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. 2026 Jan 22;16(1):e106050. doi: 10.1136/bmjopen-2025-106050

Association between vitamin D supplement use and cognitive functioning: a longitudinal cohort study

Rong Hua 1,2, Chun Sing Lam 2, Vincent Chung Tong Mok 3,4,5, Yin Ting Cheung 2,✉
PMCID: PMC12829399  PMID: 41571412

Abstract

Abstract

Objectives

The real-world evidence on the association between vitamin D supplementation and cognitive outcomes has been scant and controversial. We aimed to investigate the longitudinal association between vitamin D supplement use and subsequent cognitive functioning among US older adults.

Design

Prospective cohort study.

Setting

A nationally representative ageing cohort in USA: the Health and Retirement Study (HRS).

Participants

Participants were drawn from the HRS wave 12 and included respondents who had complete data on dietary supplement use and cognitive assessment. A total of 5065 participants (mean age: 67.5±10.2 years, 61.6% female, 76.6% White ethnicity) were included, of whom 2004 (39.6%) participants were vitamin D supplement users.

Primary and secondary outcome measures

Change in cognitive function scores over 6 years of follow-up (from HRS waves 12–15), estimated by linear mixed model adjusted for multiple covariates.

Results

Compared with non-users, vitamin D users had an accelerated decline in global cognitive function (difference in the rate of change: −0.052 points/year; 95% CI −0.092 to −0.013, p=0.010) and in executive function score (difference: −0.021 points/year; 95% CI −0.037 to −0.005, p=0.010). Sensitivity analysis suggested that accelerated cognitive decline was only observed among supplement users with normal baseline serum 25(OH)D level (p=0.004), but not the group with insufficient/deficient levels (p=0.826).

Conclusions

Our findings do not support vitamin D supplementation as a means of preventing or slowing cognitive decline in older people with adequate vitamin D status. While healthcare providers should encourage adequate vitamin D intake from dietary sources and moderate sun exposure, caution should be taken when recommending such supplements to older adults without a clear indication for it.

Keywords: Aging, Cognition, EPIDEMIOLOGIC STUDIES, GERIATRIC MEDICINE

Strengths and limitations of this study.

  • The major strengths include the use of well-validated cognitive data from a representative cohort of ageing US adults and a longitudinal prospective design to capture changes in cognitive function while adjusting for relevant confounding factors.

  • This real-world evidence provides a more realistic picture than clinical trials on the association between vitamin D supplementation and cognitive functioning.

  • Vitamin D supplement use was ascertained by self-reporting, which may have led to the misclassification of vitamin D users and biased our findings toward a null association.

  • Detailed information about the vitamin D supplement use was not collected. Nevertheless, we have considered dietary intake of vitamin D and the serum 25(OH)D levels to have a better gauge of the exposure status on cognitive function.

Introduction

Cognitive impairment is the preclinical stage of dementia.1 It has affected over 15% older adults worldwide, and the prevalence is projected to rise substantially in the future.1 2 Given the dearth of effective therapeutics for cognitive impairment, complementary and alternative medicines, especially dietary supplements that are generally affordable and easily accessible, have piqued public interest as a means of preventing or slowing cognitive decline.3 4

Vitamin D is produced endogenously by the skin on exposure to sunlight or obtained exogenously from the diet or supplements.5 Apart from its well-known benefits on bone health via regulating calcium and phosphorus metabolism, vitamin D might influence other health outcomes via mechanisms involving oxidative and inflammatory processes and neurotrophic factor production.6 7 Vitamin D is one of the most popular supplements used by older adults8 and has elicited remarkable interest in the field of cognitive-related research, as several studies have suggested that a low circulating vitamin D concentration and low dietary vitamin D intake are associated with accelerated cognitive decline or an increased incidence of dementia.9,12 However, a recent systematic review of 20 randomised controlled trials (RCTs) of the effect of vitamin D supplementation on cognitive function failed to conclude the evidence on the association due to the limited sample sizes, follow-up durations and varying controlled factors in the included RCTs.13 Therefore, real-world evidence from population-based studies with extended follow-up observation holds important significance in assessing the benefits of dietary supplements in diversified actual situations of the real world.

However, the real-world evidence on the association between vitamin D supplement use and cognitive outcomes has been scant and controversial. For example, four published epidemiological studies on this topic reported findings of protective,14 null12 15 or harmful associations.16 These conflicting results might be attributable to discrepancies in the study populations (age group, geographical and clinical settings) and measurements of cognitive function, and the insufficient adjustment of potential confounders, such as socioeconomic status, lifestyle factors, genetic susceptibility to cognitive impairment and dietary nutrient intake.1214,16 We investigated the longitudinal association between vitamin D supplement use and the rate of change in cognitive function among older adults from the US general population, using data from a representative ageing cohort with validated cognitive assessments and detailed information on multidimensional variables.

