Systematic review with dose-response meta-analyses between vitamin B-12 intake and European Micronutrient Recommendations Aligned’s prioritized biomarkers of vitamin B-12 including randomized controlled trials and observational studies in adults and elderly persons

Dullemeijer, Carla; Souverein, Olga W.; Doets, Esmée L.; Voet, Hilko van der; Wijngaarden, J.P. van; Boer, W.J. de; Plada, María; Dhonukshe-Rutten, R.A.M.; Veld, Paulette H In 't; Cavelaars, Adriënne E J M; Groot, Lisette C. P. G. M. de; Veer, P. van ‘t

doi:10.3945/ajcn.112.033951

Cited by 39 publications

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“…Furthermore, reported estimates as from this paper together with those from RCTs can serve as a basis for further modeling toward determining dietary reference values for folate, such as the Average Nutrient Requirement (ANR), which vary greatly across countries (200–320 μg/day) [47-49]. The principle of that methodology has recently been developed within the EURRECA NoE and is readily available [6]. …”

Section: Resultsmentioning

confidence: 99%

“…Positive values would translate to a monotonic concave curve on the arithmetic scale that steeply increases at low intakes and less so at higher levels, which is a common shape in biology [6, 35]. …”

Section: Methodsmentioning

confidence: 99%

“…A meta-analysis on dose-response relation between folic acid intake and plasma biomarkers from randomized controlled trials (RCTs) in adults and elderly has been recently investigated by EURRECA coworkers [3]. We now performed a systematic review that included data from observational studies in which folate intake represents intakes from its natural dietary matrix and from fortified foods and supplements, and in which populations are not confined to those strictly selected by the RCTs inclusion and exclusion criteria [5, 6]. This study fills a knowledge gap by systematically reviewing all available observational studies that investigated the relationship between folate intake and biomarkers of folate status in adults and elderly, followed by meta-analyses in order to model biomarkers of folate status as a function of dietary folate intake.…”

Section: Introductionmentioning

confidence: 99%

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Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly

et al. 2018

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Background: Dietary reference values for folate intake vary widely across Europe. Methods: MEDLINE and Embase through November 2016 were searched for data on the association between folate intake and biomarkers (serum/plasma folate, red blood cell [RBC] folate, plasma homocysteine) from observational studies in healthy adults and elderly. The regression coefficient of biomarkers on intake (β) was extracted from each study, and the overall and stratified pooled β and SE (β) were obtained by random effects meta-analysis on a double log scale. These dose-response estimates may be used to derive folate intake reference values. Results: For every doubling in folate intake, the changes in serum/plasma folate, RBC folate and plasma homocysteine were +22, +21, and –16% respectively. The overall pooled regression coefficients were β = 0.29 (95% CI 0.21–0.37) for serum/plasma folate (26 estimates from 17 studies), β = 0.28 (95% CI 0.21–0.36) for RBC (13 estimates from 11 studies), and β = –0.21 (95% CI –0.31 to –0.11) for plasma homocysteine (10 estimates from 6 studies). Conclusion: These estimates along with those from randomized controlled trials can be used for underpinning dietary recommendations for folate in adults and elderly.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly

et al. 2018

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“…Several observational studies have described the dose-response relationship between cobalamin intake and serum cobalamin concentration and showed an increase in serum cobalamin with increasing cobalamin intake which levelled off between approximately 350 and 400 pmol/L at cobalamin intakes between 7 and 10 µg/day (Tucker et al, 2000;Kwan et al, 2002;Bor et al, 2006;Vogiatzoglou et al, 2009b;Bor et al, 2010) (Section 5.1.1.3). Dullemeijer et al (2013) attempted to characterise the dose-response relationship between cobalamin intake and serum concentration based on data from 37 randomised controlled trials (RCTs) and 19 observational studies (n = 15 968 subjects). There was statistical evidence for substantial heterogeneity between studies included in the meta-analysis, which could not be explained by the differences in study designs (observational studies vs. RCTs), mean age of subjects or the doses or forms of cobalamin consumed, so that the uncertainty around the resulting dose-response relationship is high.…”

Section: Serum Cobalamin Concentrationmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for cobalamin (vitamin B12)

