Folate and homocysteine levels in pregnancy

This study aims to determine serum folate and plasma homocysteine levels in healthy pregnant women following a live birth and compare them with healthy non-pregnant women. Fifty healthy gravid multiparous women are included in the study and 25 normal non-pregnant female subjects act as controls (group I). The pregnant women are divided into two groups according to interpregnancy interval: group II (six months or less); group III (18-24 months). Venous blood samples are analysed for red blood cell folate and homocysteine, vitamin B12, serum folate and albumin, and serum aminotransferases (ALT and AST). There was a significant decrease in red cell folate and serum folate in group II compared to the control group (P<0.001). Serum vitamin B12 showed no significant difference. Plasma homocysteine and serum albumin showed significant decreases in both groups II and III compared to the control group. (P<0.001) There was significant positive correlation between homocysteine and serum albumin in the three studied groups. (r=0.42, P<0.001; r=0.45, P<0.001; r=0.51, P<0.001, respectively). There was significant negative correlation between red cell folate and homocysteine in the three studied groups. (r=-0.48, P<0.001; r=-0.53, P<0.001; r=-0.49, P<0.001, respectively). Two cases in group II showed signs of intrauterine growth retardation. The results suggest that pregnant females with short interpregnancy intervals are more likely to develop folate deficiency. Educational strategies are required to increase folate awareness among women to promote the benefits of folic acid supplementation. Mandatory folate fortification of foods should be defined and monitored.     

Combination of biomarkers to predict mortality in elderly patients with myocardial infarction

OBJECTIVE: The elderly subjects affected by Acute Myocardial Infarction (AMI) have the highest risk of mortality. Our study was designed to improve the capability of mortality risk stratification in elderly AMI patients through the concurrent evaluations of different biomarkers, including genetic markers. METHODS AND RESULTS: One-year follow-up study was performed in 250 elderly AMI patients. The combination of high total Homocysteine (tHcy), low folate and vitamin B12 plasma levels (18.0+/-9.0 micromol/l; 4.4+/-1.2 ng/ml; 404.2+/-287.5 pg/ml, respectively) and elevated CRP plasma levels (> or =6 mg/dl) identify the highest-risk pathway of heart mortality (RR=4.20, IC 95% 1.62-10.89, P<0.002) with respect to the combination of low total tHcy, high folate and vitamin B12 plasma levels (12.4+/-5.2 micromol/l; 8.9+/-2.5 ng/ml; 546.9+/-379.8 pg/ml, respectively) and low CRP plasma levels (<6 mg/dl). CONCLUSION: In elderly AMI patients the concomitant elevation of CRP and tHcy, associated with folate and vitamin B12 low levels, could be considered a significant predictive heart mortality risk factor.     

Vitamin B12, folate, and iron studies in homozygous beta thalassemia

The efficacy of serum folate (SF), red blood cell folate (RCF), and serum B12 in diagnosing folate and B12 deficiency, and the effect of iron overload on hemoglobin, were studied in 157 cases of homozygous beta thalassemia (HBT). The patients had lower SF compared with normal subjects (NS) (P less than 0.001) and higher RCF than their parents (P less than 0.001) and NS (P less than 0.001). Forty percent of patients had both low SF (less than 3 ng/mL) and high RCF (greater than 600 ng/mL). Homozygous beta thalassemia patients are known to have folate deficiency. Yet, both folate and B12 deficiency status were similar in the authors' patients and NS. These deficiencies apparently were less in patients compared with their parents, who shared the same nutritional milieu (P less than 0.001). Mean hemoglobin in patients with iron overload (transferrin saturation, TS greater than 50%) was lower than in those without (P less than 0.005). The following is concluded: (1) diagnosis of folate and B12 deficiency based on SF, RCF and serum B12 is vitiated in HBT and needs a therapeutic trial; (2) iron overload of a magnitude indicated by TS greater than 50% can aggravate anemia in HBT.     