Methods

Study population

The Health and Retirement Study (HRS) is an ongoing, nationally representative longitudinal survey of community-dwelling adults aged >50 years in the USA; the study commenced in 1992 (wave 1) and has since been conducted biennially.17

The current study included participants from the HRS core 2014 survey (wave 12) who had completed the Health Care and Nutrition Study (HCNS).18 The HCNS, a substudy of the HRS, was conducted between November 2013 and May 2014 and had 8073 respondents. The HCNS collected information about healthcare access, food purchases, food consumption and the use of vitamins and other supplements. The cognitive outcomes were repeatedly measured every 2 years in the subsequent 2016 (wave 13), 2018 (wave 14) and 2020 (wave 15) surveys. As shown in the flow chart (online supplemental method S1), the current study included 5065 participants who answered the question about vitamin D supplement use, had reasonable daily energy intake (500–3600 kcal for female and 600–4200 kcal for male),19 20 were free of dementia at baseline HRS wave 12 (defined as a self-reported diagnosis of dementia or Alzheimer’s disease, or global cognitive score less than 7 points),21 22 had completed cognitive tests at wave 12 and had at least once cognitive data during follow-up (from wave 13 to wave 15).

Patient and public involvement

Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.

Vitamin D supplement use

The HCNS participants were asked the following question: ‘Not counting multivitamins, do you currently take any of the following specific vitamins or minerals at least once every week?’ The possible responses were in multiple-choice format which included vitamin D and other supplements (online supplemental method S2). The respondents who chose ‘vitamin D’ as a response were defined as vitamin D supplement users; all others were defined as vitamin D supplement non-users.

Cognitive assessments

The HRS cognitive assessment was derived from an adapted version of the Telephone Interview for Cognitive Status.23 The HRS cognitive assessment has been demonstrated to have good validity; previous validation studies have reported that the accuracy of ascertaining dementia ranged from 81% to 87%, and was able to predict diagnoses of cognitive impairment without dementia and dementia in 74% of the HRS respondents.21 24 25 Therefore, the HRS cognitive assessment has been used widely on other cognitive studies in older adults.20 22 26 27

The cognitive domains of interest in the HRS cognitive assessment are: (1) episodic memory, measured by the immediate and delayed recall of a list containing 10 words (score range: 0–20 points) and (2) executive function, measured by one working memory test item (0–5 points) and one processing speed and attention test item (0–2 points). Therefore, the total scores of the main HRS cognitive assessment scale range from 0 to 27 points, and higher scores indicate better overall cognitive function. In addition, participants aged ≥65 years were further asked to respond to an orientation test (6 points) and an object naming test (2 points) to assess knowledge and language. Details on the measurements are presented in online supplemental method S3.

Covariates

Several covariates were selected according to the literature on the general risk factors of cognitive impairment (online supplemental method S4), as well as factors that might confound the effects of vitamin D supplement on the risk of cognitive impairment.2 12 15 20 22 28 29 The covariates included sociodemographic2 12 15 (age, sex, ethnicity, annual household income, educational attainment), lifestyle2 12 (smoking status, drinking status, physical activity), clinical2 12 22 30 (body mass index (BMI) status, depressive symptoms, history of hypertension, diabetes, heart diseases, stroke and cancers) and nutritional factors15 20 28 (calcium supplement use, other supplement use, dietary intake of vitamin D, energy and calcium) for which information was collected at baseline (wave 12). A detailed rationale behind the selection of each covariate and a Directed Acyclic Graph describing the association among the exposure, the outcome and the covariates are presented in online supplemental method S4. The missing proportion of each covariate was minimal (less than 1%). Hence, the missing values were imputed as mode values for categorical covariates or mean values for continuous covariates.31

Statistical analysis

Differences in the baseline characteristics between groups classified by vitamin D supplement use status were compared using the t-test or Wilcoxon rank sum test for continuous variables and the χ² test for categorical variables.

