Assessment of the Dose–Response Relationship Between Folate Exposure and Cognitive Impairment: Synthesizing Data from Documented Studies

Bing Wang, Nadine R. Sahyoun, Kan Shao, Enakshy Dutta, Jennifer Clarke

Research output: Contribution to journalArticle

Abstract

The dose–response relationship between folate levels and cognitive impairment among individuals with vitamin B12 deficiency is an essential component of a risk-benefit analysis approach to regulatory and policy recommendations regarding folic acid fortification. Epidemiological studies provide data that are potentially useful for addressing this research question, but the lack of analysis and reporting of data in a manner suitable for dose–response purposes hinders the application of the traditional evidence synthesis process. This study aimed to estimate a quantitative dose–response relationship between folate exposure and the risk of cognitive impairment among older adults with vitamin B12 deficiency using “probabilistic meta-analysis,” a novel approach for synthesizing data from observational studies. Second-order multistage regression was identified as the best-fit model for the association between the probability of cognitive impairment and serum folate levels based on data generated by randomly sampling probabilistic distributions with parameters estimated based on summarized information reported in relevant publications. The findings indicate a “J-shape” effect of serum folate levels on the occurrence of cognitive impairment. In particular, an excessive level of folate exposure is predicted to be associated with a higher risk of cognitive impairment, albeit with greater uncertainty than the association between low folate exposure and cognitive impairment. This study directly contributes to the development of a practical solution to synthesize observational evidence for dose–response assessment purposes, which will help strengthen future nutritional risk assessments for the purpose of informing decisions on nutrient fortification in food.

Original languageEnglish (US)
JournalRisk Analysis
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Folic Acid
Vitamins
Association reactions
Vitamin B 12 Deficiency
Risk assessment
Nutrients
Sampling
Acids
Food
Nutrition Assessment
Cognitive Dysfunction
Serum
Uncertainty
Observational Studies
Publications
Meta-Analysis
Epidemiologic Studies
Research Design
Research

Keywords

  • Folic acid
  • meta-analysis
  • nutritional risk assessment

ASJC Scopus subject areas

  • Safety, Risk, Reliability and Quality
  • Physiology (medical)

Cite this

Assessment of the Dose–Response Relationship Between Folate Exposure and Cognitive Impairment : Synthesizing Data from Documented Studies. / Wang, Bing; Sahyoun, Nadine R.; Shao, Kan; Dutta, Enakshy; Clarke, Jennifer.

In: Risk Analysis, 01.01.2019.

Research output: Contribution to journalArticle

@article{375b9f68e6944647a8e65294eca1ca8c,
title = "Assessment of the Dose–Response Relationship Between Folate Exposure and Cognitive Impairment: Synthesizing Data from Documented Studies",
abstract = "The dose–response relationship between folate levels and cognitive impairment among individuals with vitamin B12 deficiency is an essential component of a risk-benefit analysis approach to regulatory and policy recommendations regarding folic acid fortification. Epidemiological studies provide data that are potentially useful for addressing this research question, but the lack of analysis and reporting of data in a manner suitable for dose–response purposes hinders the application of the traditional evidence synthesis process. This study aimed to estimate a quantitative dose–response relationship between folate exposure and the risk of cognitive impairment among older adults with vitamin B12 deficiency using “probabilistic meta-analysis,” a novel approach for synthesizing data from observational studies. Second-order multistage regression was identified as the best-fit model for the association between the probability of cognitive impairment and serum folate levels based on data generated by randomly sampling probabilistic distributions with parameters estimated based on summarized information reported in relevant publications. The findings indicate a “J-shape” effect of serum folate levels on the occurrence of cognitive impairment. In particular, an excessive level of folate exposure is predicted to be associated with a higher risk of cognitive impairment, albeit with greater uncertainty than the association between low folate exposure and cognitive impairment. This study directly contributes to the development of a practical solution to synthesize observational evidence for dose–response assessment purposes, which will help strengthen future nutritional risk assessments for the purpose of informing decisions on nutrient fortification in food.",
keywords = "Folic acid, meta-analysis, nutritional risk assessment",
author = "Bing Wang and Sahyoun, {Nadine R.} and Kan Shao and Enakshy Dutta and Jennifer Clarke",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/risa.13404",
language = "English (US)",
journal = "Risk Analysis",
issn = "0272-4332",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Assessment of the Dose–Response Relationship Between Folate Exposure and Cognitive Impairment

T2 - Synthesizing Data from Documented Studies

AU - Wang, Bing

AU - Sahyoun, Nadine R.

AU - Shao, Kan

AU - Dutta, Enakshy

AU - Clarke, Jennifer

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The dose–response relationship between folate levels and cognitive impairment among individuals with vitamin B12 deficiency is an essential component of a risk-benefit analysis approach to regulatory and policy recommendations regarding folic acid fortification. Epidemiological studies provide data that are potentially useful for addressing this research question, but the lack of analysis and reporting of data in a manner suitable for dose–response purposes hinders the application of the traditional evidence synthesis process. This study aimed to estimate a quantitative dose–response relationship between folate exposure and the risk of cognitive impairment among older adults with vitamin B12 deficiency using “probabilistic meta-analysis,” a novel approach for synthesizing data from observational studies. Second-order multistage regression was identified as the best-fit model for the association between the probability of cognitive impairment and serum folate levels based on data generated by randomly sampling probabilistic distributions with parameters estimated based on summarized information reported in relevant publications. The findings indicate a “J-shape” effect of serum folate levels on the occurrence of cognitive impairment. In particular, an excessive level of folate exposure is predicted to be associated with a higher risk of cognitive impairment, albeit with greater uncertainty than the association between low folate exposure and cognitive impairment. This study directly contributes to the development of a practical solution to synthesize observational evidence for dose–response assessment purposes, which will help strengthen future nutritional risk assessments for the purpose of informing decisions on nutrient fortification in food.

AB - The dose–response relationship between folate levels and cognitive impairment among individuals with vitamin B12 deficiency is an essential component of a risk-benefit analysis approach to regulatory and policy recommendations regarding folic acid fortification. Epidemiological studies provide data that are potentially useful for addressing this research question, but the lack of analysis and reporting of data in a manner suitable for dose–response purposes hinders the application of the traditional evidence synthesis process. This study aimed to estimate a quantitative dose–response relationship between folate exposure and the risk of cognitive impairment among older adults with vitamin B12 deficiency using “probabilistic meta-analysis,” a novel approach for synthesizing data from observational studies. Second-order multistage regression was identified as the best-fit model for the association between the probability of cognitive impairment and serum folate levels based on data generated by randomly sampling probabilistic distributions with parameters estimated based on summarized information reported in relevant publications. The findings indicate a “J-shape” effect of serum folate levels on the occurrence of cognitive impairment. In particular, an excessive level of folate exposure is predicted to be associated with a higher risk of cognitive impairment, albeit with greater uncertainty than the association between low folate exposure and cognitive impairment. This study directly contributes to the development of a practical solution to synthesize observational evidence for dose–response assessment purposes, which will help strengthen future nutritional risk assessments for the purpose of informing decisions on nutrient fortification in food.

KW - Folic acid

KW - meta-analysis

KW - nutritional risk assessment

UR - http://www.scopus.com/inward/record.url?scp=85073922500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073922500&partnerID=8YFLogxK

U2 - 10.1111/risa.13404

DO - 10.1111/risa.13404

M3 - Article

C2 - 31536147

AN - SCOPUS:85073922500

JO - Risk Analysis

JF - Risk Analysis

SN - 0272-4332

ER -