Elevated plasma homocysteine levels in centenarians are not associated with cognitive impairment

BACKGROUND: Previous reports have shown elevated plasma total homocysteine (tHcy) levels in elderly person with impaired cognition. OBJECTIVE: To study the association between cognitive status and plasma tHcy levels in centenarians. DESIGN: Cross-sectional survey. SETTING: Centenarians living in two northern Italian provinces. PARTICIPANTS: Thirteen cognitively normal centenarians, ten cognitively impaired not-demented centenarians, and 34 demented centenarians with a clinical diagnosis of Alzheimer's disease (AD). MEASUREMENTS: Blood levels of homocysteine's biological determinants vitamin B12, folate, and vitamin B6. RESULTS: Elevated plasma tHcy levels (>17 micromol/l) were common in the general population (77% of normal centenarians, 100% of cognitively impaired not-demented centenarians, 82% of AD centenarians). Demented centenarians had the lowest folate serum levels. Low or borderline vitamin B12 serum levels (<221 pmol/l) and low vitamin B6 plasma levels (<11.7 nmol/l) were found in 33 and 66% of all centenarians independently of cognitive status. Among demented centenarians only plasma tHcy correlated inversely with both serum vitamin B12 and folate. No significant difference was found for plasma tHcy levels among the three diagnostic groups, even after adjusting for B vitamin levels. CONCLUSIONS: Hyperhomocysteinemia is very common among centenarians, probably due to vitamin deficiencies, but does not seem to be associated with cognitive impairment.     

Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes

We evaluated the prevalence of vitamin B₁₂ deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B₁₂ and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B₁₂ deficiency was defined as vitamin B₁₂ ≤ 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B₁₂ deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B₁₂ level was 662.5 ± 246.7 pg/mL. Vitamin B₁₂ deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ≥ 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B₁₂ deficiency, especially at higher dosages (> 1,000 mg) and longer durations (≥ 4 yr) of treatment.

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Depression and folate status in the US Population

BACKGROUND: Folate deficiency and low folate status have been linked in clinic studies to depression, persistent depressive symptoms, and poor antidepressant response. These relationships have not been demonstrated in general populations. This study examined associations between depression and folate status indicators in an ethnically diverse general US population sample aged 15-39 years. METHODS: Healthy subjects whose red blood cell (RBC) folate concentrations had been measured were determined to have no depression (n = 2,526), major depression (n = 301), or dysthymia (n = 121) using a diagnostic interview schedule. Serum concentrations of folate and total homocysteine (tHcy) were also measured. RESULTS: After adjustment for sociodemographic factors, serum vitamin B(12) concentration, alcohol consumption over the past year and current status as to overweight and use of vitamin/mineral supplements, cigarettes and illegal drugs, subjects who met criteria for a lifetime diagnosis of major depression had folate concentrations in serum and RBCs that were lower than those of subjects who had never been depressed. Subjects who met criteria for dysthymia alone had lower RBC folate concentrations than never-depressed subjects, but the serum folate concentrations of the two groups were comparable. Serum tHcy concentration was not related to lifetime depression diagnoses. Low folate status was found to be most characteristic of recently recovered subjects, and a large proportion of such subjects were folate deficient. CONCLUSIONS: Low folate status was detectable in depressed members of the general US population. Folate supplementation may be indicated during the year following a depressive episode.     

