Source: WASHINGTON STATE UNIVERSITY submitted to
DIETARY ASTAXANTHIN IN INFLAMMATORY DISEASE: A RHEUMATOID ARTHRITIS MODEL IN DOGS AND CATS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
HATCH
Reporting Frequency
Annual
Accession No.
0182965
Grant No.
(N/A)
Project No.
WNP00331
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Oct 1, 2003
Project End Date
Sep 30, 2006
Grant Year
(N/A)
Project Director
Chew, B. P.
Recipient Organization
WASHINGTON STATE UNIVERSITY
240 FRENCH ADMINISTRATION BLDG
PULLMAN,WA 99164-0001
Performing Department
FOOD SCIENCE & HUMAN NUTRITION
Non Technical Summary
Millions of dogs, cats and human suffer from crippling rheumatoid arthritis. This condition is immune-based and results from an inflammatory condition induced by harmful free radicals. We propose to use astaxanthin, a potent antioxidant that has immune-modulating activity, to reduce the harmful effects of reactive oxidative products, and thereby reduce rheumatoid arthritis.
Animal Health Component
100%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113830101020%
3113830104010%
3113830109020%
7023830101020%
7023830104010%
7023830109020%
Knowledge Area
311 - Animal Diseases; 702 - Requirements and Function of Nutrients and Other Food Components;

Subject Of Investigation
3830 - Pets (companion animals);

Field Of Science
1010 - Nutrition and metabolism; 1090 - Immunology; 1040 - Molecular biology;
Goals / Objectives
To investigate the action of dietary astaxanthin in reducing rheumatoid arthritis in domestic dogs and cats, and to elucidate the underlying mechanism of action of this antioxidant.
Project Methods
Large-scale clinical studies will be conducted to investigate the action of astaxanthin in reducing rheumatoid arthritis in dogs and cats. Animals with confirmed RA conditions will be recruited from private homes and fed (1) control, (2) 10 mg astaxanthin/day, or (3) 20 mg astaxanthin/day (n = 30/treatment). In addition, 30 dogs without signs of RA will be used as negative controls. The following procedures will be performed by a veterinarian on each dog at 0 (initiation of dietary supplementation), 1, 2, 3, and 6 months: body weight, physical exam, lameness exam, radiographs, and skin/ coat evaluation. Blood will be drawn during those periods for the analyses of the following immune and oxidative markers: lymphocyte phenotyping, cell adhesion molecules, plasma IgG, IgM IgA, IL-1, IL-6, TNFa, and rheumatoid factors, C-reactive proteins, DNA damage, and nitric oxide synthase activity.

Progress 10/01/03 to 09/30/06

Outputs
Dogs and cats diagnosed with rheumatoid arhtritis were fed 20 (dogs) or 10 (cats) mg astaxanthin daily for 4 to 8 weeks. Results showed that dogs astaxanthin drastically reduced lameness and increased physical activity levels in all cases. Cats fed astaxanthin similarly showed a reversal of lameness associated with arthritis. Blood parameters showed a decrease in the CD8+ cytotoxic T lymphocyte population. Therefore, astaxanthin feeding decreased rheumatoid arthritis, an immune-based joint disease.

Impacts
Aging is associated with increased incidence of chronic diseases such as arthritis, an inflammatory disease. The ability of astaxanthin, a natural dietary component, to decrease lameness and improve inflammatory immune parameters associated with rheumatoid arthritis will improve the quality of life for millions of dogs and cats that suffer from this debilitating disease.

Publications

  • Beerman, K.A., B.P.Chew, L.Fournier, J.Park, T.Ryan-Borchers, and M.K.McGuire. 2006. Soy isoflavones modulate immune function in healthy postmenopausal women. The American Journal of Clinical Nutrition. 83:1118-25.


Progress 01/01/05 to 12/31/05

Outputs
The immune modulation and antiinflammatory action of individual carotenoids were combined to study their possible additive or synergistic actions. Cats were given a combination of b-carotene, lutein, astaxanthin and bixin for 16 wk and immune response measured. At low amounts, the carotenoid combination stimulated immune response and protected immune cells against oxidative damage. In another experiment, dogs given a combination of b-carotene and vitamin E showed enhanced immune function and antiinflammatory action.

