Enhanced bone metabolism in vegetarians--the role of vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency and bone fractures are common in vegetarians. However, a direct relationship between vitamin B12 status and bone metabolism in vegetarians has not been tested sufficiently. METHODS: Our study included 96 vegetarians (23 German vegans, and 54 German and 19 Indian lacto-, lacto-ovo-vegetarians) and 89 omnivores (Germans and Asian-Indian immigrants in Oman). Blood concentrations of total vitamin B12, holotranscobalamin (holoTC), 25OH-vitamin D (25(OH)D), total homocysteine (tHcy), methylmalonic acid (MMA), and the bone turnover markers (BTMs) bone alkaline phosphatase (BAP), osteocalcin (OC), pro-collagen type I N-terminal peptide (PINP) and C-terminal telopeptides of collagen I (CTx) were measured. RESULTS: Vegetarians from both population groups exhibited significantly higher concentrations of tHcy, MMA, folate, and BAP, but lower concentrations of holoTC and cobalamin compared with omnivores from the same population. Additionally, German vegetarians had higher circulating activities of BAP as well as higher CTx, OC, and PINP compared with their omnivorous controls. HoloTC and MMA were correlated with OC, CTx and BAP. Subjects with low vitamin B12 status (holoTC < or =35 pmol/L and MMA >271 nmol/L) had significantly lower serum concentrations of 25(OH)D, but higher tHcy and the BTMs P1NP, BAP, OC, and CTx, compared with subjects with normal vitamin B12 status. Multiple regression analysis showed that the association between BTMs and markers of vitamin B12 status was independent from the association with 25(OH)D. Approximately 12%-14% of the variation in the concentration of BTMs was explained by a regression model including holoTC, MMA and 25(OH)D. The strictness of the diet was not related to the magnitude of change in BTMs. CONCLUSIONS: Low vitamin B12 status is related to increased bone turnover in vegetarians which is independent from vitamin D status.

The cardiac effects of prolonged vitamin B12 and folate deficiency in rats.

In the recent past, hyperhomocysteinemia (HHCY) has been linked to chronic heart failure. Folate and vitamin B12 deficiencies are the common causes of HHCY. The impact of these vitamins on cardiac function and morphology has scarcely been investigated. The aim of this study was to conduct an analysis of the cardiac effect of folate and vitamin B12 deficiency in vivo. Two groups of rats, a control (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10), were fed for 12 weeks with a folate and vitamin B12-free diet or an equicaloric control diet. Plasma and tissue concentrations of HCY, S-adenosyl-homocysteine (SAH), S-adenosyl-methionine (SAM), and brain natriuretic peptide (BNP) were measured. Moreover, echocardiographic and histomorphometric analyses were performed. VitDef animals developed a significant HHCY (Co vs VitDef: 6.8 +/- 2.7 vs 61.1 +/- 12.8 micromol/l, P < 0.001). Fractional shortening, left ventricular dimension at end-diastole and end-systole, posterior wall thickness, perivascular collagen, mast cell number, and BNP tissue levels were comparable in VitDef and Co animals. Interstitial collagen (Co vs VitDef: 6.8 +/- 3.0 vs 4.5 +/- 2.1%, P < 0.05), plasma BNP (Co vs VitDef: 180 +/- 80 vs 70 +/- 60 ng/l, P < 0.05), and tissue HCY (Co vs VitDef: 0.13 +/- 0.07 vs 0.07 +/- 0.04 micromol/g protein, P < 0.05) were lower in VitDef animals. Folate and vitamin B12 deficiency do not affect cardiac function and morphology.

Rapamycin, but not cyclosporine A, inhibits vascularization and incorporation of implanted surgical meshes.

