Effect of Vitamin D and Folic Acid on Mild Cognitive Impairment

March 17, 2026 updated by: Jiaxuan Tao, Capital Medical University

Effects and Mechanisms of Vitamin D Combined With Folic Acid and Vitamin B12 on Mild Cognitive Impairment Via Regulation of Key Factors in 27-Hydroxycholesterol Metabolism

The purpose of this study is to investigate the effects of Vitamin D3 combined with Folic Acid on mild cognitive impairment (MCI). Participants aged 50 to 70 years with MCI will be randomly assigned to three groups: a low-dose Vitamin D3 plus Folic Acid group, a high-dose Vitamin D3 plus Folic Acid group, and a placebo group. The intervention will last for 6 months. The main goal is to observe whether this nutritional intervention can improve or delay the decline of cognitive function.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Mild cognitive impairment (MCI) is a critical transitional stage between normal aging and Alzheimer's disease (AD). Designing precise dietary and nutritional interventions is a vital strategy for preventing and treating MCI. Based on an established cohort study, this randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy of combining Vitamin D3 and Folic Acid in MCI patients.

The study will analyze changes in overall and multi-dimensional cognitive functions before and after the 6-month intervention. Furthermore, the study will explore the underlying mechanisms by analyzing biological samples (blood, urine, and feces) for alterations in 27-hydroxycholesterol (27-OHC) and its metabolites, active Vitamin D3, Folic Acid levels, CYP27A1 activity, and related gene polymorphisms. The findings will help determine the optimal interaction ratio and effective dosage of this combined nutritional intervention for delaying cognitive decline.

Study Type

Interventional

Enrollment (Actual)

380

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100069
        • Capital Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 50 to 70 years old.
  • Derived from the established elderly chronic disease and health cohort.
  • Meet the diagnostic criteria for Mild Cognitive Impairment (MCI) (e.g., indicated by specific cut-off scores on the MoCA adjusted for education level).
  • Volunteered to participate, able to cooperate with the cognitive assessments, and signed the informed consent form.

Exclusion Criteria:

  • Diagnosis of Alzheimer's disease, other types of dementia, or severe psychiatric disorders (e.g., severe depression, schizophrenia).
  • History of severe neurological diseases (e.g., stroke, brain tumor, brain trauma) that may affect cognitive function.
  • Severe visual or hearing impairments that prevent the completion of cognitive tests.
  • Patients with liver diseases (e.g., hepatitis, liver cirrhosis) or kidney diseases (e.g., nephritis, kidney stones, renal failure).
  • Patients with hypercalcemia (serum calcium concentration > 10.5 mg/dl).
  • Patients with severe anemia, severe malnutrition, or abnormal thyroid function.
  • Current use or use within the past 3 months of cognition-improving drugs, Vitamin D, or Folic Acid supplements, and unwilling to undergo a 3-month washout period prior to the intervention.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 800IU/d Vitamin D3 + Folic Acid
Participants will receive one folic acid(0.4mg/d) tablet and one low-dose(800IU/d) Vitamin D3 tablet orally once daily at breakfast for 6 months.
Dietary supplement: Vitamin D3 (800 IU/d) and Folic Acid(0.4mg/d)
One folic acid tablet and one low-dose Vitamin D3 tablet administered orally once daily at breakfast for 6 months.
Experimental: 1600IU/d Vitamin D3 + Folic Acid
Participants will receive one folic acid(0.4mg/d) tablet and one high-dose(1600IU/d) Vitamin D3 tablet orally once daily at breakfast for 6 months.
Dietary supplement: Vitamin D3 (1600 IU/d) and Folic Acid(0.4mg/d)
One folic acid tablet and one high-dose Vitamin D3 tablet administered orally once daily at breakfast for 6 months.
Placebo Comparator: Placebo
Participants will receive two starch placebo tablets (identical in appearance, color, and smell to the active supplements) orally once daily at breakfast for 6 months.
Other: Starch Placebo
Two starch placebo tablets administered orally once daily at breakfast for 6 months. The placebo is identical in appearance, color, and smell to the active tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Global Cognitive Function Assessed by Montreal Cognitive Assessment (MoCA) Score
Time Frame: Baseline and 6 months
Global cognitive function is evaluated using the Montreal Cognitive Assessment (MoCA). The MoCA assesses different cognitive domains including attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total score ranges from 0 to 30. Higher scores indicate better cognitive performance.
Baseline and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum 25-hydroxyvitamin D [25(OH)D] Levels
Time Frame: Baseline and 6 months
Serum concentrations of 25(OH)D will be measured to assess the response to Vitamin D3 supplementation.
Baseline and 6 months
Change in Serum Folic Acid Levels
Time Frame: Baseline and 6 months
Serum concentrations of folic acid will be measured to assess the response to folic acid supplementation.
Baseline and 6 months
Change in 27-hydroxycholesterol (27-OHC) Levels
Time Frame: Baseline and 6 months
Levels of 27-OHC and its metabolites in biological samples (blood/urine/feces) will be measured to explore the underlying metabolic mechanisms.
Baseline and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Capital Medical University

Investigators

  • Principal Investigator: Rong Xiao, PhD, Capital Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

March 17, 2026

First Submitted That Met QC Criteria

March 17, 2026

First Posted (Actual)

March 20, 2026

Study Record Updates

Last Update Posted (Actual)

March 20, 2026

Last Update Submitted That Met QC Criteria

March 17, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Z2025SY068

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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