Fish oil supplementation of rats during pregnancy reduces adult disease risks in their offspring

Metabolic programming in utero due to maternal undernutrition is considered to increase the risk of adult diseases in offspring. It is therefore of relevance to investigate how dietary supplementation of specific nutrients can ameliorate the negative effects of maternal malnutrition. We examined the effects of supplementing fish oil or folic acid, both of which are conventional supplements in maternal intervention, on risk factors in the offspring as adults. Pregnant female rats from 4 groups (n = 6/group) were fed casein diets with 18 g/100 g protein (control diet), 12 g/100 g protein supplemented with 8 mg folic acid/kg diet (0.08 mg/kg diet) (FAS), 12 g/100 g protein without folic acid (FAD) or 12 g/100 g protein supplemented with 7 g/100 g fish oil (FOIL). Pups were weaned to a standard laboratory diet with 18 g/100 g protein. Serum glucose, insulin and cholesterol and plasma homocysteine levels were measured in the offspring at 6 and 11 mo of age. Serum glucose in 11-mo-old male and female pups was greater (P < 0.05) in both the FAS (males 2.46 +/- 0.51, females 2.49 +/- 0.29 mmol/L) and FAD groups (2.48 +/- 0.28 and 2.67 +/- 0.41 mmol/L) than in controls (2.03 +/- 0.15 and 2.02 +/- 0.18 mmol/L). Serum insulin concentrations were higher (P < 0.05) in the FAD group (males 1476 +/- 317, females 1441 +/- 220 pmol/L) but were lower in males from the FAS group (483 +/- 165 pmol/L) compared with controls (males 917 +/- 373, females 981 +/- 264 pmol/L). Glucose and insulin concentrations did not differ between the control and FOIL groups. Plasma homocysteine levels were lower (P < 0.05) only in 11-mo-old folate-deficient males; none of the other groups differed from the controls. Maternal supplementation of fish oil to a diet containing marginal protein was beneficial in maintaining circulating glucose, insulin, cholesterol and homocysteine levels in the offspring as adults.     

Dietary vitamin C and folic acid supplementation ameliorates the detrimental effects of heat stress in Japanese quail

We evaluated the effects of vitamin C (L-ascorbic acid) and folic acid supplementation on performance, carcass characteristics and concentrations of the oxidative stress markers [malondialdehyde (MDA), homocysteine], adrenocorticotropic hormone (ACTH), vitamins C, E, A, B-12 and folic acid, and mineral status in broiler Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature (34 degrees C, 8 h/d, 0900-1700 h). The birds (n = 150; 10-d-old) kept at 34 degrees C were fed a basal diet (HS group) or the basal diet supplemented with 250 mg of L-ascorbic acid/kg of diet (Vit C group), 1 mg of folic acid/kg of diet (FA group) or both (Vit C + FA group), whereas birds kept at 22 degrees C were fed the basal diet (TN group). Supplementing heat-stressed quail with vitamin C and folic acid improved performance compared to the HS group. Effects generally were greatest in quail supplemented with both. Although supplementation did not consistently restore concentrations to those of the TN group, it increased serum concentrations of the vitamins under study. Furthermore, serum and tissue MDA, homocysteine and ACTH concentrations were lower in the supplemented groups than in the heat-stressed controls. Retention of N, ash, Ca, P, Zn, Fe, Cu and Cr were highest in the Vit C + FA group and lowest in the HS group (P < 0.05). The results of the study indicate that vitamin C and folic acid supplementation attenuates the decline in performance and antioxidant status caused by heat stress. Such supplementation may offer protection against heat stress-related depression in performance of Japanese quail.     

