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 .
Effect of fortified spread on homocysteine concentration in apparently healthy volunteers
Objective : To determine the effect of folic acid , vitamin B6 and B12 fortified spreads on the blood concentrations of these vitamins and homocysteine . Design and setting : A 6-week r and omized , double-blinded , placebo-controlled , parallel trial carried out in a clinical research center . Subjects : One hundred and fifty healthy volunteers ( 50 % males ) . Interventions : For 6 weeks , the subjects consumed the test spreads ( 20 g/day ) : containing per 20 g ( 1 ) 200 μg folic acid , 2 μg vitamin B12 and 1 mg vitamin B6 , or ( 2 ) 400 μg folic acid , 2 μg vitamin B12 and 1 mg vitamin B6 or ( 3 ) no B-vitamins ( control spread ) . Results : The B-vitamin status increased on using the test spreads , with the largest effect on the serum folate concentration : 48 % in men and 58 % in women on spread 1 and 92 and 146 % , respectively , on spread 2 ( P-values all < 0.05 ) . The plasma homocysteine decreased in the groups treated with the fortified spreads as compared to the control group . Average decreases were for males : 0.7±1.5 μmol/l ( 6.8 % ) on spread 1 and 1.7±1.7 μmol/l ( 17.6 % ) on spread 2 and for females : 1.4±1.2 μmol/l ( 14.2 % ) and 2.4±2.0 μmol/l ( 23.3 % ) , respectively ( P-values all < 0.05 ) . Conclusions : Consumption of a spread fortified with folic acid , vitamin B6 and vitamin B12 for 6 weeks significantly increases the blood concentrations of these vitamins and significantly decreases the plasma concentration of homocysteine . Fortified staple foods like spreads can contribute to the lowering of homocysteine concentrations . Sponsorship : Unilever Research and Development , Vlaardingen , The Netherl and
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 .