-
Clinical Chemistry and Laboratory Medicine 03/2013; 51(3):455-6. · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Background: Disturbed DNA methylation is causally related to chronic diseases like cancer and atherosclerosis. B vitamins are cofactors required for methyl group synthesis and may therefore affect DNA methylation. Vitamin D has epigenetic effects. We tested if B and D vitamin supplementation has an effect on genomic long interspersed nuclear element-1 (LINE-1) methylation and the metabolites S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). Methods: Fifty subjects (median age 68.0 years) were supplemented with a daily oral dose of B vitamins (500 µg folic acid, 500 µg vitamin B12 and 50 mg vitamin B6), 1200 IU vitamin D and 456 mg calcium. Fasting blood samples were collected before and after 1 year of supplementation. LINE-1 methylation was determined in genomic DNA from blood cells as a surrogate for whole genome methylation. In addition, SAM, SAH and total homocysteine (tHcy) were measured in plasma samples. Results: Plasma homocysteine decreased significantly after supplementation (12.8 vs. 9.1 µmol/L; p<0.05), whereas SAM, SAH, the SAM/SAH ratio and LINE-1 methylation did not change significantly. LINE-1 methylation was not significantly correlated with SAH, homocysteine or B vitamins. Conclusions: Long-term vitamin B supplementation had no effect on LINE-1 methylation in blood cells nor on plasma levels of SAM and SAH. Vitamin B and D supplementation seems to have no effect on DNA methylation, especially in cases where no severe deficiency exists.
Clinical Chemistry and Laboratory Medicine 01/2013; · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin of CorA.
HC-CorA were quantified in paired samples of cord serum from newborns and serum from mothers (n = 69).
The CorA-concentration was higher in cord serum (median = 380, range: 41-780 pmol/L) than in serum from the mothers (median = 160, range: 64-330 pmol/L), (p<0.0001). HPLC-analysis showed CorA-peaks with retention times of 13.5, 14,5 and 16.5 min in samples from both the mother and cord serum. The peak with retention time 16.5 min constituted 24% (mother) and 45% (cord serum) of the total amount CorA, and eluted as does dicyanocobinamide.
Our results support that CorA in the human body are derived from Cbl.
PLoS ONE 01/2013; 8(4):e61194. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background: An elevated serum concentration of homocysteine (hyperhomocysteinemia) has been shown to disturb fracture healing. As the essential amino acid, methionine, is a precursor of homocysteine, we aimed to investigate whether excess methionine intake affects bone repair. Material/Methods: We analyzed bone repair in 2 groups of mice. One group was fed a methionine-rich diet (n=13), and the second group received an equicaloric control diet without methionine supplementation (n=12). Using a closed femoral fracture model, bone repair was analyzed by histomorphometry and biomechanical testing at 4 weeks after fracture. Blood was sampled to measure serum concentrations of homocysteine, the bone formation marker osteocalcin, and the bone resorption marker collagen I C-terminal crosslaps Results: Serum concentrations of homocysteine were significantly higher in the methionine group than in the control group, while serum markers of bone turnover did not differ significantly between the 2 groups. Histomorphometry revealed no significant differences in size and tissue composition of the callus between animals fed the methionine-enriched diet and those receiving the control diet. Accordingly, animals of the 2 groups showed a comparable bending stiffness of the healing bones. Conclusions: We conclude that excess methionine intake causes hyperhomocysteinemia, but does not affect fracture healing in mice.
