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The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics.

BACKGROUND: Previous studies reported that administration of first generation alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake. OBJECTIVES: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured. DESIGN: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption. RESULTS: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test. CONCLUSIONS: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.

1-Deoxynojirimycin↗

Comparison of thrice daily 'high' vs. 'medium' premixed insulin aspart with respect to evening and overnight glycaemic control in patients with type 2 diabetes.

BACKGROUND: The glycaemic control of thrice daily treatment with premixed biphasic insulin aspart (BIAsp) without other antidiabetic therapy was tested in type 2 diabetic patients, in order to compare the glucose control of a 'high' mixture (BIAsp 70) or a 'medium' mixture (BIAsp 50) (70 or 50% soluble IAsp and 30 or 50% protamine-crystallized IAsp, respectively) administered just before dinner. AIM: To compare these regimens to conventional 30 : 70 premixture on a twice a day basis. METHODS: This randomized, double-blind, two-period crossover study included 16 patients with type 2 diabetes. Twenty four-hour serum glucose and insulin profiles were obtained thrice: (1) after a one-week run-in period with biphasic human insulin (BHI) 30/70 twice daily (run-in), (2) after 4 weeks of treatment with thrice daily BIAsp 70 before breakfast, lunch and dinner (Dinner70 regimen) and (3) after 4 weeks of BIAsp 70 before breakfast and lunch and BIAsp 50 before dinner (Dinner50). RESULTS: Daytime average serum glucose was lower with Dinner70 compared to run-in (9.6 +/- 0.39 mmol/l vs. 11.2 +/- 0.61 mmol/l, p < 0.05). Postprandial glucose excursions after breakfast and lunch were lower, but fasting morning glucose was higher during the treatment periods than in the run-in period. Twenty four-hour C-peptide AUC was considerably lower during both treatment periods than in the run-in period (run-in/Dinner50 ratio 1.29 [1.08; 1.54] p < 0.01; run-in/Dinner70 ratio 1.31 [1.08;1.58], p < 0.01). CONCLUSIONS: Switching the dinner dose to BIAsp 50 did not alter overall glucose control significantly from that provided with BIAsp 70. Exploratory analyses between the two active treatment regimens and run-in/BHI indicate that thrice daily BIAsp 70 administration: (1) for optimization of the night-time control, the dinner dose needs adjustment or replacement by a premixed insulin with a larger proportion of basal insulin than BIAsp 50 and (2) none of the premixtures adequately provide for both the evening meal and overnight requirements.

Aged↗

Post-prandial insulin lispro vs. human regular insulin in prepubertal children with Type 1 diabetes mellitus.

AIMS: To study whether post-prandial insulin lispro (PL) could be used as a part of insulin therapy instead of premeal human regular insulin (HR) in prepubertal children with Type 1 diabetes mellitus (Type 1 DM). PATIENTS AND METHODS: In this open, randomized cross-over study patients used either PL or HR at breakfast and at dinner. After a 1-month screening period, patients were randomized to treatment with PL or HR for 3 months and then they crossed over to the other insulin for an additional 3 months. The patients were 24 prepubertal children with Type 1 DM (median age 6.2 years, duration of diabetes 37 months). Home monitoring of 1-day glucose profiles at meals (premeal, 1 h and 2 h after breakfast and after dinner) and HbA1c were measured before randomization, before cross-over, and at the last visit. Data on hypoglycaemic episodes were collected at each of the seven visits. The variables were compared between the two treatments. RESULTS: Of the patients 22/24 completed the study. There were no major differences in the glucose excursions between PL and HR after breakfast (mean +/- SD: 1-h PL 3.7 +/- 4.7 vs. HR 2.9 +/- 3.9 mmol/l, P = 0.3; 2-h -0.9 +/- 5.4 vs. 0.3 +/- 4.5 mmol/l, P = 0.2, respectively) or after dinner (1-h PL -2.5 +/- 4.8 vs. HR -0.4 +/- 3.7 mmol/l, P = 0.07, 2-h -4.1 +/- 5.2 vs. -0.7 +/- 5.0 mmol/l, P = 0.05, respectively). Mean change of HbA1c was similar in both treatment groups (PL 0.2 +/- 0.8% vs. HR -0.4 +/- 0.7%, P = 0.1). The frequency of hypoglycaemic episodes was 4.9 per patient per month during treatment with PL, and 4.4 during HR (P = 0.3). CONCLUSION: Treatment with post-prandial lispro as a meal insulin is as effective and safe as traditional treatment with regular insulin in young children.