Intact protein versus free amino acids in the nutritional support of thermally injured animals

This study compared the nutritional effects of intact protein with that of constituent amino acids as the sole source of nitrogen in a burn guinea pig model. Forty-five guinea pigs bearing a gastrostomy feeding tube were given 30% total body surface area, full thickness flame burn and were randomized into four groups. Group I (n = 12) and group III (n = 15) received a diet containing whey protein, while group II (n = 9) and group IV (n = 9) received an otherwise identical diet containing free amino acids in a whey protein pattern. Full strength continuous intragastric feeding was initiated immediately postburn in groups I and II, but a 72-hr adaptive period was provided in groups III and IV. Resting metabolic expenditure was measured by indirect calorimetry on postburn days 2, 6,9, and 13. After 14 days of enteral feeding, the animals were killed. Immediate enteral feeding of intact protein or free amino acids reduced postburn hypermetabolic response (p less than 0.01). However, the intact protein was found to maintain body weight and provide nitrogen retention better than the amino acid mixture (p less than 0.05). The animals on the intact protein diet also showed statistically significant benefits in carcass, liver, and gastrocnemius muscle weights and in serum albumin, transferrin and C3 levels. It is concluded that intact protein is superior to free amino acids for nutritional support following burn injury.     

Sex-related differences in effect of ethanol administration and folic acid supplementation on pancreatic amylase in rats

The present study was designed to determine whether folic acid supplement is sufficient to reverse the negative effects of ethanol consumption on amylase activity during gestation, lactation, and growth. Moreover, this study investigated the sex-related differences in amylase content in the pancreatic tissue, serum, and urine. The animals were randomized into three groups: Control group (CG) received water and a basic rat diet during pregnancy, lactation, and growth; Ethanol-rats (EG) were fed an ethanol diet during pregnancy, the suckling period, and growth until death; and Ethanol + folic acid group (E + FG) were handled the same way as those of EG, except they received a folic acid supplement from reproduction until the end of experimental period. Our results showed that ethanol consumption decreased the pancreatic amylase level in offspring rats at 2 months postpartum. Folic acid supplementation did not alter pancreatic amylase activities. In offspring males, ethanol administration decreased serum amylase activity at 2 months postpartum. Folic acid supplementation in males resulted in higher serum amylase levels than those corresponding to the ethanol-fed group. In females, no significant differences between groups in serum amylase levels were found. Ethanol consumption decreased urinary amylase excretion (at 30 days and 2 months postpartum), but the folic acid-supplemented group showed a more pronounced decrease in urine amylase activity than in the ethanol-fed group. At 30 days postpartum, no sex difference in urinary amylase was identified. However, in general, males showed higher values for urine amylase than females at 2 months postpartum. A folic acid-supplemented diet exerts an advantageous effect on amylase in serum in offspring males at 2 months postpartum of mothers fed ethanol during gestation and lactation periods, because amylase renal absorption is increased. In offspring females, amylase renal absorption is also increased, but we did not observed an advantageous effect on amylase in serum. It may be that sexual differentiation in females at 2 months postpartum exerts a definitive effect on amylase in serum. We found a sex-related difference in amylase activities; therefore, we suggest that in future all results of the exocrine pancreas function, in male and female animals, be analyzed separately.     

Hyperhomocysteinemia,and low intakes of folic acid and vitamin B12 in urban North India

Summary Background and Aim An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban non-slum area. Methods Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. Results Sex-adjusted serum levels of Hcy in mmol/L (Mean ± SD) were high, though statistically comparable, in both the groups (group I: 20.8 ± 5.9 and group II: 23.2 ± 5.9). Overall, higher than normal serum levels of Hcy (> 15 μmol/L) were recorded in 84 % of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4 % in group I and 96.7 % in group II, vitamin B12: 76.1 % in group I and 88.4 % in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (β = 4.6, p < 0.05) and males vs females (β = 5.3, p < 0.01). Conclusions Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent. Received: 30 October 2001, Accepted: 14 January 2002     

Effects of zinc on cadmium-induced alterations in hepatic functions and blood glucose of rats