Medical science monitor: international medical journal of experimental and clinical research 12/2012; 18(12):BR469-474. · 1.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: There is an urgent need for proper utilization of laboratory markers to diagnose vitamin B12 deficiency that should reduce false negative cases. We worked out a diagnostic algorithm that provides a two-step detection of vitamin B12 deficiency using holotranscobalamin as a first line marker and methylmalonic acid (MMA) as a second line marker. MATERIALS AND METHODS: We tested 1359 serum samples sent to our laboratory for total vitamin B12 assay. Serum samples were used for the determination of holotranscobalamin, MMA and creatinine. RESULTS: Compared with total B12, holotranscobalamin showed a higher area under the receiver operating characteristic curve for detecting MMA levels > 300 nM. However, the distribution of holotranscobalamin in individuals with elevated creatinine irrespective of MMA and in individuals with elevated MMA irrespective of creatinine was shifted into the higher ranges. In the grey zone of holotranscobalamin between 23 and 75 pM (the range extending from the 90% diagnostic sensitivity to the 90% diagnostic specificity), MMA testing as a second line marker would help detecting 18% of deficient cases. Lowering MMA after vitamin B12 treatment may help setting the diagnosis of B12 deficiency in individuals with elevated creatinine. DISCUSSION: Testing for vitamin B12 deficiency should start with holotranscobalamin measurement. Holotranscobalamin between 23 and 75 pM should be followed by MMA testing that can filter substantial number of deficient cases in the grey range in individuals with normal renal function. This diagnostic strategy may significantly improve assessing vitamin B12 deficiency.
European Journal of Clinical Investigation 11/2012; · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Background: Vitamin D and vitamin B deficiency are common in elderly subjects and are important risk factors for osteoporosis and age-related diseases. Supplementation with these vitamins is a promising preventative strategy. The objective of this study was to evaluate the effects of vitamins D3 and B supplementation on bone turnover and metabolism in elderly people. Methods: Healthy subjects (n=93; >54 years) were randomly assigned to receive either daily vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12 (0.5 mg), vitamin B6 (50 mg), and calcium carbonate (456 mg) (group A) or only vitamin D3 plus calcium carbonate (group B) in a double blind trial. We measured at baseline and after 6 and 12 months of supplementation vitamins, metabolites, and bone turnover markers. Results: At baseline mean plasma 25-hydroxy vitamin D [25(OH)D] was low (40 or 30 nmol/L) and parathormone was high (63.7 or 77.9 pg/mL). 25(OH)D and parathormone correlated inversely. S-Adenosyl homocysteine and S-adenosyl methionine correlated with bone alkaline phosphatase, sclerostin, and parathormone. One year vitamin D3 or D3 and B supplementation increased plasma 25(OH)D by median 87.6% (group A) and 133.3% (group B). Parathormone was lowered by median 28.3% (A) and 41.2% (B), bone alkaline phosphatase decreased by 2.8% (A) and 16.2% (B), osteocalin by 37.5% (A) and 49.4% (B), and tartrate-resistant-acid-phosphatase 5b by 6.1% (A) and 36.0% (B). Median total homocysteine (tHcy) was high at baseline (group A: 12.6, group B: 12.3 µmol/L) and decreased by B vitamins (group A) to 8.9 µmol/L (29.4%). tHcy lowering had no additional effect on bone turnover. Conclusions: One year vitamin D3 supplementation with or without B vitamins decreased the bone turnover significantly. Vitamin D3 lowered parathormone. The additional application of B vitamins did not further improve bone turnover. The marked tHcy lowering by B vitamins may modulate the osteoporotic risk.
Clinical Chemistry and Laboratory Medicine 11/2012; · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Folate and cobalamin are necessary for early brain development and function. Deficiency of folate or cobalamin during pregnancy can cause severe malformation in the central nervous system such as neural tube defects. After birth, folate and cobalamin deficiency can cause anemia, failure to thrive, recurrent infections, psychiatric and neurological symptoms. The folate and the homocysteine metabolic pathways interact at a central step where 5-methyltetrahydrofolate donates its methyl group to homocysteine to produce methionine and tetrahydrofolate. Methyl cobalamin and folate interact at this critical step. Both nutrients have a crucial role in DNA synthesis and in delivering S-adenosylmethionine, the universal methyl donor. Severe and mild inherited disorders in folate and cobalamin pathways have been described. The two groups of disorders share some similarities, but differ in the molecular mechanism, metabolic dysregulation, and disease management. This review summarizes selected disorders, including rare and common mutations that affect folate and cobalamin absorption, transport, or dependent enzymes. When the mutations are discovered early enough, many of the described disorders are easily treatable by B vitamin supplementation, which often prevents or reverses the manifestation of the disease. Therefore, the screening for mutations is recommended and should be carried out as early as possible: after occurrence of the first symptoms or when a certain constellations of the folate and cobalamin related markers are measured, such as elevated homocysteine and/or methylmalonic acid.