Incisional hernias are a frequent complication of upper abdominal wall interventions, especially in patients undergoing liver transplantation with subsequent immunosuppressive therapy. Therefore, we analyzed in this study the manner in which the incorporation of a surgical mesh for hernia repair is affected by the immunosuppressant drugs rapamycin and cyclosporine A (CsA). For this purpose, Ultrapro meshes were implanted into the dorsal skinfold chambers of rapamycin- and CsA-treated hamsters. Untreated animals served as controls. The angiogenic and inflammatory host tissue response to the mesh implants was then analyzed over a 14-day period by means of intravital fluorescence microscopy. Mesh incorporation was determined by histology and measurement of explantation strength. Rapamycin dose-dependently inhibited vascularization of implanted meshes, as indicated by a significantly reduced number of angiogenesis-positive regions of interest and microvessel density, when compared with CsA-treated hamsters and controls. In addition, the granulation tissue surrounding the meshes of rapamycin-treated animals exhibited only a low collagen content, resulting in an impaired mesh incorporation with a significantly reduced explantation strength. Leukocyte-endothelial cell interaction did not show marked differences between the observation groups. Thus, immunosuppressed patients should not be treated with rapamycin in case of incisional hernia repair in order to guarantee adequate mesh incorporation.

Experimental folate and vitamin B12 deficiency does not alter bone quality in rats.

Hyperhomocysteinemia (HHCY) has been linked to fragility fractures and osteoporosis. Folate and vitamin B(12) deficiencies are among the main causes of HHCY. However, the impact of these vitamins on bone health has been poorly studied. This study analyzed the effect of folate and vitamin B(12) deficiency on bone in rats. We used two groups of rats: a control group (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10). VitDef animals were fed for 12 wk with a folate- and vitamin B(12)-free diet. Co animals received an equicaloric control diet. Tissue and plasma concentrations of homocysteine (HCY), S-adenosyl-homocysteine (SAH), and S-adenosyl-methionine (SAM) were measured. Bone quality was assessed by biomechanical testing (maximum force of an axial compression test; F(max)), histomorphometry (bone area/total area; B.Ar./T.Ar.], and the measurement of biochemical bone turnover markers (osteocalcin, collagen I C-terminal cross-laps [CTX]). VitDef animals developed significant HHCY (Co versus VitDef: 6.8 +/- 2.7 versus 61.1 +/- 12.8 microM, p < 0.001) that was accompanied by a high plasma concentration of SAH (Co versus VitDef: 24.1 +/- 5.9 versus 86.4 +/- 44.3 nM, p < 0.001). However, bone tissue concentrations of HCY, SAH, and SAM were similar in the two groups. Fmax, B.Ar./T.Ar., OC, and CTX did not differ between VitDef and Co animals, indicating that bone quality was not affected. Folate and vitamin B(12) deficiency induces distinct HHCY but has no effect on bone health in otherwise healthy adult rats. The unchanged HCY metabolism in bone is the most probable explanation for the missing effect of the vitamin-free diet on bone.

Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone.

BACKGROUND: Recently, hyperhomocysteinemia (HHCY) has been suggested to have adverse effects on bone. This study investigated if an experimental HHCY in rats induces an accumulation of homocysteine (HCY) in bone tissue that is accompanied by bone loss and reduced bone strength. MATERIAL AND METHODS: HHCY was induced in healthy rats by either a methionine (Meth)- or a homocystine (Homo)-enriched diet and compared with controls. Homocystine is the product of two disulfide linked HCY molecules. Tissue and plasma concentrations of HCY, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were measured. Bones were assessed by biomechanical testing, histomorphometry, microCT and the measurement of biochemical bone turnover markers in plasma. RESULTS: Meth and Homo animals developed a significant HHCY that was accompanied by a tissue specific accumulation of HCY (1300 to 2000% vs. controls). 65% of HCY in bone was bound to collagen of the extracellular matrix. The SAH / SAM-ratio in bone and plasma of Meth and Homo animals exhibited a tissue specific increase indicating a reduced methylation capacity. Accumulation of HCY in bone was characterized by a distinct reduction of cancellous bone (proximal femur: -25 to -35%; distal femur -56 to -58%, proximal tibia: -28 to -43%). Accordingly, bone strength was significantly reduced (-9 to -12%). CONCLUSION: A tissue specific accumulation of HCY in bone may be a promising mechanism explaining adverse effects of HHCY on bone. A reduced methylation capacity of bone cells might be another relevant pathomechanism.

Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women.

BACKGROUND: Hyperhomocysteinemia and B-vitamin deficiency are associated with recurrent abortion. Recent studies have not investigated functional markers of vitamin B12 deficiency, such as methylmalonic acid. METHODS: A total of 43 consecutive Syrian women with unexplained recurrent abortion and 32 pregnant controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic acid and plasma homocysteine were determined. RESULTS: Vitamin B12 was significantly decreased in patients with recurrent abortion compared to controls (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in aborters in comparison to controls (8.3 vs. 7.1 micromol/L, p=0.093). Folate and methylmalonic acid did not differ significantly between the study groups. A highly significant correlation between homocysteine and methylmalonic acid and vitamin B12 was observed only in patients but not in controls (p<0.001 and p=0.002, respectively). In the logistic regression model, only serum vitamin B12 emerged with a significant odds ratio. CONCLUSIONS: The results confirm low serum vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not support that functional vitamin B12 plays a role in this group. This unexpected result might be due to a decrease of the metabolically inert vitamin B12 fraction (holohaptocorrin) or confounding factors. Further studies are necessary to investigate the role of vitamin B12 deficiency in recurrent abortion.

Decreased p66Shc promoter methylation in patients with end-stage renal disease.

BACKGROUND: p66Shc is a stress response protein and partially regulated by epigenetic modifications. Mice lacking p66Shc have reduced atherosclerosis, increased resistance to oxidative stress and a prolonged life time. The aim of the present study was to compare promoter methylation of the p66Shc gene between healthy controls and patients with end-stage renal disease (ESRD). There are two reasons for studying patients with ESRD. First, patients with ESRD have a disturbed homocysteine metabolism, and second an increased risk of morbidity and mortality from cardiovascular disease is a constant finding in these patients. METHODS: In our study, we measured fasting levels of homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 8-isoprostane in 22 patients and in 26 healthy, age- and sex-matched controls. The methylation of the p66Shc promoter and Line-1, as surrogate marker of whole genome methylation was quantified in peripheral blood mononuclear cells. RESULTS: In comparison to the control group, homocysteine, SAM, SAH, 8-isoprostane and whole genome methylation were significantly elevated in ESRD patients, while the p66Shc promoter methylation was significantly reduced. A significant correlation was found between SAH and p66Shc promoter methylation in the patient group. This observation underlines the role of SAH as a potent inhibitor of methyltransferases. Using backward regression analysis, we demonstrated that 8-isoprostane has a significant influence on p66Shc promoter methylation. In the control group and in patients with ESRD, increasing 8-isoprostane levels were linked to an elevated promoter methylation. CONCLUSIONS: Under physiological conditions, based on the results of the control group, the p66Shc expression is more silenced through epigenetic modifications. The atherosclerotic risk is dramatically increased in ESRD patients; therefore, our experimental results of methylation are in accordance with the clinical situation.

The vegetarian lifestyle and DNA methylation.