Child↗

Relationship between fasting and day-long plasma glucose concentrations in diet-treated patients with type 2 diabetes.

To define the relationship between fasting and postprandial hyperglycemia, plasma glucose concentrations were determined before and after breakfast and lunch in 42 diet-treated patients with type 2 diabetes. Breakfast was consumed at 8:00 AM and lunch at 12:00 PM, with blood drawn hourly from 8:00 AM to 4:00 PM for measurement of plasma glucose concentration. The results demonstrated highly significant correlation coefficients (r) between fasting plasma glucose concentration and any individual hourly value (r values varying between 0.86 and 0.91). Furthermore, fasting plasma glucose concentrations and the total integrated glucose response areas, post-breakfast (8:00 AM to 12:00 PM), post-lunch (12:00 PM to 4:00 PM), and day-long (8:00 AM to 4:00 PM) were also highly correlated, with r values of 0.95, 0.91, and 0.94, respectively. These results demonstrate that fasting and postprandial glucose concentrations are almost perfectly correlated in diet-treated patients with type 2 diabetes, and that determination of fasting plasma glucose concentrations in these individuals provides an excellent estimate of degree of glycemic control.

Adult↗

Postprandial glycemic control with biphasic insulin aspart in patients with type 1 diabetes.

We sought to investigate the ability of biphasic insulin aspart 30 (BIAsp 30) to control postprandial hyperglycemia and hyperlipidemia in a meal-test comparison with biphasic human insulin 30 (BHI 30). In this randomised crossover trial, 50 patients with type 1 diabetes (mean age, 35.7 +/- 9.4 years; body mass index [BMI], 24.0 +/- 2.6 kg/m(2); HbA(1c), 8.6% +/- 1.1%) were studied on 3 separate days, where the following treatments were given in random order: BIAsp 30 injected immediately before a standard breakfast, BHI 30 injected 30 minutes before breakfast (BHI 30(t=-30)), and BHI 30 injected immediately before breakfast (BHI 30(t=0)). The dose was 0.40 U/kg for all 3 treatments. BIAsp 30 reduced the area under the baseline adjusted 4-hour postprandial serum glucose curve (AUC(0-4h)) by 23% compared with BHI 30(t=0) (P <.0001) and by 9% compared with BHI 30(t=-30) (P =.013). Maximum serum glucose concentration (C(max)) was lower for BIAsp 30 compared with BHI 30(t=0) (14.0 +/- 2.4 v 16.5 +/- 2.8 mmol/L, P <.0001), and time to maximal serum glucose concentration (t(max)) was approximately 20 minutes shorter for BIAsp 30, irrespective of timing of BHI 30 injection (P <.0001). There were no significant differences among the 3 treatments with respect to postprandial levels of free fatty acids or triglycerides. The pharmacokinetic results were consistent with the above observations, ie, significantly larger insulin AUC(0-4h), higher C(max) and shorter t(max) were observed for BIAsp 30 compared with BHI 30, irrespective of timing of BHI 30 injection. We conclude that postprandial glycemic control was more effective with BIAsp 30 than with BHI 30, irrespective of timing of BHI 30 injection.

Adult↗

Nutrient-stimulated GLP-1 release in normal-weight men and women.

