Malondialdehyde, carbonyl proteins and albumin-disulphide as useful oxidative markers in mild cognitive impairment and Alzheimer's disease

The question arises as to whether oxidative stress has a primary role in neurodegeneration or is a secondary end-stage epiphenomenon. The aim of the present study was to determine oxidative stress parameters like malondialdehyde (MDA), carbonyl proteins (CP) and Albumin-disulphide (Alb-SSR) and relate these parameters to the immune parameter neopterin, folic acid and vitamin B12 as vitamins and homocysteine in patients with neuro-degenerative diseases (NDD), namely mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to an aged matched control group. MDA, CP and Alb-SSR were significantly increased in the NDD group compared to controls, but not vitamin B12, folic acid and neopterin. Significant correlations were found between CP and Alb-SSR, CP and MDA and between MDA and Alb-SSR including patients with NDD and the control group. These results support the hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases.     

Synergistic effect of folic acid and vitamin B12 in ameliorating arsenic-induced oxidative damage in pancreatic tissue of rat

The efficacies of two nutritional factors, folic acid and vitamin B12, were assessed in this study against arsenic-induced islet cellular toxicity. Rats were divided into four groups consisting of five rats in each group: Group A, control; Group B, arsenic-treated; Group C, arsenic+folic acid; and Group D, arsenic+folic acid+vitamin B12. The dose of arsenic, folic acid and vitamin B12, respectively, was 3 mg, 36 microg and 0.63 microg kg(-1) body weight day(-1) for 30 days. Results showed that, compared to control group, there was a significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and hydroxyl radical (OH-) formation in the pancreatic tissue of arsenic-treated rats, while the activity of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), and cellular content of antioxidant glutathione (GSH) were low in these animals. The serum level of tumor necrosis factor-alpha (TNF-alpha) and IL-6 was significantly high in these animals. Light microscopic examination showed a marked fall in the number of islet cells. Concomitant administration of either folic acid or folic acid and vitamin B12 with arsenic significantly restored all these parameters. Although folic acid alone could not restore the normal level of TNF-alpha and IL-6, combined folic acid and vitamin B12 could restore it. Folic acid and vitamin B12 combined also could recover islet cell count. These results suggest that folic acid+vitamin B12 are capable of reducing arsenic-induced cellular oxidative and inflammatory toxic changes. Thus, supplement with vitamin B12+folic acid may be predicted as a possible nutritional management strategy against arsenic-induced toxicity.     

A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid,Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

Objectives

Our earlier studies have highlighted that an altered one carbon metabolism (vitamin B₁₂, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B₁₂ and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH).

Materials and Methods

Pregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B₁₂; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B₁₂ + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation.

Results

Animals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factor–alpha (TNF–ά) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-ά levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group.

Conclusion

Key constituents of one carbon cycle (folic acid, vitamin B₁₂ and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia.     

Radioisotope binding capacity of serum in folic acid, vitamin B12 and ferritin in haematologic and rheumatologic patients

In addition to the usual parameters for haematologic an rheumatologic diseases folic acid, vitamin B12, and ferritin were investigated by radioisotope studies. In some groups folic acid was lower compared to controls, and it is possible that the disease causes the deficiency of folic acid absorption and distribution. Vitamin B12 was only slightly decreased, thus, the values may be assumed to be close to normals. Transferrin ankylosing spondylitis is similar to that of controls, however, transferrin increases in rheumatoid arthritis and in mixed groups containing patients various diseases. Finally, the deficiency of folic acid absorption can be assumed to be caused by the symptoms of the disease, whereas in the case of inflammatory diseases and in mixed group transferrin increased.     

