Vitamins and Dogs

Research in Vitamins and Dogs

Neurosci Biobehav Rev 2002 Oct;26(6):679-95 : Landmark discrimination learning in the dog: effects of age, an antioxidant fortified food, and cognitive strategy.
Milgram NW, Head E, Muggenburg B, Holowachuk D, Murphey H, Estrada J, Ikeda-Douglas CJ, Zicker SC, Cotman CW.
Life Science Division, University of Toronto at Scarborough, 1265 Military Trail, Scarborough, Ont., Canada M1C 1A4.
milgram@psych.utoronto.ca

The landmark discrimination learning test can be used to assess the ability to utilize allocentric spatial information to locate targets. The present experiments examined the role of various factors on performance of a landmark discrimination learning task in beagle dogs. Experiments 1 and 2 looked at the effects of age and food composition. Experiments 3 and 4 were aimed at characterizing the cognitive strategies used in performance on this task and in long-term retention. Cognitively equivalent groups of old and young dogs were placed into either a test group maintained on food enriched with a broad-spectrum of antioxidants and mitochondrial cofactors, or a control group maintained on a complete and balanced food formulated for adult dogs. Following a wash-in period, the dogs were tested on a series of problems, in which reward was obtained when the animal responded selectively to the object closest to a thin wooden block, which served as a landmark. In Experiment 1, dogs were first trained to respond to a landmark placed directly on top of coaster, landmark 0 (L0). In the next phase of testing, the landmark was moved at successively greater distances (1, 4 or 10 cm) away from the reward object. Learning varied as a function of age group, food group, and task. The young dogs learned all of the tasks more quickly than the old dogs. The aged dogs on the enriched food learned L0 significantly more rapidly than aged dogs on control food. A higher proportion of dogs on the enriched food learned the task, when the distance was increased to 1cm. Experiment 2 showed that accuracy decreased with increased distance between the reward object and landmark, and this effect was greater in old animals. Experiment 3 showed stability of performance, despite using a novel landmark, and new locations, indicating that dogs learned the landmark concept. Experiment 4 found age impaired long-term retention of the landmark task. These results indicate that allocentric spatial learning is impaired in an age-dependent manner in dogs, and that age also affects performance when the distance between the landmark and target is increased. In addition, these results both support a role of oxidative damage in the development of age-associated cognitive dysfunction and indicate that short-term administration of a food enriched with supplemental antioxidants and mitochondrial cofactors can partially reverse the deleterious effects of aging on cognition.

Neurobiol Aging 2002 Sep-Oct;23(5):737-45 : Dietary enrichment counteracts age-associated cognitive dysfunction in canines.
Milgram NW, Zicker SC, Head E, Muggenburg BA, Murphey H, Ikeda-Douglas CJ, Cotman CW.
Life Science Division, University of Toronto at Scarborough, 1265 Military Trail, Scarborough, Ont, Canada M1C 1A4.
milgram@psych.utoronto.ca
Advanced age is accompanied by cognitive decline indicative of central nervous system dysfunction. One possibly critical causal factor is oxidative stress. Accordingly, we studied the effects of dietary antioxidants and age in a canine model of aging that parallels the key features of cognitive decline and neuropathology in humans. Old and young animals were placed on either a standard control food, or a food enriched with a broad spectrum of antioxidants and mitochondrial enzymatic cofactors. After 6 months of treatment, the animals were tested on four increasingly difficult oddity discrimination learning problems. The old animals learned more slowly than the young, making significantly more errors. However, this age-associated decline was reduced in the animals fed the enriched food, particularly on the more difficult tasks. These results indicate that maintenance on foods fortified with complex mixtures of antioxidants can partially counteract the deleterious effects of aging on cognition. Copyright 2002 Elsevier Science Inc.

J Nutr 2002 Jun;132(6 Suppl 2):1720S-4S Related Articles, Links Role of dietary antioxidants to protect against DNA damage in adult dogs.
Heaton PR, Reed CF, Mann SJ, Ransley R, Stevenson J, Charlton CJ, Smith BH, Harper EJ, Rawlings JM.
Waltham Centre for Pet Nutrition, Leicestershire, UK.
paul.heaton@eu.effem.com
We studied the effects of feeding an antioxidant blend of vitamins, minerals and carotenoids to a mixed adult dog population (n = 40, mean 4.4 +/- 1.85 y) for a 16-wk period. Compared to the control group of dogs (n = 20), the antioxidant (AOX)-supplemented group of dogs (n = 20) demonstrated significant increases in plasma levels of vitamin E and taurine by 4 wk of supplementation (P < 0.01) and total antioxidant activity (as measured by ferric-reducing antioxidant power assay) by 8 wk of supplementation (P < 0.05). Following 8 wk of supplementation, the AOX-supplemented dogs also showed significant reductions in both endogenous and exogenous DNA damage (P < 0.005) compared to that of the control dogs, as measured by the comet assay. Over an 8-wk rabies vaccination course that started at 8 wk supplementation, the AOX-supplemented dogs also demonstrated significantly higher vaccine-specific virus-neutralizing antibody levels at 2, 4 and 6 wk postvaccination (P < 0.05) and a tendency toward establishing a vaccine-specific antibody response quicker than did the control group of dogs. These findings in dogs suggest that antioxidant supplementation can achieve sustained increases in circulating levels of antioxidants that exert a protective effect by a decrease in DNA damage, leading to improved immunological performance. These findings also have implications in a wider context where free-radical damage has been associated with a variety of degenerative disorders and the aging process in general.