The longitudinal association between vitamin D supplement use (users vs non-users) and the change in the cognitive score was evaluated using a linear mixed model, which is an appropriate method for handling missing outcomes of multiple repeated measurements during follow-up,32 and is typically used in cohort studies with longitudinal cognitive outcomes.9 15 22 26 The primary outcome was the global cognitive score. The model included vitamin D supplement use status (with non-users as the reference group), time (the duration since baseline), the interaction of time×vitamin D use status, and all the above-listed covariates. Consistent with previous studies,9 22 27 both the intercept (baseline cognitive score) and the slope of time (rate of cognitive change during follow-up) were fitted as random effects at the participant level. Therefore, the model estimated the cognitive change for each participant from their own baseline, ensuring that the group comparisons of cognitive decline rates were independent of baseline differences in cognitive performance. The coefficient of the interaction term represented the difference in the rate of change in the cognitive score (points/year) between vitamin D users and non-users, with a negative value indicating an accelerated cognitive decline. We further investigated the associations between vitamin D supplement use and different cognitive domains, namely the memory score and executive function score.

We also investigated potential modification effects by subgroup analyses. We pre-specified key sociodemographic factors (ie, age, sex and race) as primary effect modifiers, based on their established roles in modifying cognitive outcomes. Age is recognised as the strongest risk factor for cognitive decline.2 Sex differences are well-documented in both vitamin D metabolism and cognitive ageing, while racial differences encompass both physiological factors of vitamin D synthesis (eg, skin pigmentation) and broader social determinants that could modify the exposure-outcome relationship.2 33 34 Accordingly, these factors provide a strong biological and sociological basis for systematically modifying the association between vitamin D and cognitive decline. For this analysis, age was categorised into <65 years or ≥65 years. A forest plot was generated to visualise the associations, and the Z test was used to examine the interaction effects between different subgroups.35

In exploratory analysis, we investigated the potential modification effects of other covariates such as lifestyle, comorbidity and nutritional factors. These analyses are considered hypothesis-generating due to the greater potential for complex confounding and reverse causality. Dietary intake of energy, vitamin D and calcium was dichotomised by their medians. Considering that cumulative multimorbidity burden is associated with the development of dementia and that comorbidities in middle-aged and older adults are often intercorrelated,36 37 we totalled the number of comorbidities (i.e. depressive symptoms, hypertension, diabetes, heart diseases, stroke and cancer) and dichotomised it by the median. A subgroup analysis was also conducted to examine the effect of each comorbidity on cognitive outcomes in vitamin D supplement users versus non-users.

For the sensitivity analysis, we explored the potential influence of serum vitamin D level on the association between vitamin D supplementation and cognitive decline on a subset of 3394 participants from the wave 13 (2016) survey which included a baseline measurement of serum vitamin D concentrations. According to the guideline, vitamin D deficiency was defined as serum 25(OH)D below 20 ng/mL, and vitamin D insufficiency was defined as serum 25(OH)D of 21–29 ng/mL.33 Therefore, a sensitivity analysis was performed by comparing change in global cognitive scores between vitamin D users and non-users, stratified by serum 25(OH)D level (normal: serum 25(OH)D≥30 ng/mL vs insufficient/deficient: serum 25(OH)D<30 ng/mL.33 Besides, considering that genetic susceptibility to cognitive impairment might confound the analysis,2 we sequentially adjusted for the APOE ε4 carrier status and European ancestry polygenic score of Alzheimer’s disease38 in the model. The sample sizes decreased (n=4338 and 2,971, respectively) due to the unavailability of genetic data for some participants. The procedures used to measure and calculate these genetic factors are provided in the online supplemental method S5. In addition, we repeated our analysis among participants aged 65 years or older who completed all domains of HRS cognitive tests (ie, range of global cognitive score was 0–35 points). Lastly, considering that multivitamins may also contain vitamin D, we compared the change in global cognitive scores between vitamin D supplement users versus non-vitamin D and non-multivitamin users.

All analyses were performed using SAS V.9.4 (SAS Institute) and R V.4.2.1 (R Foundation, Vienna, Austria). A two-sided p value of 0.05 was considered statistically significant.

Results

Baseline characteristics

We included 5065 participants (mean age: 67.5±10.2 years, 61.6% female, 76.6% White ethnicity) in the current analysis. More than a third of these participants (n=2004, 39.6%) were vitamin D supplement users.

The vitamin D supplement users were older (68.9 years vs 66.6 years, p<0.001) and more likely to be female (73.0% vs 54.2%; p<0.001) and White (79.8% vs 74.5%; p<0.001) than non-users (table 1). The users were also more likely to have a higher level of educational attainment and a lower BMI level (both p=0.002) and were less likely to be current smokers (p<0.001). The users included a lower proportion of people with diabetes (23.0% vs 25.6%; p=0.032) but a higher proportion of people with cancer (19.5% vs 14.1%; p<0.001) than did the non-users. In terms of nutritional factors, vitamin D supplement users were more likely to use calcium supplements and other dietary supplements (both p<0.001). Users also tended to have a higher daily dietary calcium intake than non-users (p=0.003); however, there were no significant differences in dietary vitamin D intake or energy intake between vitamin D supplement users and non-users.