维生素缺乏对老年人髋部骨折的影响

目的 对比老年髋部骨折患者与老年非骨折的骨病患者维生素水平及缺乏情况,分析维生素缺乏对老年髋部骨折的影响。方法 回顾性病例对照研究。纳入2020年11月—2022年2月深圳市第二人民医院均行血清维生素水平检测的老年髋部骨折患者172例（骨折组）及老年非骨折的髋膝关节骨病患者345（非骨折组）例。骨折组患者中男50例、女122例,年龄65~97（81.0±8.2）岁;非骨折组中男89例、女256例,年龄65~90（72.1±5.9）岁。采用液相色谱串联质谱法检测血清维生素A、B1、B2、B3、B5、B6、B9、E、K1,以及25-羟基维生素D（D2和D3）的含量,将维生素水平低于正常值下限定义为相应维生素缺乏。观察指标：（1）观察骨折组与非骨折组是否缺乏维生素,并比较2组患者维生素水平的差异。（2）将标准化后的维生素水平作为自变量,骨折与否作为因变量,年龄和性别作为协变量,采用多因素logistic回归分析标准化后维生素水平对老年髋部骨折的影响。结果 （1）骨折组患者维生素A、B1、B3、B9、E缺乏情况更为严重,骨折组占比分别为62.8% （59/94）、62.4% （58/93）、19.4% （18/93）、50.0% （52/104）、14.9% （14/94）,非骨折组为20.2% （49/243）、41.2% （100/243）、5.0% （12/241）、16.3% （41/251）、4.5% （11/243）,差异均有统计学意义（χ²=56.49、12.15、15.82、43.10、10.61,P值均<0.05）。骨折组患者的血清25-羟维生素D、D3,以及维生素A、B1、B3、B5、B6、B9、E、K1水平较非骨折组明显降低,差异均有统计学意义（Z=-4.41、-2.53、-7.08、-3.43、-5.25、-2.08、-2.46、-6.80、-3.26、-7.93,P值均<0.05）;25-羟维生素D2和维生素B2水平2组差异均无统计学意义（P值均>0.05）。（2）多因素回归分析显示,维生素A[比值比（OR）=0.30,95%可信区间（CI）0.20~0.45]、维生素K1（OR=0.31,95% CI 0.21~0.46）、维生素B9（OR=0.33,95% CI 0.23~0.47）、维生素B3（OR=0.50,95% CI 0.36~0.70）、维生素B5（OR=0.50,95% CI 0.37~0.69）、维生素B1（OR=0.52,95% CI 0.38~0.72）、维生素E（OR=0.61,95% CI 0.45~0.83）、25-羟基维生素D（OR=0.70,95% CI 0.55~0.89）和维生素B6（OR=0.71,95% CI 0.54~0.95）水平的降低均会导致老年髋部骨折的风险增加（P值均<0.05）。结论 老年髋部骨折患者和老年非骨折的髋膝关节退行性骨病患者都普遍存在各种维生素缺乏,而且以25-羟基维生素D的缺乏最为严重。髋部骨折患者相对于非骨折患者的多种维生素水平更低,血清维生素A、B1、B3、B5、B6、B9、E、K1、25-羟基维生素D水平的降低会增加髋部骨折的风险。     

The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease

There is evidence that increased blood concentrations of homocysteine may be a risk factor for Alzheimer's disease. (E)-4-hydroxy-2-nonenal (HNE) is a neurotoxic product of lipid peroxidation that is increased in the ventricular fluid and brains of patients with Alzheimer's disease. We measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the plasma of 27 patients with Alzheimer's disease and 25 control subjects. There was a statistically significant increase in the plasma concentration of homocysteine (P < 0.001) and HNE (P < 0.001) in the Alzheimer's disease patients compared to the control group. There was a significant decrease in the plasma concentration of vitamin B(12) (P < 0.001) and folate (P = 0.002) in the Alzheimer's group compared to the controls. There was a significant positive correlation between the plasma concentrations of homocysteine and HNE in the patients with Alzheimer's disease (r = 0.661, P < 0.001). A significant negative correlation was found between the plasma concentration of homocysteine and the plasma concentrations of vitamin B(12) (r = -0.605, P = 0.0006) and folate (r = 0.586, P = 0.001). We also measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the cerebrospinal fluid (CSF) of 8 patients with Alzheimer's disease compared to 6 control subjects. The concentrations of homocysteine (P = 0.032) and HNE (P = 0.001) were significantly higher in the CSF of Alzheimer's patients than in the control subjects. There were significant positive correlations between the CSF concentrations of homocysteine and HNE (r = 0.924, P = 0.001). There was also a significant positive correlation between the plasma concentration of homocysteine and the CSF concentrations of homocysteine (r = 0.850, P = 0.007) and HNE (r = 0.092, P = 0.002). These results demonstrate that there is a relationship between increased homocysteine concentrations and increased HNE concentrations in Alzheimer's disease.     