血清Hcy，叶酸和维生素B12在胃癌及其癌前疾病中的作用

目的:探讨血清同型半胱氨酸(Hcy)、叶酸以及维生素B12在胃癌及癌前疾病中的水平及临床意义。方法:收集2014年1月至2016年8月我院收治的100例胃癌患者(胃癌组),及100例胃良性病变患者包括41例胃炎、34例胃溃疡、25例胃息肉(癌前病变组),并于同期随机选择200例健康体检者为对照组,采用循环酶法测定三组的血清Hcy,电化学发光免疫分析法测定叶酸及维生素B12水平,并分析各指标与胃癌临床病理特征的关系。结果:胃癌组、癌前病变组血清Hcy水平均高于对照组,叶酸及维生素B12水平均低于对照组,并且胃癌组血清Hcy水平高于癌前病变组,叶酸及维生素B12水平低于癌前病变组,差异有统计学意义(P0.05)。Ⅲ+Ⅳ期胃癌患者Hcy水平高于Ⅰ+Ⅱ期,进展期患者Hcy水平高于早期,有淋巴结转移患者Hcy水平高于无转移者,差异有统计学意义(P0.05);Hcy表达与性别、年龄、病变位置以及分化程度无关,差异无统计学意义(P0.05)。叶酸、维生素B12的表达在胃癌患者中与各临床病理特征(性别、年龄、TNM分期、肿瘤浸润深度、病变位置、有无淋巴结转移、分化程度)无明显关系,差异无统计学意义(P0.05)。结论:血清Hcy在胃癌患者中呈高水平表达,而叶酸及维生素B12呈低水平表达,联合检测三种指标有助于早期区分胃癌及癌前病变,同时血清Hcy还可能参与了胃癌的发生发展过程。Hcy、叶酸及维生素B12可作为早期鉴别诊断胃癌及其癌前病变的重要指标。     

Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats

A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases Δ5 desaturase activity but decreases mRNA levels, decreases Δ6 desaturase activity but not mRNA levels as compared to control. mRNA level of Δ5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver.     

饲料中添加叶酸和VB12对中华绒螯蟹幼蟹生长、非特异性免疫和抗病力的影响

为研究叶酸和VB12协同作用对中华绒螯蟹(Eriocheir sinensis)幼蟹生长、非特异性免疫和抗病力的影响,选取初始体重为(2.570.03) g的幼蟹600只,随机分成4组,每组5个重复,每个重复30只幼蟹,分别投喂对照组(不添加叶酸和VB12),单一VB12组(0.2 mg/kg),单一叶酸组(2.3 mg/kg)和联合处理组(0.2 mg/kg VB12 +2.3 mg/kg叶酸)的饲料8周。在养殖实验结束后,先统计成活率和称重,然后从每个处理组随机选取30只幼蟹,用2108 CFU/mL的嗜水气单胞菌注射攻毒2周。实验结果表明:幼蟹的增重率、特定生长率、饲料效率和存活率在联合处理组最高,显著高于对照组(P0.05),但与单一叶酸或VB12组相比不存在显著差异(P0.05)。联合处理组的血清酚氧化酶活性显著高于对照组(P0.05),但与单一叶酸或VB12组也无显著性差异(P0.05)。同时,联合处理组的血清酸性磷酸酶、碱性磷酸酶、溶菌酶活性和血细胞总数等指标最高,其次是单一叶酸组和VB12组,而对照组最低。投喂联合处理组饲料幼蟹的肝胰腺超氧化物歧化酶活性最高,而丙二醛含量和累积死亡率最低。以上结果表明,叶酸和VB12对幼蟹的生长、生理代谢和免疫性能均可能有互补和协同作用,养殖生产中建议饲料中叶酸和VB12添加量分别为2.3 mg/kg和0.2 mg/kg。       

A diabetes-like environment increases malformation rate and diminishes prostaglandin E(2) in rat embryos: reversal by administration of vitamin E and folic acid