Vegetarians have a lower intake of vitamin B12 than omnivores do. Vitamin B12 deficiency (holotranscobalamin II <35 pmol/L or methylmalonic acid >271 nmol/L) was found in 58% of 71 vegetarians studied. Higher homocysteine levels (>12 micromol/L) found in 45% indicate disturbed remethylation of homocysteine to methionine. The methylation of DNA is strongly linked to homocysteine metabolism. Since DNA methylation is an important epigenetic factor in the regulation of gene expression, alteration of the methylation pattern has been associated with aging, cancer, atherosclerosis and other diseases. Three observations indicate that DNA methylation could be diminished by a vegetarian lifestyle. The vegetarian diet has a low content of methionine, remethylation of homocysteine is reduced by vitamin B12 deficiency and elevated homocysteine levels can induce the generation of S-adenosylhomocysteine (SAH), a potent inhibitor of methyltransferases. In our study we observed a significant correlation between SAH and whole-genome methylation (r=-0.36, p<0.01). This observation underlines the role of SAH as a potent inhibitor of methyltransferases. The methylation status was not correlated with homocysteine or S-adenosylemethionine (SAM). These results indicate that the degree of methylation does not depend on the supply of methyl groups and that the reverse generation of SAH has no influence. In addition to whole-genome methylation, the specific promoter methylation of the p66Shc gene was studied. However, the latter did not correlate with SAH, SAM or homocysteine. Obviously, the promoter methylation of the p66Shc gene is controlled in a specific way, without following the general regulating influence of SAH. In conclusion, an inhibitory effect of SAH on whole-genome methylation was found, but from our data no interaction between vegetarian lifestyle and DNA methylation could be determined.

Disturbed homocysteine and methionine cycle intermediates S-adenosylhomocysteine and S-adenosylmethionine are related to degree of renal insufficiency in type 2 diabetes.

BACKGROUND: Diabetic nephropathy is a common complication in patients with type 2 diabetes that may increase atherothrombotic risk. Hyperhomocysteinemia (HHcy) further increases the risk in those patients. We studied concentrations of total homocysteine (tHcy) and its related metabolites S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) in relation to B-vitamin status and renal function in patients with type 2 diabetes who developed diabetic nephropathy. METHODS: The study included 93 patients with renal failure and type 2 diabetes. Chronic kidney disease was classified into four subgroups according to the National Kidney Foundation based on glomerular filtration rate plus pathologic abnormalities or markers of kidney damage. RESULTS: Serum or plasma concentrations of the metabolites increased significantly with worsening of renal function, whereas serum concentrations of the B vitamins (folate, vitamins B12 and B6) did not differ appreciably between the groups. Moreover, plasma concentrations of AdoHcy and AdoMet were markedly increased in patients with kidney failure compared with those in stage 2 (median AdoHcy, 112.7 vs 10.5 nmol/L; median AdoMet, 162.0 vs 80.0 nmol/L). The AdoMet/AdoHcy ratio was more than 80% lower in patients with renal failure compared with stage 2. Vitamin B12 was a significant determinant of concentrations of AdoMet, tHcy, methylmalonic acid (MMA), and cystathionine. CONCLUSIONS: Increased plasma concentrations of tHcy and methionine cycle intermediates (AdoMet, AdoHcy) are related to disturbed renal function in patients with type 2 diabetes. Vitamin B12 and/or folate are significant predictors of tHcy, cystathionine, MMA, and AdoMet. The effect of therapeutic doses of the B vitamins on AdoMet, AdoHcy, and their ratio should be tested in renal patients.

The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings.

Serum concentrations of homocysteine (Hcy) and methylmalonic acid (MMA) become increased in B12-deficient subjects and are therefore, considered specific markers of B12 deficiency. Serum level of holotranscobalamin (holoTC) becomes decreased before the development of the metabolic dysfunction. We investigated the usefulness of holoTC in diagnosing B12 deficiency in some clinical settings. We measured serum concentrations of holoTC, MMA, Hcy and total B12 in omnivores, vegetarians, elderly people and haemodialysis patients. Our results indicated that the incidence of holoTC <35 pmol/L was highest in the vegans (76%). Low holoTC and elevated MMA were detected in 64% of the vegans and 43% of the lacto- and lacto-ovovegetarians. An elevated MMA and a low holoTC were found in subjects with total serum B12 as high as 300 pmol/L. The distribution of holoTC in elderly people was similar to that in younger adults (median holoTC 55 pmol/L in both groups). A low holoTC and an elevated MMA were found in 16% of the elderly group. An elevated MMA and a normal holoTC were found in 20% of the elderly group who had a relatively high median serum concentration of creatinine (106.1 micromol/L). Serum concentrations of holoTC in dialysis patients were considerably higher than all other groups (median 100 pmol/L). This was also associated with severely increased serum levels of MMA (median 987 nmol/L). From these results it can be concluded that serum concentration of holoTC is a much better predictor of B12 status than total B12. This was particularly evident in case of dietary B12 deficiency. Serum concentrations of holoTC as well as MMA can be affected by renal dysfunction. Elevated MMA and normal holoTC in patients with renal insufficiency may not exclude vitamin B12 deficiency. HoloTC seems not to be a promising marker in predicting B12 status in renal patients.

