Homocysteine in dogs with systemic inflammatory response syndrome

Patterson, B. E.; Barr, James; Fosgate, Geoffrey T.; Berghoff, Nora; Steiner, Jörg M.; Suchodolski, Jan S.; Black, Dennis M.

doi:10.1111/jsap.12144

Cited by 10 publications

(15 citation statements)

References 31 publications

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“…In keeping with the finding that hyperhomocysteinemia is associated with folate status and oxidative stress, the inverse correlation observed in our study between serum concentrations of HCY and folate, but not cobalamin, agrees with findings in people with hypertension, cerebral venous thrombosis, epilepsy, and inflammatory bowel disease . However, these findings are in contrast with results in dogs with systemic inflammatory response syndrome or sepsis, dogs with chronic enteropathy, and in some people with inflammatory bowel disease…”

Section: Discussionsupporting

confidence: 91%

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Hyperhomocysteinemia in Greyhounds and its Association with Hypofolatemia and Other Clinicopathologic Variables

Heilmann

Grützner

Iazbik

et al. 2016

Veterinary Internal Medicne

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BackgroundFolate and cobalamin are essential cofactors for homocysteine (HCY) metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B vitamin deficiency and is associated with increased risk of cardiovascular disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected chronic enteropathy.ObjectivesTo evaluate the frequencies of and the association between hypofolatemia and hyperhomocysteinemia in Greyhounds.AnimalsData and serum samples from 559 Greyhounds.MethodsNested case‐control study. The frequency of hypofolatemia in Greyhounds was determined by a laboratory database search. The relationship between hyperhomocysteinemia (measured by gas chromatography‐mass spectrometry) and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy Greyhounds and Greyhounds with thrombosis or chronic diarrhea.ResultsHypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common in hypo‐ than in normocobalaminemic dogs (49% vs. 35%; P = .0064). Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more common in hypo‐ than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were inversely correlated with serum folate concentration (ρ = −0.28; P = .0386) and were positively associated with serum albumin concentration (ρ = 0.66; P = .0022).Conclusions and Clinical RelevanceHyperhomocysteinemia occurs frequently in the Greyhound population. Its association with hypofolatemia suggests decreased intracellular availability of B vitamins, but the functional implications warrant further investigation. Hyperhomocysteinemia in Greyhounds potentially may serve as a spontaneous canine model to further investigate hyperhomocysteinemia in humans.

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Section: Discussionsupporting

confidence: 91%

“…Serum cobalamin and folate concentrations were measured by means of validated automated solid‐phase chemiluminescence assays , . The lower detection limits of the assays are 150 ng/L and 1.0 μg/L, respectively …”

Section: Methodsmentioning

confidence: 98%

Hyperhomocysteinemia in Greyhounds and its Association with Hypofolatemia and Other Clinicopathologic Variables

Heilmann

Grützner

Iazbik

et al. 2016

Veterinary Internal Medicne

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“…N5‐methyl TH4, a derivative of folic acid, is a necessary substrate of the methylation reaction . Folic acid itself, administered as a dietary supplement, lowers toxic homocysteine levels, although in dogs the correlation between the concentration of the two substances is not clear . In humans, elevated concentrations of homocysteine in blood, resulting from metabolic aberrations, are a sensitive marker and a risk factor for blood clotting, cardiovascular, and neurodegenerative disorders, as well as folic acid deficiency .…”

mentioning

confidence: 99%

Relationship between Total Homocysteine, Folic Acid, and Thyroid Hormones in Hypothyroid Dogs

Gołyński

Lutnicki

Krumrych

et al. 2017

Veterinary Internal Medicne

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BackgroundBoth elevated homocysteine and decreased folic acid concentrations are observed in human patients with hypothyroidism and can influence the development of numerous secondary disorders.ObjectivesThe aim of the study was to assess total homocysteine concentration in serum and to examine its relationship with the concentration of folic acid and thyroid hormones (tT4 and fT4).AnimalsTen healthy and 19 hypothyroid client‐owned dogs.MethodsDogs with clinical signs of hypothyroidism had the diagnosis confirmed by additional tests. Total homocysteine, folic acid, total thyroxine, and free thyroxine concentrations in serum were evaluated.ResultsHypothyroid dogs were diagnosed with increased homocysteine (median 22.20 μmol/L; range, 16.50–37.75) and decreased folic acid (median 20.62 nmol/L; range, 10.54–26.35) concentrations, as compared to healthy dogs (11.52 μmol/L; range, 10.00–16.65 and 30.68 nmol/L; range, 22.84–38.52, respectively). In sick dogs, total homocysteine was inversely correlated with folic acid (ρ = −0.47, P < 0.001), total thyroxine (ρ = −0.69, P = 0.0092), and free thyroxine (ρ = −0.56, P = 0.0302).ConclusionsHypothyroidism in dogs causes hyperhomocysteinemia. Concomitant mild folic acid decrease in hypothyroid dogs might be as a result of hyperhomocysteinemia.