Elevated plasma homocysteine levels in centenarians are not associated with cognitive impairment

Background: Previous reports have shown elevated plasma total homocysteine (tHcy) levels in elderly person with impaired cognition. Objective: To study the association between cognitive status and plasma tHcy levels in centenarians. Design: Cross-sectional survey. Setting: Centenarians living in two northern Italian provinces. Participants: Thirteen cognitively normal centenarians, ten cognitively impaired not-demented centenarians, and 34 demented centenarians with a clinical diagnosis of Alzheimer's disease (AD). Measurements: Blood levels of homocysteine's biological determinants vitamin B12, folate, and vitamin B6. Results. Elevated plasma tHcy levels (>17 μmol/l) were common in the general population (77% of normal centenarians, 100% of cognitively impaired not-demented centenarians, 82% of AD centenarians). Demented centenarians had the lowest folate serum levels. Low or borderline vitamin B12 serum levels (<221 pmol/l) and low vitamin B6 plasma levels (<11.7 nmol/l) were found in 33 and 66% of all centenarians independently of cognitive status. Among demented centenarians only plasma tHcy correlated inversely with both serum vitamin B12 and folate. No significant difference was found for plasma tHcy levels among the three diagnostic groups, even after adjusting for B vitamin levels. Conclusions: Hyperhomocysteinemia is very common among centenarians, probably due to vitamin deficiencies, but does not seem to be associated with cognitive impairment.     

Major Determinants of Serum Homocysteine Concentrations in a Korean Population

The objective of this study was to identify the factors that determine serum homocysteine concentrations in Korean population. In a community-based study, 871 participants completed detailed questionnaires and physical examination. We found that increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine significantly increased the risk of hyperhomocysteinemia. However, hormonal and behavioral factors (smoking, alcohol drinking, coffee consumption, and sedentary time) were not associated with the risk of hyperhomocysteinemia. The risk of hyperhomocysteinemia was steeply increased in subjects with two or more risk factors among four selected risk factors (deficiencies of serum folate and vitamin B12, elevated creatinine, and family history of stroke) compared to subjects who did not have any risk factors, especially subjects over the age of 65 yr (odds ratio [OR], 33.5; 95% confidence interval [CI], 3.71-302.0 in men; OR, 39.2; 95% CI, 7.95-193.2 in women). In conclusion, increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine are important determinants of serum homocysteine concentrations with interaction effects between these factors.     

Effects of two continuous hormone therapy regimens on C-reactive protein and homocysteine

OBJECTIVE: To compare the effects of two continuous hormone therapy (HT) regimens on the cardiovascular risk markers, C-reactive protein (CRP) and homocysteine. DESIGN: A prospective study in which 43 postmenopausal women were randomly assigned to either tibolone 2.5 mg/day (n = 20) or 0.625 mg/day conjugated equine estrogens (CEE) plus continuous medroxyprogesterone acetate (MPA) 5 mg/day (n = 23). Serum levels of CRP, homocysteine, vitamin B12, and folate were determined before and during 12 weeks of therapy. RESULTS: C-reactive protein levels were increased by tibolone (76%; P < 0.001) and CEE+MPA (81%; P < 0.001). Neither tibolone nor CEE+MPA had any significant effect on homocysteine levels, but there was a significant difference between the effects of treatment over time (P = 0.046). Both tibolone and CEE+MPA reduced vitamin B12 levels (11%; P < 0.001, and 8%; P < 0.01, respectively), but had no statistically significant effect on folate levels. Individual changes in homocysteine levels were negatively associated with changes in vitamin B12 levels (r = -0.68; P < 0.01) after tibolone therapy. CONCLUSION: Both tibolone and CEE plus MPA increased CRP levels and reduced levels of vitamin B12. Neither therapy had any significant effect on homocysteine levels. Further long-term studies into the effect of HRT on these markers, and the relationship to cardiovascular disease risk, are required.     

Folate and vitamin B12 status of adolescent girls in northern Nigeria

The diets of populations in many developing countries are low in folate and vitamin B12 and a deficiency of either of these vitamins results in increased risk for cardiovascular disease and neural tube defects. The rates of neural tube defects in Nigeria are among the highest reported worldwide. Since many girls marry at an early age in northern Nigeria, we therefore determined the folate and vitamin B12 status of adolescent girls between 12 and 16 years of age in Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/- 5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower limit of the reference range for their age group. Serum homocysteine was measured in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The majority of subjects had serum homocysteine concentrations above the upper limit of the reference range for their age group. We conclude that the adolescent girls we studied were at greater risk for vitamin B12 deficiency than folate deficiency. This conclusion is consistent with the fact that their diet included few foods that contained vitamin B12.     

