Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation

Scope: We modeled red blood cell (RBC)-folate response to supplementation and developed personalized folate supplementation concepts.

Methods and results: The changes of RBC-folate were modeled in a time- (4 or 8 weeks) and dose- (400 or 800 μg d^-1 folate) dependent manner. Post-supplementation RBC-folate levels were predicted from folate-loading capacities (= measured RBC-folate - [baseline RBC-folate × RBC-survival]). The prediction equations were validated in 119 participants. The median increase of RBC-folate was higher in the 800 μg d^-1 than in the 400 μg d^-1 group (275 vs 169 nmol L^-1 after 4 weeks, and 551 vs 346 nmol L^-1 after 8 weeks). Medians (interquartile range) of RBC-folate loading were (4 weeks: 299 (160) vs 409 (237) nmol L^-1 ) and (8 weeks: 630 (134) versus 795 (187) nmol L^-1 ) in the 400 and 800 μg d^-1 group, respectively. The individual measured and predicted RBC-folate values (after 4 weeks/400 μg d^-1 = 25 + 1.27 × baseline RBC-folate) and (after 4 weeks/800 μg d^-1 = 65 + 1.41 × baseline RBC-folate) did not differ significantly. The measured and predicted concentrations showed high agreement in the validation cohort.

Conclusions: The models can guide nutritional recommendations in women when baseline RBC-folate concentrations are measured and the time to pregnancy between 4 and 8 weeks.