Table 1. Baseline characteristics of included participants.

Characteristics All participants (n=5065) Vitamin D supplement non-users
(n=3061)		 Vitamin D supplement users (n=2004) P value*
Sociodemographic factors
 Age (year) 67.5±10.2 66.6±10.3 68.9±9.9 <0.001
 Female (%) 3122 (61.6) 1659 (54.2) 1463 (73.0) <0.001
 White (%) 3878 (76.6) 2279 (74.5) 1599 (79.8) <0.001
 Annual household income 0.229
  Bottom tertile (%) 1611 (31.8) 996 (32.5) 615 (30.7)
  Medium tertile (%) 1710 (33.8) 1037 (33.9) 673 (33.6)
  Top tertile (%) 1744 (34.4) 1028 (33.6) 716 (35.7)
 Educational attainment 0.002
  Below high school (%) 864 (17.1) 563 (18.4) 301 (15.0)
  High school (%) 1511 (29.8) 924 (30.2) 587 (29.3)
  College or above (%) 2690 (53.1) 1574 (51.4) 1116 (55.7)
Lifestyle factors
 Smoking status <0.001
  Never smokers (%) 2379 (47.0) 1387 (45.3) 992 (49.5)
  Former smokers (%) 2172 (42.9) 1301 (42.5) 871 (43.5)
  Current smokers (%) 514 (10.1) 373 (12.2) 141 (7.0)
 Drinking status† 0.227
  Nondrinker (%) 3011 (59.4) 1823 (59.6) 1188 (59.3)
  Low-to-moderate drinker (%) 1610 (31.8) 986 (32.2) 624 (31.1)
  Heavy drinker (%) 444 (8.8) 252 (8.2) 192 (9.6)
 High physical activity‡ (%) 3688 (72.8) 2218 (72.5) 1470 (73.4) 0.485
Clinical factors
 Body mass index status 0.002
  <25 kg/m2 (%) 1337 (26.4) 754 (24.6) 583 (29.1)
  25–30 kg/m2 (%) 1823 (36.0) 1136 (37.1) 687 (34.3)
  ≥30 kg/m2 (%) 1905 (37.6) 1171 (38.3) 734 (36.6)
 Depressive symptoms (%) 622 (12.3) 375 (12.3) 247 (12.3) 0.937
 Hypertension (%) 3949 (78.0) 2385 (77.9) 1564 (78.0) 0.914
 Diabetes (%) 1244 (24.6) 784 (25.6) 460 (23.0) 0.032
 Heart diseases (%) 1137 (22.4) 670 (21.9) 467 (23.3) 0.238
 Stroke (%) 326 (6.4) 198 (6.5) 128 (6.4) 0.908
 Cancer (%) 823 (16.2) 432 (14.1) 391 (19.5) <0.001
 Osteoporosis (%) 204 (4.3) 89 (2.9) 115 (5.7) <0.001
Nutritional factors
 Calcium supplement use (%) 1427 (28.2) 566 (18.5) 861 (43.0) <0.001
 Other supplement use (%)§ 4032 (79.6) 2221 (72.6) 1811 (90.4) <0.001
 Dietary vitamin D intake (IU/day) 132.6 (84.2, 204.1) 132.0 (83.9, 203.2) 133.7 (84.6, 204.7) 0.472
 Dietary energy intake (kcal/day) 1660.2 (1246.3, 2158.2) 1657.6 (1231.9, 2161.9) 1662.0 (1278.8, 2146.6) 0.656
 Dietary calcium intake (mg/day) 640.8 (444.3, 899.0) 632.7 (435.5, 885.9) 651.6 (460.3, 918.1) 0.003
Baseline cognitive scores
 Global cognitive score 16.0±3.8 15.8±3.9 16.3±3.8 <0.001
 Memory score 10.4±3.1 10.2±3.1 10.6±3.1 <0.001
 Executive function score 5.7±1.6 5.6±1.6 5.7±1.6 0.027
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Values are presented as number (percentage), mean±SD or median (IQRs).

*

Characteristics between vitamin D supplement non-users and users were compared using the χ2 test, independent samples t-test or Wilcoxon rank sum test.

†

Low-to-moderate drinkers: <7 drinks/week for women, <14 drinks/week for men; heavy drinkers: ≥7 drinks/week for women, ≥14 drinks/week for men.

‡

High physical activity was defined as participation in moderate or vigorous activity at least once per week.

§

Other supplement use was defined as the use of supplement other than vitamin D or calcium.