The role of genetic factors in the development of hyperhomocysteinemia.

Moderate hyperhomocysteinemia has been identified as a new independent risk factor for cardiovascular and neurodegenerative diseases. This fact has produced interest in the study of genetic variants involved in homocysteine metabolism and its relationship to pathogenesis. Recently, more than 15 different genes were studied for their relationship to plasma homocysteine levels. We determined the influence of genetic variants in five genes (5,10-methylenetetrahydrofolate reductase (MTHFR) 677C --> T, serine hydroxymethyltransferase (SHMT) 1420C --> T, thymidylate synthase (TS) 2R --> 3R, catechol-O-methyltransferase (COMT) 1947G --> A and transcobalamin (TC) 776C --> G) on plasma homocysteine, folic acid and parameters of vitamin B12 metabolism in 111 vegetarians (mean age: 46 +/- 15 years) and 118 healthy seniors (mean age: 82 +/- 6.5 years). Median homocysteine concentration in plasma was significantly influenced by the MTHFR genotypes in both populations. In the vegetarians the median homocysteine level was increased by 8 micromol/l in individuals homozygous for the mutation as compared to wild-type or heterozygous genotypes (20.4 micromol/l vs. 12.9 and 12.7 micromol/l, respectively). This unexpected increase was observed although the folate levels were in medium to elevated ranges. Our results suggest that vegetarians have a higher demand for folate to neutralize the genotype effect. Preclinical vitamin B12 deficiency in vegetarians may be the cause for disturbed remethylation and folate trap. Plasma homocysteine was not significantly influenced by the SHMT, TS, COMT and TC mutations. In addition, for the TC mutation a trend toward cellular vitamin B12 deficiency was observed. The methylmalonic acid (MMA) levels were slightly elevated and the holotranscobalamin-II (holoTC-II) levels decreased. In the vegetarian group a significant relationship between the COMT genotype and holoTC-II concentration in plasma was determined, whereas the high activity COMT genotype (G/G) resulted in increased levels (35 micromol/l vs. 21 micromol/l for heterozygous and low activity genotypes). The MMA levels were inversely correlated to holoTC-II concentrations. In conclusion, the study on vegetarians and seniors documents interesting lifestyle-genotype interactions. Although the TC and COMT mutations influence cellular vitamin B12 metabolism, this effect did not result in overt homocysteine elevation.

Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk.