Gut 2002 Jan;50(1):61-4 : Interventional study of high dose folic acid in gastric carcinogenesis in beagles.
Xiao SD, Meng XJ, Shi Y, Hu YB, Zhu SS, Wang CW.
Shanghai Institute of Digestive Disease, Shanghai Second Medical University, Renji Hospital, Shanghai 200001, P R China.
sdxiao@guomai.sh.cn
BACKGROUND: A decrease in folic acid and subsequent DNA hypomethylation may be involved in gastric carcinogenesis. Epidemiological and nutritional studies have indicated that folate status modulates the risk of developing cancers. AIMS: To investigate whether folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by N-ethyl-N-nitrosoguanidine (ENNG) in beagles. METHODS: Sixteen male beagles were randomly divided into two groups: folic acid treated group and control group. In both groups beagles were fed ENNG 75 mg per day for eight months and in the treated group 20 mg folic acid was given to beagles for 15 months. Gastroscopy and biopsies were performed before and every 2-3 months after administration of ENNG until the end of the experiment. Histopathological lesions were diagnosed with regard to the criteria for human gastric mucosal biopsies. Serum and gastric mucosal tissue folic acid concentrations were measured. RESULTS: In the control group, all beagles developed gastric cancer (8/8) compared with only 3/8 in the folic acid treated group (p<0.05). Moreover, serum and gastric mucosal tissue folic acid concentrations were markedly elevated 15 months after folic acid administration. The difference was statistically significant between the two groups (p<0.05). CONCLUSIONS: Our results indicate that high dose folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by a chemical carcinogen ENNG in beagles.

Altern Med Rev 2001 Sep;6 Suppl:S38-45 : Nutritional therapy in the treatment of heart disease in dogs.
Dove RS.
Companion Animal Clinic, 14760 Lee Hwy., Gainesville, VA 20155, USA.
A number of diseases affecting the heart are prevalent in canines. Acquired diseases, those which develop over the course of an animal's lifetime (rather than congenital defects present at birth), have recently been the subject of several studies to determine the efficacy of dietary supplementation on symptom presentation, disease severity, and mortality rates. Specifically, coenzyme Q10 (CoQ10), vitamin E (as alpha-tocopherol), L-carnitine, taurine, and fish oil (omega-3 fatty acids) have all been evaluated in the prevention and treatment of many types of heart disease in dogs. Other supplements with preliminary evidence, meriting further investigation, include magnesium, Crataegus, and the B vitamins. Both clinical observation and interventional trials with various breeds have provided clear evidence for the benefit of numerous supplements on canine heart disease. Appropriate levels of certain dietary nutrients have been shown to increase life span, improve life quality, reduce symptoms and physical evidence of disease, and decrease mortality rates in these animals.

Vet Dermatol 2002 Dec;13(6):301-5 Related Arti Influence of vitamin E on mast cell mediator release.
Gueck T, Aschenbach JR, Fuhrmann H.
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany. gueck@vetmed.uni-leipzig.de
We investigated the influence of vitamin E on mediator activity and release in a canine mastocytoma cell line (C2) as a model for canine atopic dermatitis. Cells were incubated without and with vitamin E (100 microm) for 24 h. The histamine and prostaglandin D2 (PGD2) release as well as the chymase and tryptase activity were measured. To stimulate the PGD2 and histamine release, cells were incubated with the wasp venom peptide mastoparan (50 microm) for 30 or 45 min. Nonstimulated as well as mastoparan-stimulated histamine and PGD2 release was reduced significantly in vitamin E-treated cells. The activity of chymase tended to decrease, but the tryptase activity of C2 cells was not influenced by vitamin E. These results indicate that vitamin E decreased the production and release of inflammatory mediators in C2 cells, suggesting that vitamin E might have a possible beneficial effect in inflammatory diseases.