Clinical Chemistry and Laboratory Medicine 11/2012; · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Contradictory results for concentrations of vitamin B12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) have been reported. We tested the hypothesis that the extracellular vitamin B12 markers are not reflecting the intracellular vitamin B12-dependent biochemical reactions in individuals with type 2 diabetes. The study included 92 patients with diabetes and 72 controls with similar age and sex distribution. We measured vitamin B12 markers [MMA, total serum vitamin B12, holoTC, total homocysteine (tHcy)], red blood cell (RBC)-B12, and the plasma concentrations of the methylation markers [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)]. In comparison to controls, diabetic patients showed significantly higher concentrations of plasma SAH (median 15.1 vs. 11.8 nmol/L; p<0.001) and lower SAM/SAH ratio (9.1 vs. 8.2; p=0.006). Concentrations of total vitamin B12 and holoTC did not differ significantly between the groups, but plasma MMA concentrations were significantly higher in diabetics (250 vs. 206 nmol/L). However, RBC-B12 was lower in diabetics compared to controls (median 230 vs. 260 pmol/L; p=0.001). The inverse correlation between MMA and RBC-B12 was stronger in the controls compared to that in the patients (correlation coefficient in controls R= -0.446, p=0.001; in patients R= -0.289, p=0.022). Metformin treatment was associated with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index. In conclusion, patients with type 2 diabetes showed normal extracellular vitamin B12, but disturbed intracellular B12-dependent biochemical reactions. Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12.
Biochimie 11/2012; · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The study tests the metabolites of the methylation cycle in individuals with Down syndrome (DS) and applies a mathematical model in order to change this cycle by nutritional factors.
We measured concentrations of the metabolites related to the methylation cycle in the blood of 35 young individuals with DS and 47 controls of comparable age. Moreover, we applied a mathematical model to learn more about the regulation of the methylation cycle in DS. Concentrations of cystathionine, cysteine, betaine, choline, dimethylglycine, S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), and holotranscobalamin were significantly higher in DS compared to the controls. The median SAM/SAH ratio was lower in DS and that of methionine and reduced glutathione did not differ significantly between the groups. The mathematical model showed that enhanced methionine turnover and accelerated Hcy-remethylation might explain the shift in the methylation cycle in DS.
In addition to the DS-related excess of cystathionine beta synthase (CBS) activity, increases in the activities of MS and betaine homocysteine methyl transferase, and in methionine input were necessary to account for the changes in metabolite levels observed in DS. A low-methionine diet might offer a perspective for reversing the metabolic imbalance in DS, but this awaits clinical investigations.
Molecular Nutrition & Food Research 08/2012; 56(10):1582-9. · 4.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An increase in folate intake before and during pregnancy can prevent many neural tube defects. This prompted over 50 countries worldwide to mandate fortification of breakfast cereals or staple foods with folic acid (FA), which is the synthetic oxidised form of the vitamin used in supplements and fortified foods. After ingestion, FA is reduced by dihydrofolate reductase (DHFR) and then converted to the biologically active forms. The presence of detectable amounts of unmetabolised FA in blood of individuals who have consumed supplements or fortified foods has attracted attention in recent years. A direct correlation exists between FA intake and unmetabolised FA in serum and suggests that a saturable level of DHFR exists. Factors affecting FA reduction, such as age, intestinal pH, alcohol, FA dose and duration of supplement usage, and possibly polymorphisms of folate-metabolising enzymes, can affect the presence of FA in blood. However, minor amounts of FA might also be produced during sample preparation. In pregnant women taking supplements, FA does not seem to accumulate in the newborns. Concentrations of unmetabolized FA are correlated to and predicted by those of total folate or 5-MTHF. Evidence of a negative health effect of free FA in blood is not consistent and suggests rather artificial factors. FA has no known cofactor function that would increase the likelihood of a causal role for free FA in disease development.