The aim of the present study was to investigate the effect of a monosaccharide/fiber preload (galactose/guar gum) in combination with a standard breakfast (GG) on plasma GLP-1, insulin, glucose, free fatty acid concentrations, and appetite ratings (satiety, hunger, fullness and desire to eat) in 30 normal-weight subjects. GG was compared to water in combination with the standard breakfast (W). We also tested for differences in GLP-1 release in the described conditions between genders. In women, postprandial plasma GLP-1 concentrations after GG were significantly increased compared to W (p < 0.05). The area under the curve (AUC) for DeltaGLP-1 after GG was related to body fat (%BF) in women (r = 0.48; p = 0.02), but not in men. The rise in plasma insulin was delayed, and plasma glucose concentration was blunted after GG. Deltasatiety was significantly related to DeltaGLP-1 (W). In conclusion, galactose with guar gum increased and extended the GLP-1 release due to breakfast in women, but not in men. This may be partly explained by %BF, which is higher in women than in men since GLP-1 release appears to be related to %BF.

Administration, Oral↗

Relationship between diurnal glucose levels and HbA1c in type 2 diabetes.

AIMS AND METHODS: Study results still conflict on the contribution of diurnal blood glucose (BG) values to Hb (A1c) in type 2 diabetes. We investigated the relationship between Hb (A1c) and diurnal BG obtained under standardized conditions - before breakfast, two hours after breakfast, before lunch, two hours after lunch, before dinner, two hours after dinner, and at 10 PM, 12 midnight and 3 AM in 68 type 2 diabetic patients before and after optimizing glycemic control. The areas under the curve above fasting BG (AUC1) and above 5.6 mmol/l (AUC2) were calculated for further evaluation. Hb (A1c) was measured at baseline and after a mean of 89 (74 to 108) days. RESULTS: Each BG value at baseline and after treatment optimization significantly correlated with baseline and follow-up Hb (A1c), respectively. The pre-breakfast BG showed the closest correlation with Hb (A1c). The relative contribution of postprandial BG concentrations (AUC1) to overall hyperglycemia (AUC2) decreased with poorer glycemic control. However, treatment optimization mainly resulted in improved blood glucose values in patients with the poorest glycemic control at baseline. Multiple regression analysis demonstrated that fasting (AUC2-AUC1) and postprandial (AUC1) hyperglycemia independently determined Hb (A1c) or the change in Hb (A1c) after treatment optimization. CONCLUSIONS: Our findings indicate that intensive blood glucose monitoring during fasting and postprandial states is important for glycemic control, and is therefore an essential part of good clinical practice.

Blood Glucose↗

Dietary intake of 9-10-year-old and 11-12-year-old children in Liverpool.

OBJECTIVE: To describe the eating habits of children in Liverpool and compare two age groups that bridge the transition from primary to secondary school. DESIGN: Two cross-sectional studies carried out one year apart using a food intake questionnaire that records whether or not each child claims to have eaten specific marker foods on the previous day. SETTING: Primary and secondary schools in Liverpool. SUBJECTS: Six hundred and forty-nine children aged 11 or 12 years and 3556 children aged 9 or 10 years. RESULTS: Fewer older children ate breakfast (68-82%), especially the girls, and not eating breakfast was associated with eating on the way to school in the younger children. More of the older girls ate nothing at breakfast or on the way to school. Overall, the less desirable foods were reported to have been eaten by more children, of both ages, than the more desirable foods. Fruit, however, was mentioned by most children (69-77%) but the next 10 foods mentioned by most children were all less desirable ones. Only 31% of primary and 21% of secondary children ate both fruit and vegetables but 23% of primary and 26% of secondary children ate neither fruit nor vegetables. Overall, more of the girls of both age groups claimed to have eaten foods that would normally be encouraged. CONCLUSIONS: Food choice changes appreciably between primary and secondary school and, in some key respects, for the worse. In particular, far more children of both age groups need to be eating fruit and vegetables every day.

Age Factors↗

The glycaemic index: importance of dietary fibre and other food properties.