Compared with non-users, vitamin D supplement users exhibited a higher global cognitive score (16.3 points vs 15.8 points; p<0.001), memory score (10.6 points vs 10.2 points; p<0.001) and executive function score (5.7 points vs 5.6 points; p=0.027) at baseline.

Associations between vitamin D supplement use and cognitive functioning

Table 2 shows the longitudinal associations between vitamin D supplement use status and the rates of change in cognitive function, after adjusting for multiple covariates. Compared with the non-users, the vitamin D supplement users exhibited a significantly accelerated decline in the global cognitive score (estimated difference in the rate of change in global cognitive scores: −0.052 points/year; 95% CI −0.092 to −0.013, p=0.010). The vitamin D supplement users also showed a significantly accelerated decline in the executive function score (difference: −0.021 points/year; 95% CI −0.037 to −0.005, p=0.010). There was no significant association between vitamin D supplement use and the rate of change in the memory score (difference: −0.031 points/year; 95% CI −0.066 to 0.004, p=0.080). Figure 1 provides a further visualisation of the observed associations.

Table 2. Associations between vitamin D supplement use status and rate of change in cognitive scores (points/year) among included participants (n=5065), using linear mixed models.

Status of vitamin D supplement use Global cognitive score Memory score Executive function score
Beta
(95% CI)		 P value Beta
(95% CI)		 P value Beta
(95% CI)		 P value
Non-users (n=3061) Reference group / Reference group / Reference group /
Users (n=2004) −0.052 (−0.092 to −0.013) 0.010 −0.031 (−0.066 to 0.004) 0.080 −0.021 (−0.037 to −0.005) 0.010
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Models are adjusted for sociodemographic factors (baseline age, sex, race, household income level and educational attainment), lifestyle factors (smoking status, alcohol consumption status and physical activity), clinical factors (body mass index level, depressive symptoms, hypertension, diabetes, self-reported history of heart disease, stroke and cancer), and nutritional factors (calcium supplement use, other supplement use, dietary vitamin D intake, dietary energy intake and dietary calcium intake).

Figure 1. Associations between vitamin D supplement use status and rate of change in (A) global cognitive score, (B) memory score, (C) executive function score among included participants (n=5065). Estimates were obtained using linear mixed models adjusted for sociodemographic factors (baseline age, sex, race, household income level and educational attainment) lifestyle factors (smoking status, alcohol consumption status and physical activity), clinical factors (body mass index level, depressive symptoms, hypertension, diabetes, self-reported history of heart disease, stroke and cancer) and nutritional factors (calcium supplement use, other supplement use, dietary vitamin D intake, dietary energy intake and dietary calcium intake).

Figure 1

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In our prespecified subgroup analyses (figure 2), a significant modification effect was only observed for age (P for interaction=0.009), but not for sex (P for interaction=0.202) or race (P for interaction=0.158). Online supplemental table S1 further presents the estimates of the observed significant modification effects. Among participants aged ≥65 years, the difference in the rate of change in global cognitive scores between vitamin D supplement users and non-users was significantly larger (difference: −0.076 points/year; 95% CI −0.129 to −0.022, p=0.006) than that among people aged <65 years (difference: 0.030 points/year; 95% CI −0.028 to 0.089, p=0.311).

Figure 2. Prespecified subgroup analyses of the difference in the rate of decline in global cognitive function between vitamin D supplement users and non-users. Estimates were obtained using linear mixed models adjusted for sociodemographic factors (baseline age, sex, race, household income level and educational attainment) lifestyle factors (smoking status, alcohol consumption status and physical activity), clinical factors (body mass index level, depressive symptoms, hypertension, diabetes, self-reported history of heart disease, stroke and cancer) and nutritional factors (calcium supplement use, other supplement use, dietary vitamin D intake, dietary energy intake and dietary calcium intake, except where the adjusting variable was directly tested.

Figure 2

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In our exploratory subgroup analyses of other covariates (online supplemental figures S1 and S2), a significant modification effect was only observed for physical activity (P for interaction=0.001). Online supplemental table S2 presents the estimates of the observed significant modification effects. The difference in the rate of change in global cognitive scores between vitamin D supplement users and non-users was larger among participants who were physically inactive (difference: −0.169 points/year; 95% CI −0.251 to −0.088, p<0.001) than among those who were physically active (difference: −0.013 points/year; 95% CI −0.058 to 0.033, p=0.564).