: Berl Munch Tierarztl Wochenschr 2001 Jul-Aug;114(7-8):257-66 : [The role of the kidneys in vitamin metabolism]
[Article in German]
Raila J, Schweigert FJ.
Universitat Potsdam, Institut fur Ernahrungswissenschaft, Arthur-Scheunert-Allee 114-116, D-14558 Potsdam-Rehbrucke.
jraila@rz.uni-potsdam.de
It is well established that the kidney plays an essential role in regulating the homeostasis of body fluids. Recent studies provided evidence for the kidney to be an important organ for the regulation in the metabolism of both fat (vitamin A, D) and water soluble vitamins (e.g. vitamin B12). This regulation is mediated by glomerular filtration as well as reabsorption and secretion processes of protein-bound vitamins. Vitamin transport proteins such as retinol-binding protein, vitamin D-binding protein and transcobalamin II are filtered in renal glomeruli and subsequently reabsorbed in the proximal tubules by endocytosis from the tubular fluid. Megalin, a scavenger receptor belonging to the LDL receptor family, is probably the most important receptor in this process in the proximal tubule cells. The carrier proteins are degraded in lysosomes whereas the vitamins are probably stored, may become coupled to newly synthesized carriers and secreted at the basolateral plasma membrane. A renal vitamin excretion is observed in dogs and other species of the family Canidae, in form of fat soluble retinol and retinyl esters bound to Tamm-Horsfall protein. This and the high vitamin A concentrations in renal tissue of canines suggest an important role of the kidneys in vitamin A metabolism of these species.

Neurosci Lett 1999 Oct 22;274(2):83-6 : Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular free magnesium ions in canine cerebral vascular smooth muscle cells: possible relationship to [Ca2+]i, atherogenesis and stroke.
Li W, Zheng T, Wang J, Altura BT, Altura BM.
Department of Physiology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
Homocysteine (HC) at concentrations of from 0.05 to 1.0 mM caused dose-dependent loss of [Mg2+]i in cultured cerebral vascular smooth muscle cells (VSMC), whereas cysteine and methionine (its metabolic products) failed to interfere with changes in [Mg2+]i. HC, methionine and cysteine did not produce any changes in [Ca2+]i. Lowering [Mg2+]o to 0.3 mM resulted in elevation of [Ca2+]i and loss of [Mg2+]i. Depletion of [Mg2+]i, induced by HC, was potentiated by low Mg2+. Preincubation of these cells with vitamin B6, vitamin B12, folic acid, alone, did not alter [Ca2+]i or [Mg2+]i. Likewise, concomitant addition of vitamin B6, vitamin B12, or folic acid, together with HC (1 mM) did not change the reduction in [Mg2+]i induced by HC. However, concomitant addition of HC and the three vitamins inhibited completely the loss of [Mg2+]i. Exposure of these cells to each vitamin, alone, or combination of the three vitamins failed to interfere with reduction in [Mg2+]i induced by low [Mg2+]i, but it did suppress the rise in [Ca2+]i. Interestingly, in the presence of low [Mg2+]o, the vitamin combination did not retard depletion of [Mg2+]i. The present findings are compatible with the hypothesis that an increased serum HC concentration causes abnormal metabolism of Mg2+ in cerebral VSMC, thus priming these cells for HC-induced atherogenesis, cerebral vasospasm and stroke. Our results suggest the need for the three B-vitamins, together with normal physiological levels of Mg2+, in order to prevent [Mg2+]i depletion and occlusive cerebral vascular diseases induced by homocysteinemia.

Res Vet Sci 1982 Jan;32(1):17-22 : Role of serum folate and vitamin B12 concentrations in the differentiation of small intestinal abnormalities in the dog.
Batt RM, Morgan JO.
Serum folate and vitamin B12 concentrations have been measured in 53 dogs presented for an investigation of malabsorption. Abnormal concentrations have permitted the differentiation of animals with small intestinal disease into three main groups, each with distinct biochemical abnormalities in the jejunal mucosa. The first group had reduced folate and vitamin B12 concentrations. Jejunal biopsies revealed marked villous atrophy and generalised biochemical abnormalities in the brush borders, lysosomes and endoplasmic reticulum. The second group had reduced folate but normal vitamin B12 concentrations and although histological changes were minimal there were specific biochemical changes confined to the brush borders. In the third group, increased folate and reduced vitamin B12 concentrations suggested a bacterial overgrowth in the proximal small intestine. Minor histological changes were accompanied by marked biochemical changes in brush borders and lysosomes. A group of animals with severe exocrine pancreatic insufficiency had increased mean folate but reduced mean vitamin B12 concentrations. These changes are consistent with bacterial overgrowth, but could be due to defective degradation of a B12-binding protein.

