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Objective: To determine if a dietary supplement (PDS-2865) can enhance NK cell cytotoxicity.
Methods: Five healthy patients, 2 men and 3 women, between 18–68 years of age were enrolled in the pilot study. Baseline blood samples were drawn from all participants at the same time and were hand delivered to the reference lab at the University of Miami Clinical Immunology Laboratory. Following a daily dose of 3 grams of the study product for two weeks, blood was again drawn and sent to the reference laboratory to measure natural killer cells (NKC) cytotoxicity as compared to baseline. Cytotoxicity was measured using the 51Cr release assay.
Results: Post treatment results demonstrated a clinically and statistically significant increase of 17.08%. As shown in Table 1, natural killer cell cytoxocity increased nearly threefold from a mean of 10.1% (range 5.5% to 18.7% at baseline) to 27.2%, (range 13.0% to 45.3% post treatment), p< 0.05. NK cell cytotoxicity (NKCC) increased in all 5 study participants. There were no reported adverse effects.
Conclusion: As PDS-2865 demonstrated its ability to serve as a potent immunostimulator in the 5 patients that participated in this pilot study, the results were significant enough to warrant an expanded controlled study that has enrolled 20 patients and will begin in June 2003.
Hemicellulose containing nutritional supplements demonstrate benefits to the immune system in vitro and in vivo. Here we show that Natramune (PDS-2865) stimulates phagocytosis, nitric oxide production and boosts viability in J774A.1 murine machrophages. We also show that dietary sup- plementation with Natramune (PDS-2865) significantly increases the levels of circulating lympho- cytes in human subjects.
In order to measure the beneficial effects of Natramune (PDS-2865) on cells of the immune sys- tem, phagocytosis was measured by J774A.1 uptake of fluorescently labeled E. Coli bioparticles, ni- tric oxide production was measured by the formation of nitrite, and cell proliferation and viabil- ity was measured by NADH reduction of WST-8. The effect of Natramune (PDS-2865) on human circulating leukocyte levels was measured in 18 volunteers after an 8 week regimen of two 250 mg doses daily after which blood was collected and blood cell number and types were counted.
Natramune (PDS-2865) stimulated phagocytosis, nitric oxide production and promoted prolifer- ation/viability in J774A.1 cells by 65%, 517%, and 155% respectively. Further, Natramune (PDS- 2865) did boost human circulating total lymphocyte levels (18%) in a statistically significant man- ner and while all lymphocyte subtype levels also increased, the individual subtype increases were not statistically significant.
Dietary supplementation with Natramune (PDS-2865) enhances immune system function and vitality.
The immune system is the interface between an individual's health, pathogens, and antigens present in the environment1. Young stranded pinnipeds with health problems and challenged immune systems2 offer an opportunity to examine factors affecting immunity and survival. Clinically, a dietary supplement that enhances the immune response in these patients would likely be beneficial in their medical management. Imuno-2865® (Animal Necessity LLC, New York, NY, 10001) is a new immune supplement that shows encouraging findings in enhancing human lymphocyte activation and interleukin activity6-7. Imuno-2865® is a form of beta-glucan, a polysaccharide, that is delivered as a microparticle, which helps promote improved absorption3.
This research study is performed by Dr. David Williams and pending publication.
In vitro and in vivo studies demonstrate that nutritional supplementation reduces inflammation and inflammatory markers associated with T-cell adhesion mechanisms. Here, we investigate the effects of the nutritional supplements, Natramune (PDS-2865) and PureWay-C, on xenobiotic-in- duced a5b1 integrin-mediated T-cell adhesion to fibronectin.
The human CD4+ lymphoblastoid cell line CEM SS was treated with combinations of bifenthrin, blocking antibodies to human b1 and a5 integrin, and nutrient supplements. After 30 minutes un- attached cells were aspirated and the percent of attached cells was determined.
Bifenthrin stimulated T-cell adhesion to fibronectin at concentrations between 1.0 and 100 µM with a maximal stimulation of 8.3-fold at 10 µM. At 500 µg/ml, Natramune reduced 100 µM bifenthrin- induced adhesion by nearly 90%. PureWay-C reduced by 1.5-fold the level of T-cell adhesion stim- ulated by bifenthrin concentrations of both 10 µM and 100 µM. The combination of Natramune and PureWay-C resulted in a 6.3 and 7.5-fold inhibition at 10 µM and 100 µM bifenthrin respec- tively. Antibody blocking studies demonstrated that bifenthrin induced CEM SS adhesion to fibro- nectin is mediated through a5b1 integrin. Inhibition of T-cell adhesion achieved by anti-integrin antibodies was further reduced with 50 and 500 µg/ml Natramune treatment. Pretreatment of fi- bronectin with Natramune did not alter induced T-cell adhesion to fibronectin.
These data demonstrate that xenobiotic-induced a5b1 integrin mediated T-cell adhesion to fibro- nectin is reduced by nutritional supplementation with Natramune (PDS-2865) and PureWay-C. These data suggest the possibility that inflammatory responses associated with exposure to pollut- ants can be mitigated by nutritional supplementation.
Benjamin S. Weeks, Pedro P. Perez. Med Sci Monit, 2007; 13(3): BR51-58.
Vitamin C (ascorbic acid, ascorbate) has been shown to enhance neurite outgrowth, promote fibro- blast adhesion during wound healing, and reduce xenobiotic-induced leukocyte hyperactivity and inflammatory damage. In this study, a comparison was made between Ester-C® and PureWay-C™ on these various cellular activities.
PC12 cells were stimulated to form neurites with nerve growth factor, NIH 3T3 fibroblasts were seeded on fibronectin and H9 T-cells were stimulated to aggregate with the pyrethroid pesticide bifenthrin. The rate of neurite formation, fibroblast adhesion and T-cell homotypic aggregation was then measured in the absence and presence of various formulations of vitamin C including Ester-C® and PureWay-C™.
With PureWay-C™ treatment, 12% of PC12 cells extended neurites within one hour of treatment and 45% of the cells extended neurites by hour nine. With Ester-C®, 0% and 15% extended neu- rites at one and nine hours, respectively. NIH-3T3 fibroblast adhesion to fibronectin was enhanced by 4.7-fold with a 30 minute PureWay-C™ treatment while Ester-C® increased fibroblast adhesion by only 1.5 fold. Further, PureWay-C™ reduced pesticide-mediated T-cell homotypic aggregation by 83% within 30 minutes of treatment while the reduction seen with Ester-C® was only 33%.
These data confirm the previous observations that vitamin C supplementation can promote neurite outgrowth, increase fibroblast adhesion and reduce xenobiotic induce immunocytes aggregation. More importantly, these data show that PureWay-C™ has a faster and greater beneficial effect on these parameters when compared to other vitamin C formulations.
An estimated three year old male Atlantic Ridley Sea Turtle (Lepidocheyls kempii) was acquired by the Minnesota Zoological Garden in 2006 following rehabilitation for boat strike injuries. Although injuries healed, the turtle was deemed non-releasable due to a persistent state of positive buoyancy and inactivity.
Elevated liver enzymes were first noted on routine blood analysis in the summer of 2008, and were found to be persistent with subsequent testing. In June 2009, a laparoscopic liver biopsy revealed hepatic lipidosis. Diet modification and treatment with S-adenosyl methionine and meloxicam had limited effect.
Objective: To determine if PolicosanolPlus® and Neuroprevin™ supplementation of neuronal cell culture system promotes neurite formation and prevents neurite degeneration.
Methods: The PC12 neuronal cells were seeded in wells of a twenty-four tissue cluster and immediately treated with nerve growth factor, Neuroprevin, PolicosanolPlus, the Neuroprevin ingredients, and PolicosanolPlus and Neuroprevin combined. Neurite formation was quantified at 200X magnification by visual inspection over a six-day period. Neurite outgrowth was determined as the percent of cells with neurites at least one cell diameter in length. Photomicrographs were also taken at 400X magnification.
Results: Ten percent of nerve growth factor treated expressed neurites at 9 hours. With the Neuroprevin ingredients, N1, N2, and N3, and complete Neuroprevin (NT), 52%, 47%, 42%, and 55% of the cells, respectively, had neurites. Of cells treated with PolicosanolPlus (P) and NT +P, 45% and 57% expressed neurites. As the cell cultures aged, 7% of control cells maintained neurites, while 55% of the NT treated cells maintained neurites, and 17% of the NT and P treated cells maintained neurites.
Conclusion: Both Neuroprevin and PolicosanolPlus are dietary supplements that can enhance nerve regeneration, prevent neurodegeneration and reduce nerve damage upon stress or injury.
The articles below are studies of the ingredients that are in supplements. Click on each article title to learn more. The articles referenced in this research section are for reference only and do not claim to support any product.
Aren't grapes toxic to dogs?
There are a few articles in the literature about this topic, let me explain. There are two components to grapes that have nutritional benefits. The seeds of grapes are completely safe for all species evaluated so far, including dogs. The seeds of grapes contain proanthocyanidins, a group of antioxidants that benefit eyes and the rest of the body. There have been no side effects to grapeseeds known as of yet. However, there are compounds in the skins of grapes and raisins, especially darker varieties of the fruits, that cause kidney damage in dogs. Resveratrol is a potent antioxidant found in grape skins that has also been shown to potentially damage dog kidneys, at higher doses.
Tell me more about Grapeseed Extract and Proanthycyanidins!
Proanthocyanidins are naturally occurring compounds found at high concentrations in fruits, vegetables, wine, tea, nuts, seeds, flowers, bark and cacao. Proanthocyanidins have a wide range of biological activities such as antioxidant and free radical scavenging capabilities, anti-inflammatory and antimicrobial properties, inhibition of cancer cell growth, prevention of low-density lipoproteins oxidation, cardioprotection, and inhibition of viral replication.[1-4] In vitro experiments utilizing grape seed proanthocyanidin extract have shown GSE to be a more potent free radical scavenger than vitamin C or vitamin E. Furthermore, GSE has been shown to prevent cataract formation in a hereditary cataractous rat model and in a diabetic rat model.[5, 6] GSE may have use as a dietary supplement to prevent and/or delay cataract formation, depending on the cataract's etiology. GSE significantly decreases TBHP-induced intracellular ROS production and oxidant-induced cell signaling pathways associated with cataractogenesis. It also lowers blood glucose levels in diabetics and improves endothelial cell function. Glaucoma is also a devastating and blinding disease affecting numerous purebred dogs. Oxidative stress has been shown to be an important part of this disease especially in the trabecular meshwork cells.[9, 10] Therefore, antioxidant supplementation, including polyphenols (grapeseed extract), ubiquinol and EGCG (green tea extract) may help slow the progression of the damage occurring in glaucoma.
 Oligomeric Proanthocyanidins (OPCs). Alternative Medicine Review. 2003; 8: 442-450.
 Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS, Preuss HG. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology. 2000; 148: 187-197.
 Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ. Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Research Communications in Molecular Pathology and Pharmacology. 1997; 93: 179-189.
 Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG, Vinson JA. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res. 2003; 523-524: 87-97.
 Yamakoshi J, Saito M, Kataoka S, Tokutake S. Procyanidin-rich extract from grape seeds prevents cataract formation in hereditary cataractous (ICR/f) rats. J Agric Food Chem. 2002; 50: 4983-4988.