Results of sensitivity analyses

As shown in table 3, among participants with normal serum 25(OH)D level as stipulated by existing guidelines, vitamin D supplement users showed a significant accelerated global cognitive decline (difference: −0.088 points/year; 95% CI −0.148 to −0.029, p=0.004) and memory decline (difference: −0.077 points/year; 95% CI −0.128 to −0.025, p=0.003), as compared with non-users. There was no significant association among those with insufficient/deficient serum 25(OH)D level (difference: 0.010 points/year; 95% CI −0.078 to 0.098, p=0.826) in the global cognitive score, memory score or executive function score.

Table 3. Associations between vitamin D supplement use status and rate of change in cognitive scores (points/year), by serum 25(OH)D level.

Vitamin D supplement use, stratified by serum 25(OH)D level Global cognitive score Memory score Executive function score
Beta
(95% CI)		 P value Beta
(95% CI)		 P value Beta
(95% CI)		 P value
Normal serum 25(OH)D level (≥30 ng/mL)*
 Non-users (n=1007) Reference group / Reference group / Reference group /
 Users (n=1012) −0.088 (−0.148 to −0.029) 0.004 −0.077 (−0.128 to −0.025) 0.003 −0.009 (−0.033 to 0.015) 0.463
Insufficient/deficient serum 25(OH)D level (<30 ng/mL)*
 Non-users (n=1045) Reference group / Reference group / Reference group /
 Users (n=330) 0.010 (−0.078 to 0.098) 0.826 0.032 (−0.045 to 0.108) 0.415 −0.021 (−0.056 to 0.014) 0.233
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Models are adjusted for sociodemographic factors (baseline age, sex, race, household income level and educational attainment), lifestyle factors (smoking status, alcohol consumption status and physical activity), clinical factors (body mass index level, depressive symptoms, hypertension, diabetes, self-reported history of heart disease, stroke and cancer) and nutritional factors (calcium supplement use, other supplement use, dietary vitamin D intake, dietary energy intake and dietary calcium intake).

*

According to the 2011 Endocrine Society clinical practice guideline, vitamin D deficiency was defined as a serum 25(OH)D below 20 ng/mL (50 nmol/L), and vitamin D insufficiency was defined as a serum 25(OH)D of 21–29 ng/mL (52.5–72.5 nmol/L).

The associations remained consistent in the sensitivity analyses after further adjusting for genetic susceptibility to cognitive impairment (online supplemental table S3) and in a subsample of participants aged ≥65 years who underwent a more comprehensive cognitive assessment (online supplemental table S4). When compared with non-vitamin D and non-multivitamin users (n=1576), the vitamin D supplement users showed a trend towards accelerated global cognitive decline (difference: −0.044 points/year; 95% CI −0.091 to 0.002, p=0.061), though this trend is not statistically significant (online supplemental table S5).

Additionally, to address potential confounding due to sex imbalance, we conducted a post hoc propensity score matched analysis (1:1 nearest-neighbour matching without replacement). In the well-balanced matched cohort (n=2004 per group, each with 73.0% females), vitamin D supplement use remained significantly associated with an accelerated global cognitive decline (difference: −0.062 points/year; 95% CI −0.106 to −0.019, p=0.005) (online supplemental table S6).

Discussion

In this study based on a large, nationally representative sample of older adults in the US, more than one-third of the participants were vitamin D supplement users (39.6%). Although the difference in the baseline dietary vitamin D intake was negligible between vitamin D supplement users and non-users, vitamin D supplement use was significantly associated with accelerated declines in global cognitive function and executive function. These associations remained consistent in the sensitivity analyses after further adjusting for genetic susceptibility to cognitive impairment and in a subsample of participants aged ≥65 years who underwent a more comprehensive cognitive assessment. When considering baseline serum 25(OH)D level, accelerated cognitive decline was only observed among supplement users with normal serum 25(OH)D level and not in the group with insufficient/deficient levels. Overall, our findings do not support vitamin D supplement use as a means of preventing or slowing cognitive decline in older people.

Despite the well-established evidence on the important role of physiological vitamin D in maintaining bone health, the benefits of vitamin D supplementation remain a subject of debate. Particularly, there is conflicting real-world evidence regarding the impact of vitamin D supplementation on cognitive outcomes.34 39 40 One study on 1759 multiethnic older participants observed that participants with the highest tertile of vitamin D intake from food sources were significantly related to a 28% decreased dementia risk, compared with those with the lowest tertile; however, when accounting for supplement use into the total vitamin D intake, the association was insignificant.12 Similarly, based on 2061 Black and 1329 White older adults from the Chicago Health and Aging Project, Dhana et al found that higher vitamin D intake from food was associated with slower cognitive decline among Black participants, while no significant associations were observed regarding vitamin D intake from supplements among both racial groups.15 In terms of investigating vitamin D supplement use and the risk of dementia, another study based on National Alzheimer’s Coordinating Center database suggested that vitamin D use was related to a 40% lower risk of developing dementia.14 However, confounding bias may not be ruled out from this study given that socioeconomic status, lifestyle and comorbidities were not adjusted.14 The above studies were mostly conducted among individuals ≥65 years.12 15 By comparison, our study used a relatively larger sample with a wider age range (50–97 years) which is more representative of the ageing population from a community-based setting in the USA and has adjusted for multidimensional potential confounders. This approach has significantly strengthened the robustness of the association findings we observed in this study.