An increasing body of evidence suggests that a low-glycaemic-index (GI) diet has a therapeutic as well as a preventive potential in relation to the insulin resistance syndrome. The implementation of a low-GI diet, however, will require an extended list of low-GI foods to be available on the market. The tailoring of low-GI bread products offers a particular challenge due to their generally high GI and abundance in the diet. Low-GI bread products can be tailored by, for example,enclosure of cereal kernels, sour dough fermentation and/or addition of organic acids, or use of cereal genotypes with elevated contents of amylose or f-glucans. Low-GI cereal foods appear to vary in effect on 'second-meal' glucose tolerance in healthy subjects. In addition to the slow-release properties of such foods, the content of dietary fibre appears to play a role. The low glycaemia to starch in a pasta breakfast (GI 54) promoted a higher glucose tolerance and lowered triacylglycerol levels at a standardized lunch ingested 4 h later, compared with a white-wheat-bread breakfast (GI 100). The metabolic benefits of the low GI properties per se have been demonstrated also in the longer term. Thus, a reduction in dietary GI improved glucose and lipid metabolism and normalized fibrinolytic activity in type 2 diabetics, while maintaining a similar amount and composition of dietary fibre. However, the higher dietary fibre content frequently associated with low-GI foods may add to the metabolic merits of a low-GI diet. Consequently, a low-GI barley meal rich in dietary fibre (GI 53) improved glucose tolerance from evening meal to breakfast, whereas an evening meal with pasta had no effect (GI 54). The exchange of common high-GI bread for low-GI high-fibre bread, as the only dietary modification, improved insulin economy in women at risk of type 2 diabetes. These results are in accordance with epidemiological evidence of a reduced risk of type 2 diabetes with a low-GI diet rich in cereal fibre. It is concluded that low-GI cereal foods developed should preferably be rich in dietary fibre.

Blood Glucose↗

Time course of oxidative stress status in the postprandial and postabsorptive states in type 1 diabetes mellitus: relationship to glucose and lipid changes.

OBJECTIVE: The aim of this study was to compare oxidative stress status (OSS) with blood glucose and lipid changes during the fasting, postprandial and postabsorptive phases in type 1 diabetes mellitus. METHODS: Twenty-three patients on intensive insulin treatment received a standard fat-rich breakfast and lunch. OSS was monitored at fasting (F), just after the post-breakfast glycemia peak (BP) (identified by continuous subcutaneous glucose monitoring), 3.5-h post-breakfast (B3.5), just after the post-lunch peak (LP), just after the post-lunch dale (LD) and 5 hours after lunch (L5). RESULTS: Whereas whole blood glutathione and plasma protein thiols increased in the postprandial period (from 6.52 +/- 1.20 (F) to 7.08 +/- 1.45 micromol/g Hb (BP), p = 0.005), ascorbate decreased gradually from 44 +/- 17 (F) to 39 +/- 19 micromol/L (LD), p = 0.015. Retinol and alpha-tocopherol also decreased from 27.1 +/- 7.0 (F) to 25.3 +/- 5.2 micromol/L (BP), p = 0.005. Uric acid decreased later, from 213 +/- 77 (BP) to 204 +/- 68 micromol/L (B3.5), p = 0.01, but then increased in LP (231 +/- 70 micromol/L) and LD to values higher than F (215 +/- 64, micromol/L, p = 0.01). Malondialdehyde increased gradually from 1.02 +/- 0.36 (F) to a maximum of 1.14 +/- 0.40 micromol/L (LP). In the postabsorptive phase (L5) all parameters except for thiols reverted to fasting concentrations. CONCLUSIONS: In type 1 diabetes lipid peroxidation increases during the postprandial phase in parallel to glucose and triglyceride changes. Blood antioxidants, however, followed diverse patterns of change.

Absorption↗

Determination of vitamin A in blood. Some practical considerations on the time of collection of the specimens and the stability of the vitamin.