Current Drug Metabolism 06/2012; · 5.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Folates act as essential coenzymes in many biological pathways, including the synthesis and methylation of DNA. Low folate concentration in serum and whole blood (WB) is associated with several disease conditions. We describe a stable-isotope-dilution ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantification of (6S)-5-CH(3)-H(4)folate (where H(4)folate is tetrahydrofolate) and non-CH(3)-H(4)folate [sum of HCO-H(4)folate, (6R)-5,10-CH(+)-H(4)folate, (6R)-5,10-CH(2)-H(4)folate, (6S)-H(4)folate, dihydrofolate, and folic acid] in WB. The assay includes a solid-phase extraction procedure after the hemolysis and deconjugation. The method was linear over the concentration range from 0.2 to 200 nmol/L. The limits of detection were 0.40 nmol/L or lower for the folate forms. The interassay coefficients of variation were 7.4% for (6S)-5-CH(3)-H(4)folate and 15.4% for non-CH(3)-H(4)folate. For the folate forms, the recoveries were between 97.1% and 102.7%. Sample preparation caused the generation of artificial folic acid in WB and serum in a dose-dependent manner, which can lead to misinterpretation of the results. The use of antioxidants could not prevent the formation of folic acid. The median fasting WB folate concentrations from 42 nonsupplemented and nonfortified adults were 576 nmol/L (6S)-5-CH(3)-H(4)folate and 73.6 nmol/L non-CH(3)-H(4)folate, and 1,206 nmol/L (6S)-5-CH(3)-H(4)folate and 155 nmol/L non-CH(3)-H(4)folate for 35 adults who had taken 500 μg of folic acid, 50 mg of vitamin B(6), and 500 μg of vitamin B(12) per day orally for 6 months. In conclusion, the UPLC-MS/MS method is fast and has a good sensitivity and selectivity for WB folates. We observed a dose-dependent oxidation of (6S)-H(4)folate, which resulted in the formation of artificial folic acid in serum and WB. To minimize this effect, we recommend a fast sample preparation.
Analytical and Bioanalytical Chemistry 06/2012; 404(3):895-902. · 3.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Disturbed copper (Cu) homeostasis may be associated with the pathological processes in Alzheimer’s disease (AD). In the present
report, we evaluated the efficacy of oral Cu supplementation in the treatment of AD in a prospective, randomized, double-blind,
placebo-controlled phase 2 clinical trial in patients with mild AD for 12months. Sixty-eight subjects were randomized. The
treatment was well-tolerated. There were however no significant differences in primary outcome measures (Alzheimer’s Disease
Assessment Scale, Cognitive subscale, Mini Mental Status Examination) between the verum [Cu-(II)-orotate-dihydrate; 8mg Cu
daily] and the placebo group. Despite a number of findings supporting the hypothesis of environmental Cu modulating AD, our
results demonstrate that oral Cu intake has neither a detrimental nor a promoting effect on the progression of AD.
Acta Neurovegetativa 04/2012; 115(8):1181-1187. · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: We investigated the roles of age, vitamin B(12) markers, and the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism as determinants of folate forms in serum. METHODS: We measured the serum concentrations of (6S)-5-CH(3)-H(4)folate, (6S)-H(4)folate, (6S)-5-HCO-H(4)folate, (6R)-5,10-CH(+)-H(4)folate, and folic acid in 146 non-supplemented older participants (median age 74 years). The concentrations of total vitamin B(12), holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) were also measured. RESULTS: Elevated metabolites (MMA > 271 nmol/L and tHcy > 12.0 μmol/L) were found in 24.0 and 63.0 % of the participants, respectively. We found a significant age-dependent decrease (participants with a median age of 87 years compared with participants with a median age of 60 years) in the sum of serum folate levels, the (6S)-5-CH(3)-H(4)folate concentration, and the (6S)-5-CH(3)-H(4)folate proportion. In addition, participants with elevated metabolite levels were older, had lower concentrations of the sum of folates and (6S)-5-CH(3)-H(4)folate, and had higher concentrations of (6S)-5-CHO-H(4)folate and creatinine but had a comparable holoTC/total vitamin B(12) ratio. No association was found between the MTHFR C677T genotype and serum folate forms. CONCLUSION: Low serum (6S)-5-CH(3)-H(4)folate concentrations and the proportion of (6S)-5-CH(3)-H(4)folate (percentage of the sum of folate forms) are related to older age and elevated MMA and tHcy levels.