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Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for cobalamin (vitamin B12). The Panel considers that the approach based on a combination of biomarkers of cobalamin status, i.e. serum cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA) and plasma total homocysteine (tHcy), is the most suitable approach to derive DRVs for cobalamin. The Panel notes the uncertainties with respect to cut-off values for cobalamin insufficiency of these indicators and that an Average Requirement (AR) cannot be determined from the limited data available. There is consistent evidence in adults that a cobalamin intake of 4 µg/day and greater is associated with serum concentrations of holoTC and cobalamin within the reference ranges derived from healthy subjects, together with MMA and tHcy concentrations below the cut-off values for adults, which indicates an adequate cobalamin status. Therefore, the Panel sets an Adequate Intake (AI) for cobalamin at 4 µg/day for adults based on data on different biomarkers of cobalamin status and in consideration of observed mean intakes, which range between 4.2 and 8.6 μg/day in adults in several EU countries. AIs for infants and children are calculated by extrapolation from the AI for adults using allometric scaling and applying a growth factor. Estimated AIs range from 1.5 µg/day in infants aged 7-11 months to 4 µg/day in children aged 15-17 years. For pregnancy and lactation, additional cobalamin intakes related to the accumulation of cobalamin in fetal tissues and transfer of cobalamin into breast milk are considered and AIs of 4.5 and 5 µg/day, respectively, are proposed. Cobalamin is a metal complex with a central cobalt atom bonded to six ligands. The upper or β-axial ligand varies (R-group: cyano-, hydroxo-, aquo-, methyl-or adenosyl-group), giving rise to the correspondingly named chemical forms of the vitamin. In humans, two reactions are known to require cobalamin as coenzyme. One is the rearrangement of methylmalonyl-coenzyme A (CoA) to succinylCoA in propionate metabolism by methylmalonyl-CoA mutase in mitochondria. The other is the cytosolic transmethylation of homocysteine by 5-methyl-tetrahydrofolate to methionine by methionine synthase. The most frequent clinical expression of cobalamin deficiency is megaloblastic anaemia. Independent of megaloblastic anaemia, neurological dysfunction is another clinical feature of cobalamin deficiency. Cobalamin insufficiency is characterised by biochemical abnormalities, such as elevated total homocysteine (tHcy) and/or methylmalonic acid (MMA) concentrations in blood resulting from impaired cobalamin metabolic activity, with no specific clinical symptoms. © EuropeanCobalamin absorption consists of several steps, including its release from proteins, its binding by gastric intrinsic factor and the absorption of intrinsic factor-cobalamin complexes through receptormediated endocytosis in the terminal ileum. Fractional absor...

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“…However, so far methods to derive recommendations based on dose-response evidence are still under development and there is no strong consensus on appropriate cutoff levels for defining health [13,14,15]. The factorial approach may serve as an alternative until more dose-response evidence becomes available.…”

Section: Introductionmentioning

confidence: 99%

Systematic Review on Daily Vitamin B12 Losses and Bioavailability for Deriving Recommendations on Vitamin B12 Intake with the Factorial Approach

et al. 2013

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Aims: To systematically review the literature on daily losses and bioavailability of vitamin B12. These estimates could be used for deriving recommendations on vitamin B12 intake for adults and elderly. Methods: We identified publications on daily vitamin B12 losses (July 2011) and publications on the bioavailability of vitamin B12 from foods or diets (June 2010) in MEDLINE, EMBASE and the Cochrane Library. Results: A pooled analysis of five studies (52 subjects) showed that 0.13 ± 0.03% of the total body store is lost per day. Absorption of vitamin B12 ranged from 4.5 (dose of 38 µg from consumption of liver) to 83% (dose of 3.0 µg from consumption of mutton meat). Data from eight studies including 83 subjects suggested that the amount of vitamin B12 absorbed from food (A_i) increased with increasing doses of vitamin B12 (D_i) as described by the equation: ln(A_i) = 0.7694 * ln(D_i) - 0.9614. Conclusion: Daily vitamin B12 losses in apparently healthy adults and elderly probably range from 1.4 to 5.1 µg. Vitamin B12 intakes needed to compensate for these losses seem to range from 3.8 to 20.7 µg. More evidence is needed on the relationships between biochemical markers of vitamin B12 status, vitamin B12 body store and long-term health outcomes to evaluate whether current recommendations on vitamin B12 intake (1.4-3 µg) need to be changed.

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Systematic review with dose-response meta-analyses between vitamin B-12 intake and European Micronutrient Recommendations Aligned’s prioritized biomarkers of vitamin B-12 including randomized controlled trials and observational studies in adults and elderly persons

Abstract: The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of populations.

Cited by 39 publications

References 58 publications

Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly

Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly

Scientific Opinion on Dietary Reference Values for cobalamin (vitamin B12)

Systematic Review on Daily Vitamin B12 Losses and Bioavailability for Deriving Recommendations on Vitamin B12 Intake with the Factorial Approach

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