 Nguyen VC, Laki JV, Oizumi A, Ariga T, Kataoka S. Anti-cataract activity of proanthocyanidin-rich grape seed extract in streptozotosin-induced diabetic rats. The Annual Meeting of the Japan Society for Biotechnology and Agrochemistry 1999; 73: 133.
 Barden CA, Chandler HL, Lu P, Bomser JA, Colitz CMH. The effect of grape polyphenols on oxidative stress in canine lens epithelial cells. Am J Vet Res. 2008; 69: 94-100.
 Liu X, Wei J, Tan F, al e. Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. Life Sci. 2004; 9: 449.
 Zanon-Moreno V, Garcia-Medina JJ, Gallego-Pinazo R, Vinuesa-Silva I, Moreno-Nadal MA, Pinazo D, M.D. Antioxidant status modifications by topical administration of dorzolamide in primary open-angle glaucoma. Eur J Ophthalmol. 2009; 19: 565-571.
 Izzotti A, Sacca SC, Longobardi M, Cartiglia C. Sensitivity of ocular anterior-chamber tissues to oxidative damage and its relevance to glaucoma pathogenesis. Invest Ophthalmol Vis Sci. 2009; Epub ahead of print.
 Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P, Gonzalez P. Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol. 2009; 47: 198-204.
Lutein (LUT) and zeathanthin (ZEA) are oxycarotenoids (xanthophylls) important in ocular health. They selectively accumulate in the lens and the retina, and also in the macular region in primates.[3-5] There are also trace levels of lutein and zeaxanthin in the cornea and sclera; the lens and uveal structures have higher levels. The macula has 33ng and the peripheral retina has 65 ng of these carotenoids. Trace levels of LUT and ZEA are found in the cornea and sclera. These compounds may be particularly effective in preventing cataracts and age-related macular degeneration (ARMD) in primates. Indeed, increased dietary levels of these carotenoids are associated with significantly decreased risk of developing cataracts and AMRD. Conversely, primates fed diets lacking LUT and ZEA are significantly more susceptible to developing cataracts. LUT and ZEA appear beneficial in preventing ARMD and cataract formation, and this observation has resulted in a plethora of lutein supplements in the human health marketplace.
Unfortunately, almost all dietary supplements for human vision health contain only enough LUT/ ZEA for a mouse.
The exact importance of dietary LUT and ZEA in canine vision and cataractogenesis is unknown. Kim et al. recently reported that LUT was not detectable in the plasma of 18 month old beagles fed a standard canine dietHowever, plasma LUT increased rapidly and immune function was enhanced in response to dietary supplementation with LUT. The possibility that LUT supplementation resulted in the accumulation of xanthophylls in ocular tissues was not examined. Since supplementation of humans and primates with xanthophylls induces gradual increases in retinal xanthophylls, it is feasible that LUT and ZEA will accumulate and benefit canine ocular tissues in response to supplementation.
 Bernstein PS. New insights into the role of the macular carotenoids in age-related macular degeneration. Resonance Raman studies. Pure Appl Chem. 2002; 74: 1419-1425.
 Osakabe N, Yamagishi M, Natsume M, Yasuda A, Osawa T. Ingestion of proanthocyanidins derived from cacao inhibits diabetes-induced cataract formation in rats. Exp Biol Med. 2004; 229: 33-39.
 Kim HW, Chew BP, Wong TS, Park JS, Weng BB, Byrne KM, Hayek MG, Heinhart GA. Dietary lutein stimulates immune response in the canine. Vet Immunol Immunopathol. 2000; 74: 315-327.
Puppies fed diets high in omega-rich fish oils had improved visual performance as evidenced by increased rod response using electroretinography. They also had shorter response times, improved response to dim light and increased activation of the neural cascade. Puppies fed either flaxseed oil or only ALA (alpha linoleic acid, the precursor to EPA and subsequently DHA) had lower or minimal improvements in these parameters. This is likely due to the slow and inefficient conversion of ALA to EPA, and then to DHA. Therefore, feeding preformed dietary n-3 long chain PUFAs (polyunsaturated fatty acids) is a more efficient way to enrich diets with DHA. A review of the human literature that evaluated evidence for effectiveness of omega-3 fatty acids in preventing the development or progression of retinitis pigmentosa found trends in clinical improvement. Research has also demonstrated the efficacy of omega-3 fatty acids in preventing ARMD from progressing to its advanced form. Omega-3 fatty acids may protect the vascular and neural retina against inflammatory-, light-, ischemia-, oxygen-, and age-related pathology. Omega-3 fatty acids have also been shown to be beneficial for the prevention of cataract in humans.
 Bauer JE. Responses of dogs to dietary omega-3 fatty acids. J Am Vet Med Assoc. 2007; 231: 1657-1661.
 Hodge WG, Barnes D, Schachter HM, Pan YI, Lowcock EC, Zhang L, Sampson M, Morrison A, Tran K, Miguelez M, Lewin G. Evidence for the effect of omega-3 fatty acids on progression of age-related macular degeneration: a systematic review. Retina. 2007; 27: 216-221.
 SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005; 24: 87-138.
 Seddon JM. Multivitamin-multimineral supplements and eye macular degeneration and cataract. Am J Clin Nutr. 2007; 85 (suppl): 304S-307S.
Vitamin C is a hydrophilic molecule that scavenges free radicals. It is the strongest physiological antioxidant acting in the host's aqueous environment. It is a very safe antioxidant, with no safe upper dose limit set by the Expert Group on Vitamins and Minerals of 2003. Vitamin C is found in the lens and in the aqueous humor of most species, including dogs, cats, humans, and cattle, Its function relates to the redox reactions and is coupled to glutathione metabolism. One ten-year study found that Vitamin C protects against nuclear cataract formation in humans. Numerous other studies found that Vitamin C supplementation and elevated blood levels of this antioxidant were associated with decreased incidence of cataract. In humans, Vitamin C concentrations decrease with age and more so in patients with senile cataract. A study in Cocker Spaniels found that dogs with cataracts had lower Vitamin C levels than those without cataracts, suggesting that there is a decrease in antioxidant capacity in the aqueous humor of dogs with cataracts.
 Kutlu M, Naziroglu M, Simsek H, Yilmaz T, Kukner AS. Moderate exercise combined with dietary vitamins C and E counteracts oxidative stress in the kidney and the lens of streptozotocin-induced diabetic rat. Int J Vitam Nutr Res. 2005; 75: 71-80.
 Bartlett H, Eperjesi F. An ideal ocular nutritional supplement? Ophthal Physiol Opt. 2004; 24: 339-349.
 Gum GG, Gelatt KN, Esson DW. Physiology of the Eye. In: Veterinary Ophthalmology. (ed. Gelatt KN). 4 ed. Blackwell Publishing Ltd, Ames, 2007; 149-182.
 Mares-Perlman JA, Klein BEK, Klein R, Ritter LL. Relationship between lens opacities and vitamin and mineral supplement use. Ophthalmology. 1994; 101: 315-325.
 Chiu C-J, Taylor A. Nutritional antioxidants and age-related cataract and maculopathy. Exp Eye Res. 2007; 84: 229-245.
 Purcell EF, Lerner LH, Kinsey VE. Ascorbic acid in aqueous humor and serum of patients with and without cataract; physiologic significance of relative concentrations. AMA Arch Ophthalmol. 1954; 51: 1-6.
 Barros PSM, Angelotti AC, Nobre F, Morales A, Fantoni DT, Barros SBM. Antioxidant profile of cataractous English Cocker Spaniels. Veterinary Ophthalmology. 1999; 2: 83-86.
Vitamin E is a lipophilic antioxidant that interferes with lipid peroxidation. Vitamin C works synergistically with Vitamin E; i.e. Vitamin E is oxidized to tocopheroxyl radical that is reduced back to tocopherol by Vitamin C. Numerous studies strongly suggest that consistent intake of Vitamin E and high plasma Vitamin E levels have a lower prevalence of various types of cataracts in humans. Higher blood levels of Vitamin E are also protective against ARMD in humans. Vitamin E is the major antioxidant present in cell membranes; it is highly concentrated in ROS and the RPE. It may also protect Vitamin A from oxidative degeneration in the retina.
 Kutlu M, Naziroglu M, Simsek H, Yilmaz T, Kukner AS. Moderate exercise combined with dietary vitamins C and E counteracts oxidative stress in the kidney and the lens of streptozotocin-induced diabetic rat. Int J Vitam Nutr Res. 2005; 75: 71-80.
 Bartlett H, Eperjesi F. An ideal ocular nutritional supplement? Ophthal Physiol Opt. 2004; 24: 339-349.
Lycopene is a major carotenoid found primarily in tomatoes. Of all known carotenoids, lycopene has been shown to have the highest physical quenching rate constant with singlet oxygen species. Lycopene has been shown to protect against cataract formation in vitro and in vivo.
 Gupta SK, Trivedi D, Srivastava S, Joshi S, Halder N, Verma SD. Lycopene attenuates oxidative stress induced experimental cataract development: an in vitro and in vivo study. Nutrition. 2003; 19: 794-799.
Zinc is an essential trace element necessary for numerous homeostatic functions. It is an antioxidant that offers protection against some, but not all, ROS-mediated injury. It competitively displaces iron from binding sites on negatively charged phospholipids and prevents its redox cycling. When combined with Vitamin E, it has synergistic protection against Fe-mediated lipid peroxidation. It is also important to the health of the retina and in the function of Vitamin A. Zinc deficiency reduces plasma levels of retinol-binding protein and retinol reductase, with a subsequent decrease in retinal Vitamin A levels. It has been shown to slow the progression of ARMD. Zinc is also important in protecting the lens from cataractogenesis by its antioxidant effects. Zinc deficiency in some species is associated with increased risk of cataract formation.
 Zago MP, Oteiza PI. The antioxidant properties of zinc interactions with iron and antioxidants. Free Radic Biol Med. 2001; 31: 266-274.
 Russell RM, Cox ME, Solomons N. Zinc and the special senses. Ann Intern Med. 1983; 99: 227-239.
 Barash H, Poston HA, Rumsey GL. Differentiation of soluble proteins in cataracts caused by deficiencies of methionine, riboflavin or zinc diets fed to Atlantic salmon, Salmo salar, rainbow trout, Salmo gairdneri, and lake trout, Salvelinus namaycush. Cornell Vet. 1982; 72: 361-371.
Both green and black teas significantly inhibit diabetic cataracts by reducing certain biochemical indicators as well as glucose; it might also increase insulin activity. ECGC retards the progression of cataract in selenite-induced cataracts in rats. EGCG fed to albino rats attenuated light-induced photoreceptor damage. Additionally, EGCG given to rats wherein one eye had induced increase in IOP attenuated retinal neuronal death. This supports evidence of EGCG's neuroprotective capabilities, especially in glaucomatous eyes.
 Vinson JA, Zhang J. Black and green teas equally inhibit diabetic cataracts in a streptozotocin-induced rat model of diabetes. J Agric Food Chem. 2005; 53: 3710-3713.
 Thiagarajan G, Chandan S, Sundari CS, Rao SH, Kulkarni AV, Balasubramanian D. Antioxidant properties of green and black tea, and their potential ability to retard the progression of eye lens cataract. Exp Eye Res. 2001; 73: 393-401.