Impacts
Combinations of certain carotenoids promote immune function and protect immune cells from oxidative damage.

Publications

  • Fransson, B. A., Lagerstedt, A-S, Bergstrom, A., Hagman, R., Park, J. S., Chew, B. P., Evans, M. A. & Ragle, C. A. 2005. C-Reactive protein, tumor necrosis factor alpha, and interleukin-6 in dogs with pyometra and SIRS J. Vet. Emergency Critical Care (in press).
  • Ritzenthaler, K.L., McGuire, M.K., Shultz, T.D., McGuire, M.A., Williams, J, Dasgupta, N. & Chew, B.P. 2005. Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women. J Nutr 135:422-430


Progress 01/01/04 to 12/31/04

Outputs
Studies in dogs, cats and human demonstrated dramatic improvement after astaxanthin supplementation. Initial data showed a sown-regulation of the CD8 T cytotoxic lymphocyte population.

Impacts
If proven to be effective, astaxanthin supplementation will offer dog and cat owners a nutritional means to decrease this crippling inflammatory disease and improve their quality of life.

Publications

  • Massimino, S., Kearns, R.J., Loos, K.M., Burr, J., Park, J.S., Chew, B.P., Adams, S. & Hayek, M.G. (2004) The effects of age and dietary b-carotene on immunological parameters in the dog. J. Vet. Internal Med. 17:835-842.


Progress 01/01/03 to 12/31/03

Outputs
We demonstrated that astaxanthin, when fed to dogs and cats: (1) are taken up in significant amounts by subcellular organelles of immune cells, (2) stimulated both cell-mediated and humoral immune responses, (3) inhibited the growth of mammary cancer cells.

Impacts
Our studies provide a nutritional basis for including astaxanthin in the diet to enhance immune function and inhibit cancer.

Publications

  • Chew, B. P., Brown, C. M., Park, J. S. & Mixter, P. F. (2003) Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis. Anticancer Res. 23:3333-3339.


Progress 01/01/02 to 12/31/02

Outputs
Astaxanthin and immunity in humans: Supplemental astaxanthin at physiological doses (2 or 8 mg/d) enhanced both the cell-mediated and humoral immune response in human subjects. In addition, astaxanthin dramatically reduced DNA damage in circulating lymphocytes, thus demonstrating its protective effect against oxidative damage. Lutein and mammary tumor development: Dietary lutein up-regulated the expression of the pro-apoptotic genes and down-regulated the antiapoptotic genes in mouse tumors, thus signaling increased death of tumor cells. In contrast, lutein down-regulated the pro-apoptotic genes and up-regulated the antiapoptotic genes in blood lymphocytes, thus helping to maintain a viable population of immune cells. Therefore, lutein seems to play a favorable selective role in its anticancer action. Bixin Uptake Kinetics: Bixin, when fed to dog and cats, is taken up by the blood and subsequently transferred to circulating leukocytes. In the leukocytes, bixin is taken up by the mitochondria, nuclei and microsomes, where they may protect the immune cells against oxidative damage.

Impacts
Our findings that dietary astaxanthin and lutein possess potent anticancer activity serve to re-emphasize the importance of these carotenoids in the health of humans and animals. Furthermore, our studies show that dietary bixin can potentially provide protection against oxidative damage in immune cells.

Publications

  • Abonyi, B. I., H. Feng, J. Tang, C. G. Edwards, B. P. Chew, D. S. Mattinson, and J. K. Fellman. 2002. Quality retention in strawberry and carrot purees dried with Refractrance WindowTM System. J. Food Sci. 67:1051-1056.


Progress 01/01/01 to 12/31/01

Outputs
In addition to demonstrating the importance of B-carotene and lutein to the health of dogs and cats, we recently showed the importance of astaxanthin, another naturally-occurring carotenoid, in stimulating the immune response. Work in progress have similarly demonstrated the immune-stimulating action of astaxanthin in humans.

Impacts
Our research has resulted in the Iams's Company incorporating several carotenoids in dog and cat food to improve their immune health. In fact some of these carotenoids have similarly been added into dog and cat food by other pet food companies.

