RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs .
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 population
BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers .
The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence .
OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12  status and estimated dose-response relations with the use of a meta- analysis .
Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial.
BACKGROUND M and atory fortification of flour with folic acid has reduced the number of neural tube defects in North America . Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries . Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status . OBJECTIVE The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherl and s , where folic acid fortification is not taking place . DESIGN Men and women aged 50 - 75 y were r and omly assigned in this 12-wk double-blind , placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily ( n = 72 ) or unfortified bread ( n = 70 ) . RESULTS The consumption of fortified bread increased serum folate concentrations by 45 % ( mean : 6.3 nmol/L ; 95 % CI : 4.5 , 8.1 nmol/L ) and serum vitamin B-12 concentrations by 49 % ( mean : 102 pmol/L ; 95 % CI : 82 , 122 pmol/L ) relative to the placebo group . Fortified bread increased erythrocyte folate concentrations by 22 % and holotranscobalamin concentrations by 35 % ; it decreased homocysteine concentrations by 13 % and methylmalonic acid concentrations by 10 % . Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations ( < 133 pmol/L ) from 8 % at enrollment to 0 % after 12 wk . CONCLUSION Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people . This trial was registered at clinical trials.gov as NCT00353353
RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs .
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 population
BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers .
The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence .
OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12  status and estimated dose-response relations with the use of a meta- analysis .