Interaction between common folate polymorphisms and B-vitamin nutritional status modulates homocysteine and risk for a thrombotic event

We have assessed the relationship between homocysteine, its thiol metabolites, specific folate coenzymes, and vitamin B12 according to the two main functionally relevant genotype-genotype categories that maintain the balance between homocysteine transsulphuration to cysteine, and homocysteine remethylation via folate dependent methionine biosynthesis, namely 2756A-->G-MS/66A-->G-MSR and 677C-->T-MTHFR/1298A-->C-MTHFR. We examined 152 individuals who were being treated for either thromboembolic (TE) or non-thromboembolic (non-TE) events. Chi2 test for linear trend in odds ratio provides reasonable evidence for an altered risk of thromboembolism within the range of compound MS/MSR genotypes encountered (wt/wt-->recessive/recessive) (p< or =0.05), but not within the same range of MTHFR/MTHFR genotypes. Logistic regression analysis of the risk for a TE event gave OR=0.49 (95% CI, 0.26-0.92; p=0.026) for 2756A-->G-MS, OR=1.08 (95% CI, 0.65-1.78) for 66A-->G-MSR, OR=1.19 (95% CI, 0.69-2.06) for 677C-->T-MTHFR and OR=0.98 (95% CI, 0.52-1.85) for 1298A-->C-MTHFR. When genotypes were examined individually, one-way ANOVA showed only 677C-->T-MTHFR (p=0.005 [TE]) and 2756A-->G-MS (p=0.005 [non-TE] and p=0.0006 [all subjects]) influence homocysteine. One-way ANOVA also showed that MTHFR/MTHFR compound genotype significantly influences TE homocysteine distribution (p=0.044), but no other variable. In MS/MSR, homocysteine distribution is not significantly affected in TE subjects, but approaches significance in non-TE individuals (p=0.062). However, the increased power obtained when all subjects are analysed demonstrates a significant influence of MS/MSR upon homocysteine distribution (p=0.008). Other significant influences of MS/MSR were on total cellular 5-methyl-H4folate in non-TE subjects (p=0.042) and vitamin B12 in TE subjects (p=0.018). Given the central role of vitamin B12 in MS/MSR activity, 5-methyl-H4folate and homocysteine were also looked at by vitamin B12 quartile, independent of genotype: Vitamin B12 quartile significantly affected homocysteine distribution in TE (p=0.013) but not non-TE individuals, with no effect on 5-methyl-H4folate distributions. Similarly, the prevalence of clinical phenotypes (p=0.013) and of 'high risk' 2756A-->G-MS wildtypes (p=0.039) was associated with the disposition of homocysteine/B12 in TE but not non-TE subjects. Overall, results indicate compound MS/MSR genotype is associated with risk for a TE event. This may be related to variation in activity of the functional enzymes coded for by polymorphic forms of compound MS/MSR, resulting in altered catalytic cycling of methylcobalamin/cob(I)alamin, which in turn influences Hcy (and total 5-methyl-H4folate). The effect on vitamin B12 is greater in TE than non-TE subjects. The compound MTHFR/MTHFR genotype also influences variation in Hcy in TE subjects, but seemingly without the same level of mediation by vitamin B12. These results are consistent with accepted paradigms and offer a plausible explanation for the effect and interaction of specific SNPs in the TE phenotype. The biological implications of the limited number of MTHFR/MTHFR mutant alleles that can coexist, usually no more than two, may be explained by the serious consequences to folate status that these genotype combinations precipitate. We show that lowering of all folate 1-C pools occurs in the rare ct/cc compound genotype, except for the 5,10-methenyl-H4folate pool, which expands. 5,10-methenyl-H4folate is the immediate product of 5,10-methylene-H4folate, which is likely diverted away from methionine biosynthesis via the aberrant MTHFR enzyme. Consequences for the methylation cycle may be severe, and in most cases lethal for the developing embryo, where methylation is required for dozens of critical processes, but particularly for maintaining DNA methylation patterns that are now known to regulate the expression of half the complement of human genes via CpG islands located in the 5' promotor region, or within the first few exons of the gene.     

Importance of low serum vitamin B12 and red cell folate concentrations in elderly hospital inpatients.

