Relationships between plasma methylmalonic acid and ruminal succinate in cobalt-deficient and -repleted sheep

2007 ◽  
Vol 58 (4) ◽  
pp. 367 ◽  
Author(s):  
S. C. Wiese ◽  
C. L. White ◽  
I. H. Williams ◽  
J. G. Allen
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Plasma Concentrations ◽  
Plasma Vitamin ◽  
Normal Range ◽  
Deficient Diet ◽  
Wool Growth ◽  
Cobalt Deficiency ◽  
Vitamin B12 Supplementation ◽  
Effective Degree

We measured methylmalonic acid (MMA) in plasma and succinate in the rumen during the depletion of sheep to a state of severe cobalt deficiency and repletion by various forms of supplementation. Groups of 10, cobalt-deficient weaners were allocated to one of 4 treatments: no supplement, 0.1 or 4.0 mg/day of cobalt as a solution of CoSO4.7H2O per os, or intramuscular vitamin B12. Plasma concentrations of MMA were elevated above the normal range (5 µmol/L) after 35 days on the cobalt-deficient diet, before a reduction in feed intake and while liveweights were still increasing. In all 3 supplemented groups of sheep, plasma vitamin B12 concentrations increased to normal levels within 10 days of supplementation (P < 0.001). Plasma MMA concentrations were reduced to normal levels within 10 days with vitamin B12 supplementation but took 31 days with oral cobalt supplementation (P < 0.001). Plasma MMA concentration in the unsupplemented group continued to rise and remain high for the duration of the experiment and did not show the peak and decline to levels indistinguishable from cobalt adequate levels as observed by others. Rumen succinate concentrations were elevated within 6 days of sheep being introduced to a cobalt-deficient diet and in the unsupplemented sheep remained elevated for the duration of measurement. This rise in rumen succinate was seen at a wider range of cobalt intakes than previously reported. In both oral cobalt treatments, vitamin B12 concentrations increased (P < 0.001) and succinate concentrations decreased (P < 0.001) in the rumen to normal levels within 6 days of supplementation. However, the vitamin B12 provided to the sheep by injection was not recycled to the rumen to any effective degree, as demonstrated by the persistence of high rumen succinate concentrations. The ability of the vitamin B12-supplemented sheep to maintain higher rates of wool growth than deficient sheep, while still exhibiting elevated succinate concentrations in the rumen, demonstrates that overcoming the blockage of the methylmalonyl CoA mutase pathway in the rumen is not essential for restoring metabolic pathways such as those responsible for wool growth. This work contributes to the knowledge of plasma MMA and rumen succinate as useful indicators of functional cobalt status and cobalt intake in sheep.

scholarly journals Methylmalonic acid in the diagnosis of cobalt deficiency in barley-fed lambs

1989 ◽  
Vol 62 (3) ◽  
pp. 729-738 ◽  
Author(s):  
F.P.M. O'Harte ◽  
D. G. Kennedy ◽  
W. J. Blanchflower ◽  
D. A. Rice
Keyword(s):  
Methylmalonic Acid ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Elevated Plasma ◽  
Normal Range ◽  
Cobalt Deficiency ◽  
Upper Level ◽  
Liquid Chromatographic

Eight lambs were fed on a cobalt-deficient whole-barley diet supplemented with urea, vitamins and minerals. Four control lambs were fed on the same diet which had been further supplemented with Co. Plasma vitamin B12 levels in the Co-depleted group declined rapidly, falling below the normal range within 5 weeks. Differences between the live weights of the animals in the two groups approached statistical significance by week 14. However, methylmalonic acid (MMA) rose above normal levels in the Co-depleted group within 7 weeks. This suggested that an elevated plasma concentration of MMA is a comparatively early indicator of functional vitamin B12 deficiency. It is recommended that 10 μmol/l be the upper level of normality for plasma MMA concentration in barley-fed animals, in contrast with the level of 5 μmol/l for grass-fed animals. Changes in the plasma concentrations of MMA and ethylmalonic acid associated with feeding the barley-based diet per se did not significantly affect the validity of the gas-liquid chromatographic assay for MMA.

scholarly journals Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency

2020 ◽  
Vol 9 (8) ◽  
pp. 2335 ◽  
Author(s):  
Sopak Supakul ◽  
Floris Chabrun ◽  
Steve Genebrier ◽  
Maximilien N’Guyen ◽  
Guillaume Valarche ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Plasma Homocysteine ◽  
Plasma Vitamin ◽  
Creatinine Ratio ◽  
Normal Range ◽  
B12 Deficiency ◽  
High Degree

Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function (p = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62–0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0–98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.

Effects of cobalt deficiency in the pregnant ewe on neonatal lamb survival

1992 ◽  
Vol 15 ◽  
pp. 169-171 ◽  
Author(s):  
G. E. J. Fisher ◽  
A. MacPherson
Keyword(s):  
Reproductive Performance ◽  
Dry Matter ◽  
Methylmalonic Acid ◽  
Milk Powder ◽  
Vitamin B ◽  
Deficient Diet ◽  
Cobalt Deficiency ◽  
Acid Status ◽  
Pregnant Ewe ◽  
Skimmed Milk Powder

It has been suggested (Mills, 1981) that there was a lack of research on the effects of cobalt (Co) deficiency on the reproductive performance of sheep. Duncan, Morrison and Garton (1981) reported that clinically Co-deficient ewes produced fewer lambs with a higher incidence of stillbirths and neonatal mortalities than Co-sufficient animals. Garton, Duncan and Fell (1981) related these findings to the vitamin B12 and methylmalonic acid status of dams. However, their investigations used few animals and were therefore inconclusive. The objectives of this work were to investigate the effects of subclinical Co deficiency in pregnant hill sheep on reproductive performance and neonatal lamb viability.Experiment 1 (1985/86) comprised 60 Scottish Blackface × Swaledale ewes, while experiment 2 (1986/87) included 30 of these animals plus 30 pure Scottish Blackface sheep. In both experiments the ewes were housed and bedded on sawdust and a Co-deficient diet of timothy hay, micronized maize, maize gluten, dibasic calcium phosphate and sodium chloride was offered. Skimmed milk powder was introduced to the diet during lactation. The Co content of the diet was 0.06 mg Co per kg dry matter.

scholarly journals Effects of cobalt deficiency in pregnant and post-parturient ewes and their lambs

1981 ◽  
Vol 46 (2) ◽  
pp. 337-344 ◽  
Author(s):  
W. R. H. Duncan ◽  
E. Rona Morrison ◽  
G. A. Garton
Keyword(s):  
Perinatal Mortality ◽  
Methylmalonic Acid ◽  
Post Partum ◽  
Acid Synthesis ◽  
Urinary Concentration ◽  
Vitamin B ◽  
Deficient Diet ◽  
Cobalt Deficiency ◽  
Group A ◽  
Group B

1. Two groups of ewes were fed on a cobalt-deficient diet throughout pregnancy; one group (group A) was given the diet from the beginning of pregnancy, whilst the other (group B) received the diet for 16 weeks before mating. The ewes in group A continued to receive the diet for 12 weeks post-partum.2. The vitamin B12 content of serum was estimated on three occasions before parturition and, for group A ewes, at 12 weeks post partum. Urinary concentration of methylmalonic acid was also determined at intervals before the lambs were born.3. Serum values for vitamin B12 indicated that the ewes in both groups were depleted of the vitamin, though those in group B were more severely affected, as was evidenced by the high incidence of perinatal mortality among the lambs born to these ewes. Perinatal mortality appeared to be associated with abnormally-high values for urinary concentration of methylmalonic acid.4. Analysis of liver lipids and adipose tissue triacylglycerols of some of the vitamin B12-deprived lambs which died before, or within 1 d of, birth showed that, compared with the corresponding tissues of control lambs, these lipids contained unusually high proportions of odd-numbered fatty acids (mostly 15:0, 17:0 and 19:0). This observation is discussed in relation to the likelihood that, in vitmain B12-deprived lambs, propionate becomes available as a primer unit for fatty acid synthesis when the metabolism of its carboxylation product, methylmalonic acid, is impaired due to partlal lack of a vitamin B12-containing enzyme system.

scholarly journals Evaluation of the cobalt requirement of beef cattle based on vitamin B12, folate, homocysteine and methylmalonic acid

2000 ◽  
Vol 84 (5) ◽  
pp. 645-653 ◽  
Author(s):  
G. I. Stangl ◽  
F. J. Schwarz ◽  
H. Müller ◽  
M. Kirchgessner
Keyword(s):  
Linear Model ◽  
Methylmalonic Acid ◽  
Plasma Concentrations ◽  
Haemoglobin Concentration ◽  
Response Criterion ◽  
Quadratic Model ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Line Model ◽  
Growing Cattle

This investigation was designed to estimate the Co requirement of growing cattle on the basis of plasma and liver levels of vitamin B12 and folate, plasma levels of homocysteine and methylmalonic acid (MMA) and haematological variables. For this purpose thirty-four male intact cattle of the German Simmental breed (236 kg) were assigned randomly to ten groups and were fed corn silage-based diets which contained 70, 90, 109, 147, 184, 257, 327, 421, 589 or 689 μg Co/kg DM for 40 weeks. One-slope broken-line model analysis and a quadratic model with plateau were used to estimate the Co requirement. The broken-line model estimated the dietary Co requirement of growing cattle to be 257 (SE 29) ΜG/KG DIETARY DM BASED ON PLASMA VITAMIN B12 AS RESPONSE CRITERION. THE DIETARY CO LEVELS NEEDED TO MAXIMISE THE LIVER VITAMIN B12 AND LIVER FOLATE WERE 236 (se 8) and 190 (se 8) μg/kg dietary DM respectively. Plasma folate did not show any response to the different Co levels. The dietary Co was inversely correlated with the plasma concentrations of homocysteine and MMA. Estimates of the dietary Co concentration required to minimise homocysteine were 161 (se 10) μg/kg DM. When MMA was used as response criterion, the linear model yielded a Co requirement of 124 (se 3) μg/kg dietary DM. The quadratic model did not provide a better closeness of regression fit and yielded similar requirements to the linear model. Haemoglobin concentration and haematocrit tended to have a slight response to increasing dietary Co and were only decreased in cattle on diets containing less than 100 μg Co/kg DM. On the basis of the present data, recommended levels of dietary Co for normal folate metabolism and minimum homocysteine and MMA levels can be set to be 150–200 μg/kg DM; for maximum vitamin B12 levels, the desired Co content in the diet seems to be 250 μg/kg DM.

