Estimation of Trends in Serum and RBC Folate in the U.S. Population from Pre- to Postfortification Using Assay-Adjusted Data from the NHANES 1988–2010

Abstract

The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999-2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was ≤ 1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups. The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and postfortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact.

Genetic polymorphisms and folate status

“…In the USA and Canada, these folic supplementation programs were thought to be successful because the population folate status was improved (Ray et al 2002) and reduced rates of NTDs were noted (Honein et al 2001; Williams et al 2002), although the results varied depending on ethnicity (Williams et al 2005). Data from the USA reported from the NHANES trial (Pfeiffer et al 2012) showed that the mean concentration of serum and RBC folate increased dramatically from the prefortification period (1988–1994) to the postfortification period (1990–2010), from 16.7 ± 0.5 to 41.0 ± 0.3 nM and from 747 ± 10 to 1120 ± 7 nM, respectively, resulting in a 31% reduction in the occurrence of NTDs (Williams et al 2002). …”

B-Vitamin dependent methionine metabolism and alcoholic liver disease

“…More recently, chronic alcoholics in Portugal were found to have significantly lower red blood cell and serum vitamin B6 levels, but, paradoxically, higher serum vitamin B12 levels together with higher serum homocysteine levels than found in healthy control subjects [21] . Since the onset of folic acid fortification of the US diet in 1998, the population incidence of low serum and red blood cell folate levels has decreased from 24 % and 3 % to < 1 % for each [22] . A recent post-folic acid fortification study of 77 intoxicated patients in an emergency room setting found none with low serum folate or vitamin B12 levels [23] .…”

Haematological implications of folate food fortification

“…The post-fortification prevalence of low SF (<10 nmol/l) or RCF (<340 mol/l) was <1%, compared with 24% for SF and 3.5% for RCC before fortification. [4] A comparable reduction in the prevalence of subnormal folate concentrations after fortification was subsequently reported in population surveys in Canada and other countries that had implemented FFF. At the clinical level, US and Canadian hospitals reported a fall in the number of patients with low folate values following the FFF, with folate-deficient anaemia extremely rare.…”