BACKGROUND: The prevalence of a sub-clinical functional vitamin B12 deficiency in the general population is higher than previously expected. Total serum vitamin B12 may not reliably indicate vitamin B12 status. To get more specificity and sensitivity in diagnosing vitamin B12 deficiency, the concept of measuring holotranscobalamin II (holoTC), a sub-fraction of vitamin B12, has aroused great interest. HoloTC as a biologically active vitamin B12 fraction promotes a specific uptake of its vitamin B12 by all cells. In this study we investigated the diagnostic value of storage (holoTC) of vitamin B12 and functional markers (methylmalonic acid (MMA)) of vitamin B12 metabolism in populations who are at risk of vitamin B12 deficiency. SUBJECTS AND METHODS: Our study included 93 omnivorous German controls, 111 German and Dutch vegetarian subjects, 122 Syrian apparently healthy subjects, 127 elderly Germans and finally 92 German pre-dialysis renal patients. Serum concentrations of homocysteine (Hcy) and MMA were measured by gas chromatography-mass spectrometry, folate and vitamin B12 by chemiluminescence immunoassay, and holoTC by utilizing a RIA test. RESULTS: High Hcy (>12 micromol/l), high MMA (>271 nmol/l) resp. low holoTC (vitamin B12) in serum were detected in 15%, 8% resp. 13% (1%) of German controls, 36%, 60%, resp. 72% (30%) of vegetarians, 42%, 48% resp. 50% (6%) of Syrians, 75%, 42%, resp. 21% (7%) of elderly subjects and 75%, 67% resp. 4% (2%) of renal patients. The lowest median levels of holoTC were observed in vegetarians, followed by the Syrian subjects (23 and 35 pmol/l, respectively). Renal patients had significantly higher levels of holoTC compared to the German controls (74 vs. 54 pmol/l). In the vitamin B12 range between 156 pmol/l (conventional cut-off level) and 241 pmol/l, both mean concentrations of holoTC and MMA were in the pathological range. HoloTC was the earliest marker for vitamin B12 deficiency followed by MMA. Vitamin B12 deficiency causes folate trapping. A higher folate level is required to keep Hcy normal. The relationship between MMA and holoTC seemed dependent on renal function. In renal patients with a glomerular filtration rate below 36 ml/min, a significantly lower mean level of MMA was detected within the highest tertile of holoTC concentration, compared to the lowest tertile. Thus, in renal patients, a higher serum concentration of circulating holoTC is required to deliver sufficient amounts of holoTC into the cells. CONCLUSION: Our data support the concept that the measurement of holoTC and MMA provides a better index of cobalamin status than the measurement of total vitamin B12. HoloTC is the most sensitive marker, followed by MMA. The use of holoTC and MMA enables us to differentiate between storage depletion and functional vitamin B12 deficiency. Renal patients have a higher requirement of circulating holoTC. In renal dysfunction, holoTC cannot be used as a marker of vitamin B12 status.

Homocysteine increases during endurance exercise.

Hyperhomocysteinemia is a risk factor for cardiovascular and other diseases. Recently many endogenous and exogenous modulators of homocysteine (Hcy) have become known, e.g., B-vitamins. However, little is known about the effect of exercise on Hcy. The purpose of this study was to investigate the effect of three different types of acute endurance exercise on serum Hcy. We measured Hcy in 100 recreational athletes (87 males, 13 females) who participated in a marathon race (n = 46), a 100 km run (100 km; n = 12) or a 120 km mountain bike race (n = 42). Blood samples were taken before, 15 min and 3 h after the race. In athletes with pre-race Hcy > 12 micromol/l we also determined folate and vitamin B12. Marathon running induced a Hcy increase of 64%, while mountain biking and 100 km running had no significant effect on Hcy. Pre-race Hcy (25th-75th percentile) overall; marathon race; 100 km; mountain bike race was 9.7 (7.1-11.5) micromol/l; 9.8 (7.4-11.1) micromol/l; 10.2 (6.6-13.2) micromol/l; 9.1 (6.9-13.5) micromol/l, respectively. At 15 min and 3 h post-race, Hcy was 11.9 (8.4-16.4) micromol/l; 16.1 (12.7-20.4) micromol/l; 9.5 (7.8-15.9) micromol/l; 8.8 (7.1-11.2) micromol/l, respectively, and 11.5 (8.9-15.7) micromol/l; 14.9 (11.5-20.0) micromol/l; 10.0 (8.1-11.8) micromol/l; 9.4 (7.4-12.1) micromol/l, respectively. The change in Hcy correlated negatively with the running time. Twenty-three athletes had pre-race Hcy levels > 12 micromol/l, which were associated with relatively low folate (14.3 (11.6-18.9) nmol/l) and vitamin B12 levels (231 (183-261) pmol/l). Endurance exercise may induce a considerable Hcy increase, which varies between different disciplines and is most probably determined by the duration and intensity of exercise. Furthermore, about 25% of recreational endurance athletes exhibited hyperhomocysteinemia in association with low vitamin B12 and folate levels.