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“…However, a higher prevalence of AD in offspring was observed in the offspring of women with elevated circulating levels of vitamins B 12 and folate, and hence upregulation of the homocysteine pathway may be related (109). Homocysteine is highly toxic for dogs (110), and blood homocysteine concentrations are kept low, lying within a narrow concentration range (111). Studies on mice have shown that homocysteine concentrations are kept low even in the case where serum concentrations of methionine (100), as well as cystathionine (106), are significantly increased.…”

Section: Diet Cohorts Readily Distinguished By Distinct Serum and Urimentioning

confidence: 99%

Targeted Metabolomics With Ultraperformance Liquid Chromatography–Mass Spectrometry (UPLC-MS) Highlights Metabolic Differences in Healthy and Atopic Staffordshire Bull Terriers Fed Two Different Diets, A Pilot Study

et al. 2020

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Background: While anecdotal evidence has long claimed that a raw meat-based diet (RMBD) improves the metabolic health of canines, no rigorous scientific study has clarified this issue. Canine atopic dermatitis (CAD) has also been linked to metabolic health, but its relation to diet remains poorly understood. This study investigates whether dietary choice is linked to metabolic health in healthy and CAD-diagnosed canines via targeted serum and urine metabolomic analysis of polar, non-ionic metabolites, as well as whether the underlying CAD condition modulates the response to nutritional intake. Materials and Methods: Serum metabolites of client-owned Staffordshire bull terriers, divided into CAD-diagnosed (n = 14) and healthy (n = 6) cohorts, were studied. Urine metabolites of a subset of the CAD-diagnosed canines (n = 8) were also studied. The canines were split into two cohorts based on diet. The first cohort were fed a commercially available high-fat, moderate-protein, low-carbohydrate RMBD (n = 11, CAD diagnosed n = 8, healthy n = 3). Those in the second cohort were fed a commercially available moderate-fat, moderate-protein, high-carbohydrate kibble diet (KD) (n = 9: CAD diagnosed n = 6, healthy n = 3). The diet intervention period lasted approximately 4.5 months (median 135 days). Statistical analyses of the serum profiles across all dogs (n = 20) and the urine profiles of the CAD-diagnosed subset (n = 8) were performed. Results and Discussion: The KD cohort was found to have higher concentrations of methionine than the RMBD cohort, both in serum (all dogs, p < 0.0001) and in urine (CAD-only cohort, p < 0.0002), as well as cystathionine and 4-pyridoxic acid. Methionine plays important roles in homocysteine metabolism, and elevated levels have been implicated in various pathologies. The CAD (n = 14) cohort dogs showed starker Moore et al. Canine Targeted Metabolomics Diet Intervention metabolic changes in response to diet regarding these pathways compared to the healthy (n = 6) cohort. However, there was no significant change in CAD severity as a result of either diet. Likely due to the higher meat content of the RMBD, higher concentrations of several carnitines and creatine were found in the RMBD cohort. Citrulline was found in higher concentrations in the KD cohort. Our findings provide insight into the relationship between diet and the serum and urine metabolite profiles of canines. They also suggest that neither diet significantly affected CAD severity.

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Homocysteine in dogs with systemic inflammatory response syndrome

Cited by 10 publications

References 31 publications

Hyperhomocysteinemia in Greyhounds and its Association with Hypofolatemia and Other Clinicopathologic Variables

Hyperhomocysteinemia in Greyhounds and its Association with Hypofolatemia and Other Clinicopathologic Variables

Relationship between Total Homocysteine, Folic Acid, and Thyroid Hormones in Hypothyroid Dogs

Targeted Metabolomics With Ultraperformance Liquid Chromatography–Mass Spectrometry (UPLC-MS) Highlights Metabolic Differences in Healthy and Atopic Staffordshire Bull Terriers Fed Two Different Diets, A Pilot Study

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