Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment: A Randomized Controlled Trial in China

Ma, Fei; Wu, Tianfeng; Zhao, Jiangang; Han, Fengmei; Marseglia, Anna; Liu, Huan; Huang, Guowei

doi:10.1093/gerona/glv183

Cited by 51 publications

(55 citation statements)

References 42 publications

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“…VIQ and PIQ, with the former encompassing those tests most related to verbal skills, such as the information, vocabulary and digit span tests, while the latter being more independent of verbal skills, for instance, the block design and picture arrangement tests. A cohort study carried out in Australia found the risk of women with vitamin D insufficiency (≤46 nmol/L) during pregnancy having a child with clinically significant language difficulties increased close to twofold compared with women with vitamin D levels >70 nmol/L, which indicated vitamin D is crucial to language development 28. Participants in our study allocated to vitamin D 3 group scored more in VIQ when comparing the 12th month with baseline, which conforms to the evidence.…”

Section: Discussionsupporting

confidence: 86%

Effects of vitamin D₃supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Jia

Zhang

et al. 2018

J Neurol Neurosurg Psychiatry

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Section: Discussionsupporting

confidence: 86%

Effects of vitamin D₃supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Jia

Zhang

et al. 2018

J Neurol Neurosurg Psychiatry

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“…Evidence from observational studies confirm our findings that tHcy concentrations are predictive of CVD and/or mortality ( 2 , 5 , 8 , 11 , 20–22 ). Folate donates methyl groups for homocysteine transmethylation to form methionine and, typically, folic acid supplementation lowers homocysteine concentrations by 13%–25% ( 23 , 24 ). Although it is still debatable whether homocysteine is a causal factor or a marker of CVD and mortality ( 25 ), others have shown that supplementation with folic acid decreased the risk of CVD, especially stroke ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study

Mendonça

Jagger

Granic

et al. 2018

The Journals of Gerontology: Series A

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BackgroundFolate and vitamin B12 are keys to the correct functioning of one-carbon (1-C) metabolism. The current evidence on associations between 1-C metabolism biomarkers and mortality is inconclusive and generally based on younger or institutionalized populations. This study aimed to determine the associations between biomarkers of 1-C metabolism and all-cause and cardiovascular (CVD) mortality in the very old.MethodsThe Newcastle 85+ Study is a prospective longitudinal study of participants aged 85 at recruitment living in Northeast England. Baseline red blood cell folate (RBC folate), plasma vitamin B12, and total homocysteine (tHcy) concentrations were available for 752–766 participants. Associations between biomarkers of 1-C metabolism and all-cause and CVD mortality for up to 9 years were assessed by Cox proportional hazard models and confirmed by restricted cubic splines.ResultsParticipants with higher tHcy concentrations had higher risk of death from any cause (hazard ratio [HR] [×10 μmol/L]: 1.24, 95% confidence interval [CI]: 1.10–1.41) and cardiovascular diseases (HR [×10 μmol/L]: 1.23, 95% CI: 1.04–1.45) than those with lower concentrations; and women with higher plasma vitamin B12 concentrations had increased risk of all-cause and cardiovascular mortality (HR [×100 pmol/L]: 1.10, 95% CI: 1.04–1.16) after adjustment for key sociodemographic, lifestyle, and health confounders.ConclusionHigher concentrations of tHcy in all participants and plasma vitamin B12 in women were associated with increased risk of all-cause and CVD mortality in the very old. This confirms findings for tHcy in younger populations but the adverse relationships between elevated plasma vitamin B12 concentrations and mortality in this setting are novel and require further investigation.

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“…Our previous studies have observed the effects of folic acid on elderly people with mild cognitive impairment, animal, and cell models of AD. Those results showed a beneficial effect from folic acid supplementation on cognitive functioning in later life [ 22 ]. It was also demonstrated that folic acid may modify Aβ accumulation in vivo [ 18 , 20 ] and in vitro [ 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

Tian

Dong

et al. 2016

Nutrients

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Alzheimer’s disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component—presenilin 1 (PS1)—in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression.

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Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment: A Randomized Controlled Trial in China

Abstract: There was a beneficial effect from relatively short-term folate supplementation on cognitive functioning in later life. Larger-scale, randomized, controlled trials of longer duration in selected age groups are needed.

Cited by 51 publications

References 42 publications

Effects of vitamin D₃supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Effects of vitamin D₃supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study

Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

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Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment: A Randomized Controlled Trial in China

Abstract: There was a beneficial effect from relatively short-term folate supplementation on cognitive functioning in later life. Larger-scale, randomized, controlled trials of longer duration in selected age groups are needed.

Cited by 51 publications

References 42 publications

Effects of vitamin D3supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Effects of vitamin D3supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study

Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

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Effects of vitamin D₃supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Effects of vitamin D₃supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial