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

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.

2007 ◽  
Vol 58 (4) ◽  
pp. 367 ◽  
Author(s):  
S. C. Wiese ◽  
C. L. White ◽  
I. H. Williams ◽  
J. G. Allen

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.


2000 ◽  
Vol 84 (5) ◽  
pp. 645-653 ◽  
Author(s):  
G. I. Stangl ◽  
F. J. Schwarz ◽  
H. Müller ◽  
M. Kirchgessner

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.


1992 ◽  
Vol 15 ◽  
pp. 169-171 ◽  
Author(s):  
G. E. J. Fisher ◽  
A. MacPherson

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.


Author(s):  
G.E.J. Fisher ◽  
A. MacPherson

Experiments were designed to investigate the effect of sub-clinical cobalt deficiency in pregnant hill sheep, on lamb viability. This form of the deficiency is not characterised by clinical symptoms. The disease is therefore difficult to detect, and may be of economic importance to farms on land of marginal cobalt status.In each of two trials, both with sixty Scottish Blackface x Swaledale ewes, animals were randomly assigned to three treatment groups: A. Cobalt-deficient intake throughout pregnancy; B. Initially cobalt-sufficient intake, but deficient from mid-pregnancy (Trial 1) or initially cobalt-deficient intake, but repleted from mid-term (Trial 2); C. Cobalt-sufficient intake throughout pregnancy. A cobalt-deficient ration (<0.06 mg Co/kg DM) of Timothy hay, micronised maize and maize gluten, was fed from tupping in Trial 1, and from two months before tupping in Trial 2. Treated animals received a weekly oral dose of 0.7 mg Co/head.Vitamin B12 (microbiological and radio-immuno assays) and methylmalonic acid (capillary gas chromatography) were analysed in ewe and lamb sera, as indicators of cobalt status. Levels of passively acquired immunity were measured by analysis of lamb sera, sampled at two and four weeks post-partum, for immunoglobulin G (IgG) and by the zinc sulphate turbidity test (ZSTT).


1981 ◽  
Vol 46 (2) ◽  
pp. 337-344 ◽  
Author(s):  
W. R. H. Duncan ◽  
E. Rona Morrison ◽  
G. A. Garton

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.


2020 ◽  
Vol 9 (8) ◽  
pp. 2335 ◽  
Author(s):  
Sopak Supakul ◽  
Floris Chabrun ◽  
Steve Genebrier ◽  
Maximilien N’Guyen ◽  
Guillaume Valarche ◽  
...  

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.


2013 ◽  
Vol 111 (6) ◽  
pp. 1085-1095 ◽  
Author(s):  
Esmée L. Doets ◽  
Per M. Ueland ◽  
Grethe S. Tell ◽  
Stein Emil Vollset ◽  
Ottar K. Nygård ◽  
...  

A combination of high folate with low vitamin B12plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72–74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12in relation to cognitive performance. Plasma vitamin B12concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.


2021 ◽  
Vol 17 (6) ◽  
pp. 1811-1815
Author(s):  
Valentin Lacombe ◽  
Anne Patsouris ◽  
Estelle Delattre ◽  
Carole Lacout ◽  
Geoffrey Urbanski

IntroductionThe direction of the causal link between solid cancers and elevated plasma vitamin B<sub>12</sub> (B<sub>12</sub>) remains uncertain.Material and methodsWe retrospectively included patients having two B<sub>12</sub> measurements with a B<sub>12</sub> initially ≥ 1000 ng/l and a solid cancer diagnosed between the measurements. Patients were included in the Curative or Supportive group according to their treatments.ResultsB<sub>12</sub> changes over time differed among groups (<i>p</i> = 0.001): +157.4 ng/L/month in the Supportive care group versus -171.6 ng/L/month in the Curative care group.ConclusionsThe decrease of plasma B<sub>12</sub> in cases of curative care could suggest that this B<sub>12</sub> elevation is secondary to solid cancers.


2002 ◽  
Vol 88 (3) ◽  
pp. 253-263 ◽  
Author(s):  
Frédéric Guay ◽  
J. Jacques Matte ◽  
Christiane L. Girard ◽  
Marie-France Palin ◽  
Alain Giguère ◽  
...  

The present experiment aimed to determine the effects of supplements of folic acid (FA) alone or in combination with vitamin B12 on folate and homocysteine metabolism in gestating nulliparous Yorkshire–Landrace (YL) and multiparous Landrace (LD) occidental sows and multiparous Chinese Meishan–Landrace (ML) sows. LD sows were randomly assigned to two treatments: 0 or 15 mg FA/kg diet while YL and ML sows were assigned to three treatments: 0 mg FA/kg diet, 15 mg FA/kg or 15 mg FA+160 μg vitamin B12/kg diet. Supplements were given from the oestrus preceding insemination up to slaughter on day 15 of gestation. At slaughter, a uterine flush was collected to determine uterine contents of homocysteine, methionine, tetrahydrofolate (THF), 5-methyl-THF, pyridoxal 5-phosphate (P5P) and vitamin B12. Blood samples were taken at first oestrus, at insemination and on days 5, 10 and 15 of gestation to determine plasma concentrations of homocysteine, methionine, THF, 5-methyl-THF, P5P, vitamin B12 and relative total folate-binding capacity. In occidental sows (YL and LD), the FA supplement tended to decrease uterine flush content of homocysteine (P=0·06) and concentrations of plasma homocysteine (P=0·09). Nulliparous YL sows had lower concentrations of plasma homocysteine, methionine, THF and 5-methyl-THF (P<0·05) than multiparous LD sows. Multiparous ML and LD sows had similar concentrations of plasma THF, 5-methyl-THF, methionine and vitamin B12, but ML sows had lower concentrations of plasma homocysteine (P<0·05). The vitamin B12 supplement increased concentrations of plasma vitamin B12 (P<0·05) both in multiparous ML and nulliparous YL sows, but had no effect on the composition of either uterine flush or plasma. The present results showed also that sows had a low vitamin B12 status (<200 pg/ml) and high circulating homocysteine levels (>15 μM) during the first 15 d of gestation. Furthermore, the vitamin B12 content in uterine secretions represented between 180 and 300 % of the total content in plasma. The low plasma concentrations of homocysteine in multiparous ML sows suggest a more efficient remethylation pathway which may not be dependent upon dietary supply of FA or vitamin B12. In nulliparous YL sows, low concentrations of both homocysteine and methionine suggest that the methionine requirement for protein deposition might have reduced the amount of methionine available for the methylation pathway. The results of the present experiment suggest that the reduction of uterine homocysteine may be an important aspect of the role of FA supplement on the uterine environment in occidental sows. The presence of high levels of vitamin B12 in uterine secretions merits further investigation in relation to embryonic development.


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