scholarly journals Reference intervals for plasma vitamin B12 and plasma/serum methylmalonic acid in Danish children, adults and elderly

2021 ◽  
Author(s):  
Abildgaard Anders ◽  
Knudsen Cindy Soendersoe ◽  
Hoejskov Carsten Schriver ◽  
Greibe Eva ◽  
Parkner Tina
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Reference Intervals ◽  
Plasma Vitamin

scholarly journals Plasma Vitamin B12, Supplementation and Mortality

2018 ◽  
Vol 74 (1) ◽  
pp. 138-138 ◽  
Author(s):  
Nuno Mendonça ◽  
Carol Jagger ◽  
Antoneta Granic ◽  
Carmen Martin-Ruiz ◽  
John C Mathers ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Plasma Vitamin ◽  
Vitamin B12 Supplementation

scholarly journals The effect of antibiotics on rats receiving a vitamin B12-deficient diet

1970 ◽  
Vol 24 (2) ◽  
pp. 405-412 ◽  
Author(s):  
D. L. Williams ◽  
G. H. Spray
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
Malonic Acid ◽  
Methylmalonic Acid ◽  
Deficient Diet

1. Rats fed on a vitamin B12-deficient or -supplemented diet were given either neomycin or a mixture of streptomycin and erythromycin by mouth for between 7 and 15 d. The urinary excretion of methylmalonic acid and the levels of vitamin B12 in plasma and tissues and of acetic and propionic acids in caecal contents were measured.2. Both treatments caused prompt reduction of methylmalonate excretion in the deficient rats. This was apparently due to depression of the production of some precursor of methyl-malonic acid, probably propionate, rather than to an immediate effect on vitamin B12 nutrition.3. After withdrawal of the antibiotics, neomycin-treated vitamin B12-deficient rats appeared to become partly repleted in vitamin B12, but the change in the vitamin B12 status of those which had received streptomycin and erythromycin was much smaller.

scholarly journals Determinants of Plasma Methylmalonic Acid in a Large Population: Implications for Assessment of Vitamin B12 Status

2009 ◽  
Vol 55 (12) ◽  
pp. 2198-2206 ◽  
Author(s):  
Anna Vogiatzoglou ◽  
Abderrahim Oulhaj ◽  
A David Smith ◽  
Eha Nurk ◽  
Christian A Drevon ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Large Population ◽  
Dietary Factors ◽  
Plasma Vitamin ◽  
Middle Aged ◽  
Anthropometric Measures ◽  
Upper Limits ◽  
Unselected Population ◽  
The Difference

Abstract Background: Methylmalonic acid (MMA) in plasma or serum is widely used for assessment of vitamin B12 status. However, data are sparse regarding factors, besides renal function, that may influence MMA concentrations. We searched for important determinants of plasma MMA in the general population. Methods: In 6946 middle-aged (47–49 years) and elderly (71–74 years) individuals from the Hordaland Homocysteine Study in Norway, we collected anthropometric measurements, lifestyle data, and plasma MMA, vitamin B12, and creatinine measurements. For 5820 individuals, we also collected dietary data. Results: Age and plasma creatinine were positively associated with plasma MMA, whereas plasma vitamin B12 was negatively associated. These variables together with sex were the strongest determinants of plasma MMA, accounting for 16% of the variation (R2 = 0.16). Addition of anthropometric measures and lifestyle and dietary factors only gave slight improvement (total R2 = 0.167). Increased plasma MMA was seen when plasma vitamin B12 was &lt;400 pmol/L. In individuals with vitamin B12 ≥400 μmol/L (vitamin B12–replete), the 2.5th–97.5th percentile reference limits for MMA were 0.10–0.28 μmol/L (middle-aged) and 0.10–0.36 μmol/L (elderly). When plotted against creatinine (nomograms), the 97.5th percentile of MMA was similar in men and women but approximately 0.15 μmol/L higher in elderly than middle-aged individuals. Vitamin B12–replete participants had MMA upper limits approximately 0.1 μmol/L (elderly) and 0.04 μmol/L (middle-aged) below those of the unselected population at all creatinine concentrations. Conclusions: Identified determinants accounted for &lt;17% of the overall variation in plasma MMA. The difference in MMA between middle-aged and elderly individuals is only partly explained by creatinine and vitamin B12 concentrations.

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