The role of zinc (Zn) in preventing cadmium (Cd)-induced alterations of liver function and carbohydrate metabolism was studied in female rats. The animals were divided into four groups. To the diet for Group I was added 200 μg Cd/g of diet, to that for Group II was added 200 μg Zn/g of diet, and to that for Group III were added 200 μg Cd/g and 200 μg Zn/g of diet. Group IV was the control group fed normal diet. At the 11th, 26th, and 40th week of exposure, one-third of each group of animals were sacrificed and serum GPT and ALP activities, and glucose and insulin levels were measured. At the 26th and 40th week, serum GPT activity of Group I was significantly higher compared with those of Groups III and IV, and the serum glucose value of Group I was lower than that of Group III. At the 40th week, the serum insulin value of Group I was significantly higher than that of Group III. From these results, it is suggested that orally administered Zn prevents Cd-induced alterations of liver functions and the regulation of blood glucose in rats.     

High-dose folic acid supplementation in rats: effects on gestation and the methionine cycle

There is new evidence that a good folate status may play a critical role in the prevention of neural-tube defects and in lowering elevated homocysteine concentrations. This adequate folate status may be achieved through folic acid dietary supplementation. Folate is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term high-dose folic acid supplementation are unknown, especially those related to the methionine cycle, where folate participates as a substrate. With the aim of evaluating such possible effects, four groups of Wistar rats were classified on the basis of physiological status (virgin v. pregnant) and the experimental diet administered (folic-acid-supplemented, 40 mg/kg diet v. control, 2 mg folic acid/kg diet). Animals were fed on the diets for 3 weeks. Results showed that gestation outcome was adequate in both groups regardless of the dietary supplementation. However, there were reductions (P < 0.001) in body weight and vertex-coccyx length in fetuses from supplemented dams v. control animals. Folic acid administration also induced a higher (P < 0.01) S-adenosylmethionine: S-adenosylhomocysteine value due to increased S-adenosylmethionine synthesis (P < 0.01). However, hepatic DNA methylation and serum methionine concentrations remained unchanged. Serum homocysteine levels were reduced in supplemented dams (P < 0.05). Finally, pregnancy caused lower serum folate, vitamin B6 and vitamin B12 levels (P < 0.05). Folic acid administration prevented the effect of pregnancy and raised folate levels in dams, but did not change levels of vitamins B12 and B6. These new findings are discussed on the basis of potential benefits and risks of dietary folic acid supplementation.     

Effects of milk enriched with omega-3 fatty acid, oleic acid and folic acid in patients with metabolic syndrome

BACKGROUND & AIMS: Patients with metabolic syndrome (MS) have increased cardiovascular risk factors. Dietary modifications mainly polyunsatturated fatty acids intake, can improve them. The present study was performed to assess the effects of enriched milk with omega-3 and oleic fatty acids, folic acid and vitamin E, in these patients. METHODS: We performed a randomized, placebo-controlled and open clinical trial, among 72 patients with MS for 3 months. Thirty-six of them consumed 500 cm(3) per day of semi-skimmed milk (control group), and the others consumed 500 cm(3) per day of enriched milk (test group). Daily supplements in this group were 5.7 g of oleic acid, 0.2g of omega-3 fatty acid, 150 microg of folic acid and 7.5mg of vitamin E. Serum for total and HDL cholesterol, triglycerol, Apo B, glucose, insulin, hs-CRP, homocysteine and fatty acids contents in serum phospholipids, was obtained at the beginning and at the end of the study. LDL cholesterol was calculated by Friedewald formula. RESULTS: Four patients in the test group, and two in the control group dropped out. In the test group a decrease in serum total cholesterol (-6.2%, P=0.006), LDL cholesterol (-7.5%, P=0.032), triglycerol (-13.3%, P=0.016), Apo B (-5.7%, P=0.036), glucose (-5.3%, P=0.013), and homocysteine (-9.5%, P=0.00) was observed. Any of these parameters changed in the control group. CONCLUSIONS: Dietary supplementation with 500 cm(3) of enriched milk with omega-3 fatty acid, oleic acid and folic acid, reduces serum tryglicerides, total and LDL cholesterol, Apo B, glucose and homocysteine in patients with MS. This milk is well tolerated and accepted by the patients.     