The stability of vitamin A and retinol-binding protein (RBP) in serum separated from the clot at different times after blood extraction and the effect of ingesting a vitamin A-rich breakfast on postprandial serum levels of retinol, carotenoids, and RBP were investigated. In the stability trials, venous blood was drawn from 12 well-nourished young adult subjects and sample aliquots were maintained, respectively, at 4 degree C or at room temperature (26 to 28 degrees C). The serum was separated from the clot either immediately after blood clotting or at 2, 4, 6, 12, and 24 h after blood extraction. Serum retinol and RBP were stable either at 4 degrees C or at room temperature, even if the serum was separated from the clot 24 h after blood extraction. In the breakfast experiment, seven young adult subjects ingested a meal containing 291 microgram of retinol equivalents. The serum levels of retinol, carotenoids, and RBP were measured pre- and postprandially up to a period of 4 h. The ingestion of the breakfast meal did not alter significantly the postprandial serum levels of retinol, carotenoids, or RBP. These results are of practical importance for the performance of vitamin A nutrition surveys involving field work, when as is common, blood specimens cannot be collected under fasting and, in addition, they have to be transported from far away localities to the laboratory.

Adult↗

Significance of postprandial blood concentrations of retinol, retinol-binding protein, and carotenoids when assessing the vitamin A status of children.

The effect of ingesting a breakfast rich in vitamin A on postprandial blood serum concentration of retinol, retinol-binding protein, and carotenoids has been investigated in children between 5 and 8 yr of age. They were divided by age in two groups (5 to 6 and 7 to 8 yr) and then randomly assigned in three groups to be studied cross-sectionally immediately before and at 2 and 4 h after the ingestion of a meal containing 337 micrograms of retinol equivalents (48% as retinol and 52% as carotenoids). The ingestion of breakfast did not alter significantly (p greater than 0.05) the postprandial serum concentrations of retinol, retinol-binding protein; or carotenoids in any of the age groups. These results indicate that up to 4 h the postprandial blood serum concentrations of these parameters are representative of their corresponding basal concentrations. Therefore, in practice and particularly under field survey conditions, the blood samples required to assess the vitamin A status of children can be obtained either fasting or within 4 h after breakfast without altering the results.

Administration, Oral↗

All bran vs corn flakes: plasma glucose and insulin responses in young females.

Plasma glucose and insulin responses to breakfasts containing all bran or corn flakes were determined in 11 normal female volunteers aged 21-27 y. The test meals provided 50 g egg, 133 g orange juice, 129 g 2% milk, 180 g coffee, 5 g margarine, and 30 g available carbohydrate from either all bran or corn flakes with 19 g or 1 g of dietary fiber, respectively. Plasma glucose and insulin responses were higher for the corn flake breakfast and the incremental area under the glucose curve was 40% greater than that for the all bran breakfast (t test, p less than 0.05). These results are consistent with the reported glycemic indices for these cereals when consumed alone but the glucose responses differ to a lesser degree when the cereals are ingested with other foods. Thus, in this group of well-defined subjects the effect of all bran and corn flakes on plasma glucose responses is attenuated when these cereals are incorporated into mixed meals.

Adult↗

Psyllium fiber reduces rise in postprandial glucose and insulin concentrations in patients with non-insulin-dependent diabetes.

The ability of psyllium fiber to reduce postprandial serum glucose and insulin concentrations was studied in 18 non-insulin-dependent diabetic patients in a crossover design. Psyllium fiber or placebo was administered twice during each 15-h crossover phase, immediately before breakfast and dinner. No psyllium fiber or placebo was given at lunch, which allowed measurement of residual or second-meal effects. For meals eaten immediately after psyllium ingestion, maximum postprandial glucose elevation was reduced by 14% at breakfast and 20% at dinner relative to placebo. Postprandial serum insulin concentrations measured after breakfast were reduced by 12% relative to placebo. Second-meal effects after lunch showed a 31% reduction in postprandial glucose elevation relative to placebo. No significant differences in effects were noted between patients whose diabetes was controlled by diet alone and those whose diabetes was controlled by oral hypoglycemic drugs. Results indicate that psyllium as a meal supplement reduces proximate and second-meal postprandial glucose and insulin concentrations in non-insulin-dependent diabetics.

Adult↗

Comparing the effects of aspartame and sucrose on motivational ratings, taste preferences, and energy intakes in humans.