Cas Lek Cesk 2002 Jul;141(13):417-20 : [Nutritional determinants of homocysteinemia]
[Article in Slovak]
Krajcovicova-Kudlackova M, Blazicek P.
Ustav preventivnej a klinickej mediciny, Bratislava Nemocnica Ministerstva obrany, Bratislava. kudlackova@upkm.sk
BACKGROUND: Vitamin B12, folate and vitamin B6 are the main determinants of homocysteinemia. These B-group vitamins influence two metabolic pathways of homocysteine reduction, which prevail in dependence to methionine intake. Transsulfuration (vitamin B6) dominates under condition of overnutrition with prevalence of animal food sources, remethylation (vitamin B12 and folic acid) is decisive under conditions of malnutrition, alternative nutrition or optimal traditional diet. METHODS AND RESULTS: Plasma homocysteine and folic acid, vitamins B12 and B6 in serum were measured in alternative nutrition groups of adults (vegans, vegetarians (lacto + lactoovo), semivegetarians, n = 39) and compared with those values in group consuming traditional diet--control group, general population (n = 35). In alternative nutrition groups, the average homocysteine level is significantly higher (vegans 17.2 mumol/l, vegetarians 12.9 mumol/l, semivegetarians 10.1 mumol/l, control group 9.9 mumol/l); the frequency of hyperhomocysteinemia (over 15 mumol/l) is 50%, 32%, 14% vs. 6% in control group. Vegetarians and vegans have a significantly higher levels of vitamin B6 and folic acid; the frequency of vitamin B6 deficit is 60% and 57% in control group and semivegetarian group vs. 16% and 0% in vegetarian and vegan group. Folate deficit was found in 16% of traditional group vs. 0% in alternative groups. Serum levels of vitamin B12 are significantly reduced in subjects consuming alternative nutrition with deficiency observed in 67% of vegans, 32% of vegetarians, 14% of semivegetarians vs. 0% in control group. CONCLUSIONS: Vitamin levels in relation to nutritional regime and metabolic pathways of homocysteine show that the mild hyperhomocysteinemia in alternative nutrition is a consequence of vitamin B12 deficiency. In traditionally fed population, higher plasma homocysteine values is caused by folate deficiency. These conclusions are supported by a significantly negative linear correlation of homocysteine--folic acid levels (traditional nutrition) and homocysteine--vitamin B12 levels (alternative nutrition). In case of vitamin B6, a similar correlation was not found.

Lancet 2002 Jan 19;359(9302):227-8 : Comment in: Lancet. 2002 Jul 13;360(9327):171-2; discussion 172-3. Lancet. 2002 Jul 13;360(9327):173.
Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease.
Quinlivan EP, McPartlin J, McNulty H, Ward M, Strain JJ, Weir DG, Scott JM.
Fortification of food with folic acid to prevent neural-tube defects in babies also lowers plasma total homocysteine, which is a risk factor for vascular disease. We investigated the effect of folate and vitamin B12 on homocysteine concentrations. 30 men and 23 women received sequential supplementation with increasing doses of folic acid. After supplementation, the usual dependency of homocysteine on folate diminished, and vitamin B12 became the main determinant of plasma homocysteine concentration. This finding suggests that a fortification policy based on folic acid and vitamin B12, rather than folic acid alone, is likely to be much more effective at lowering of homocysteine concentrations, with potential benefits for reduction of risk of vascular disease.

Minerva Urol Nefrol 2001 Sep;53(3):159-70 : Therapy of hyperhomocysteinemia in end-stage renal disease patients.
Hagen W, Fodinger M, Horl WH, Sunder-Plass-Mann G. Division of Nephrology and Dialysis, Department of Medicine III, University of Vienna, Vienna, Austria.
Because of a potential association with cardiovascular disease, birth defects, and various other conditions, an elevation of tHcy plasma levels has gained broad interest. The majority of chronic renal failure patients present with hyperhomocysteinemia, the causes of which are not completely understood. An increasing number of studies addressed the treatment of hyperhomocysteinemia in chronic renal failure patients. Folic acid combined with vitamin B6 and vitamin B12 is more effective in lowering tHcy levels than either cofactor alone. The optimal dose of folic acid appears to be 1 mg orally per day. Intravenous application of vitamin B12, giving 1 to 1.5 mg per week may be more effective than therapy with 1 mg orally per day. The role of vitamin B6 is far from clear. It may play a role in combination with folic acid and/or vitamin B12. Finally, general screening for and treatment of hyperhomocysteinemia is not recommended.