To determine the functional importance of the low B12 and red cell folate concentrations repeatedly observed in the elderly 200 consecutive patients admitted to a geriatric unit were studied. Forty six of the patients had low serum concentrations of B12 (15), red cell folate (26), or both (five). Serum B12 and red cell folate concentrations correlated with mean cell volume, and serum B12 correlated with the neutrophil lobe count. Bone marrow deoxyuridine suppression was abnormal in 35% of the patients with low vitamin concentrations, but 55% of those with abnormal deoxyuridine suppression had morphologically normal bone marrow, and 73% had a normal mean cell volume. In patients with low vitamin values the deoxyuridine suppressed value correlated with the haemoglobin concentration and neutrophil lobe count. Thus synthesis of thymidylate was impaired by vitamin B12 or folate deficiency in at least 8% of newly admitted elderly patients, many of whom had normal blood counts despite the biochemical disturbance affecting haemopoiesis. A nutritionally depleted diet may have been responsible for many of the low vitamin values.     

Vitamin B12 and folic acid deficiency in chronic pancreatitis: a relevant disorder?

Summary Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency.137 patients (84 males, 53 females, age 34–72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n=24), moderate (n=61) or severe (n=38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190–1020 pg/ml for serum vitamin B12 and 2.4–16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512±48 pg/ml in mild, 493±52 pg/ml in moderate and 428±45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34±0.76 ng/ml in mild, 6.34±0.52 ng/ml in moderate and 7.45±0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency. In clinical practice enzyme supplementation in patients with severe pancreatic insufficiency is obviously sufficient for normal vitamin B12 absorption. Folic acid deficiency is also unfrequently found in chronic pancreatitis.     

血清胱抑素C、叶酸、维生素B12在慢性肾脏病早期肾损伤中的应用价值

目的 探讨血清胱抑素C(Cys-C),叶酸(FA)、维生素B12(Vit B12)在慢性肾脏病早期肾损伤中的应用价值.方法 选择2014年3月至2016年8月在我院就诊的慢性肾脏病患者167例作为研究对象,按照慢性肾脏病的分期分为五组:第1期组(A组,32例)、第2期组(B组,32例)、第3期组(C组,33例)、第4期组(D组,34例)、第5期组(E组,36例),选择同期体检健康志愿者30例作为健康对照组,采用胶乳免疫比浊法测定血清Cys-C,电化学发光法测定血清FA和VitB12,尿素酶-谷氨脱氢酶法测定血清尿素(Urea),苦味酸法测定血清肌酐(Scr)含量水平.结果 A组各指标测定结果与对照组比较差异无统计学意义(P＞0.05);B组Scr、Urea与对照组及A组比较差异也无统计学意义(P＞0.05),而血清Cys-C高于对照组和A组(P＜0.05);C组、D组和E组各指标测定结果与对照组及A组比较差异均有统计学意义(P＜0.05).ROC曲线显示,Cys-C、Urea、FA、Vit B12、Scr的AUC及95％ CI分别为:0.697 (0.668 ～0.887)、0.538(0.491～0.792)、0.502(0.504～0.822)、0.481(0.532 ～0.865)、0.457(0.484 ～0.775).结论 血清胱抑素C、叶酸和维生素B12检测有助于早期肾功能损伤的判断,对控制慢性肾脏病发展有重要的临床意义.     

A folate-rich diet is as effective as folic acid from supplements in decreasing plasma homocysteine concentrations

Background & Aims: At least 500 mug of folic acid are required daily to treat hyperhomocysteinemia. To reach this amount by dietary changes alone may be difficult because food has a low folic acid content and bioavailability. No studies have compared the effects of similar amounts of additional folate derived from a combination of folate-rich and fortified foods or folic acid from supplements on plasma total homocysteine (tHcy) concentrations, which was the aim of this study. Methods: Twenty male patients with hyperhomocysteinemia and coronary artery disease were included in a randomized, crossover intervention trial. Patients were treated daily with a combination of foods containing approximately 500 mug of folate or with one 500 mug capsule of synthetic folic acid over two five-week periods separated by a five-week wash-out period. Results: Plasma folate increased markedly (p<0.001) and plasma tHcy decreased (p<0.001) with both therapies. Folate-rich foods decreased tHcy by 8.6% (95% CI: -15.9 to -1.2) and synthetic folic acid capsules by 8% (95% CI: -13.3 to -2.7). Conclusions: This study shows, for the first time in the literature, that a folate-rich diet is as effective as folic acid capsules in decreasing plasma tHcy concentrations and adds further support to the recommendation of those diets to prevent cardiovascular disease.     