European Journal of Nutrition 04/2012; · 2.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor for neurodegenerative diseases an early diagnosis of a low B12 status is required which should be followed by an effective treatment in order to prevent irreversible damages.
Sub-cellular biochemistry 01/2012; 56:301-22.
-
[show abstract]
[hide abstract]
ABSTRACT: Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is required for cell growth and functions, and its deficiency causes serious complications. Diabetics and renal patients show high concentrations of Cbl, but metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl might be sequestered in blood and cannot be delivered to the cell. Megalin mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells. Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake. Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin receptor under glycation conditions is also a possible mechanism of this phenomenon.
Medical Hypotheses 08/2011; 77(5):884-8. · 1.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Trefoil factors (TFF1-3) are cysteine-rich peptides secreted by mucosal surfaces. Changing levels of expression are reflected in serum concentrations. Serum levels of TFF2 and TFF3 are highly elevated during pregnancy. Here, we explore a possible foetal origin of these increased levels.
We examined the expression of trefoil peptides in foetal tissues, placentas and foetal membranes from midterm abortions by immunohistochemistry. Employing in-house ELISAs, serum concentrations of TFF1-3 were measured in 92 paired samples of cord and maternal blood prior to delivery. Size exclusion chromatography was used to investigate the molecular forms of TFF1-3.
Immunohistochemistry showed all trefoil peptides to be present during foetal life, but compared to adults with a more widespread expression of TFF2 and TFF3 in the stomach and Brunner's glands. No trefoil peptides were seen in placentas or foetal membranes. Median serum concentrations of TFF1 in cord blood were comparable to those observed in the (mother) [0·42 (0·37) nM, P = 0·25], whereas TFF2 and TFF3 showed lower values than in the mother [0·11 (0·69), and 1·2 (6·7) nM, respectively, P < 0·0001 for both peptides]. Size exclusion chromatography showed comparable patterns in mothers and newborns.
All three trefoil peptides are expressed in foetal tissues but not in placenta or foetal membranes. Cord blood contains high levels of all three peptides, although for TFF2 and TFF3 at considerably lower levels than observed in the mother. Thus, the elevated serum levels of TFF2 and TFF3 in the pregnant women were most likely not of foetal origin.
European Journal of Clinical Investigation 07/2011; 41(7):785-92. · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We describe a fast and robust ultra performance liquid chromatography tandem mass spectrometry method for the quantification of phospholipid (PL) species in EDTA-plasma samples. We quantified total phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), and sphingomyelin (SM) and several species within these classes using one or two external calibrators and one internal standard for each class. Inter-assay coefficients of variation were <10% for the most abundant species and <20% for all quantified PC, LPC, and SM species and the three most abundant PE species. Coefficients of linear regression were R(2) > 0.98. Mean recoveries were between 83% and 123%. The limits of detection were 0.37 μmol/L for PC, 4.02 μmol/L for LPC, 3.75 μmol/L for PE, and 0.86 μmol/L for SM. Quantification was linear over the physiological ranges for PE, LPC, and SM and up to 500 μmol/L for PC. The concentrations of PLs in the plasma of healthy donors yielded results that were comparable with those of previous works.
Analytical and Bioanalytical Chemistry 06/2011; 401(3):891-9. · 3.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Protein phosphatase PP2A dephosphorylates phosphorylated tau (P-tau) and neurofilaments (pNFs). PP2A is S-adenosylmethionine (SAM)-dependent and might thus link methylation with neurodegeneration. Low SAM and increased S-adenosylhomocysteine (SAH) can enhance the risk of dementia. We studied the effect of hyperhomocysteinemia on P-tau (Ser396), pNF-H (heavy chain), and PP2A-activity and level (the C subunit) in rat brain. Wistar rats (total n=55) were fed either on a standard, a homocystine 1.7% or a methionine 2.4%-rich diet for 5 months. P-tau was tested in 21 frontal cortex tissue slices using immuno-fluorescence. Concentrations of pNF-H and the activity and level of PP2A were measured in brain extracts. Concentrations of homocysteine, SAM and SAH strongly increased in plasma of rats on the modified diets. The diets caused lowering of plasma folate and vitamin B12 and a significant increase in P-tau (Ser396) in brain tissues but PP2A activity and level were unchanged. Plasma folate correlated to brain tissue PP2A activity (r=0.28), pNF-H (r=-0.30), and P-tau (Ser396) staining (r=-0.57) all p<0.05. Phosphorylation of brain functional proteins was related to folate. The effect of the diet on P-tau and pNF-H seemed not to be explained by a lower activity or protein level of PP2A. Folate might prove protective against multiple steps in the process of neurodegeneration.