BACKGROUND: Offspring of women with diabetes are at increased risk for congenital malformations and disturbed growth compared with infants from nondiabetic pregnancies. The precise biological process behind these effects is not yet completely clarified. Previous studies have suggested that diabetic embryopathy is associated with increased level of oxidative stress and disturbed arachidonic acid metabolism. The aim of the present study was to investigate whether a diabetes-like environment both in vivo and in vitro increases embryonic levels of isoprostanes and alters embryonic prostaglandin E(2) (PGE(2)) concentration. Furthermore, we studied whether vitamin E and folic acid treatment rectify such alterations. METHODS: Embryos from diabetic and nondiabetic rats at gestational days (GDs) 10 and 11 were used. In the in vitro experiments, we used whole embryo culture, which mimics pregnancy. GD 9 embryos from nondiabetic rats were cultured for either 24 hr (corresponding to GD 10) or 48 hr (corresponding to GD 11) and exposed to 10 or 30 mM glucose concentration with or without folic acid. RESULTS: Embryos from diabetic rats and embryos cultured in a high glucose concentration showed increased malformation rates. Dietary treatment with vitamin E in vivo and supplementation of folic acid in the culture medium with 30 mM glucose in vitro decreased the malformation rate, decreased embryonic isoprostane levels, and increased PGE(2) concentration. CONCLUSIONS: Diabetes-induced oxidative stress and disturbance of PGE(2) production may contribute to the embryonic dysmorphogenesis in the offspring of diabetic rodents and, thereby, may also have a role in human diabetic embryopathy.     

Sialic acid and oxidizability of lipid and proteins and antioxidant status in patients with coronary artery disease

The aim of this study was to investigate the possible relationship between serum total sialic acid (TSA) concentration, recently shown to be a cardiovascular risk factor, and lipid and protein oxidation and antioxidant status and the severity of coronary artery disease (CAD) according to the obstructive vessel number in patients. The study was carried out on a total of 200 patients (142 men and 58 women) who were hospitalized for elective coronary angiographic evaluation with complaint of typical angina pectoris. According to the results of angiography, 150 patients had angiographically proven CAD (CAD group) and 50 patients had a history suggestive of angina pectoris but normal coronary angiograms (control group). The CAD group was further divided into single-, double- and triple-vessel disease groups according to the number of vessels involved. Lipid parameters were determined by routine laboratory methods. Plasma malondialdehyde (MDA) and vitamin E concentrations were determined by high-performance liquid chromatography. TSA and other oxidant and antioxidant parameters were studied spectrophotometrically. Our results demonstrated significant increases both in TSA levels and in indicators of oxidative stress in the patients with CAD compared with the controls. However, antioxidant parameters were decreased in the patients with CAD. We found strong positive correlations between TSA and plasma MDA, Delta-MDA which represents the degree of oxidative modification of apolipoprotein B-containing lipoproteins, serum protein carbonyls and apolipoprotein B and weak correlations between TSA and low density lipoprotein cholesterol, triacylglycerol, paraoxonase, glutathione peroxidase (GPx), vitamin C and vitamin E. In conclusion, TSA is related to markers of lipid and protein oxidation, paraoxonase and GPx activities, vitamin C and E levels and the severity of CAD.     

The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

Folic acid (FA), is a group B vitamin, has high reactive oxygen radicals quenching ability, resulting in protection against oxidative damage in aerobic cell. Acetaminophen (N-acetyl-p-aminophenol, APAP) is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in liver and kidney tissues. The aim of this study was to investigate whether folic acid has protective effects on oxidative liver and kidney injury caused by experimental APAP toxication. Forty female Sprague dawley rats were divided into 5 groups; control, APAP, FA, APAP+FA, and APAP+N-acetylcysteine (NAC) groups. APAP toxication was induced by oral gavage (3 g/kg bodyweight). FA (20 mg/kg bodyweight) and NAC (150 mg/kg bodyweight) were given by oral gavage to the specified groups. Oxidant and antioxidant parameter were determined in liver and kidney tissues. In addition, the liver and kidney tissues were histological evaluated. When compared with APAP group, superoxide dismutase (SOD) and catalase activities and glutathione levels were statistically higher, malondialdehyde (MDA) level and myeloperoxidase activity (except liver tissue) were statistically lower in both APAP+FA and APAP+NAC. Liver and kidney MDA level and kidney SOD activity were significantly lower in APAP+NAC group compared with APAP+FA group. Co-administration of NAC with APAP was found to provide protection, but hepatic cords were defective in some places and some glomerular tubules also had dilatation. Necrotic areas was reduced in the liver and the glomerular structure was in good condition in the APAP+FA group. As a result, FA might have a protective effect against APAP-induced hepato-nephrotoxicity and oxidative stress in rat.     

Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia

In this article, oxidative stress and enzymic-non-enzymic antioxidants status were investigated in children with acute pneumonia. Our study included 28 children with acute pneumonia and 29 control subjects. The age ranged from 2 to 11 years (4.57+/-2.13 years) and 2 to 12 years (4.89+/-2.22 years) in the study and control groups, respectively. Whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, catalase (CAT), ceruloplasmin (CLP), total bilirubin, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were studied in all subjects. There was a statistically significant difference between the groups for all parameters except for serum CAT. Whole blood MDA, serum CLP and total bilirubin levels were higher in the study group than those of the control group. However, SOD, GPx, beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the study group compared with the control group. All antioxidant vitamin activities were decreased in children with acute pneumonia. Our study demonstrated that oxidative stress was increased whereas enzymic and non-enzymic antioxidant activities were significantly decreased in children with acute pneumonia.     

Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats

Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12) are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.     

Folic acid fortification: why not vitamin B12 also?

Folic acid fortification of cereal grains was introduced in many countries to prevent neural tube defect occurrence. The metabolism of folic acid and vitamin B12 intersect during the transfer of the methyl group from 5-methyltetrahydrofolate to homocysteine catalyzed by B12-dependent methioine synthase. Regeneration of tetrahydrofolate via this reaction makes it available for synthesis of nucleotide precursors. Thus either folate or vitamin B12 deficiency can result in impaired cell division and anemia. Exposure to extra folic acid through fortification may be detrimental to those with vitamin B12 deficiency. Among participants of National Health And Nutrition Examination Survey with low vitamin B12 status, high serum folate (>59 nmol/L) was associated with higher prevalence of anemia and cognitive impairment when compared with normal serum folate. We also observed an increase in the plasma concentrations of total homocysteine and methylmalonic acid (MMA), two functional indicators of vitamin B12 status, with increase in plasma folate under low vitamin B12 status. These data strongly imply that high plasma folate is associated with the exacerbation of both the biochemical and clinical status of vitamin B12 deficiency. Hence any food fortification policy that includes folic acid should also include vitamin B12.     

The prophylactic effect of vitamin C on induced oxidative stress in rat testis following exposure to 900 MHz radio frequency wave generated by a BTS antenna model

Radio frequency wave (RFW) generated by base transceiver station (BTS) has been reported to make deleterious effects on reproduction, possibly through oxidative stress. This study was conducted to evaluate the effect of RFW generated by BTS on oxidative stress in testis and the prophylactic effect of vitamin C by measuring the antioxidant enzymes activity, including glutathione peroxidase, superoxide dismutase (SOD) and catalase, and malondialdehyde (MDA). Thirty-two adult male Sprague–Dawley rats were randomly divided into four experimental groups and treated daily for 45 days as follows: sham, sham+vitamin C (l-ascorbic acid 200 mg/kg of body weight/day by gavage), RFW (exposed to 900 MHz RFW) ‘sham’ and ‘RFW’ animals were given the vehicle, i.e., distilled water and the RFW+vitamin C group (received vitamin C in addition to exposure to RFW). At the end of the experiment, all the rats were sacrificed and their testes were removed and used for measurement of antioxidant enzymes and MDA activity. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p < 0.05). In the treated group, vitamin C improved antioxidant enzymes activity and reduced MDA compared with the test group (p < 0.05). It can be concluded that RFW causes oxidative stress in testis and vitamin C improves the antioxidant enzymes activity and decreases MDA.     

