Falling folate levels sound alarm for urgent UK food fortification

In a recent study published in The American Journal of Clinical Nutrition, researchers at the University of Cambridge assessed pre-fortification United Kingdom (UK) folate trends (2008-2019), especially in females of reproductive age, using National Diet and Nutrition Survey data.

Study: National Diet and Nutrition Survey data reveal a decline in folate status in the UK population between 2008 and 2019. Image Credit: Ivanova Ksenia / ShutterstockStudy: National Diet and Nutrition Survey data reveal a decline in folate status in the UK population between 2008 and 2019. Image Credit: Ivanova Ksenia / Shutterstock


Folate, critical for deoxyribonucleic acid (DNA) synthesis and cell growth, is vital during rapid developmental phases. Its deficiency often results in megaloblastic anemia, given the substantial folate demands for red blood cell (RBC) production. In pregnant women, insufficient folate can cause neural tube defects (NTDs) like spina bifida and anencephaly, and it is linked to higher risks of cardiovascular, cancerous, and neurological conditions. From 2008-2020, England and Wales saw a prevalence of 12.4 per 10,000 pregnancies affected by non-genetic NTDs. Enhancing folate intake via supplements or fortified foods can mitigate these risks, and fortifying flour has proven efficacious and economical. Although 69 countries mandated folic acid fortification by 2022, only Kosovo and Moldova in Europe had by May 2023. The UK, allowing voluntary fortification, plans to mandate folic acid in non-wholemeal wheat flour, likely by 2024. Monitoring folate levels before and after this mandate is crucial, yet national data is sparse, and varying assays and standards complicate data interpretation. Further research is needed to establish a comprehensive pre- and post-fortification folate status baseline, facilitate global data comparison through assay standardization, and continuously monitor the impact of mandatory folic acid fortification on public health outcomes.

About the study 

The National Diet and Nutrition Survey Rolling Programme (NDNS RP) stands as a comprehensive governmental initiative in the UK, thoroughly gathering data on dietary intakes and nutritional status across various demographics. Annually, this survey reaches approximately 1,000 participants, comprising both adults and children from diverse regions within the UK. A significant subset of these participants also contribute blood samples for detailed biomarker analyses.

From 2008 to 2019, the NDNS RP precisely organized data, with blood samples being a crucial component. These samples were obtained via venepuncture, with specific protocols for children and those unable to fast. Notably, blood samples were processed and analyzed for several indicators, including whole blood (WB) and serum folate levels, employing stringent measures to ensure accuracy and consistency over the years.

In this process, the survey employed advanced techniques like Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) for a detailed analysis of various folate vitamers in the serum. Quality control was paramount, involving both internal measures and external checks through participation in proficiency testing schemes like the United Kingdom National External Quality Assessment Service (UK NEQAS) and Centers for Disease Control and Prevention Vitamin A Laboratory - External Quality Assessment (CDC VITAL-EQA).

However, the survey faced challenges, particularly with the stability of samples, as an increasing number were received by the laboratory over 48 hours post-collection, raising concerns about the reliability of the data. Consequently, stringent criteria were applied, excluding delayed samples from Year 10 onwards.

Analyzing these comprehensive data sets, the survey conducted time trend and regression analyses, exploring the intricate relationships between folate levels and various demographic and health-related factors, including age, Body Mass Index (BMI), and household income. The approach was methodical, with adaptations for different age groups, especially concerning BMI categorizations.

Study results 

From 2008 to 2019, the present study was conducted to evaluate the RBC and serum folate levels among different age groups. The research encompassed various age segments: children aged 1.5 to 3 years with 122 and 118 samples for RBC and serum folate, respectively; those aged 4 to 10 years with 557 and 569 samples; individuals aged 11 to 18 years with 1,053 and 1,106 samples; adults between 19 and 64 years with 2,856 and 3,104 samples; and adults aged 65 years and above with 807 and 891 samples. The comprehensive participant flow and specific sample sizes, categorized by both age and gender, were recorded and are accessible in the study's supplemental materials.

In an intriguing revelation, the geometric mean RBC folate and serum folate concentrations were typically higher in the youngest and oldest participants, with children aged 11 to 18 exhibiting the lowest concentrations. These concentrations were observed to decline over the study period. The exclusion of MeFox concentration from calculations led to a minor reduction in serum folate concentration across all demographics, yet the overall trends remained consistent. Folic acid concentrations, however, presented a more complex picture due to analytic sensitivities, with median levels ranging between 0.07 and 0.47 nmol/L across all groups.

Time trend analysis disclosed a significant decrease in both RBC and serum folate concentrations over the years. Specifically, there was an average annual decrease of 2 to 3% in RBC folate and 2 to 4% in serum folate across all age and gender groups. This trend signified a substantial 22 to 31% decline in RBC folate and 16 to 34% fall in serum folate over the 11-year span.

Folate Receptor Autoantibodies (FRA) were analyzed separately for individuals aged 16 to 49. Similar to the broader adult population, there was a notable decrease in both RBC and serum folate levels over the study period. Moreover, the incidence of FRA with RBC folate levels below 748 nmol/L alarmingly surged from 69 to 89 percentage points.

Regression analyses revealed that older children had significantly lower folate concentrations, whereas older adults had higher levels than the general adult population. Distinct disparities were also evident based on ethnicity, smoking habits, supplement use, and income levels. For instance, participants from black ethnic groups had substantially lower folate concentrations than their white counterparts. Smokers and those with lower incomes also typically had reduced folate levels, while supplement users showed increased concentrations.

Notably, serum folic acid concentrations were significantly higher in supplement users and younger children than non-users and adults. Ethnic variances were also apparent in folic acid concentrations. However, certain determinants could not be conclusively analyzed due to insufficient data, particularly regarding non-white participants with RBC folate deficiency. This led to inevitable gaps in the study's comprehensive tables.

Journal reference:
Vijay Kumar Malesu

Written by

Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.    


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