Journal of Neurochemistry 06/2011; 117(6):1047-54. · 4.06 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Folate deficiency can cause age-related disease. Folic acid (FA) has been used in studies aiming at disease prevention. Recently, unmetabolized FA in plasma raised public health concerns; but numerous studies used FA for disease prevention. Concentrations of the folate forms FA, 5-methyltetrahydrofolate (5-MTHF), and tetrahydrofolate (THF) were measured before and after 3-week placebo or FA 5 mg, vitamin B6 40 mg, and cyanocobalamin 2 mg per day administrated to 74 older adults (median age, 82 years). Concentrations of 5-MTHF and total homocysteine (tHcy) (r = -0.392) and S-adenosylmethionine (r = 0.329) were correlated at baseline. Twenty-six percent of the elderly subjects had unmetabolized FA in plasma at the start, and concentrations of FA were increased after 3 weeks of FA treatment (median FA = 0.08 nmol/L at baseline and 15.3 nmol/L at the end of the treatment in the vitamin group). Folic acid caused a 10- and a 5-fold increase in 5-MTHF and THF, respectively, and lowered tHcy (median tHcy = 17.2 μmol/L at baseline vs 9.0 μmol/L after treatment). Concentrations of unmetabolized FA were positively related to those of 5-MTHF and THF. People showed wide variations in folate forms at baseline, but these were reduced after FA treatment. Folic acid given to older adults is mostly converted to THF and 5-MTHF and lowered concentrations of tHcy, but caused a substantial increase in unmetabolized FA in the plasma.
Metabolism: clinical and experimental 05/2011; 60(5):673-80. · 2.59 Impact Factor
-
Joerg H Holstein,
Markus Herrmann,
Christina Splett, Wolfgang Herrmann,
Patric Garcia,
Tina Histing,
Moritz Klein,
Karsten Kurz,
Thomas Siebel,
Tim Pohlemann,
Michael D Menger
[show abstract]
[hide abstract]
ABSTRACT: Accumulation of homocysteine and S-adenosylhomocysteine in bone has been shown to be associated with reduced bone quality in rats. The aim of the present study was to investigate whether high bone concentrations of homocysteine and S-adenosylhomocysteine as well as a low methylation capacity are related to an impaired bone morphology in humans. Concentrations of homocysteine and its precursors S-adenosylhomocysteine and S-adenosylmethionine were measured in femoral bone samples of eighty-two males and females (age 71 (SD 8) years) who underwent elective hip arthroplasty. Cancellous bone structure was analysed by histomorphometry. In addition, blood was sampled to measure serum concentrations of homocysteine. Results of bone and serum analyses were grouped for individuals with high or low bone concentrations of homocysteine, S-adenosylhomocysteine and S-adenosylmethionine, as well as for individuals with a high or a low methylation capacity, which is indicated by a low or a high S-adenosylhomocysteine:S-adenosylmethionine ratio (n 41, each). Histomorphometry showed a higher trabecular separation and a lower trabecular thickness, trabecular number and trabecular area in individuals with high bone concentrations of homocysteine and S-adenosylhomocysteine compared with individuals with low bone concentrations of homocysteine and S-adenosylhomocysteine. There was no association between the S-adenosylhomocysteine:S-adenosylmethionine ratio and bone morphology. It was found that 48 % of bone homocysteine was bound to the collagen of the extracellular bone matrix. Blood analyses demonstrated a significant correlation between serum and bone homocysteine. The results of the present study indicate an association between altered bone morphology and elevated bone concentrations of homocysteine and S-adenosylhomocysteine, but not between altered bone morphology and methylation capacity.
The British journal of nutrition 04/2011; 106(3):378-82. · 3.45 Impact Factor