Protective effect of curcumin and chlorophyllin against DNA mutation induced by cyclophosphamide or benzo[a]pyrene

The current study was carried out to evaluate the potency of curcumin and chlorophyllin as natural antioxidants to reduce the oxidative stress markers induced by cyclophosphamide (CP) and benzo[a]pyrene [B(a)P] which were used as free radical inducers. For this purpose, 126 male albino rats were used. The animals were assigned into 4 main groups: negative control group; oxidant-treated group (subdivided into two subgroups: cyclophosphamide-treated group and benzo[a]pyrene-treated group); curcumin-treated group; and chlorophyllin-treated group. Liver samples were collected after two days post the oxidant inoculation and at the end of the experimental period (10 weeks). These samples were examined for determination of liver microsomal malondialdehyde (MDA), DNA fragmentation, restriction fragment length polymorphism (RFLP) and 8-hydroxy deoxyguanosine (8-OHdG) concentration. Both CP and B(a)P caused increments in DNA fragmentation percentages, liver microsomal MDA, concentration of 8-OHdG and induced point mutation. Treatment of rats with either curcumin or chlorophyllin revealed lower DNA fragmentation percentages, liver microsomal MDA concentration, concentration of 8-OHdG and prevented induction of mutations, i.e., reversed the oxidative stress induced by CP and B(a)P and proved that they were capable of protecting rats against the oxidative damage evoked by these oxidants.     

Molecular analysis of homocysteic acid-induced neuronal stress

Hyperhomocysteinemia is a risk factor for vascular and neuronal lesions often observed with concomitant high levels of homocysteic acid. In contrast to homocysteine, homocysteic acid induces calcium influx into neurons, with characteristics of an excitotoxic glutamatergic agonist at elevated concentrations. On the molecular level this is correlated to fast modifications of proteins (phosphorylation and proteolysis). Within the homocysteic acid induced molecular signature we focused in more detail on phosphorylation of two proteins implicated as risk factors in schizophrenia and neurodegeneration: Dihydropyrimidinase related protein and 14-3-3 protein isoforms. Among the identified proteins there are known chaperones and oxidative metabolism enzymes, but a few are new in context of neuronal stress: Lasp-1, a vitamin D associated factor and an expressed sequence with features of a Rho GDP dissociation inhibitor. Moreover, we detect a specific proteolytic processing of heat shock protein 70 and proteindisulfide isomerase, which is abolished by vitamins (folic acid, vitamin B12, and vitamin B6), which also decrease elevated intracellular calcium levels induced by homocysteic acid.     

Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats

BACKGROUND: Oxidative stress and enhanced apoptosis may be involved in the induction of embryonic dysmorphogenesis in diabetic pregnancy. Administration of folic acid or vitamin E diminishes embryonic dysmorphogenesis. We aimed to evaluate the effect of combined treatment with folic acid and vitamin E on the disturbed development in embryos of diabetic rats. METHODS: Pregnant nondiabetic and diabetic rats were treated with daily injections of 15 mg/kg folic acid or with 5% vitamin E in the diet. A third group received combined treatment. Day 10 and day 11 embryos were evaluated for development and apoptotic profile. RESULTS: We found increased malformations, resorptions, and profound growth retardation in embryos of diabetic rats compared to control embryos. Vitamin E or folic acid alone, or the 2 compounds combined, normalized embryonic demise. Maternal diabetes caused decreased nuclear factor-kappaB (NF-kappaB) activity and B-cell lymphoma 2 (Bcl-2) protein level, and increased Bcl-2-associated x proteins (Bax) in embryos. Supplementation of vitamin E alone normalized the Bax protein level in a diabetic environment. Administration of folic acid to diabetic rats increased NF-kappaB activity and Bcl-2 protein level. Combined treatment normalized Bcl-2 and Bax protein level in a diabetic environment. CONCLUSIONS: Combined supplementation of folic acid and vitamin E to pregnant diabetic rats diminished diabetes-induced malformations and resorptions, concomitant with normalization of apoptotic protein levels. No treatment completely abolished the embryonic demise; therefore, other mechanisms than oxidative stress and apoptosis are likely to be involved in diabetic embryopathy.     