Comparison of the influence of volume-oriented training and high-intensity interval training on serum homocysteine and its cofactors in young, healthy swimmers.

BACKGROUND: Since homocysteine (Hcy) is a risk factor for cardiovascular and other diseases, it is important to know how exercise can modify it. Previous studies have suggested that endurance training influences Hcy. However, little is known about the effect of training intensity on Hcy. MATERIALS AND METHODS: We investigated Hcy, vitamin B12, vitamin B6, folate and methylmalonic acid (MMA) before and after 3 weeks of volume-oriented training (VOL) (30 km/week) and high-intensity interval training (HIT) (20 km/week) in 20 young swimmers (16 +/- 2 years). Afterward, the athletes completed 5 days of recovery training. RESULTS: The training induced a Hcy increase in HIT and VOL (6.47 +/- 0.95 micromol/l vs. 7.44 +/- 1.17 micromol/l and 7.33 +/- 1.92 micromol/l vs. 8.28 +/- 1.42 micromol/l, respectively) that persisted during the recovery period (8.02 +/- 1.69 micromol/l and 8.00 +/- 1.81 micromol/l, respectively). Vitamin B12 was unchanged after the training (539 +/- 166 ng/l vs. 556 +/- 192 ng/l and 480 +/- 144 ng/l vs. 491 +/- 124 ng/l, respectively) but decreased during the recovery period (459 +/- 134 ng/l and 451 +/- 116 ng/l, respectively). Folate showed an increase during the training (9.07 +/- 2.01 microg/l vs. 11.71 +/- 4.08 microg/l and 10.34 +/- 2.32 microg/l vs. 11.13 +/- 4.64 microg/l, respectively), which was reversible by the end of the recovery training (8.57 +/- 1.98 microg/l and 9.60 +/- 2.38 microg/l, respectively). Vitamin B6 and MMA did not change. For none of the measured parameters were there significant differences between HIT and VOL. CONCLUSION: Three weeks of strenuous swimming caused a prolonged Hcy increase, which was accompanied by changes in vitamin B12 and folate. The magnitude of these effects was not influenced by the training intensity.

Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians.

BACKGROUND: Vegetarians have a lower intake of vitamin B-12 than do omnivores. Early and reliable diagnosis of vitamin B-12 deficiency is very important. OBJECTIVE: The objective was to investigate vitamin B-12 status in vegetarians and nonvegetarians. DESIGN: The study cohort included 66 lactovegetarians or lactoovovegetarians (LV-LOV group), 29 vegans, and 79 omnivores. Total vitamin B-12, methylmalonic acid, holotranscobalamin II, and total homocysteine concentrations were assayed in serum. RESULTS: Of the 3 groups, the vegans had the lowest vitamin B-12 status. In subjects who did not consume vitamins, low holotranscobalamin II (< 35 pmol/L) was found in 11% of the omnivores, 77% of the LV-LOV group, and 92% of the vegans. Elevated methylmalonic acid (> 271 nmol/L) was found in 5% of the omnivores, 68% of the LV-LOV group, and 83% of the vegans. Hyperhomocysteinemia (> 12 micromol/L) was present in 16% of the omnivores, 38% of the LV-LOV group, and 67% of the vegans. The correlation between holotranscobalamin II and vitamin B-12 was weak in the low serum vitamin B-12 range (r = 0.403) and strong in the high serum vitamin B-12 range (r = 0.769). Holotranscobalamin II concentration was the main determinant of total homocysteine concentration in the vegetarians (beta = -0.237, P < 0.001). Vitamin B-12 deficiency led to hyperhomocysteinemia that was not probable in the upper folate range (> 42.0 nmol/L). CONCLUSIONS: Vegan subjects and, to a lesser degree, subjects in the LV-LOV group had metabolic features indicating vitamin B-12 deficiency that led to a substantial increase in total homocysteine concentrations. Vitamin B-12 status should be monitored in vegetarians. Health aspects of vegetarianism should be considered in the light of possible damaging effects arising from vitamin B-12 deficiency and hyperhomocysteinemia.

Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism and the B-vitamins: a facet of nature-nurture interplay.

BACKGROUND: Methylenetetrahydrofolate reductase 677 (MTHFR 677) polymorphism may provoke hyperhomocysteinemia when folate status is low. The influence of MTHFR 677 mutation on homocysteine (HCY) levels in relation to vitamin B12 and folate status was investigated in the current study. SUBJECTS AND METHODS: 113 vegetarians, 123 omnivorous Germans, and 117 omnivorous Syrians were recruited. MTHFR 677 genotype, HCY, methylmalonic acid (MMA), total serum vitamin B12, serum folate, and vitamin B6 were determined using conventional methods. RESULTS: Omnivorous Germans displayed the lowest HCY levels compared with vegetarians and Syrians (median 8.0, 10.4, and 11.3 micromol/l, respectively). The highest serum folate and the highest MMA levels were found in vegetarians (median folate = 30.0; MMA = 355 nmol/l). Among vegetarians and Syrians, TT subjects had higher HCY levels than other genotypes which were, however, no longer significant in the highest folate tertiles. When the data were pooled, the odds ratio (OR, 95% CI) for HCY > 12 micromol/l was 3.81 (1.55-9.34) in TT compared with CC subjects. The OR increased to 28.85 (4.63-179.62) in TT subjects who had folate in the lowest tertile, and to 21.84 (4.81-99.1) in TT subjects who had MMA in the highest MMA tertile. CONCLUSION: MTHFR 677 TT individuals are more liable to hyperhomocysteinemia under vitamin B12 deficiency than the other two genotypes. In such a case, relative folate shortage may progressively increase HCY levels. TT individuals may have increased folate and vitamin B12 requirements compared to the other CC and CT genotypes.

The impact of vegetarianism on some haematological parameters.

OBJECTIVE: Subjects adopting a vegetarian diet are liable to vitamin B12 and iron deficiencies. Co-existing vitamin B12 and iron deficiencies may give an equivocal haematological picture, which may, in turn, delay making an early diagnosis. The current work was undertaken to investigate some haematological parameters in relation to vitamin B12 and iron status in vegetarians. SUBJECTS AND METHODS: Twenty-nine vegans, 64 lacto- and lacto-ovo-vegetarians, in addition to 20 occasional meat eaters, were enrolled for this study. The total group included 49 males and 64 females aged [mean (SD) = 46(15) yr]. Complete blood count, methylmalonic acid (MMA), homocysteine (HCY), ferritin, and transferrin concentrations and percentage transferrin saturation were assayed, using conventional methods. RESULTS: Vegans displayed the highest MMA and HCY levels (median MMA = 708 nmol L(-1); HCY = 12.8 micromol L(-1)). A lower lymphocyte count and a higher mean corpuscular volume (MCV) were found in vegans compared with lacto- or lacto-ovo-vegetarians (median = 1.51 x 10(9) vs. 1.83 x 10(9) L(-1); 92 vs. 89 fL, respectively). Vitamin B12-deficient subjects in the higher range of transferrin saturation percentage had higher MCV than vitamin B12-deficient subjects in the lower transferrin saturation range (mean MCV = 92 vs. 89 fL). A lower platelet count was found in the highest quartile of MMA (mean = 211 x 10(9) L(-1)) and in the highest quartile of HCY (mean = 215 x 10(9) L(-1)), compared with the other quartiles. Lower lymphocyte and platelet counts and higher MCV were found in subjects with elevated MMA and HCY, compared to those with normal metabolites. Factors that explained the variations in MCV were red blood cell count, ferritin, transferrin saturation, and methylmalonic acid levels. CONCLUSION: vitamin B12 and iron status were compromised by a vegetarian diet. Variations in mean corpuscular volume were determined by iron and vitamin B12 status. Lower lymphocyte and platelet count were accompanied by metabolic evidence that indicated vitamin B12 deficiency.