 Costa BL, Fawcett R, Li GY, Safa R, Osborne NN. Orally administered epigallocatechin gallate attenuates light-induced photoreceptor damage. Brain Res Bull. 2008; 76: 412-423.
 Zhang B, Rusciano D, Osborne NN. Orally administered epigallocatechin gallate attenuates retinal neuronal death in vivo and light-induced apoptosis in vitro. Brain Res. 2008; 1198: 141-152.
 Mozaffarieh M, Grieshaber MC, Orgul S, Flammer J. The potential value of natural antioxidative treatment in glaucoma. Surv Ophthalmol. 2008; 53: 479-505.
Alpha lipoic acid is an antioxidant that potentiates Vitamin C and Vitamin E levels; it also has anti-inflammatory effects. It has traditionally been used in humans for diabetic neuropathy and in ischemia-reperfusion injury. Alpha lipoic acid's primary function is to increase the body's production of glutathione, an important antioxidant mechanism in the crystallin lens. One study found that alpha lipoic acid protects the lens from oxidative stress. Alpha lipoic acid was included in Ocu-GLO™ primarily to help benefit diabetic canine patients as it promotes normal insulin sensitivity and glucose metabolism, though actual levels of insulin and glucose may not change.[3, 4] Note: It is not safe in cats at a dose higher than 30 mg/day.
 Mandelker L, Wynn S. Cellular effects of common nutraceuticals and natural food substances. Vet Clin Small Anim. 2004; 34: 339-353.
 Maitra I, Serbinova E, Trischler H, Packer L. Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats. Free Radic Biol Med. 1995; 18: 823-829.
 Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung WI, Augustin HJ, Dietze GJ. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung. 1995; 45: 872-874.
 Nichols TRJ. Alpha-lipoic acid: Biological effects and clinical implications. Alternative Medicine Review. 1997; 2: 177-182.
Alpha Lipoic Acid
The B Vitamins function in a variety of essential processes and contribute to overall health of the body. Vitamin B1 (thiamine) is important in neuromuscular development and maintenance as well as carbohydrate and fat utilization for energy production and cellular metabolism. Vitamin B3 (niacin) is likewise involved in energy production but also in fat and steroid synthesis and lowers total levels of serum cholesterol, low density lipoproteins, very low density lipoproteins, and triglycerides. Vitamin B5 (pantothenic acid) is essential for breakdown of fatty acids, steroids, cholesterol and amino acids and functions as an antioxidant. It is incorporated into Coenzyme A, which is important in oxidative phosphorylation. Vitamin B6 (pyridoxine) is essential for hemoglobin formation and important for utilization for stored glucose. It is essential in the metabolism of fats, proteins, and carbohydrates. Vitamin B12 (cyanocobalamin) is an enzyme cofactor essential for normal cell growth and red blood cell development. Folic acid (aka Vitamin B9) is essential for cell growth and development and for preventing neural tube defects in the fetus. It has anticarcinogenic abilities in elderly humans and insufficient intake may result in anemia. Biotin (aka Vitamin H) is an enzyme cofactor involved in biosynthesis of fats and carbohydrates and metabolism of amino acids. Biotin has been shown to improve glucose tolerance and decrease insulin resistance. The oral administration of antioxidants in humans, including Vitamins A, B1, B2, B6 and E as well as omega-3-fatty acids, improve the quality and quantity of tears in patients with dry eye.
 Drouault-Holowacz S, Bieruvelet S, Burckel A, Rigal D, Dubray C, Lichon JL, Bringer P, Pilon F, Chiambaretta F. Antioxidants intake and dry eye syndrome: a crossover, placebo-controlled, randomized trial. Eur J Ophthalmol. 2009; 19: 337-342.
Co-enzyme Q10 (aka CoQ10 or ubiquinol) is a lipid-soluble antioxidant that functions to protect against lipid peroxidation and therefore acts as an antioxidant. Ubiquinol mediates electron transport in the mitochondrial respiratory chain, it supports energy metabolism, and is a catalyst in ATP production. CoQ10 has been measured in the human retina and it was found to decline with aging, suggesting a decrease in antioxidant capacity of the retina with age that is linked to the progression of ARMD. CoQ10 also protects retinal ganglion cells from ischemia/reperfusion injury in a rat model wherein intraocular pressure was elevated to cause ischemia; synaptic glutamate became elevated and delayed the apoptosis of the retinal ganglion cells. CoQ10 with and without Vitamin E (analogue as trolox) exerts neuroprotective effects against oxidative stress in retinal ganglion cells including inhibition of apoptosis. Therefore, antioxidant supplementation, including CoQ10/ubiquinol, polyphenols (grapeseed extract), and EGCG (green tea extract) may help manage the oxidative damage occurring in glaucoma.[4, 5]
 Center SA. Metabolic, antioxidant, nutraceutical, probiotic, and herbal therapies relating to the management of hepatobiliary disorders. Vet Clin Small Anim. 2004; 34: 67-172.
 Qu J, Kaufman Y, Washington I. Coenzyme Q10 in the human retina. Invest Ophthalmol Vis Sci. 2009; 50: 1814-1818.
 Nakajima Y, Inokuchi Y, Nishi M, Shimazawa M, Otsubo K, Hara H. Coenzyme Q10 protects retinal cells against oxidative stress in vitro and in vivo. Brain Res. 2008; 1226: 226-233.
 Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P, Gonzalez P. Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol. 2009; 47: 198-204.
 Mozaffarieh M, Grieshaber MC, Orgul S, Flammer J. The potential value of natural antioxidative treatment in glaucoma. Surv Ophthalmol. 2008; 53: 479-505.
In general, a true white progressing cataract cannot be stopped. It is like asking a frying egg to stop being fried and become liquid again! There are so many reactions and protein changes going on, there is no way back to clear.
Aging changes in the lens are normal in all species' eyes. This occurs because the lens grows continually throughout your life but all the cells must remain within the lens capsule. Think of an M&M candy. The candy coating remains intact and grows gradually too, but the cells must stay inside and must remain clear. Once the host (human, dog, cat, etc) become older, the cells start becoming very compressed and they start to refract light. This change, called nuclear sclerosis can cause glare in humans but typically does not affect your pet's vision. These aging changes also have protein damage and modifications and can be hastened due to environmental stressors especially the sun, smoking (second hand in our pet's case), poor diets, and environmental toxins.
The lens has antioxidant systems in the cells that are strongest while your pet and you are young, but as we all age, these systems slow down and do not keep the normal daily damage from sun, etc under control. Once this happens, the proteins and cell components that remain can become irreparably damaged, leading to cataract formation. There are numerous studies showing that people who have diets high in vitamins, antioxidants, low in carbohydrates, do not smoke, and protect themselves from the sun, have a lower incidence of this type of cataract.
Ocu-GLO™ is rich in antioxidants that may slow the aging type of cataract. Once your dog has extensive changes, Ocu-GLO™ will not reverse these changes.
There are also other types of cataract that occur in dogs and cause blindness. These include genetic cataracts, cataracts secondary to retinal degeneration, and diabetic cataracts.
Genetic cataracts typically occur when your dog is under 6 years of age. They are white in color and progress at varying rates. Once these are evident, it is unlikely that anything will slow them down as there are numerous cellular pathways that have been activated in response to the genetic mutation. These pathways are changing the protein folding inside the cells as well as turning on other genes that should not be on and are damaging the cells and causing opacities seen as cataracts.
Cataracts secondary to inherited retinal degeneration occur slowly and become evident once a dog has lost significant night vision. Inherited retinal degeneration occurs in dogs and, depending on the breed, can progress rapidly or slowly. Please see the article by Dr. McCalla on this subject at on her website. Briefly, the toxins released by the dying retinal cells are toxic to the lens cells. The lens cells can only respond by becoming opaque i.e. a cataract. Ocu-GLO™ may protect the lens cells from this toxic type of damage and certainly can slow down the retinal degeneration in most cases.
Cataracts secondary to diabetes mellitus occur because there is too much glucose (sugar) in the circulation and in the fluid encircling the lens (aqueous humor). The lens cannot tolerate a high glucose level without developing cataracts. There is an enzyme called aldose reductase which is responsible for this rapidly occurring cataract. If it can be inhibited, then the diabetic cataract can be stopped or significantly slowed. Ocu-GLO™ has ingredients that may inhibit this enzyme, though but we have not yet proven how well it can inhibit diabetic cataracts. Some of our clinical patients are still cataract free after over 2 years of taking Ocu-GLO™, so we are very hopeful this will help our diabetic patients!
An important thing to remember is that even if Ocu-GLO™ does not stop your dog's cataracts, it will make the eye cells' environments healthier so that surgery may be more successful! The most devastating problem with cataracts and the reason that the eye can develop irreparable damage is due to inflammation. Cataracts cause inflammation and likewise, inflammation can cause cataracts. Some of the ingredients in Ocu-GLO™ also help control inflammation so they will work with the topical and oral medications used before and after cataract surgery.
While we would love to give this product to cats, there is one ingredient in it that makes it not ideal for our little kitty friends. Alpha Lipoic Acid is safe in most species but when tested in cats, it showed damage to the liver.
So, we dont want to risk this!
If you would like to give your kitty a supplement for his/her eyes, use lutein 12mg as it is safe for kitties. You can find these at many health food stores for humans but just pop them down the throat as the taste inside is bitter.
Most people understand glaucoma as a high pressure inside the eye...but, there is so much more!
First, we must understand what normal intraocular pressure is, that is, pressure inside the eye.
There is a normal amount of aqueous humor made that is equal to its outflow from the eye. This production and outflow is analogous to your kitchen sink faucet turned on and the drain being open and normal; there is no build up. Aqueous humor is the fluid in the front portion of the eye and is made by special cells called ciliary body epithelial cells. These ciliary body cells are located behind the iris and next to the lens. This fluid is secreted from the ciliary body cells into the space between the iris and the lens, then through the pupil into the anterior chamber (space between the iris and cornea). From the anterior chamber, the aqueous humor exits the eye primarily through the iridocorneal angle (spaces located between the iris and cornea 360 degrees around the eye). This angle then leads out of the eye and into the general circulation. It is not possible for the ciliary body cells to make too much fluid, however in cases such as inflammation (uveitis) or normal aging in dogs, these cells can make less fluid.
Amiel D, Healey R and Oshima Y
Published, FASEB J. 2008; 22:1094.3.
OA is characterized as articular cartilage degeneration, & a recent study shows that MSM supplementation is clinically effective (1). The mechanism, however, is still unclear. We examined the effect of MSM in OA.
The ACL was transected in the right knee joints of mature NZW rabbits (n=10) (2). 5 wks after ACLT, MSM constant delivery system to the joint was created by implanting an Alzet osmotic pump. In the control group no add'l treatment was done. The rabbits were sac'd 9 wks postop, & OA grades of the femoral surface were: (Grade I intact surface; Grade II minimal fibrillation; Grade III overt fibrillation; & Grade IV erosion of the articular cartilage surface) (2).
Results showed 2 Grade III & 1 Grade IV (avg 3.3) in the control group (ACLT). The MSM-treated group showed 1 Grade I, 3 Grade II, 1 Grade III & 2 Grade IV (avg 2.6). Expression of type II collagen and aggrecan on cartilage showed no difference between control (ACLT) & experimental groups, however expression of TNF-∝ in both cartilage and synovial tissue was decreased (p<0.01).