Seasonal changes in markers of oxidative damage to lipids and DNA; correlations with seasonal variation in diet

We have addressed the question whether the relatively high incidence of cardiovascular disease and certain cancers in countries of central/eastern Europe might be associated with nutritional imbalance, in particular a lack of fresh fruit and vegetables in the diet in winter months. Nutritional parameters and markers of oxidative stress were studied in three Slovak population groups: 46 survivors of myocardial infarction (MI group) and 48 healthy, normolipidemic subjects (NL), living in or near Bratislava; and 70 rural controls (RC group) living a more traditional life style in a country town. Data were collected in February/March and September/October of two consecutive years, representing times of minimum and maximum local availability of fresh fruits and vegetables. Oxidative stress was monitored using two biomarkers; plasma malondialdehyde (MDA, a product of lipid peroxidation), and oxidation of lymphocyte DNA. Dietary antioxidants, folic acid, homocysteine, total antioxidant status (FRAP) and uric acid were measured in plasma. Food frequency questionnaires were administered. Vegetable consumption in summer/autumn was twice as high as in winter/spring. DNA damage did not vary consistently across the seasons. Mean plasma MDA levels for the MI and NL groups showed a clear pattern, with high levels in winter/spring and low levels in summer/autumn. Folic acid showed a reciprocal pattern, similar to the pattern of vegetable consumption. The RC group had the smallest seasonal variations in vegetable consumption, folic acid levels, and MDA. High winter MDA levels are seen in those individuals with relatively low folic acid; they never occur in subjects with high plasma folic acid, implying that folic acid might directly protect against lipid oxidation. This study illustrates the value of the molecular epidemiological approach, while emphasising the need for well characterised population groups and valid biomarkers.     

Effect of vitamin B12 and folate on biosynthesis of methionine from homocysteine in the nematode Caenorhabditis briggsae.

(i) Omission of L-methionine from the medium resulted in an 80% population reduction. Substitution of D,L-homocysteine corrected methionine deficiency in C. briggsae in the presence of supraoptimal vitamin B12 and folic acid. (ii) An absolute vitamin B12 requirement in C. briggsae developed in the medium containing homocysteine at the second subculture. Concentration of 6 ng/ml of vitamin B12 (at 100 ng/ml of folic acid) was sufficient to support maximum growth of C. briggsae in the medium containing homocysteine. (iii) It was found that either supraoptimal folic acid (2000 ng/ml) or supraoptimal vitamin B12 (3750 ng/ml), with homocysteine, supported very little population growth of C. briggsae. However, supraoptimal folic acid and supraoptimal vitamin B12 together supported a maximum population growth. Therefore, it was concluded that both vitamin B12 and folic acid were required for the biosynthesis of methionine from homocysteine. Studies also showed that the two vitamins spared each other for population growth in the medium containing homocysteine.     

A relationship between vitamin B12, folic acid, ascorbic acid, and mercury uptake and methylation

Ingestion of megadoses of certain vitamins appears to influence the in vivo methylation of mercuric chloride in guinea pigs. The addition of megadoses of vitamin B12 fed either singularly or in combination with folic acid resulted in increased methylmercury concentrations in the liver. Moreover, percent methylmercury levels were significantly increased with B12 treatment in the liver (B12 only and B12/folic acid) and brain (B12/vitamin C). Incorporation of high levels of folic acid into the dietary regime also increased the methylmercury concentration particularly in the liver and hair tissues. The addition of vitamin C in the diet, particularly in combination with B12 (brain) or folic acid (muscle) resulted in increased methylmercury levels in these tissues and percent methylmercury values with B12 in the muscle and brain tissue.