Several mechanisms might underlie the observed harmful association between vitamin D supplement use and accelerated cognitive decline in the current study. As proposed in some animal studies on Alzheimer’s disease pathology,16 41 vitamin D supplementation may form a complex with p53 to exacerbate the non-genomic signalling pathway of the vitamin D receptor, thereby worsening Alzheimer’s disease progression by increasing Aβ plaque deposition. We acknowledged that the effect size of the difference in cognitive change between vitamin D supplement users and non-users (−0.052 points/year) seemed small. However, similar effect sizes were observed in other studies of this nature,15 22 30 and it is demonstrated that even minuscule cognitive decline could contribute to a substantially elevated risk of developing dementia over years.42 This finding may be translated to real-world situations involving older people who have been characterised as susceptible to ageing-related chronic diseases. It is reasonable to conclude that while vitamin D deficiency may be a risk factor for dementia or Alzheimer’s disease, there is no conclusive scientific evidence regarding the beneficial effects of vitamin D supplementation on cognitive impairment.

Insufficient dietary vitamin D intake is common among older adults,8 43 and this phenomenon is supported by the observation that the median dietary vitamin D intake (132.6 IU/day) in our study cohort was far lower than the recommended level. Of note, our sensitivity analysis suggested that vitamin D supplementation-related cognitive decline was observed among participants with normal serum 25(OH)D level,33 and not in those with insufficient/deficient level. We speculate that hypervitaminosis D from vitamin D supplementation may have accounted for this phenomenon, particularly in individuals with normal serum vitamin D level at baseline. Studies have shown that the long-term intake of vitamin D at doses higher than the daily recommended dose might lead to adverse outcomes, such as hypercalcaemia and adverse cardiovascular events.44 45 In particular, recent real-world evidence suggested that the adverse outcomes were even more frequent when vitamin D supplementation was associated with alfacalcidol or other active vitamin D receptor agonists.46 However, our study could not account for this factor, as information on the specific formulations of vitamin D supplementation was not available. Besides, another study based on National Health and Nutrition Examination Survey (NHANES) data suggested that, among people with serum 25(OH)D ≥50 nmol/L, the use of a daily vitamin D supplement was associated with higher risks in all-cause mortality and cancer mortality.8 Our study contributes novel evidence regarding the adverse impact of vitamin D supplementation on cognitive function; however, the unavailability of data on vitamin D supplementation dosages has limited our ability to further examine the potential dose–response relationship. From a clinical perspective, healthcare providers should encourage adequate vitamin D intake from dietary sources and moderate sun exposure, but should be cautious when recommending such supplements to older adults without a clear indication for it.

Our prespecified subgroup analyses identified a significant modification effect of age. The stronger association observed in adults aged ≥65 years may reflect age-related physiological vulnerabilities. With advancing age, the accumulation and progression of vascular impairment, metabolic dysfunction and immune dysregulation might create a systemic milieu that may increase susceptibility to adverse cognitive effects related to vitamin D supplementation. We did not detect significant effect modification by sex or race, though these analyses may be underpowered due to the small sample sizes within each subgroup and hence warrant verification in larger studies. Interestingly, our exploratory analyses further identified a significant modification effect of physical activity status. Physical activity has long been recommended as a means of maintaining or improving cognitive function.2 Our analysis suggested that among participants who were physically inactive, vitamin D supplementation was associated with greater cognitive decline than non-users, indicating a potential synergistic adverse effect on cognitive function. However, this finding should be interpreted cautiously due to potential residual confounding, as people who are physically inactive might have other risk factors for dementia such as comorbidities and a poor frailty status and lifestyle habits.47 Further studies are warranted to investigate the mechanisms involved in the interaction among vitamin D supplement use and physical activity on cognitive function in older adults.