MSM has preserved the articular cartilage surface during development of OA & relieved the inflammation level (i.e. TNF-∝) in both cartilage & synovium statistically. MSM therapy is a potential application for non-invasive treatment of OA joints.
Support from Bergstrom Nutrition and UCSD Ortho Connective Tissue Rsrch.
Oshima Y, Theodosakis J, Amiel D
Published, 2007 World Congress on Osteoarthritis, Ft. Lauderdale, Florida; Osteoarthritis and Cartilage 2007; 15:213.
The study examined the effect of OptiMSM at varying concentrations on four grades of articular cartilage from post-mortem human knees, from healthy to osteoarthritic. Researchers focused on the expression of specific genes related to cartilage degradation and markers of inflammation, called cytokines, including TNF-alpha and IL-1. Over-expression of these genes and their related proteins are associated with the progression of osteoarthritis. The MSM concentrations were estimated to correspond to human oral dosing at between 0 and 30g/day.
In Grade II osteoarthritis, chondrocytes treated with MSM at the concentration of 12mcg/ml demonstrated a strong trend for MSM to reduce the mRNA expression of inflammatory markers: TNF-alpha -33 per cent and IL-1 -29 per cent when compared to lower concentrations of MSM and control. These results did not apply for osteoarthritis chondrocytes of Grade III or IV. MSM did not show an increase in proteoglycan synthesis in cultured chondrocytes or an increase of cartilage matrix production in normal and osteoarthritic chondrocytes at the mRNA level.
MSM might have an ability to protect articular cartilage in early osteoarthritis by reducing expression of inflammatory cytokinds. The effective concentration of 12mcg/ml MSM correlates with the dosage used in a recent clinical trial — 3g twice daily for a total of 6g/day for 12 weeks. MSM did not elicit an anabolic response in this study.
Chrubasik S, Eisenberg E, Balan E, Weinberger T, Luzzati R, Conradt C.
Am J Med. 2000 Jul;109(1):9-14.
Purpose: Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain.
Subjects and Methods: We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study.
Results: The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract.
Conclusion: Willow bark extract may be a useful and safe treatment for low back pain.
Walker AF, Bundy R, Hicks SM, Middleton RW.
Phytomedicine. 2002 Dec;9(8):681-6.
There is preliminary clinical evidence to support the contention that the anti-inflammatory and analgesic properties of bromelain help to reduce symptoms of osteo- and rheumatoid arthritis. However, there have been no controlled studies of its effects on joint health in healthy subjects who lack such diagnosis. The current study investigated the effects of bromelain on mild acute knee pain of less than 3 months duration in otherwise healthy adults. The study was an open, dose-ranging postal study in volunteers who had been recruited through newspaper and magazine articles. Two validated questionnaires (WOMAC knee health Index and the Psychological Well-Being Index) were completed at baseline and after one month's intervention with bromelain, randomly allocated to volunteers as either 200 mg or 400 mg per day. Seventy seven subjects completed the study. In both treatment groups, all WOMAC symptom dimension scores were significantly reduced compared with baseline, with reductions in the final battery (total symptom score) of 41 and 59% (P = 0.0001 and <0.0001) in the low and high dose groups respectively. In addition, improvements in total symptom score (P = 0.036) and the stiffness (P = 0.026) and physical function (P = 0.021) dimensions were significantly greater in the high-dose (400 mg per day) compared with the low-dose group. Compared to baseline, overall psychological well-being was significantly improved in both groups after treatment (P = 0.015 and P = 0.0003 in the low and high dose groups respectively), and again, a significant dose-response relationship was observed. We conclude that bromelain may be effective in ameliorating physical symptoms and improving general well-being in otherwise healthy adults suffering from mild knee pain in a dose-dependant manner. Double blind, placebo-controlled studies are now warranted to confirm these results.
Darshan S, Doreswamy R.
Phytother Res. 2004 May;18(5):343-57.
Patents secured on antiinflammatory plant drugs derived from 38 plants are reviewed. An attempt has been made to compare the modern and traditional use of plant drugs and to establish the relevance of folk claims in developing modern drugs. The role of plant botanicals such as polysaccharides, terpenes, curcuminoids, alkaloids, etc. in alleviating inflammatory diseases including arthritis, rheumatism, acne skin allergy and ulcers is highlighted. Chemicals that alleviate swelling are derived from plants including grape, boswellia, turmeric, devil's claw and some essential oils such as clove, eucalyptus, rosemary, lavender, mint, myrrh, millefolia and pine have been patented and used as mixed formulations. Plants containing polysaccharides are the most potent in curing inflammatory diseases.
Krieglstein CF, Anthoni C, Rijcken EJ, Laukötter M, Spiegel HU, Boden SE, Schweizer S, Safayhi H, Senninger N, Schürmann G.
Int J Colorectal Dis. 2001 Apr;16(2):88-95.
The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.
Zupanets IA, Drogovoz SM, Bezdetko NV, Rechkiman IE, Semenov AN.
Farmakol Toksikol. 1991 Mar-Apr;54(2):61-3.
The study of the antiexudative activities of voltaren, indomethacin and piroxicam in combination with glucosamine on the model of carrageenan inflammation showed that the combination makes it possible to decrease the effective doses of nonsteroidal anti-inflammatory drugs by 2-2.7 times with the preservation of the pronounced antiexudative activity. A diverse influence of aminosugar on the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs depending on the sequence and routes of administration is connected with their membrane mechanisms and metabolic features of amino sugar.
Voltaren, Indomethacin, Piroxicam, Glucosamine
Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, Royle P, Thomas S.
Health Technol Assess. 2009 Nov;13(52):1-148.
Objective: To assess the clinical effectiveness and cost-effectiveness of glucosamine sulphate/hydrochloride and chondroitin sulphate in modifying the progression of osteoarthritis (OA) of the knee.
Data Sources: Electronic databases were searched from 1950 to 2008 and included: MEDLINE and PubMed; EMBASE; Cochrane Library (including Cochrane Systematic Reviews Database, CENTRAL, DARE, NHS EED and HTA databases); Allied and Complementary Medicine (AMED); National Research Register (NRR); Web of Science Proceedings; Current Controlled Trials; and Clinical Trials.gov. Other sources included bibliographies of retrieved papers, registered but unpublished trials, internet searches and the Food Standards Agency website.
Review Methods: A search was conducted for systematic reviews of randomised controlled trials (RCTs), which were used to identify RCTs of at least 12 months' duration and updated with searches for primary studies. A cost-effectiveness model was constructed using cohort simulation and drawing on available evidence. Sensitivity analysis was undertaken and value of information analysis conducted. A review of studies of mechanism of action was carried out to explore the biological plausibility of the preparations.
Results: Five systematic reviews and one clinical guideline met the inclusion criteria. They reported inconsistent conclusions with only modest effects on reported pain and function. A reduction in joint space narrowing was more consistently observed, but the effect size was small and the clinical significance uncertain. A separate review of eight primary trials of > 12 months' duration showed evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulphate, but the clinical importance of these differences was not clear. In two studies of glucosamine sulphate, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years' follow-up. For other preparations of glucosamine, chondroitin and combination therapy, there was less evidence to support a clinical effect. Cost-effectiveness modelling was restricted to glucosamine sulphate. Over a lifetime horizon the incremental cost per quality-adjusted life-year (QALY) gain for adding glucosamine sulphate to current care was estimated to be 21,335 pounds. Deterministic sensitivity analysis suggested that the cost-effectiveness of glucosamine sulphate therapy was particularly dependent on the magnitude of the quality of life (QoL) gain, the change in knee arthroplasty probability with therapy and the discount rate. At a cost per QALY gained threshold of 20,000 pounds, the likelihood that glucosamine sulphate is more cost-effective than current care is 0.43, while at a threshold of 30,000 pounds, the probability rises to 0.73. Probabilistic sensitivity analysis showed that estimates were imprecise and subject to a degree of decision uncertainty. Value of information analysis demonstrated the need for further research. Several biologically plausible mechanisms of action for glucosamine sulphate and chondroitin were proposed.
Conclusions: There was evidence that glucosamine sulphate shows some clinical effectiveness in the treatment of OA of the knee. No trial data came from the UK and caution should be exercised in generalising the findings to the UK health-care setting. Cost-effectiveness was not conclusively demonstrated. There was evidence to support the potential clinical impact of glucosamine sulphate. The value of information analysis identified three research priorities: QoL, structural outcomes and knee arthroplasty. The biological mechanism of glucosamine sulphate and chondroitin remains uncertain and, in particular, the proposal that the active substance may be sulphate should be explored further.
Bruyere O, Reginster JY.
Drugs Aging. 2007;24(7):573-80.
Osteoarthritis (OA), the most common form of arthritis, is a public health problem throughout the world. Several entities have been carefully investigated for the symptomatic and structural management of OA. This review evaluates published studies of the effect of glucosamine salts and chondroitin sulfate preparations on the progression of knee or hip OA. Despite multiple double-blind, controlled clinical trials of the use of glucosamine and chondroitin sulfate in OA, controversy regarding the efficacy of these agents with respect to symptomatic improvement remains. Several potential confounders, including placebo response, use of prescription medicines versus over-the-counter pills or food supplements, or use of glucosamine sulfate versus glucosamine hydrochloride, may have relevance when attempting to interpret the seemingly contradictory results of different clinical trials. The National Institutes of Health-sponsored GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) compared placebo, glucosamine hydrochloride, chondroitin sulfate, a combination of glucosamine and chondroitin sulfate and celecoxib in a parallel, blinded 6-month multicentre study of patients with knee OA. This trial showed that glucosamine hydrochloride and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with OA of the knee. However, exploratory analyses suggest that the combination of glucosamine hydrochloride and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. For decades, the traditional pharmacological management of OA has been mainly symptomatic. However, in recent years, several randomised controlled studies have assessed the structure-modifying effect of glucosamine sulfate and chondroitin sulfate using plain radiography to measure joint space narrowing over years. There is some evidence to suggest a structure-modifying effect of glucosamine sulfate and chondroitin sulfate. On the basis of the results of recent randomised controlled trials and meta-analyses, we can conclude that glucosamine sulfate (but not glucosamine hydrochloride) and chondroitin sulfate have small-to-moderate symptomatic efficacy in OA, although this is still debated. With respect to the structure-modifying effect, there is compelling evidence that glucosamine sulfate and chondroitin sulfate may interfere with progression of OA.
Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF.
Osteoarthritis Cartilage. 2006 Mar;14(3): 286-94.
Objective: Osteoarthritis (OA) is the most common form of arthritis and the second most common cause of long-term disability among middle-aged and older adults in the United States. Methylsulfonylmethane (MSM) is a popular dietary supplement used as a single agent and in combination with other nutrients, and purported to be beneficial for arthritis. However, there is paucity of evidence to support the use of MSM.
Methods: A randomized, double-blind, placebo-controlled trial was conducted. Fifty men and women, 40-76 years of age with knee OA pain were enrolled in an outpatient medical center. Intervention was MSM 3g or placebo twice a day for 12 weeks (6g/day total). Outcomes included the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale (WOMAC), patient and physician global assessments (disease status, response to therapy), and SF-36 (overall health-related quality of life).