Publications

  • Park, J. S., T. S. Wong, B. P. Chew, M. G. Hayek, and G. A. Reinhart. 2001. Immune assays using whole blood versus separated blood leukocytes in the canine. FASEB J. 15:A647.
  • Hinchcliff, K. W., M. G. Traber, M. G. Hayek, G.A. Reinhart, S.P. Massimino, R.A. Swenson, B.P. Chew, and J.S. Park. 2001. Effect of repeated endurance exercise on plasma vitamin e kinetics in alaskan sled dogs. XXXIV Internat. Congress Physiol. Sci., Christchurch, New Zealand. (8-26-2001).
  • Chew, B. P. and J. S. Park. 2001. Carotenoids on immunity and health. Jean Mayer Human Nutrition Research Center, Tufts Univ., Boston, MA (5-21-2001).
  • Chew, B. P. 2001. The influence of vitamins on reproduction in pigs. in Recent Developments in pig nutrition 3 (J. Wiseman & P.C. Garnsworthy, eds). pg. 483-497. Nottingham Univ. Press, Nottingham, England.
  • Chew, B. P., B. C. Weng, H. W. Kim, T. S. Wong, J. S. Park, and A. J. Lepine. 2001. Uptake of B-carotene by ovarian and uterine tissues and effects on steroidogenesis during the estrous cycle in cats. Amer. J. Vet. Res. 62:1063-1067.
  • Brown, C. M., J. S. Park, B. P. Chew, and T. S. Wong. 2001. Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis. FASEB J. 15:A954.
  • Chew, B. P., H. J. Park, J. S. Park, T. S. Wong, H. W. Kim, M. G. Hayek, and G. A. Reinhart. 2001. Anti-inflammatory action of dietary fish and flaxseed oils in cats. FASEB J. 15:A294.
  • Kim, H. W., J. S. Park, and B. P. Chew. 2001. B-Carotene and astaxanthin inhibit mammary tumor cell growth and induce apoptosis in mice in vitro. FASEB J. 15:A298.


Progress 01/01/00 to 12/31/00

Outputs
The ability of carotenoids such as B-carotene, astaxanthin and lutein to enhance immune function and suppress mammary tumor growth seems to be mediated through their ability to modulate apoptosis (programmed cell death) and angiogenesis (development of new blood vessels). Furthermore, B-carotene and lutein, together with vitamin E, can alleviate exercise-induced tissue injury.

Impacts
Our data on the importance of dietary antioxidants on immunity and tissue injury have resulted in the incorporation of these nutrients into the diets of companion animals, especially to improve the immune health of geriatric animals.

