, copy editing, and proofreading the text.


Contact Information.

Comments, questions, or corrections should be addressed to Douglas W. Kiburz, M.D. at kibz@charter.net or Linda A. Landon, Ph.D. at LandonPhD@ResearchCommunique.com. For product information, visit https://ha-topshelf.com/.


Citation.

The citation for this work is: Kiburz, D.W., Hermanson, D., & Landon, L.A. (2020) Hyaluran: The Most Important Molecule in Your Body. Warsaw, MO, USA: HA-TOPSHELF.