Results: Compared to placebo, MSM produced significant decreases in WOMAC pain and physical function impairment (P<0.05). No notable changes were found in WOMAC stiffness and aggregated total symptoms scores. MSM also produced improvement in performing activities of daily living when compared to placebo on the SF-36 evaluation (P<0.05).
Conclusion: MSM (3g twice a day) improved symptoms of pain and physical function during the short intervention without major adverse events. The benefits and safety of MSM in managing OA and long-term use cannot be confirmed from this pilot trial, but its potential clinical application is examined. Underlying mechanisms of action and need for further investigation of MSM are discussed.
Heather Johnston, DVM, Heather Barron, DVM, DABVP-avian, Nicole Gottdenker, DVM, MS, PhD, DACVP, Carmen Colitz, DVM, PhD, DACVO
Affiliation: From Harmony Animal Hospital, 1401 W. Indiantown Rd, Jupiter, FL 33478 (Johnston), Clinic for the Rehabilitation of Wildlife, 3883 Sanibel-Captiva Rd, Sanibel Island, FL 33957 (Barron), Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602 (Gottdenker), Jupiter Pet Emergency and Specialty Center, 300 South Central Boulevard, Jupiter FL 33458 (Colitz).
Antioxidants, such as vitamin E, lutein, alpha lipoic acid, and carotenoids, are used in wild bird species as predictors for reproductive success and health assessment1. Increasing levels of antioxidants provide protection for metabolic functions including reproduction, immunity, plumage, and ability to handle environmental stressors2- 6. In mammals, supplementation of antioxidants can provide protection to eye structures and delays progression of some disease processes7, 8. Because birds depend heavily on their visual system to interpret and interact with their environment, maintaining eye health is a priority in captive and wild populations.
An antioxidant blend (Eye-SEA®, Animal Necessity, New York, New York, USA) that has shown promise for supporting eye health in mammals, was used in this pilot study to investigate the absorption and safety in birds. Twenty-one Eastern screech owls were supplemented for 6 weeks; complete blood count, biochemistry profile, exams, histopathology, and on a small subset blood levels of vitamin E, lutein/zeaxanthin, and alpha lipoic acid were evaluated. No significant changes were found in white blood count, AST, uric acid, histopathology, weight, or antioxidant levels before and after supplementation. A trend of increased lutein concentration was observed in all animals, but was not significant. This combination of antioxidants appears to be safe in these animals.
Acknowledgements: The authors would like to acknowledge Animal Necessity, LLC for funding the study and providing Eye-SEA®. Special thanks to Amy Kight, CVT for her help with treatment and sample collection.
1. Giraudeau M, Hill GE, Toomey MB, Staley M. Ketocarotenoid circulation, but not retinal carotenoid accumulation, is linked to eye disease status in a wild songbird. Arch Biochem Biophys. 2013;15;539(2):156-62.
2. Peluc SI, Reed WL, McGraw KJ, Gibbs P. Carotenoid supplementation and GnRH challenges influence female endocrine physiology, immune function, and egg-yolk characteristics in Japanese quail (Coturnix japonica). J Comp Physiol B. 2012;182(5):687-702.
3. Hallcl M, Imik H, Koc M, Gümüs R. Effects of α-lipoic acid, vitamins E and C upon the heat stress in Japanese quails. J Anim Physiol Anim Nutr. 2012; 96(3):408-15.
4. Giraudeau M, Sweazea K, Butler MW, McGraw KJ. Effects of carotenoid and vitamin E supplementation on oxidative stress and plumage coloration in house finches (Haemorhous mexicanus). Comp Biochem Physiol A Mol Integr Physiol. 2013;166(3):406-13
5. Thomson L, Toyoda F, Delori K, et al. Long term dietary supplementation with zeaxanthin reduces photoreceptor death in light- damaged Japanese quail. Exp Eye Res 2002;75:529-542.
6. Li Y, Ma QG, Zhao LH, Wei H, Duan GX5, Zhang JY6, Ji C7. Effects of lipoic Acid on immune function, the antioxidant defense system, and inflammation-related genes expression of broiler chickens fed aflatoxin contaminated diets. Int J Mol Sci. 2014; 2;15(4):5649-62.
7. Koutsos EA, Schmitt T, Colitz CM, Mazzaro L. Absorption and ocular deposition of dietary lutein in marine mammals. Zoo Biol. 2013;32(3):316-23.
8. Barden CA, Chandler HL, Lu P, Bomser JA, Colitz CM. Effect of grape polyphenols on oxidative stress in canine lens epithelial cells. Am J Vet Res. 2008;69(1):94-100.
Aging pets often suffer a decline in cognitive function (eg, memory, learning, perception, awareness) likely associated with age-dependent brain alterations. Clinically, cognitive dysfunction may result in various behavioral signs, including disorientation; forgetting of previously learned behaviors, such as house training; alterations in the manner in which the pet interacts with people or other pets; onset of new fears and anxiety; decreased recognition of people, places, or pets; and other signs of deteriorating memory and learning ability . Many medical problems, including other forms of brain pathologic conditions, can contribute to these signs. The practitioner must first determine the cause of the behavioral signs and then determine an appropriate course of treatment, bearing in mind the constraints of the aging process. A diagnosis of cognitive dysfunction syndrome is made once other medical and behavioral causes are ruled out.
 Pease see attached study: Behavior Problems In Geriatric Pets
Extracts of Hypericum, Passiflora and Valeriana are used for the treatment of mild depression and anxiety. We were interested whether a combination of Hypericum and Passiflora exerts comparable effects to Hypericum alone. We used two well-established models for investigating extracts for their anti-depressant activity, namely the effects on synaptic uptake of serotonin and the forced-swimming-test. We show here for the first time, that Passiflora significantly enhances the pharmacological potency of Hypericum in both models.
Our data suggest that anti-depressive therapeutic effects of Hypericum are possible with lower doses, when it is combined with Passiflora, than with mono-preparations of Hypericum.
The cortex of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. has been used extensively in Russia, China, Korea and Japan as an adaptogen whose properties are the ability to increase as non-specific body resistance to stress and fatigue. Although it has been reported that Eleutherococcus senticosus has anti-fatigue and anti-stress actions, their actions are still unclear on the relationship between immune system, especially natural killer (NK) activity and endocrine system (corticosterone level). We compared the effects of the water extracts (A, B, C, D and E) of five Eleutherococcus senticosus cortex on the swimming time, NK activity and blood corticosterone level using forced swimming stressed mice. Among five kinds, C, D and E extracts significantly prolonged the swimming time. C and D extracts inhibited the reduction of NK activity and the corticosterone elevation induced by forced swimming. The contents of eleutheroside E, isoflaxidin and eleutherosides B plus E were in the order C>D>E>B>A and C>E>D>A>B extracts, respectively. Therefore, it is suggested that eleutheroside E may be contributed to the anti-fatigue action, the recovery of the reduction of NK activity and the inhibition of corticosterone elevation induced by swimming stress.
Background: Extracts of Hypericum perforatum (St. John's wort) have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration.
Methods: CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgiimpregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined.
Results: The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration.
Conclusion: These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.
 Crupi R, Mazzon E, Marino A, La Spada G, Bramanti P, Battaglia F, Cuzzocrea S, Spina E. 2011. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice. BMC Complement Altern. Med. 11:7.
Juvenile rainbow trout Oncorhynchus mykiss were isolated in individual compartments in observation aquaria and allowed to acclimate for 1 week, during which they were fed commercial trout feed. Thereafter, the fish were tested for aggressive behaviour using a resident/intruder test. Following this first resident/intruder test, the feed was exchanged for an experimental wet feed supplemented with 0.15 % or 1.5 % L-tryptophan (by wet mass). Controls received the same feed but without L-tryptophan supplementation. The fish were fed to satiety daily, and their individual feed intake was recorded. Aggressive behaviour was quantified again after 3 and 7 days of L-tryptophan feeding using the resident/intruder test. Feeding the fish L-tryptophan-supplemented feed for 3 days had no effect on aggressive behaviour, whereas feeding the fish L-tryptophan-supplemented feed for 7 days significantly suppressed aggressive behaviour in the fish, an effect seen at both levels of L-tryptophan supplementation. Fish fed L-tryptophan-supplemented feed showed elevated plasma and brain levels of L-tryptophan. The amino acid L-tryptophan is the precursor of serotonin, and supplementary dietary L-tryptophan was found to elevate levels of 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA/serotonin concentration ratio in the brain. Neither feed intake nor plasma cortisol level was significantly affected by dietary L-tryptophan. Central serotonin is believed to have an inhibitory effect on aggressive behaviour, and it is suggested that the suppressive effect of dietary L-tryptophan on aggressive behaviour is mediated by an elevation of brain serotonergic activity.
Winberg S, Řverli Ř, Lepage O. 2001. Suppression of aggression in rainbow trout (Oncorhynchus mykiss) by dietary L-tryptophan. J Exp Biol. 204:3867-76.
This article reports that 1-docosanol, a 22-carbon-long saturated alcohol, exerts a substantial inhibitory effect on replication of certain viruses (e.g., herpes simplex virus and respiratory syncytial virus) within primary target cells in vitro. To study the basis for its viral inhibitory activity, a suspension of 1-docosanol was formulated in an inert and nontoxic surfactant, Pluronic F-68; this suspension exerted potent inhibitory activity on the ability of susceptible viruses to infect cultured target cells. Susceptible viruses included wild type herpes simplex viruses 1 and 2 as well as acyclovir-resistant herpes simplex virus 2 and also respiratory syncytial virus - all of which are lipid-enveloped. In contrast, non enveloped polio virus was not susceptible to the inhibitory action of 1-docosanol. Although the precise mechanism has yet to be defined, current evidence suggests that 1-docosanol inhibits viral replication by interfering with the early intracellular events surrounding viral entry into target cells. It is possible that interaction between the highly lipophilic compound and components of target cell membranes renders such target cells less susceptible to viral fusion and/or entry. If this mechanism proves to be correct, 1-docosanol may provide a broad spectrum activity against many different viruses, especially those with lipid-containing envelopes.
This study tested in vitro activity of the essential oil from flowers of Calendula officinalis using disk- diffusion techniques. The antifungal assay results showed for the first time that the essential oil has good potential antifungal activity: it was effective against all 23 clinical fungi strains tested.
n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1/2 of approximately 3 h. Reduced expression of viral genes in n-docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins - an immediate post entry event - was indicated by a 75% reduction in the expression of i-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate - early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-docosanol.
A mixture of the aliphatic alcohol, triacontanol, aiid other chemically associated naturally occurritig alcohols was ap- plied to the denuded dorsal cutaneous surface of guinea pigs to evaluate anti-inflammatory activity. In the setting of a chemical irritation with 2% croton oil and in an allergic dermatitis created with dinitrochlorobenzene sensitization and challenge, the triacontanol-containing preparation was signiftcantly more effective than vehicle alone (DHL skin cream) but not as effective as 0.05% Diprolene® ointment. Lymphocyte stimulation was studied by tritiated thymi- dine uptake and morphologic examination for blast trans- formation. When triacontanol-containing compounds were solubilized in aqueous media, effects on lymphocytes were insignificant. When solubilized in ethanol, there was a marked effect on thymidine uptake but not on blast transformation when compared to parallel controls.