Publications

  • Baskin, C. R., K. W. Hinchcliff, R. A. DiSilvestro, G. A. Reinhart, M. G. Hayek, B. P. Chew, J. R. Burr and R. A. Swensen. 2000. Effects of dietary antioxidant supplementation on oxidative damage and resistance to oxidative damage during prolonged exercise in sled dogs. Amer. J. Vet. Res. 61:886-891.
  • Byrne, K. M., H. W. Kim, B. P. Chew, G. A. Reinhart and M. A. Hayek. 2000. A standardized gating technique for the generation of flow cytometry data for normal canine and normal feline blood lymphocytes. Vet. Imunol. Immunopath. 73:167-182.
  • Chew, B. P. and J. S. Park. 2000. Lipid-soluble antioxidant vitamins on immunity. ADSA-ASAS Joint Annual Meeting, Baltimore, MD (7-24-2000) (abstract.)
  • Chew, B. P. and J. S. Park. 2000. Lipid-soluble antioxidant vitamins on immunity. ADSA-ASAS Joint Annual Meeting, Baltimore, MD (7-24-2000) (abstract).
  • Chew, B. P., B. C. Weng, H. W. Kim, T. S. Wong, J. S. Park, and A. J. Lepine. 2000. Role of dietary B-carotene on reproduction in the canine: uptake and steroidogenesis. in Recent Advances in Canine and Feline Nutrition. Vol. III. 2000 Iams Nutrition Symposium Proceedings. Pg 255-265 (eds. G.A. Reinhart and D.P. Carey). Chicago, IL (5-11-2000).
  • Chew, B. P., H. J. Park, J. S. Park, T. S. Wong, J. S. Park, M. G. Hayek and G. A. Reinhart. 2000. Role of omega-3 fatty acids on immunity and inflammation in cats. in Recent Advances in Canine and Feline Nutrition. Vol. III. 2000 Iams Nutrition Symposium Proceedings. Pg 55-67 (eds. G.A. Reinhart and D.P. Carey). Chicago, IL (5-11-2000).
  • Chew, B. P., J. S. Park, B. C. Weng, T. S. Wong, M. G. Hayek and G. A. Reinhart. 2000. Dietary B-carotene is taken up by blood plasma and leukocytes in dogs. J. Nutr. 130:1788-1791.
  • Chew, B. P., J. S. Park, B. C. Weng, T. S. Wong, M. G. Hayek and G. A. Reinhart. 2000. The domestic cat as an animal model for studying dietary uptake of B-carotene by blood plasma and leukocytes. J. Nutr. 130:2322-2325.
  • Chew, B. P., J. S. Park, H. W. Kim, T. S. Wong, C. R. Baskin. K. W. Hinchcliff, R. A. Swenson, G. A. Reinhart, J. R. Burr, and M. G. Hayek. 2000. Effects of Heavy Exercise and the Role of Dietary Antioxidants on Immune Response in the Alaskan Sled Dog. in Recent Advances in Canine and Feline Nutrition. Vol. III. 2000 Iams Nutrition Symposium Proceedings. Pg 531-539 (eds. G.A. Reinhart and D.P. Carey). Chicago, IL (5-11-2000).
  • Chew, B. P., J. S. Park, T. S. Wong, H. W. Kim, B. C. Weng, K. M. Byrne, M. G. Hayek and G. A. Reinhart. 2000. Dietary B-carotene stimulates cell-mediated and humoral immune response in dogs. J. Nutr. 130:1910-1913.
  • Kearns, R. J., K. M. Loos, B. P. Chew, S. Massimino, and M. G. Hayek. 2000. The effect of age and dietary B-carotene on immunological parameters in the dog. in Recent Advances in Canine and Feline Nutrition. Vol. III. 2000 Iams Nutrition Symposium Proceedings. Pg 389-401 (eds. G.A. Reinhart and D.P. Carey). Chicago, IL (5-11-2000).
  • Kearns, R. J., Loos, K. M., Chew, B. P., Kim, H. W., Massimino, S. P., Burr, J. R. and Hayek, M. G. 2000. The influence of dietary B-carotene on T-cell function in young and aged dogs. FASEB J. 14:A727.
  • Kim, H. W., B. P. Chew, T. S. Wong, J. S. Park, B. C. Weng, K. M. Byrne, M. G. Hayek and G. A. Reinhart. 2000. Modulation of humoral and cell-mediated immune responses by dietary lutein in cats. Vet. Immunol. Immunopath. 73:331-341.
  • Kim, H. W., B. P. Chew, T. S. Wong, J. S. Park, B. C. Weng, K. M. Byrne, M. G. Hayek, and G. A. Reinhart. 2000. Dietary lutein stimulates immune response in the canine. Vet. Immunol. Immunopath. 74:315-327.
  • Park, J. S., Y. K. Lee, T. S. Wong and B. P. Chew. 2000. Comparison of carotenoid uptake in balb/c mice. FASEB J. 14:A235.
  • Piercy, R. J., C. R. Baskin, R. A. DiSilvestro, G. A. Reinhart, M. G. Hayek, B. P. Chew, and K. W. Hinchcliff. 2000. Oxidant stress, oxidant damage and antioxidants: review and studies in Alaskan sled dogs. In Recent Advances in Canine and Feline Nutrition. Vol. III. 2000 Iams Nutrition Symposium Proceedings. Pg 517-529 (eds. G.A. Reinhart and D.P. Carey). Chicago, IL (5-11-2000).
  • Weng, B. C., B. P. Chew, T. S. Wong, J. S. Park, H. W. Kim and A. J. Lepine. 2000. B-Carotene uptake and changes in ovarian steroids and uterine proteins during the estrous cycle in the canine. J. Anim Sci. 78:1284-1290.


Progress 01/01/99 to 12/31/99

Outputs
The project was initiated 2 months ago (October 1999). Under objective 1, we have completed two studies on the uptake of dietary astaxanthin into the blood and leukocytes of the dog and cat. The data are currently being analyzed.

Impacts
(N/A)

Publications

  • No publications reported this period