叶酸拮抗高同型半胱氨酸血症大鼠Bcl-2基因低甲基化研究

目的探讨叶酸对蛋氨酸饮食诱导高同型半胱氨酸血症(Hhcy)大鼠主动脉组织Bcl-2基因甲基化水平影响。方法健康6周龄雄性wistar大鼠36只,体重(160±10)g,适应性喂养一周后随机分为对照组、高同型半胱氨酸组、叶酸干预组、每组12只。对照组给予AIN-93G配方饲料,高同型半胱氨酸组饲以含1.7%蛋氨酸的AIN-93G配方饲料,叶酸干预组饲以含1.7%蛋氨酸和0.008%叶酸的AIN-93G配方饲料。喂养18周后,全自动生化仪测定血浆Hcy浓度、叶酸浓度和维生素B12浓度;免疫组化检测大鼠主动脉组织Bcl-2表达;巢式降落式PCR联合甲基化特异性PCR检测Bcl-2基因启动子区甲基化水平,荧光RT-PCR检测主动脉组织Bcl-2基因mRNA表达。结果 18周蛋氨酸饮食可以诱导大鼠高同型半胱氨酸血症(P<0.01),叶酸摄入可以拮抗血浆同型半胱氨酸水平升高(P<0.01);与对照组比较,高Hcy组大鼠主动脉组织Bcl-2阳性细胞数目增加,Bcl-2基因启动子区甲基化水平降低(P<0.05),Bcl-2 mRNA表达增加(P<0.05)。叶酸干预后,主动脉组织Bcl-2阳性细胞数目减少,Bcl-2基因启动启动子区甲基化水平高于高Hcy组(P<0.05),Bcl-2 mRNA表达低于高Hcy组(P<0.05)。结论叶酸摄入可以拮抗高同型半胱氨酸血症大鼠主动脉组织Bcl-2低甲基化,使Bcl-2表达减弱,可能是其参与抗动脉粥样硬化形成的分子机制之一。     

Increasing the folic acid content of maternal or post-weaning diets induces differential changes in phosphoenolpyruvate carboxykinase mRNA expression and promoter methylation in rats

Environmental exposures throughout the life course, including nutrition, may induce phenotypic and epigenetic changes. There is limited information about how timing affects the nature of such effects induced by a specific nutritional exposure. We investigated the effect of increased exposure to folic acid before birth or during the juvenile-pubertal period in rats on the epigenetic regulation of glucose homeostasis. Rats were fed either a folic acid-adequate (AF; 1?mg/kg feed) or a folic acid-supplemented (FS; 5?mg/kg feed) diet from conception until delivery and then an AF diet during lactation. Juvenile rats were fed either the AF or the FS diet from weaning for 28?d and then an AF diet. Liver and blood were collected after a 12?h fast between postnatal days 84 and 90. Maternal FS diet increased plasma glucose concentration significantly (P?相似文献   

Effect of folic acid supplementation on mood and serotonin response in healthy males

Evidence suggests that low folate status may be detrimental to mood and associated with depleted cerebrospinal fluid levels of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT). A placebo-controlled trial was carried out to determine the effect of folic acid supplementation (100 microg for 6 weeks followed by 200 microg for a further 6 weeks) upon subjective mood (Positive and Negative Affect Schedule) and biochemical markers of mood (5-HT) in healthy males (n 23). Blood samples were obtained at baseline (week 0) and during the intervention at week 6 and week 12. Subjective mood assessments were obtained at week 0 and week 12. The results showed an increase in serum and erythrocyte folate concentrations (P=0.02 and P=0.003, respectively) and a corresponding decrease in plasma homocysteine (P=0.015) in response to the folic acid intervention. Neither subjective mood nor 5-HT levels, however, were significantly altered in response to the change in folate status. Folic acid given at physiological doses did not appear to improve the mood of healthy folate-replete individuals over a 12-week period. Further research is needed to address the effect of folic acid supplementation or of longer duration or increased dose, particularly in the face of sub-optimal folate status.     