The effect of the plant growth regulator, triacontanol (TRIA) on lipid peroxidation was studied in three different systems: (i) isolated chloroplasts of spinach (Spinacea oleracea L.) leaves; (ii) egg lecithin liposomes; and (iii) soybean lipoxygenase (LOX) system. The nonenzymatic lipid peroxidation in isolated chloroplasts and egg lecithin liposomes was measured as the amount of thiobarbituric acid reactive substances (TBARS) formed. Inhibition of Fe2+ and/or light-induced lipid peroxidation by TRIA was observed in both isolated chloroplasts and egg lecithin liposomes. The kinetics of soybean lipoxygenase-I (LOX-1) was studied using linoleic acid as the substrate. The enzyme was competitively inhibited by TRIA. The Ki for TRIA inhibition of the enzyme was estimated to be 3.2-5.0 mM according to different methods of estimation. TRIA has been known to exhibit anti- inflammatory action in animals and this anti-in ̄ammatory effect of TRIA might be mediated through inhibition of lipid peroxidation. Since LOX inhibitors have been extensively used as therapeutic agents, TRIA, being a natural compound has been suggested to be an effective anti-inflammatory drug.
Polyene antibiotic, through interacting with membranous sterols, has shown to alter membrane permeability., Antifungal effects of various drugs such as -fluorocytosine, rifampicin and fusidic acid were potentiated when combined with polyene antibiotics.[3~6] Larger polyene antibiotics such as amphotericin B (AMB) or nystatin showed much higher affinity for fungi than for mammalian cells., Synergism induced by the polyene antibiotics has been evaluated as an invaluable antifungal therapy. Ergosterol- or fatty acid is supposed to involve susceptibility of fungi polyene antibiotics, we examined whether the antifungal effect of AMB is stimulated when combined with squalene, an obligatory intermediate for sterol formation. In this report, we describe a new synergism of a polyene antibiotic AMB and squalene.
Lipoxygenase (LOX: EC 126.96.36.199) (linoleate : oxygen oxidoreductase) constitute large gene family of non heme iron containing fatty acid dioxygenases. LOXs have been hypothesized to play a role in response to many plant pathogens and significant in plant microbe interactions. Increased LOX activity and rapid lipid peroxidation are a general response to biotic and abiotic stress. The increase in LOX activity has been observed in plant tissue and cells in response to infections with bacteria, fungal and viral pathogens. Plant LOX preferentially introduce molecular oxygen in to linoleic (LA) and Linolenic Acids (ALA) either at C9 (9-LOX) or C13 (13-LOX) of the hydrocarbon backbone of the fatty acid to produce 9S or 13S-hydroperoxy octadecadienoic acid (9S- or 13S- HPODE) or 9S- or 13S- hydroperoxy octadecatrienoic acid (9S- or 13S HPOTE). These hydroperoxides are significant in regulating Aflatoxin (AD)-a toxic secondary metabolite, biosynthesis by fungi, namely Aspergillus flavus and Aspergillus parasiticus. The 9S-HPODE promotes where as 13S-HPODE, 13S-HPOTE and down stream derivatives of 13S-HPODE as well as 13S-HPOTE inhibits alfatoxin production by A. flavus. Aldehyde products of 13S-HPODE and 13S-HPOTE have been observed to inhibit the germination of A. flavus spores and/or aflatoxin production. The differential expression of LOX and the subsequent effect of LOX metabolites on aflatoxin production in different plant varieties are presented in this review.
Lipoxygenase, hydroperoxy octadecadienoic acid, hydroperoxy octadecatrienoic acid, Aspergillus flavus, Aspergillus parasiticus and aflatoxin
Prepared for the National Cancer Institute (NCI) for consideration by the Chemical Selection Working Group (CSWG) by Technical Resources International, Inc.
Acetyl-L-carnitine/-lipoic acid supplements were identified by the National Cancer Institute (NCI) Division of Cancer Biology (DCB) as a popular combination anti-aging and vitality formula that would be consumed over a period of many years to maximize potential beneficial effects.
In this formulation, acetyl-L-carnitine hydrochloride is thought to increase general metabolic activity and to improve cognitive function. alpha-Lipoic acid is added as a potent antioxidant to protect against the elevated levels of free radicals produced from the increase in metabolism. Thus, acetyl carnitine/alpha-lipoic acid dietary supplements have a potential market of tens of millions of middle-aged and elderly Americans who desire to improve their general health.
Acetyl-L-carnitine is a mitochondrial metabolite that facilitates the movement of fatty acids into the mitochondria for energy and is also used to generate acetyl coenzyme A. Alpha-Lipoic acid is a coenzyme involved in mitochondrial ATP production and its reduced form can recycle other antioxidants.
Virtually no information on the potential toxicity of acetyl-L-carnitine/alpha-lipoic acid combinations was found in the available literature. Alpha-Lipoic acid was not mutagenic in the Ames assay.
Alpha Lipoic Acid
Type 2 Diabetes Mellitus (T2DM) which is characterised by insulin resistance, is closely linked to the triad of glucolipotoxicity, inflammation and oxidative stress. Increased adiposity, leading to increased free fatty acids (FFAs), contributes to insulin resistance by disrupting the signal transduction pathway of insulin mediated glucose disposal, and causes impaired insulin secretion. Hyperglycaemia and dyslipidaemia driven oxidative stress resulting from enhanced free-radical formation and/or defects in antioxidant defence is implicated in the pathogenesis of diabetic neuropathy (DN). This and other inflammatory pathways account for a complex network of interacting metabolic factors responsible for causing diabetes and her complications. There is growing evidence that Alpha Lipoic Acid (ALA) has beneficial effects on the treatment of T2DM and some of its complications. It represents an attractive pharmacological target in the treatment of T2DM by modulating the signal transduction pathways in insulin resistance and antagonizing the oxidative and inflammatory stresses, which are major players in the pathogenesis of this disorder. A potent anti-oxidant and free radical scavenger, ALA also targets cellular signal transduction pathways which increases glucose uptake and utilization, thus providing specific targeted therapy in the treatment of insulin resistance and diabetic neuropathy. Apart from the rare risk of Insulin Autoimmune Syndrome (IAS), ALA has shown to be relatively safe, even in patients with renal and liver failure. This review focuses and summarises the molecular mechanisms of T2DM, and underlines the therapeutic value of ALA in this globally significant disease.
Alpha Lipoic Acid
Diabetes is a common metabolic disorder that is usually accompanied by increased production of reactive oxygen species or by impaired antioxidant defenses. Importantly, oxidative stress is particularly relevant to the risk of cardiovascular disease. Alpha-lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. LA is a very important micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, LA improves glycemic control and polyneuropathies associated with diabetes mellitus; it also effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions, increases cytosolic glutathione and vitamin C levels, and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically. Its biosynthesis decreases as people age and is reduced in people with compromised health, thus suggesting a possible therapeutic role for LA in such cases. Reviewed here is the known efficacy of LA with particular reference to types 1 and 2 diabetes. Particular attention is paid to the potential benefits of LA with respect to glycemic control, improved insulin sensitivity, oxidative stress, and neuropathy in diabetic patients. It appears that the major benefit of LA supplementation is in patients with diabetic neuropathy.
Alpha Lipoic Acid
Beagle dogs between 7.6 and 8.8 years of age administered a twice daily supplement of alpha-lipoic acid (LA) and acetyl-L-carnitine (ALC) over approximately 2 months made significantly fewer errors in reaching the learning criterion on two landmark discrimination tasks compared to controls administered a methylcellulose placebo. Testing started after a 5 day wash-in. The dogs were also tested on a variable delay version of a previously acquired spatial memory task; results were not significant. The improved performance on the landmark task of dogs supplemented with LA + ALC provides evidence of the effectiveness of this supplement in improving discrimination and allocentric spatial learning. We suggest that long-term maintenance on LA and ALC may be effective in attenuating age-associated cognitive decline by slowing the rate of mitochondrial decay and cellular aging.
Alpha Lipoic Acid
The excretion and biotransformation of rac-alpha-lipoic acid (LA), which is used for the symptomatic treatment of diabetic polyneu- ropathy, were investigated following single oral dosing of [14C]LA to mice (30 mg/kg), rats (30 mg/kg), dogs (10 mg/kg), and unlabeled LA to humans (600 mg). More than 80% of the radioactivity given was renally excreted. Metabolite profiles obtained by radiometric high-performance liquid chromatography revealed that LA was extensively metabolized irrespective of the species. Based on a new on-line liquid chromatography/tandem mass spectroscopy assay developed for negative ions, LA and a total of 12 metabolites were identified. Mitochondrial beta-oxidation played the paramount role in the metabolism of LA. Simultaneously, the circulating metabolites were subjected to reduction of the 1,2-dithiolane ring and subsequent S-methylation. In addition, evidence is given for the first time that the methyl sulfides formed were partly oxidized to give sulfoxides, predominantly in dogs. The disulfoxide of 2,4- bismethylmercapto-butanoic acid, the most polar metabolite iden- tified, was the major metabolite in dogs. Furthermore, new data are presented that suggest conjugation with glycine occurred as a separate metabolic pathway in competition with beta-oxidation, pre- dominantly in mice.
Alpha Lipoic Acid
Alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. a-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both ot-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-KB transcription factor. We review the properties of lipoate in terms of (l) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.
Alpha Lipoic Acid
With increasing age, dogs develop a form of neurodegenerative disease which has many similarities to age related cognitive impairment and Alzheimer's disease in humans. A decline in learning and memory can be demonstrated in dogs beginning as young as 7 years of age using a variety of neuropsychological tests. However, clinical cases of cognitive dysfunction syndrome are seldom identified until the age of 11 years or older. This is likely due to the fact that the owners are relying on clinical observations such as house-soiling, sleep-wake cycles and disorientation, rather than tests of learning and memory. On the other hand, dogs that are trained to more exacting tasks such as guide dogs for the visually impaired, or bomb detection and agility trained dogs might be noticed to have a decline in performance at a much earlier age. Through the use of standardized neuropsychological testing protocols, a number of drugs, natural products and supplement formulations have been developed for use in dogs with cognitive dysfunction and, in some cases clinical trials have validated their efficacy. Furthermore, the testing of products currently licensed and in the pipeline for the treatment of cognitive decline and Alzheimer's in humans, may provide additional therapeutic agents for the treatment of senior dogs, as well as provide insight as to the potential for the efficacy of these compounds in humans. This review will examine those products that are now marketed along with some that might be considered for use in senior dogs with cognitive dysfunction as well as the research that has been used to validate the efficacy (or lack thereof) of these compounds. D 2005 Elsevier Inc. All rights reserved.