This study has several strengths. We used well-validated cognitive data from a large representative cohort of ageing US adults, ensuring the generalisability and robustness of the findings. We also adjusted for a wide range of potential confounders, such as sociodemographic, lifestyle, clinical and nutritional factors, which were often insufficiently addressed in previous studies; a sensitivity analysis additionally accounted for genetic susceptibility to cognitive impairment. Moreover, to further reduce the potential confounding bias due to sex, we performed a post hoc analysis using propensity score matching on sex and yielded consistent findings. This supports the robustness of the observed association and suggests that the finding is unlikely to be confounded by the overrepresentation of females in the vitamin D user group. Therefore, this study provides a more rigorous and robust evaluation of the real-world association between vitamin D supplement use and cognitive functioning. This real-world evidence illustrates a more realistic picture than findings from clinical trials. However, there were also some limitations. First, causality cannot be established given the observational nature. Our cohort did not collect information about the motivation behind taking vitamin D supplements. It is widely known that older adults might take vitamin D supplements for bone health. Interestingly, only 4% of our participants reported osteoporosis as a comorbidity; hence, this may suggest that most of them were taking vitamin D supplements for preventing osteoporosis or other health reasons. Although we have adjusted for multiple covariates, other unmeasured and unavailable determinants may confound our results. Particularly, we could not account for individual sunlight exposure, which is a major source of vitamin D synthesis. We were also unable to use seasonality as a proxy, as the specific dates of vitamin D assessment were unavailable. Therefore, our findings should be interpreted with caution given the potential residual confounding. Future studies incorporating measures of sun exposure are warranted to confirm our results. Second, detailed information about the vitamin D supplement formulation, dosage and indication of use was not collected in this study. However, we considered dietary intake of vitamin D as a confounder in the multivariable analyses and conducted a sensitivity analysis based on the serum 25(OH)D levels to have a better gauge of the exposure status on cognitive function. The change in vitamin D supplement use status during follow-up cannot be further accounted for due to data unavailability. Although the duration of use for each dietary supplement (including vitamin D) was not captured in the questionnaire, users of vitamins were asked to report the duration of use in a related question; our post hoc analysis (not presented) showed that more than 70% of vitamins users reported they had been taking vitamins for 5 or more years, hence it is reasonable to extrapolate these findings and assume that vitamin D supplement use among users is likely to be chronic. Additionally, vitamin D supplement use was ascertained by self-reporting, which may have led to the misclassification of vitamin D users and biased our findings toward a null association. However, other data sources (eg, electronic health records or claims data) may not fully capture dietary supplements use, which are often purchased over-the-counter rather than by prescriptions.48 Although the specific ingredients of ‘multivitamins’ were not reported in the HRS, we conducted a sensitivity analysis to exclude both non-vitamin D and non-multivitamin users as the reference group and obtained a similar association trend with cognitive functioning. Third, the cognitive tests adopted in the HRS were screening assessments and were appropriate in the context of a large-scale population-based setting; however, using a more elaborate neuropsychological assessment might better capture subtle cognitive decline. In addition, we acknowledged that a COVID-19 diagnosis or imposed restrictions during the pandemic may have influenced cognitive outcomes in the 2020 survey, as well as the changes in lifestyle factors that may affect cognitive outcomes, such as mood and psychological distress, social isolation and physical activity.49 50 Finally, the findings derived from the US population, in which most residents are of White ethnicity, may not be generalisable to populations of other countries or ethnicities.

In conclusion, we found that vitamin D supplement use was associated with accelerated cognitive decline. The findings from real-world data do not support the use of vitamin D supplements to prevent cognitive decline in older people with adequate vitamin D status. Future large-scale and prospective studies are needed to validate our results to support the development and refinement of nutritional recommendations for preventing cognitive impairment in older people.

Supplementary material

online supplemental file 1
bmjopen-16-1-s001.docx (1MB, docx)
DOI: 10.1136/bmjopen-2025-106050

Acknowledgements

We would like to acknowledge the developers and participants of the Health and Retirement Study.

Footnotes

Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2025-106050 ).

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient consent for publication: Not applicable.

Ethics approval: This study involves human participants and the HRS was approved by the Institutional Reviewing Board at the University of Michigan and the National Institute on Aging (HUM00061128) and written informed consents were obtained from all participants. The analysis of the present study was approved by the Survey and Behavioral Research Ethics Committee of the Chinese University of Hong Kong (Reference no. SBRE-22-0384). Participants gave informed consent to participate in the study before taking part.

Data availability free text: The datasets generated and/or analysed during the current study are available from https://hrs.isr.umich.edu/.

Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Data availability statement

Data are available in a public, open access repository.

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    online supplemental file 1
    bmjopen-16-1-s001.docx (1MB, docx)
    DOI: 10.1136/bmjopen-2025-106050

    Data Availability Statement

    Data are available in a public, open access repository.

    Articles from BMJ Open are provided here courtesy of BMJ Publishing Group

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