Background diet influences the anti-inflammatory effect of alpha-linolenic acid in dyslipidaemic subjects

Long-chain n-3 PUFA from fish oils are known to have anti-inflammatory effects. We evaluated the effect of alpha-linolenic acid (ALA), precursor of n-3 fatty acids, on serum inflammatory markers and soluble cellular adhesion molecules (sCAM) of dyslipidaemic males, relative to their background diet. Participants were assigned to two groups, based upon food intake patterns: (a) twenty-one dyslipidaemic subjects who habitually ate a Mediterranean-Cretan-type diet; (b) nineteen dyslipidaemic subjects who normally ate a Westernised Greek diet. All were supplemented with 8.1 g ALA/d for 12 weeks. We determined serum amyloid A (SAA), C-reactive protein (CRP), macrophage colony-stimulating factor (MCSF), IL-6, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 and soluble E-selectin concentrations at the beginning and the end of the ALA supplementation period. Serum baseline concentrations of inflammatory markers and sCAM were similar across the diet groups. Type of diet had a significant impact on the response of inflammatory markers to ALA supplementation. The Westernised Greek diet group showed a reduction in SAA (P<0.001), CRP (P=0.002), MCSF (P=0.005) and IL-6 (P=0.04) concentrations. The Mediterranean-Cretan-type background diet group showed a significant reduction only in MCSF concentrations (P=0.003). The sVCAM-1 concentrations were significantly reduced in both the Westernised Greek diet group (P=0.001) and the Mediterranean-Cretan-type diet group (P<0.001). The present study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when the background diet was rich in saturated fatty acids and poor in MUFA.     

上海市社区老年人轻度认知障碍的潜在危险因素

目的探寻社区老年人轻度认知功能障碍(MCI)的潜在危险因素,为MCI的一级预防提供依据。方法对上海市社区的老年人进行一项横断面研究。选择了368名年龄在65~80岁的受试者,完成简易智力状态检查量表(MMSE)、基本信息问卷调查和体格检查。采用Logistic回归分析MCI的潜在危险因素。结果所有参与调查的368名受试者中,共53例MCI患者,患病率为14.4%。单因素分析发现:高龄,受教育程度低,无叶酸补充,中风,骨质疏松症和高脂血症是MCI的危险因素。Logistic回归分析显示,高龄[OR=1.146(95%CI:1.052~1.249)]和骨质疏松症[OR=2.371(95%CI:1.042~5.396)]是MCI独立危险因素,高教育程度[OR=0.073(95%CI:0.011~0.478)]是保护因素。年龄可以影响MMSE评分各方面(所有P值<0.05)。定期补充叶酸的受试者MMSE评分更高,特别是语言能力得分(P=0.002)。骨质疏松症患者注意力和计算力得分较低(P=0.022)。结论MCI患病率随年龄增长而增加,教育程度低、骨质疏松症可能是老年人MCI的独立危险因素。叶酸补充剂虽与MCI间未观察到相关性,但可以改善其语言和实践表现。     

