Hyaluronan for nutrition - Nutrihyl®
an active ingredient of biotechnological origin
Sodium hyaluronate (hyaluronan, sodium salt of hyaluronic acid) is a non-sulfated glycosaminoglycan. It is a polysaccharide with a non-branched chain composed of disaccharide units formed from D-glucuronic acid and N-acetylglucosamine, held together by β (1 3) bonds. These disacharide units are joined together by β (1 4) bonds forming a negatively charged poly (β-D-glucuronate-[1 3]-β-N-acetyl-D-glucosamine-[1 4]). The molecular formula of β-sodium-D-glucuronate-[1 3]-β-N-acetyl-D-glucosamine is [C14H20O11NNa]n, where n = 250 - 5000.
Sodium hyaluronate is a substance found in all vertebrates, mainly in connective tissue such as cartilage, bone, skin etc. and body fluids. From this point of view it is a non-toxic, non-cytotoxic, non-immunogenic and non-mutagenic substance.
Chemical name: Sodium Hyaluronate
Supplied forms: powder
Human: 20–90 mg per day, depending on the intended use
Horse: 50–250 mg per day
Dog: 30-150 mg per day
Skin and hair support
Application forms: Capsules, tablets, gels, syrups, health bars
Storage: store in originally sealed packaging in a cool and dry place
Shelf-life: 24 months
The influence of Nutrihyl® on experimental adjuvant arthritis
We studied the influence of Nutrihyl® on the development of adjuvant arthritis induced by the suspension of thermally killed mycobacterium in incomplete Freud adjuvans in rats. Nutrihyl® with different molecular weight was administered per orally by sound in various dosages.
Distribution of per orally applied Nutrihyl®
To evaluate the mechanism of per orally applied hyaluronan, it is essential to start with observation of its pharmacokinetics. Looking in the literature, we will find many references about hyaluronan pharmacokinetics after intravenous and also topical application, but very little is known about its pharmacokinetics after per oral application. 1-5 An article about pharmacokinects of technetium labeled hyaluronan was published. In this article, the authors describe the biological test with 99m technetium labeled hyaluronan (Nutrihyl®) at rats, where only 5% of the labeled HA was absorbed. Over 90% of radioactivity appeared in feces after 72 hours. The radioactivity was measured in blood, muscles, salivary glands and bone as early as after 30 minutes, and peaked 4-6 hours in all non-alimentary tissues examined after oral administration. There were transient increases in radioactivity in shoulder joints and vertebrae 4 hours after oral administration of HA. These results demonstrate that HA is absorbed and distributed to organs and joints after a single oral administration. 6-7
1) Smedsrod, B., Pertoft, H., Eriksson, S., Fraser, J.R.E. and Laurent, T. Studies in vitro on the uptake and degradation of sodiumhyaluronate in rat liver endothelial cells, Biochem J. (1984), 223, 617-626
2) Nimrod, A., Ezra, E., Ezov, N., Nachum, G., and Parisada, B. Absorption, distribution, metabolism, and excretion of bacteria-derived hyaluronic acid in rats and rabbits, J. Ocul Pharmacol (1992), 8, 161-172
3) Reed, R.K., Townsley, M.I., Laurent, T.C., Taylor A.E. Hyaluronan flux from from cat intestine: changes with lymph flow, Am J. Physiol Heart Circ Physiol (1992), 262,H457-H462
4) Brown, T.J., Alcorn, D., Robert, J. and Fraser, E. Absorption of hyaluronan applied to the surface of intact skin, J. Invest Dermatol (1999) , 113, 740-746
5) Breborowicz, A., Polubinska, A., Pawlaczyk, K., Kuzlan-Pawlaczyk, M., Moberly, J., Martis, L. and Oreopoulos, D., Interperitoneal hyaluronan administration in concious rats: absorption, metabolism, and effects on peritoneal fluid dynamics, Peritoneal Dial Internat (2001), 21, 130-136
6) Schauss, A.G., Balogh, L.G., Polyak A.G., Mathe D.G., Kiraly R.G. and Janoki, G.G. Absorption, distribution and excretion of the 99mtechnetium labeled hyaluronan after single oral doses in rats and beagle dogs, Experimental biology (2004), Washington (2004)
7) Thierry, B., Winnik, F.M., Merhi, Y., Silver, J. And Tabrizian, M. Radionuclides-hyaluronan-conjugate thomboresistant coating to prevent in-stent restenosis, Biomaterials (2004), 25, 3895-3905
The influence of Nutrihyl® on various inflammatory and degenerative processes in joints and tendons in horses
The study was made as a simple open multicentric study in 7 veterinary clinics. 53 race horses with acute, subacute and chronic synovitis, osteochondorsis, arthritis, tendinitis and tendovaginitis were administered with Nutrihyl® per orally for 30 days. The treatment effect was evaluated by veterinary doctors for the following parameters: overall clinical state, swelling, painfulness of the passive movements, degree of hobbling, stiffness of the legs after rest, functional evaluation before and after 30 days application and also after a further 30 days from the end of the application.