Molecular genetic analysis of the human dihydrofolate reductase gene: relation with plasma total homocysteine, serum and red blood cell folate levels

Disturbances in folate metabolism may increase the risk of certain malignancies, congenital defects and cardiovascular diseases. The gene dihydrofolate reductase (DHFR) is primarily involved in the reduction of dihydrofolate, generated during thymidylate synthesis, to tetrahydrofolate in order to maintain adequate amounts of folate for DNA synthesis and homocysteine remethylation. In order to reveal possible variation that may affect plasma total homocysteine (tHcy), serum folate and red blood cell (RBC) folate levels, we sequenced the DHFR coding region as well as the intron-exon boundaries and DHFR flanking regions from 20 Caucasian individuals. We identified a 9-bp repeat in the 5'-upstream region that partially overlapped with the 5'-untranslated region, and several single-nucleotide polymorphisms, all in non-coding regions. We screened subjects for the 9-bp repeat (n=417), as well as the recently reported 19-bp deletion in intron 1 (n=330), and assessed their associations with plasma tHcy, serum and RBC folate levels. The 19-bp del/del genotype was associated with a lower plasma tHcy (-14.4% [95% confidence interval: -23.5 to -4.5], P=0.006) compared with the wild-type genotype. This may suggest that intracellular folate levels are affected.     

Diagnostic value of the serum folate assay

The diagnostic value of the serum folate assay has been assessed in 90 patients, each of whom had a macrocytic anaemia and a low serum vitamin B(12) level. Twenty-nine (32%) patients were found to have anaemia due primarily to folate deficiency. The cause of the low serum vitamin B(12) levels is uncertain in the 22 (25%) patients with normal or borderline vitamin B(12) absorption. The effect of folic acid therapy was studied in four of these patients, and in each case the serum vitamin B(12) rose slowly to a normal level.The serum folate was low in only four (7.5%) of the 54 patients with pernicious anaemia, and the levels rose to normal on treatment with vitamin B(12) alone. A high serum folate occurred in eight (15%) pernicious anaemia patients. A normal serum folate indicated the diagnosis of pernicious anaemia or megaloblastic anaemia following partial gastrectomy. However, a normal serum folate and a very low vitamin B(12) level was found in two patients with idiopathic steatorrhoea.It is concluded that the serum folate assay is a valuable routine test in patients who have a macrocytic anaemia and low serum vitamin B(12). A low folate level makes the diagnosis of pernicious anaemia unlikely and is a strong indication for full investigation of small intestinal function.     

Measurement of melatonin,indole-dioxygenase,IL-6, IL-18, ferritin,CRP, and total homocysteine levels during herpes zoster

The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses. The present study aimed to assess the levels of oxidative/inflammatory stress biomarkers in HZ patients compared with the controls. This case-control study included 43 HZ patients and 47 age-matched controls. Melatonin (MLT), Indole-dioxygenase (IDO), Interleukin-18 (IL-18), Interleukin-6 (IL-6), ferritin, C-reactive protein (hsCRP), and total homocysteine (tHcy) levels were measured and compared in both groups. The significant high levels of IDO, IL-18, IL-6, ferritin, hsCRP, and tHcy, as well as low levels of MLT were found in HZ patients compared with the controls (P < 0.001); these significant differences were also associated with rash and pain severity (P < 0.001). The final logistic regression model with the area under the curve (0.99; 95% confidence interval [CI], 0.98-1.00) showed the association of HZ with decreased level of MLT (odds ratio [OR], 0.95; 95% CI, 0.92-0.98; P = 0.007) and increased levels of tHcy (OR, 1.53; 95% CI, 1.06-2.19; P = 0.02). The findings showed increased inflammation-associated oxidative stress in HZ patients. Elevated tHcy levels and reduced MLT levels may be associated with the manifestation of HZ. More investigations are required to confirm the results.