The effects of regular consumption of a multiple micronutrient fortified milk beverage on the micronutrient status of school children and on their mental and physical performance.

Multiple micronutrient deficiencies exist in school going children in India and bridging the gap between nutrient intake and requirements is an effective way to combat the deficiencies. This study aimed to test the effect of a multi-micronutrient fortified malt and cocoa based milk beverage on the micronutrient status, cognition, physical performance and nutritional deficiencies of 7-10 years old south Indian children. A randomized, double blind placebo controlled study design was used with normal healthy children from low to middle income families, aged 7-10 years randomly assigned to receive either a multi-micronutrient fortified or an unfortified milk based control drink. The drinks were provided 6 days/week for 5 months. Assessments included anthropometry, blood biochemistry, physical performance and cognition at baseline and endline. The baseline characteristics of the study groups were similar. The changes in body weight and height were similar between the groups at the end of the study. Levels of vitamin B12, red cell folate and vitamin B2 significantly improved in the intervention group, while vitamin D, selenium and body iron showed no difference. The Hemoglobin (Hb) and serum ferritin levels of the control group decreased at endline, while those in the intervention group maintained their levels. The serum transferrin receptor levels increased in both the groups. The prevalence of iron deficiency and Vitamin B2 deficiency were significantly lower in the intervention group at endline. Overall improvement in cognitive and physical performance was seen in both the groups at endline, with no significant differences between the groups. The micronutrient fortified milk based drink was efficacious in improving the micronutrient status of Vitamin B2, Vitamin B12 and red cell folate and in preventing a decline in Hb level compared to an unfortified milk based drink. It also reduced anemia and the risk of deficiencies of iron, and B12, in apparently healthy children. ClinicalTrials.gov IdentifierNCT01415557. Clinical Trial RegistryIndia - REF/2012/12/004332.

Increased dietary α-linolenic acid has sex-specific effects upon eicosapentaenoic acid status in humans: re-examination of data from a randomised, placebo-controlled, parallel study.

BACKGROUND: There is a metabolic pathway by which mammals can convert the omega-3 (n-3) essential fatty acid α-linolenic acid (ALA) into longer-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). As far as we know there are currently no studies that have specifically examined sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans, although acute studies with isotope-labelled ALA identified that women have a significantly greater capacity to synthesise EPA and DHA from ALA compared to men. FINDINGS: Available data from a placebo-controlled, randomised study were re-examined to identify whether there are sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans. There was a significant difference between sexes in the response to increased dietary ALA, with women having a significantly greater increase in the EPA content of plasma phospholipids (mean +2.0% of total fatty acids) after six months of an ALA-rich diet compared to men (mean +0.7%, P = 0.039). Age and BMI were identified as predictors of response to dietary ALA among women. CONCLUSIONS: Women show a greater increase in circulating EPA than men during increased dietary ALA consumption. Further understanding of individual variation in the response to dietary ALA could inform nutrition advice, with recommendations being specifically tailored according to habitual diet, sex, age and BMI.

Response variability to glucose facilitation of cognitive enhancement.

Glucose facilitation of cognitive function has been widely reported in previous studies (including our own). However, several studies have also failed to detect glucose facilitation. There is sparsity of research examining the factors that modify the effect of glucose on cognition. The aims of the present study were to (1) demonstrate the previously observed enhancement of cognition through glucose administration and (2) investigate some of the factors that may exert moderating roles on the behavioural response to glucose, including glucose regulation, body composition (BC) and hypothalamic­pituitary­adrenal axis response. A total of twenty-four participants took part in a double-blind, placebo-controlled, randomised, repeated-measures study, which examined the effect of 25 and 60 g glucose compared with placebo on cognitive function. At 1 week before the study commencement, all participants underwent an oral glucose tolerance test. Glucose facilitated performance on tasks of numeric and spatial working memory, verbal declarative memory and speed of recognition. Moderating variables were examined using several indices of glucoregulation and BC. Poorer glucoregulation predicted improved immediate word recall accuracy following the administration of 25 g glucose compared with placebo. Those with better glucoregulation showed performance decrements on word recall accuracy following the administration of 25 g glucose compared with placebo. These findings are in line with accumulating evidence that glucose load may preferentially enhance cognition in those with poorer glucoregulation. Furthermore, the finding that individuals with better glucoregulation may suffer impaired performance following a glucose load is novel and requires further substantiation.

The effect of glucose dose and fasting interval on cognitive function: a double-blind, placebo-controlled, six-way crossover study.

RATIONALE: Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. OBJECTIVES: Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. METHODS: The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. RESULTS: Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. CONCLUSIONS: The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved.

Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

Glucose effects on long-term memory performance: duration and domain specificity.

RATIONAL: Previous research has suggested that long-term verbal declarative memory is particularly sensitive to enhancement by glucose loading; however, investigation of glucose effects on certain memory domains has hitherto been neglected. Therefore, domain specificity of glucose effects merits further elucidation. OBJECTIVES: The aim of the present research was to provide a more comprehensive investigation of the possible effects of glucose administration on different aspects of memory by 1) contrasting the effect of glucose administration on different memory domains (implicit/explicit memory; verbal/non-verbal memory, and recognition/familiarity processes), 2) investigating whether potential effects on memory domains differ depending on the dose of glucose administered (25 g versus 60 g), 3) exploring the duration of the glucose facilitation effect (assessment of memory performance 35 min and 1 week after encoding). METHODS: A double-blind between-subjects design was used to test the effects of administration of 25 and 60 g glucose on memory performance. RESULTS: Implicit memory was improved following administration of 60 g of glucose. Glucose supplementation failed to improve face recognition performance but significantly improved performance of word recall and recognition following administration of 60 g of glucose. However, effects were not maintained 1 week following encoding. CONCLUSIONS: Improved implicit memory performance following glucose administration has not been reported before. Furthermore, the current data tentatively suggest that level of processing may determine the required glucose dosage to demonstrate memory improvement and that higher dosages may be able to exert effects on memory pertaining to both hippocampal and non-hippocampal brain regions.

Role of familiarity on effects of caffeine- and glucose-containing soft drinks.

Familiarity, through conditioned responses and expectations, may play a significant role in the expression of liking for, and mood and performance effects of, food and drink constituents. The role of familiarity and the effects of caffeine and glucose in Lucozade Energy were investigated by testing this familiar soft drink, and its non-caffeine/non-CHO placebo match, against novel coloured/flavoured full and placebo drinks. Both the familiar drink and its placebo improved alertness, mental energy and mental performance compared to baseline and compared to the novel placebo drink. After repeated exposure, that is, after having gained familiarity with the novel drinks in addition to the already existing familiarity with Lucozade Energy, only the full (caffeine and CHO containing) drinks showed sustained beneficial effects compared to placebo drinks and baseline measures, as well as an increase in liking compared to placebo drinks. Therefore, participants appeared to have learned that beneficial effects were mainly linked to the full products. The results illustrate the restorative combination of caffeine and CHO in the drink, and emphasises the need to implement the appropriate placebo(s) in any study design employing familiar foods or drinks.

Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men.

The effect of increased dietary intakes of alpha-linolenic acid (ALNA) or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 2 months upon plasma lipid composition and capacity for conversion of ALNA to longer-chain metabolites was investigated in healthy men (52 (SD 12) years). After a 4-week baseline period when the subjects substituted a control spread, a test meal containing [U-(13)C]ALNA (700 mg) was consumed to measure conversion to EPA, docosapentaenoic acid (DPA) and DHA over 48 h. Subjects were then randomised to one of three groups for 8 weeks before repeating the tracer study: (1) continued on same intake (control, n 5); (2) increased ALNA intake (10 g/d, n 4); (3) increased EPA+DHA intake (1.5 g/d, n 5). At baseline, apparent fractional conversion of labelled ALNA was: EPA 2.80, DPA 1.20 and DHA 0.04 %. After 8 weeks on the control diet, plasma lipid composition and [(13)C]ALNA conversion remained unchanged compared with baseline. The high-ALNA diet resulted in raised plasma triacylglycerol-EPA and -DPA concentrations and phosphatidylcholine-EPA concentration, whilst [(13)C]ALNA conversion was similar to baseline. The high-(EPA+DHA) diet raised plasma phosphatidylcholine-EPA and -DHA concentrations, decreased [(13)C]ALNA conversion to EPA (2-fold) and DPA (4-fold), whilst [(13)C]ALNA conversion to DHA was unchanged. The dietary interventions did not alter partitioning of ALNA towards beta-oxidation. The present results indicate ALNA conversion was down-regulated by increased product (EPA+DHA) availability, but was not up-regulated by increased substrate (ALNA) consumption. This suggests regulation of ALNA conversion may limit the influence of variations in dietary n-3 fatty acid intake on plasma lipid compositions.

Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans.

Dietary alpha-linolenic acid (ALA) can be converted to long-chain (n-3) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on risk factors for coronary heart disease (CHD). This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects. A placebo-controlled, parallel study was conducted in 150 moderately hyperlipidemic subjects, age 25-72 y. Subjects were randomly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA, 4.5 or 9.5g/d ALA or control (linoleic acid; LA) for 6 mo. Fatty acids were incorporated into 25 g of fat spread, which replaced the subject's normal spread and three capsules. Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa, VIIc, VIIag, XIIa, XIIag, fibrinogen concentrations, plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control. (n-3) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors.

Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, free-living subjects aged 25-72 y.

BACKGROUND: There is little information about the relation between the fatty acid composition of human immune cells and the function of those cells over the habitual range of fatty acid intakes. OBJECTIVE: The objective of the study was to determine the relation between the fatty acid composition of human peripheral blood mononuclear cell (PBMC) phospholipids and the functions of human immune cells. DESIGN: One hundred fifty healthy adult subjects provided a fasting blood sample. The phagocytic and oxidative burst activities of monocytes and neutrophils were measured in whole blood. PBMCs were isolated and used to measure lymphocyte proliferation in response to the T cell mitogen concanavalin A and the production of cytokines in response to concanavalin A or bacterial lipopolysaccharide. The fatty acid composition of plasma and PBMC phospholipids was determined. RESULTS: Wide variations in fatty acid composition of PBMC phospholipids and immune cell functions were identified among the subjects. The proportions of total polyunsaturated fatty acids (PUFAs), of total n-6 and n-3 PUFAs, and of several individual PUFAs in PBMC phospholipids were positively correlated with phagocytosis by neutrophils and monocytes, neutrophil oxidative burst, lymphocyte proliferation, and interferon gamma production. The ratios of saturated fatty acids to PUFAs and of n-6 to n-3 PUFAs were negatively correlated with these same immune functions. The relation of PBMC fatty acid composition to monocyte oxidative burst was the reverse of its relation to monocyte phagocytosis and neutrophil oxidative burst. CONCLUSION: Variations in the fatty acid composition of PBMC phospholipids account for some of the variability in immune cell functions among healthy adults.

Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function.

BACKGROUND: Greatly increasing dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALA)] or fish oil [rich in the long-chain n-3 PUFAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] can reduce markers of immune cell function. The effects of more modest doses are unclear, and it is not known whether ALA has the same effects as its long-chain derivatives. OBJECTIVE: The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes. DESIGN: In a placebo-controlled, double-blind, parallel study, 150 healthy men and women aged 25-72 y were randomly assigned to 1 of 5 interventions: placebo (no additional n-3 PUFAs), 4.5 or 9.5 g ALA/d, and 0.77 or 1.7 g EPA+DHA/d for 6 mo. The n-3 PUFAs were provided in 25 g fat spread plus 3 oil capsules. Blood samples were taken at 0, 3, and 6 mo. RESULTS: The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA. The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity, the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester, the proliferation of lymphocytes in response to a T cell mitogen, the production of numerous cytokines by monocytes and lymphocytes, or the in vivo delayed-type hypersensitivity response. CONCLUSION: An intake of

Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects.

BACKGROUND: Dietary alpha-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. OBJECTIVE: This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. DESIGN: This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. RESULTS: The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean (+/- SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma alpha-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. CONCLUSION: At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects.

UK Food Standards Agency alpha-linolenic acid workshop report.

The UK Food Standards Agency convened a group of expert scientists to review current research investigating whether n-3 polyunsaturated fatty acids (PUFA) from plant oils (alpha-linolenic acid; ALA) were as beneficial to cardiovascular health as the n-3 PUFA from the marine oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The workshop also aimed to establish priorities for future research. Dietary intake of ALA has been associated with a beneficial effect on CHD; however, the results from studies investigating the effects of ALA supplementation on CHD risk factors have proved equivocal. The studies presented as part of the present workshop suggested little, if any, benefit of ALA, relative to linoleic acid, on risk factors for cardiovascular disease; the effects observed with fish-oil supplementation were not replicated by ALA supplementation. There is a need, therefore, to first prove the efficacy of ALA supplementation on cardiovascular disease, before further investigating effects on cardiovascular risk factors. The workshop considered that a beneficial effect of ALA on the secondary prevention of CHD still needed to be established, and there was no reason to look further at existing CHD risk factors in relation to ALA supplementation. The workshop also highlighted the possibility of feeding livestock ALA-rich oils to provide a means of increasing the dietary intake in human consumers of EPA and DHA.

Influence of the APOC3 -2854T>G polymorphism on plasma lipid levels: effect of age and gender.

The APOC3 -2854T>G polymorphism lies in the APOC3-A4 intergenic region. In a group of healthy adults, this polymorphism was associated with circulating triglycerides, with 55% lower fasting levels in the homozygous wild-type (TT) compared to the homozygous rare allele (GG) genotype. Age and gender had a significant impact on genotype-triglyceride interactions.