This study compared the effects of four breakfast preloads on motivational ratings, taste preferences, and energy intakes of 24 normal-weight nondieting young men and women. The preloads, composed of creamy white cheese (fromage blanc), were either plain or sweetened with aspartame or sucrose. Their energy value was either 1255 or 2929 kJ (300 or 700 kcal). Taste preferences were measured before and 150 min after breakfast. Motivational ratings were obtained at 30-min intervals. The subjects ate lunch, snack, and dinner meals in the laboratory. The consumption of low-energy as opposed to high-energy breakfasts, regardless of sweetness, led to elevated motivational ratings and increased energy intakes at lunch. However, intakes at subsequent meals were the same for all preloads, and no overall compensation in energy was observed. Aspartame did not promote hunger or lead to increased energy intakes in normal-weight subjects.

Adult↗

Dietary intakes of students.

This paper relies on 24-h dietary recall data from a nationally representative sample of approximately 3350 students to analyze the dietary intakes of students. Most US students eat at least five times during the day, and nearly all eat at least three times per day. The average daily intake of vitamins and minerals at least meets the recommended dietary allowances (RDAs). Overall, students consume more food energy on average than recommended, suggesting that some may be at risk of consuming more food energy than is optimal. Students also consume more protein, total fat, saturated fat, and sodium than is recommended for good health. National School Lunch Program (NSLP) participants' mean intakes of most nutrients at lunch meet the program goal of at least one-third of the RDA. NSLP participants, however, consume more fat, saturated fat, and sodium than is recommended. School Breakfast Program (SBP) participants' mean intakes of most nutrients at breakfast also exceed the program goal of one-fourth of the RDA. However, their breakfast intakes of saturated fat as a percentage of food energy, cholesterol, and sodium exceed dietary recommendations.

Adolescent↗

Evaluation of school feeding programs: some Jamaican examples.

It is hypothesized that giving children a daily breakfast at school may improve their scholastic achievement through several mechanisms: increasing the time spent in school, improving certain cognitive functions and attention to tasks, and, perhaps indirectly, improving nutritional status. Two Jamaican studies showed that providing breakfast to students at school improved some cognitive functions, particularly in undernourished children. However, changes in classroom behavior varied depending on the quality of the school. Children in better-organized schools concentrated on tasks for longer periods and made fewer undesirable movements, whereas in poorly organized schools the children's behavior deteriorated. Studies to date have provided insufficient evidence to determine whether children's long-term scholastic achievement is improved by eating breakfast daily. Well-designed, randomized, controlled, long-term trials are essential for determining public policy on the implementation of school feeding programs.

Attention↗

Dietary strategies for lowering homocysteine concentrations.

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are associated with increased risk of vascular disease, and there is a strong inverse association between dietary and blood folate and blood tHcy concentrations. Increased folate consumption may lower the risk of tHcy-mediated cardiovascular disease. OBJECTIVES: The objective was to determine the most appropriate means of increasing dietary folate to reduce plasma tHcy. DESIGN: Sixty-five free-living subjects aged 36-71 y with tHcy concentrations >/=9 micromol/L participated in a randomized, controlled trial to compare 3 approaches for increasing dietary folate to approximately 600 microg/d: folic acid supplementation, consumption of folic acid-fortified breakfast cereals, and increased consumption of folate-rich foods. RESULTS: An intake of 437 microg folic acid/d from supplements resulted in a 27-nmol/L increase in serum folate and a 21% reduction in tHcy, relative to the change in a control group. In subjects who consumed folic acid-fortified breakfast cereal, folate intake increased by an average of 298 microg, serum folate increased by 21 nmol/L, and tHcy concentrations decreased by 24%. Increased intakes of folate-rich foods resulted in a 418-microg increase in dietary folate, a 7-nmol/L increase in serum folate, and a 9% reduction in tHcy concentrations. The decrease in tHcy was negatively correlated (r = -0.66) with the increase in serum folate. CONCLUSIONS: Daily consumption of folic acid-fortified breakfast cereals and the use of folic acid supplements appear to be the most effective means of reducing tHcy concentrations. The reduction in tHcy was significantly negatively correlated with the increase in serum folate, which may be a useful marker for measuring dietary change.

Adult↗