武汉地区孕妇同型半胱氨酸水平与妊娠结局的相关性研究

目的 探讨武汉地区孕妇同型半胱氨酸、叶酸水平与妊娠结局的相关性。方法 选取在某院就诊的先兆流产孕妇200例作为观察组,健康孕妇200例为对照组,比较2组Hcy和叶酸水平之间差异,同时比较2组妊娠结局之间的差异。结果 观察组Hcy水平高于对照组,叶酸水平低于对照组,差异具有统计学意义(t = 34.895,P＜0.001;t = 12.152,P＜0.001)。经相关性分析,观察组和对照组血清Hcy与叶酸水平均呈负相关(r = - 0.91,P＜0.05; r = - 0.842,P＜0.05)。观察组自然分娩率低于对照组,早产率和流产率高于对照组,2组的妊娠结局差异有统计学意义(P＜0.05)。观察组妊娠结局中流产组Hcy水平高于早产组和自然分娩组(F = 271.800,P＜0.001)。同时,流产组叶酸水平明显低于早产组和自然分娩组,差异具有统计学意义(F = 5.192,P = 0.006)。对孕妇进行个体规范化补充叶酸,2组中规范补充叶酸组叶酸水平高于未按医嘱规范补充叶酸组(t = 5.243,P＜0.05;t = 6.095, P＜0.05),相应的,规范组Hcy水平低于不规范组,差异有统计学意义(t = 11.341,P＜0.05;t = 10.552, P＜0.05)。结论 在先兆流产孕妇体内血清Hcy增高,叶酸低表达,且Hcy和叶酸水平与孕妇的妊娠结局有关。     

Changes in plasma zinc and folic acid concentrations in pregnant adolescents submitted to different supplementation regimens

Zinc and folic acid nutritional status was evaluated in 74 low-income pregnant adolescents ranging from 13 to 18 years of age who received prenatal care at the Evangelina Rosa Maternity Hospital in Teresina, Piau State, Brazil. In order to evaluate the effects of different supplementation regimens on nutritional status, the adolescents were distributed into five groups. Groups I and II received equal amounts of folic acid (250 micro;g) and different doses of iron (ferrous sulfate), 120 and 80 mg, respectively. Groups III and IV received equal amounts of folic acid (250 micro;g) associated with zinc sulfate and iron at doses of 120 and 80 mg, respectively, while group V received only 120 mg of iron (routine dosage). There was a reduction in the zinc plasma concentration, and this decline was significant only in those groups which did not receive zinc supplementation. In relation to combination iron/folic acid and iron/folic acid/zinc, an excellent response was observed for folic acid, and this effect was larger in the groups that received folic acid combined with zinc, suggesting a possible role for zinc in folic acid metabolism.     

血清同型半胱氨酸、叶酸浓度水平与老年阿尔茨海默病发病的相关性研究

目的研究血清同型半胱氨酸(Hcy)、叶酸浓度水平与老年阿尔茨海默病(AD)发病的相关性,以期为临床防治提供指导。方法将2016年5月-2018年10月于本院接受诊治的92例老年阿尔茨海默病患者作为研究组,另选择同期于本院健康体检者80例为对照组。选择高效液相法对2组人员的血清Hcy表达水平进行测定,并应用化学发光法对血清叶酸水平进行检测;分析血清Hcy、叶酸与AD患者认知功能、生活质量的相关性。结果研究组患者的血清Hcy水平高于对照组,但血清叶酸水平、MMSE评分均低于对照组,差异有统计学意义(P<0.05);研究组患者的血清Hcy过高表达检出率、叶酸过低表达检出率均高于对照组,差异有统计学意义(P<0.05);AD过高Hcy组患者的血清叶酸水平显著低于AD正常Hcy组,差异有统计学意义(P<0.05);经Spearman相关性分析发现,血清叶酸和认知功能、生活质量显示为正相关(r=0.328、r=0.339,P<0.05),而血清Hcy和认知功能、生活质量显示为负相关(r=-0.517、r=-0.502,P<0.05)。结论血清同型半胱氨酸过高表达和老年阿尔茨海默病发病存在直接相关性,即高Hcy血症可能是引发AD的独立危险因素;而人体缺乏叶酸能导致血清Hcy表达升高,故认为叶酸的缺乏可能是引发AD的间接危险因素。     

6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults

OBJECTIVES: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups. DESIGN: A randomized, double-blind intervention study. SUBJECTS: A total of 12 young (<30 y) and 12 middle-aged (> or =50 y) healthy volunteers were recruited. METHODS: Volunteers were randomized to receive daily supplementation with 400 mug folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [(2)H(2)]folic acid test doses using isotope kinetics in plasma. RESULTS: Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P = 0.03) and after (P = 0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P = 0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young (+50%; P = 0.05) but not in the middle-aged (+18%; P = 0.5) adults. CONCLUSIONS: Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults.Sponsorship:Financial support was received from the European Union 5th Framework Programme (Grant QLRT-1999-00576).     