Alpha Lipoic Acid
Ocular disease is well documented in captive pinnipeds.  Supplementation with antioxidants may protect against ocular, cardiac, renal, and hepatic diseases. , .  Disinfectants such as chlorine and ozone are dissociated by ultraviolet radiation to produce reactive free radicals which likely cause cellular damage if exposed.  Alpha lipoic (ALA) is a fatty acid that acts as a powerful water and fat-soluble antioxidant found in the body in trace amounts. ALA increases the body's production of glutathione, the body's most important endogenous antioxidant. ALA helps dissolve toxic substances in the liver.  Imbalance of the glutathione redox cycle contributes to cataractogenesis and ALA has been shown to protect lenses from oxidative stress that causes cataract.  The objective of this study was to determine if ALA, at a dose 2-3mg/kg a day, is a safe antioxidant for California sea lions. CBC/chemistry panel was collected from seven animals pre and post ALA supplementation with no evidence of hepatic toxicity (6 out of the 7 animals decreased in GGT values). The mean length of time the animals were on the supplement was 35 days. Currently, there is no method known to quantify ALA in sea lion serum. Serum (100mls total) was collected and and frozen at a -80 C freezer from 73 sea lions, followed by a novel LC-MS/MS analysis to quantify ALA levels in sea lion serum. Current research is in progress to determine if higher doses of ALA would still be safe and well-tolerated in California sea lions.
Alpha Lipoic Acid
Objective: To determine the pharmacokinetics of dl-α-lipoic acid in dogs when administered at 3 dosages via 3 methods of delivery.
Animals: 27 clinically normal Beagles.
Procedures: In a 3 X 3 factorial Latin square design, 3 dosages (2.5, 12.5, and 25 mg/ kg) of dl-α-lipoic acid were administered orally in a capsule form and provided without a meal, in a capsule form and provided with a meal, and as an ingredient included in an extruded dog food. Food was withheld for 12 hours prior to dl-α-lipoic acid administration. Blood samples were collected before (0 minutes) and at 15, 30, 45, 60, and 120 minutes after administration. Plasma concentrations of dl-α-lipoic acid were determined via high-performance liquid chromatography. A generalized linear models procedure was used to evaluate the effects of method of delivery and dosage. Noncompartmental analysis was used to determine pharmacokinetic parameters of dl-α-lipoic acid. Nonparametric tests were used to detect significant differences between pharmacokinetic parameters among treatment groups.
Results: A significant effect of dosage was observed regardless of delivery method. Method of delivery also significantly affected plasma concentrations of dl-α-lipoic acid, with extruded foods resulting in lowest concentration for each dosage administered. Maximum plasma concentration was significantly affected by method of delivery at each dosage administered. Other significant changes in pharmacokinetic parameters were variable and dependent on dosage and method of delivery.
Conclusions and Clinical Relevance: Values for pharmacokinetic parameters of orally administered dl-α-lipoic acid may differ significantly when there are changes in dosage, method of administration, and fed status. (Am J Vet Res 2010;71:1377-1383)
Alpha Lipoic Acid
Objective: To report a suspected toxicity in 2 dogs; to discuss therapy and prognosis.
Series Summary: Suspected alpha lipoic acid (ALA) toxicity was diagnosed based on clinical history and compatible laboratory findings in 2 dogs. Case 1 was presented within 10 hours of ALA ingestion, with initial behavioral changes likely due to hypoglycemia. During the course of hospitalization, hypoglycemia persisted and evidence of acute hepatic insult developed. With aggressive supportive care (including IV fluids with dextrose supplementation, hepatoprotective medications, and a plasma transfusion), he made a full recovery. Case 2 was presented approximately 60 hours after ALA ingestion, and was found to be in oliguric renal failure. She was treated with IV fluids, gastroprotective medications, and furosemide, but her condition deteriorated and she was ultimately euthanized within 16 hours of admission to the hospital. NEW OR UNIQUE INFORMATION PROVIDED: ALA is an uncommon but serious toxin that should be considered in cases presenting with hypoglycemia, acute renal failure, or acute hepatic insult.
Alpha Lipoic Acid
Previous work has shown that a diet enriched with antioxidants and mitochondrial co-factors improves cognition in aged dogs, which is accompanied by a reduction in oxidative damage in the brain. The objective of the present study was to assess the effects of supplementation with mitochondrial co-factors on cognition and plasma protein carbonyl levels in aged dogs. Specifically, we aimed to test whether the individual or combined action of lipoic acid (LA) and acetyl-L-carnitine (ALCAR) could account for the beneficial effects of the enriched diet that contained both plus antioxidants. Dogs were given LA or ALCAR, alone and then in combination and cognition was assessed using a spatial learning task and two discrimination and reversal paradigms. Dogs receiving the ALCAR supplement showed an increase in protein carbonyl levels that was associated with increased error scores on the spatial task, and which was reduced upon additional supplementation with LA. We did not observe significant positive effects on cognition. The present findings suggest that short-term supplementation with LA and ALCAR is insufficient to improve cognition in aged dogs, and that the beneficial effects of the full spectrum diet arose from either the cellular antioxidants alone or their interaction with LA and ALCAR.
Alpha Lipoic Acid
Objective: To study the changes of plasma fatty acids and lipophilic vitamins during normal pregnancy.
Design: Plasma fatty acid profile and the concentration of carotenoids, tocopherols and retinol were measured in healthy women at the first and third trimesters of pregnancy, at delivery, and in cord blood plasma.
Results: Maternal plasma cholesterol and triglycerides increased from the first to the third trimester of gestation, while free fatty acids progressively increased from the first trimester through the third trimester to delivery, suggesting an enhanced lipolytic activity. Plasma levels of a- and g-tocopherols, lycopene and b-carotene also progressively increased with gestation, but values in cord blood plasma were lower than in mothers at delivery. Retinol levels declined with gestational time and values in cord blood plasma were even lower. The proportion of total saturated fatty acids increased with gestation, and it further increased in cord blood plasma. Total n-9 fatty acids remained stable throughout pregnancy, and slightly declined in cord blood plasma, the change mainly corresponding to oleic acid. Total n-6 fatty acids declined with gestation and further decreased in cord blood plasma, and a similar trend was found for linoleic acid. However, arachidonic acid declined in women at the third trimester and at delivery as compared to the first trimester, but was enhanced in cord blood plasma. The proportion of total n-3 fatty acids remained stable throughout pregnancy at the expense of decreased a-linolenic acid at delivery but enhanced eicosapentaenoic acid, with small changes in docosahexaenoic acid. The proportion of these n-3 fatty acids was similar in cord blood plasma and maternal plasma at delivery.
Conclusions: Owing to the different placental transfer mechanisms and fetal capability to metabolize some of the transferred fatty acids and lipophilic vitamins, the fetus preserves the essential compounds to assure their appropriate availability to sustain its normal development and to protect itself from the oxidative stress of extrauterine life.
Sponsorship: The studies reported herein have been carried out with financial support from the Commission of the European Communities, specific RTD programme 'Quality of Life and Management of Living Resources', QLK1-2001-00138 'Influence of Dietary Fatty Acids on the Pathophysiology of Intrauterine Foetal Growth and Neonatal Development' (PeriLip). It does not necessarily reflect its views and in no way anticipates the Commission's future policy in this area. European Journal of Clinical Nutrition (2004) 58, 1231-1238. doi:10.1038/sj.ejcn.1601954 Published online 31 March 2004
Pregnancy places increased demands on the mother to provide adequate nutrition to the growing conceptus. A number of micronutrients function as essential cofactors for or themselves acting as antioxidants. Oxidative stress is generated during normal placental development; however, when supply of antioxidant micronutrients is limited, exaggerated oxidative stress within both the placenta and maternal circulation occurs, resulting in adverse pregnancy outcomes. The present paper summarises the current understanding of selected micronutrient antioxidants selenium, copper, zinc, manganese, and vitamins C and E in pregnancy. To summarise antioxidant activity of selenium is via its incorporation into the glutathione peroxidase enzymes, levels of which have been shown to be reduced in miscarriage and preeclampsia. Copper, zinc, and manganese are all essential cofactors for superoxide dismutases, which has reduced activity in pathological pregnancy. Larger intervention trials are required to reinforce or refute a beneficial role of micronutrient supplementation in disorders of pregnancies.
Essential fatty acids (EFAs) and their long-chain polyenes (LCPs) are indispensable for human development and health. Because humans cannot synthesize EFAs and can only inef- fectively synthesize LCPs, EFAs need to be consumed as part of the diet. Consequently, the polyunsaturated fatty acid (PUFA) sta- tus of the developing fetus depends on that of its mother, as con- firmed by the positive relation between maternal PUFA consump- tion and neonatal PUFA status. Pregnancy is associated with a decrease in the biochemical PUFA status, and normalization after delivery is slow. This is particularly true for docosahexaenoic acid (DHA) because, on the basis of the current habitual diet, birth spac- ing appeared to be insufficient for the maternal DHA status to nor- malize completely. Because of the decrease in PUFA status during pregnancy, the neonatal PUFA status may not be optimal. This view is supported by the lower neonatal PUFA status after multiple than after single births. The neonatal PUFA status can be increased by maternal PUFA supplementation during pregnancy. For opti- mum results, the supplement should contain both n-6 and n-3 PUFAs. The PUFA status of preterm neonates is significantly lower than that of term infants, which is a physiologic condition. Because the neonatal DHA status correlates positively with birth weight, birth length, and head circumference, maternal DHA supplementa- tion during pregnancy may improve the prognosis of preterm infants. In term neonates, maternal linoleic acid consumption cor- relates negatively with neonatal head circumference. This suggests that the ratio of n-3 to n-6 PUFAs in the maternal diet should be increased. Consumption of trans unsaturated fatty acids appeared to be associated with lower maternal and neonatal PUFA status. Therefore, it seems prudent to minimize the consumption of trans fatty acids during pregnancy.
The effect of Spirulina supplementation was studied in relation to maternal serum retinal (55). Spirulina given to pregnant women from 7th month of pregnancy till delivery at 1.4g/day was effective for better maternal Vitamin A status and better pregnancy outcome. Percentage increase in the serum retinal levels ranged from 44-46% of the initial value. A follow-up study (56) was undertaken by the same author to study the effect of supplementing their diets with Spirulina on the Vitamin A status. Serum retinal, beta-carotene and breast milk retinal were estimated at various stages of pregnancy. Spirulina supplements fulfilled around 100 and 65% of betacarotene requirement for Indian pregnant and lactating mothers. Spirulina supplementation from third trimester of pregnancy determined to be the most propitious and breast milk retinal was maintained at higher level in pregnant women group. Lactating mothers who received Spirulina for 45 days showed 20 & 30% increase in serum retinal and betacarotene concentration respectively. There was 58 & 46% increase in serum retinal and betacarotene concentration respectively in pregnant women group. The study also confirmed the bioavailability of betacarotene to the fetus. The study revealed no impact of Spirulina supplementation of fetoplacental function test. An increase in haemoglobin levels was found in women belonging to the pregnant group. The study confirms that low-physiological-daily dose of betacarotene from Spirulina is efficacious in improving maternal and neonatal vitamin A status during pregnancy and lactation. Consumption of Spirulina was shown to support the iron status and haemoglobin of rats during pregnancy and lactation (63). The results of the study (65) with the supplementation of Spirulina at 1g/day in pregnant women for a period of 60 days have shown that there was a significant increase in the body mass index of the subjects after supplementation with Spirulina at 5% level. There was also a slight increase in the serum protein, serum iron level and blood haemoglobin level.