The influence of Nutrihyl® and chondroitin sulphate combination on joints after knee surgery
The study was made in the university orthopaedic clinic in Prague with 27 patients recovering from knee surgery. The group was treated with the mixture of Nutrihyl® and chondroitin sulphate per orally for 90 days. The efficiency of the treatment was expressed for the following parameters: swelling and painfulness of the joint and movement capability. The disposition of the patient was evaluated before and after the treatment by a patient (subjective finding) as well as by a doctor (clinical finding). The overal results are presented in Fig. 2.
The effect of chondroitin sulphate in a dose which is markedly below the therapeutic dose is most probably insignificant as it was proven in our study on race horses and therefore we can conclude that the effectiveness of the preparation used for this study can be assigned to Nutrihyl® only.
The influence of Nutrihyl® on the state of knee joint in ice-hockey players
The study was made in the Musculosceletal Institute in Prague with 24 ice-hockey players of the premier league. The group was treated for 90 days during the sport season. The efficiency of the treatment was expressed for the following parameters: joint movement, muscle strength, joint stability and intra-articular problems. The disposition of the sportsman was evaluated before and after the treatment by a doctor. The overal results are presented in Fig. 3.
The influence of Nutrihyl® on experimentally cause osteoporoses
Osteoporoses was experimentally caused in laboratory female rats by ovarectomy. We have observed the effect of p.o. applied Nutrihyl® with different molecular weight and at different dosages on parameters characterizing bone degradation and bone density. The experiment with ovarectomized rats simulates women after menopause.
The influence of Nutrihyl® on skin and hair
Our findings 8 showed that Nutrihyl® activates nitric oxide (NO) synthesis. The content of nitrate and nitrite, the „metabolites" of NO, in blood serum is increasing after per oral use of Nutrihyl®. It is known that NO has positive effect on wound healing, hair growth and other processes in skin 9-11. These findings suggest that per orally applied Nutrihyl® could have a positive effect of overall state of skin and hair thus could become an ideal nutritional supplement to a topical cosmetic care for ageing and damaged skin.
8) Stancikova, M., Svik, K., Istok, R. and Velebny, V. The effects of hyaluronan on bone resorption and bone mineral density in rat model of estrogen deficiency-induced osteopenia, Tissue reaction, in press
9) Schwentker, A., Vodovotz, Y., Weller, R. And Billiar, T.R. Nitric oxide and wound repair: role of cytokines Nitric oxide (2002), 7, 1-10
10) Frank, S., Kaempfer, H., Wetzler, C., Pfeilchifter, J., Nitric oxide drives skin repair: Novel function of an established mediator, Kidney Internat (2002), 61, 882-888
11) Mochizuki, S., Vink, H., Hiramatsu, O., Kajita, T., Shigeto, F., Spaan, J.A.E. and Kajiya, F. Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release, Am J. Physiol Heart Circ Physiol (2003), 285, H722-H726
Pharmacokinetics after per oral use
The study available upon request.