叶酸对孤独症谱系障碍儿童甲基化水平和氧化应激状态的影响

了解孤独症谱系障碍(autism spectrum disorders,ASD)儿童叶酸、同型半胱氨酸(Hcy)和谷胱甘肽(GSH)代谢状况,为探讨叶酸对ASD儿童甲基化水平和氧化应激状态的作用提供参考.方法 采用病例对照研究方法,收集哈尔滨医科大学儿童发育行为研究中心就诊的ASD儿童53例,选取53例性别年龄匹配的儿童为对照组,应用传统方法检测血清叶酸,Hcy,GSH和氧化型谷胱甘肽(GSSG)水平.招募参与结构化教学训练的ASD儿童83例,根据是否补充叶酸分为叶酸干预组和非叶酸干预组.采用自闭症儿童心理教育评核第3版(Psychoeducational Profile-third edition,PEP-3)对干预前后的ASD儿童进行发育水平评估,同时应用高效液相色谱检测叶酸干预组中29例ASD儿童干预前后的血浆叶酸,Hcy,GSH以及GSSG水平,并与对照儿童进行比较.结果 病例对照研究中,ASD组血清叶酸,GSH和GSH/GSSG比值明显低于对照组,Hcy和GSSG明显高于对照组,差异均有统计学意义(P值均<0.05).叶酸干预组的ASD儿童认知、语言理解和情感表达方面较非叶酸干预组提高.叶酸干预前,ASD儿童血浆叶酸,GSH,GSH/GSSG低于正常儿童,Hcy和GSSG高于正常儿童;叶酸干预后,ASD儿童叶酸,GSH,GSH-/GSSG明显升高,Hcy和GSSG明显降低,差异均有统计学意义(P值均<0.05);且与正常儿童相比,叶酸水平升高而Hcy降低.相关分析显示,Hcy的改变与行为特征—语言评分的改变呈负相关(r=-0.411,P=0.027).结论 ASD儿童体内叶酸水平低、Hcy水平高、氧化应激强.叶酸干预能够有效调节甲基化水平和氧化应激状态,对于参与结构化训练的ASD儿童具有良好的辅助治疗作用.     

Maternal DHA Supplementation during Pregnancy and Lactation in the Rat Protects the Offspring against High-Calorie Diet-Induced Hepatic Steatosis

Maternal supplementation during pregnancy with docosahexaenoic acid (DHA) is internationally recommended to avoid postpartum maternal depression in the mother and improve cognitive and neurological outcomes in the offspring. This study was aimed at determining whether this nutritional intervention, in the rat, protects the offspring against the development of obesity and its associated metabolic disorders. Pregnant Wistar rats received an extract of fish oil enriched in DHA or saline (SAL) as placebo by mouth from the beginning of gestation to the end of lactation. At weaning, pups were fed standard chow or a free-choice, high-fat, high-sugar (fc-HFHS) diet. Compared to animals fed standard chow, rats exposed to the fc-HFHS diet exhibited increased body weight, liver weight, body fat and leptin in serum independently of saline or DHA maternal supplementation. Nevertheless, maternal DHA supplementation prevented both the glucose intolerance and the rise in serum insulin resulting from consumption of the fc-HFHS diet. In addition, animals from the DHA-fc-HFHS diet group showed decreased hepatic triglyceride accumulation compared to SAL-fc-HFHS rats. The beneficial effects on glucose homeostasis declined with age in male rats. Yet, the preventive action against hepatic steatosis was still present in 6-month-old animals of both sexes and was associated with decreased hepatic expression of lipogenic genes. The results of the present work show that maternal DHA supplementation during pregnancy programs a healthy phenotype into the offspring that was protective against the deleterious effects of an obesogenic diet.