1. Mridula Malandkar. Effect of Spirulina supplementation on Vitamin A status during pregnancy March 1995-55
2. Mridula A Naik. Effect of Spirulina supplementation on Vitamin A stauts during pregnancy and Lactation September 2001 - 56
3. Kapoor R, Mehta Supplementary effect of Spirulina on hematological status of rats during pregnancy and lactation. U Department of Home Science, Sri Sathya Sai Institute of Higher LearningAnantapur, AndhraPradesh, India. Plant Foods Hum Nutr 1998; 52(4):315-24 - 63
4. Mubheena Ghori. Dept. of Nutrition Food Service Mgt & Diet. Islamiah Women's Arts & Science College, Vaniyambadi. Effect of Supplementation of Spirulina on the nutritional status of pregnant women 2001.
Both cultured Spirulinaplatensis (Nordst.) Geitl,a blue-green alga, and commercially available dried Spirulina contained high levels of iron, 300-400 ppm on a dry weight basis. Iron availability to rats from cultured S. platensis and from commercial Spirulina equaled that of FeSO4. Ingestion of the daily dose of Spirulina (10 g) recommended for human consumption by the commercial source would provide up to 1.5-2 mg absorbed iron. However, both cultured and commercial Spirulina contained approximately 9.5 ppm Hg, so that chronic use may lead to mercury intakes above prudent levels.
From April to May 2010 eight Pacific harbor seals presented with acute neurologic signs; two additional animals were unexpectedly found dead. Keepers reported no abnormal behavior prior to presentation. Affected animals ranged from four to eight years of age. Nine out of ten animals were female; five of these had recently delivered pups. Seals were housed in a large feeder pool with California sea lions. Animals were fed a mixture of herring, capelin, and lake smelt and supplemented with Mazuri pinniped vitamins with lutein.
Clinical signs included depression, ataxia, blindness, muscle fasiculations, vertical nystagmus, diminished reflexes, and in some cases grand mal seizures. Bloodwork was unremarkable except for mild hyperglycemia. Supportive therapy included intravenous fluids, steroids and diazepam. Anti-convulsive therapy seemed to exacerbate symptoms and in several cases preceded respiratory arrest. Three seals were successfully treated with high dose infusions of intravenous thiamine and Vitamin B complex.
Thiamine, Vitamin B Complex, Lutein
During pregnancy and lactation, mothers require significant amounts of calcium to pass on to the developing fetus and suckling neonate, respectively. Given the dependence of adult calcium con- centrations and bone metabolism on vitamin D, one might anticipate that vitamin D sufficiency would be even more critical during preg- nancy and lactation. However, maternal adaptations during pregnancy and lactation and fetal adaptations provide the necessary calcium relatively independently of vitamin D status. It is the vitamin D-deficient or insufficient neonate who is at risk of problems, including hypocalcemia and rickets. Due to poor penetrance of vitamin D and 25-hydroxyvitamin D [25(OH)D] into milk, exclusively breastfed infants are at higher risk of vitamin D deficiency than are formula-fed infants. Dosing recommendations for women during pregnancy and lactation might be best directed toward ensuring that the neonate is vitamin D-sufficient and that this sufficiency is maintained during infancy and beyond. A dose of vitamin D that provides 25(OH)D sufficiency in the mother during pregnancy should provide normal cord blood concentrations of 25(OH)D. Research has shown that during lactation, supplements administered directly to the infant can easily achieve vitamin D sufficiency; the mother needs much higher doses (100 ug or 4000 IU per day) to achieve adult- normal 25(OH)D concentrations in her exclusively breastfed infant. In addition, the relation (if any) of vitamin D insufficiency in the fetus or neonate to long-term nonskeletal outcomes such as type 1 diabetes and other chronic diseases needs to be investigated.
Background: Few data exist on the effects of the 2 most abundant isomers of vitamin E (a- and y-tocopherols) on fetal growth.
Objective: We measured maternal plasma concentrations of a- and y-tocopherols and examined their relation with measures of fetal growth. We also examined the relation, controlled for associated maternal factors, of diet and supplement use to tocopherol concen- trations at week 28 of gestation.
Design: A cohort of 1231 gravid women from Camden, NJ, was studied from entry to care (16.0 +/- 0.15 wk gestation); plasma tocopherol concentrations were measured at entry and at week 28.
Results: Plasma concentrations of a-tocopherol at entry and at week 28 were positively related to increased fetal growth (birth weight for gestation), a decreased risk of small-for-gestational-age births, and an increased risk of large-for-gestational-age births. Concentration of a-tocopherol at week 28 was positively related to use of prenatal multivitamins and dietary intake of vitamin E; concentration of y-tocopherol was related positively to dietary fat intake and nega- tively to multivitamin use.
Conclusion: Early and late circulating concentrations of y-tocopherol are positively associated with fetal growth.
The studies below have been conducted to support understanding of marine mammal nutrition. Click on each article title to learn more. The articles referenced in this research section are for reference only and do not claim to support any product.
Freezer storage of fish is needed to preserve nutrients, but at the same time can result in degradation.1-4 We investigated levels of vitamins A, B1, E, C, minerals (calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K), manganese (Mn), zinc (Zn), copper (Cu), chromium (Cr), molybdenum (Mo), nickel (Ni), selenium (Se), iodine (I)), and fatty acid composition in Canadian capelin (Mallotus villosus) and Canadian Lake Smelt (Osmerus mordax), over a period of 9 months in freezer storage. All tests, except minerals, were also run on Atlantic herring (Clupea harengus).
Presented at the 2014 American College of Veterinary Ophthalmology Meeting
Glaucoma is a neurodegenerative disease, affecting optic nerve and retinal ganglion cells. The pathogenesis of glaucoma involves various factors, one of which is hypothesized to be oxidative stress. Strategies to reduce oxidative stress help support eye health in dogs with glaucoma, including supplementation with Ocu-GLO™.
This clinical research study, presented last month at the 2014 American College of Veterinary Ophthalmologists Annual Conference by Dr. Corey Schmidt of Colorado State University, shows that Ocu-GLO™ significantly decreased oxidative stress and the intraocular pressures (IOPs) of 8 month old D2 mice compared to untreated D2 mice (D2 mice develop genetic glaucoma). Also, density image analysis revealed significantly more malondialdehyde (MDA) and nuclear transcription factor (nrf2) staining in the ganglion cell layer (GCL) of untreated D2 mice compared to the control and treated D2 mice. MDA is a marker for lipid peroxidation of polyunsaturated fatty acids, and is used to measure the level of oxidative stress present. Nrf2 regulates the expression of antioxidant proteins that protect against oxidative damage. In untreated D2 mice, IOPs and also oxidative stress markers in the GCL neurons were increased by 8 months of age compared to the controls. The oxidative stress in the treated eyes was almost completely halted. These results suggest that the elevations in IOP and changes in oxidative stress present in untreated D2 mice were reduced by feeding Ocu-GLO™.
While Ocu-GLO™ has been a retail nutraceutical product for 5 years, it previously existed for 3 years as a compounded prototype and was dispensed for patients of veterinary ophthalmologists Carmen Colitz and Terri McCalla as part of a clinical study. During 8 years of clinical experience with Ocu-GLO™, Drs. Colitz and McCalla have noted clinical benefits in patients with glaucoma, progressive retinal atrophy (PRA), senile retinal degeneration, uveitis regardless of underlying cause, mild keratoconjunctivitis sicca, immune-mediated blepharitis/conjunctivitis, and in pre- and post-operative cataract surgery patients. Additionally, dogs with PRA and also most diabetic dogs placed on Ocu-GLO™ prior to the development of significant cataract formation were found to have reduced incidence of cataractogenesis (PRA causes secondary "toxic" cataracts to form).
Ocu-GLO™ is also recommended as a lifetime supplement for dogs of breeds (and mixed breeds) at risk for developing ocular disease. Breeds at risk for developing primary (inherited) glaucoma include: Boston Terrier, Basset Hound, Cocker Spaniel, Jack Russell Terrier, Shih Tzu, Chow Chow, Shiba Inu, and Arctic Circle breeds (such as the Siberian Husky and Norwegian Elkhound).
Dr. Carmen Colitz is a board certified veterinary ophthalmologist with a PhD in Comparative and Experimental Medicine.
A Placebo Controlled Masked Study Using Antioxidant Blend OCU-GLO™.
(DL Williams,1, CMH Colitz, 2, 1) Department of Veterinary Medicine, University of Cambridge UK, 2 Animal HealthQuest Solutions, LLC, USA)
Purpose. To evaluate Ocu-GLO™ an orally administered antioxidant/vitamin blend including the aldose reductase inhibitor alpha lipoic acid (ALA), to prevent diabetic cataracts in dogs.
Methods. 30 dogs diagnosed with diabetes mellitus, but without blinding lens changes, seen by DLW in the Department of Veterinary Medicine or in first opinion clinics visited though his ambulatory referral service, were randomly assigned to two groups. One group received Ocu-GLO™ daily PO. The other received placebo, containing the vitamin mix alone, daily PO. All dogs received a full ophthalmic examination and lens clarity was recorded photographically using a Genesis D fundus camera at +10D after pharmacological mydriasis. Dogs were followed for up to one year with examinations monthly. Duration of time without changes in lens opacification was documented for each dog and the two groups compared using Kaplan Meier survival curve statistics.
Results. Mean time without change in lens opacification was 136±66 days with Ocu-GLO™ and 64±24 days in the placebo group. Median duration without lens change was 112 and 65 days, respectively, this difference being statistically significant at p=0.0007. Nine of 15 dogs taking the placebo developed significant cataract while only 3 of 15 dogs taking Ocu-GLO™ developed significant cataract. These three dogs did not receive daily Ocu-GLO™ as directed due to unrelated illness or owner non-compliance.
Supplements for Exotic Pets
Published in Vet Clinics of North America
Congratulations to our Co-Founding Veterinarian Dr. Jo Fava and Veterinary Ophthalmology Specialist Dr. Carmen Colitz for their work, publishing the latest section on Supplements for Exotic Animals in the 2015 Veterinary Clinics of North America.
Supplementation with Imuno-2865® in gilthead sea bream (Sparus aurata Linnaeus, 1758): Effects on hematological and antioxidant parameters
The aim of this study was to evaluate the effects of IMUNO-2865® on hematological and antioxidative parameters in sea bream. Total of 640 sea bream were fed with diets containing 0 (Group 1), 1 (Group 2), 10 (Group 3) and 25 (Group 4) g of IMUNO-2865® kg-1 feed during 90 days. Samples were taken each month and three months after the supplementation. A signiﬁcant heterophils increase was observed in group 4 compared to group 1 after two months, and an increase in monocytes number was observed in group 4 compared to the other groups after one month. Glutathione peroxidase (GSH-Px) and paraoxonase-1 (PON1) were signiﬁcantly increased in groups 3 and 4 compared to the control group three months into the experiment. Superoxide dismutase (SOD) was increased in group 4 compared to the control group from day 60 until the end of the experiment, and in groups 2 and 3 compared to the control after three months. Based on the differences in the cellular immunity and oxidative stress pa- rameters, with an overall absence of mortality, the results of this study suggest that the use of IMUNO- 2865® in aquaculture is safe and possess a cumulative immunostimulatory effect on sea bream.
© 2015 Elsevier Ltd. All rights reserved.