on October 09, 2026
Vitamin D Beyond Bone Health
Vitamin D is traditionally associated with the regulation of calcium and phosphorus metabolism and skeletal health. However, its biological activity is much broader.
The vitamin D receptor, VDR, is expressed in numerous tissues, including the central nervous system. The brain also contains the enzymes needed to convert vitamin D into its biologically active forms.
This distribution has led to hypotheses about vitamin D's role in regulating processes involved in brain health, including neuroinflammation, oxidative stress, energy metabolism, vascular function, and neuronal plasticity.
This perspective gives rise to interest in a possible relationship between vitamin D levels and cognitive ability during aging.
The problem, however, is distinguishing a biological association from a causal relationship.
Lower vitamin D levels can indeed be associated with conditions that, independently of vitamin D, increase the risk of cognitive decline: advanced age, greater adiposity, less physical activity, chronic diseases, metabolic alterations, and reduced sun exposure.
25(OH)D: the parameter used to assess vitamin status
Vitamin D status is generally assessed by measuring the blood concentration of 25-hydroxyvitamin D [25(OH)D], the main circulating form of the vitamin.
The distinction between sufficiency, insufficiency, and deficiency must be interpreted in a clinical context and according to the criteria used by the laboratory or relevant guidelines. There is no single universally valid value to define the optimal level for every possible health outcome.
In the study published in 2025 in Nutrients, deficiency was defined as a concentration below 20 ng/mL, while values below 30 ng/mL were considered indicative of insufficiency. In the studied population, composed of people between 55 and 80 years old, the prevalence of deficiency was about 6.5%, while that of insufficiency reached about 40%.
This finding is significant because it shows how vitamin D insufficiency can be relatively common even in older people who do not necessarily have a true deficiency.
Vitamin D and cognitive decline: far from a simple association
Epidemiological interest arises primarily from the observation that low levels of 25(OH)D have been associated, in several prospective studies, with an increased risk of cognitive decline and dementia.
A meta-analysis published in 2024, which included 23 prospective studies, found an association between vitamin D deficiency and an increased risk of dementia, Alzheimer's disease, and cognitive decline. Compared to subjects not classified as deficient, deficiency was associated with about a 1.42-fold higher risk of dementia and about a 1.57-fold higher risk of Alzheimer's. The risk of cognitive decline was also increased.
These results are interesting, but they do not prove that vitamin D deficiency causes cognitive decline.
In fact, it is possible that part of the association is explained by confounding factors.
A person with cognitive decline may spend less time outdoors, move less, have a less balanced diet, or exhibit greater overall frailty. All these factors can contribute to reduced vitamin D.
This raises a fundamental question: does low vitamin D contribute to cognitive decline, or is it, at least in part, an indicator of an already compromised organism?
Vitamin D, adiposity, and insulin resistance
The concentration of 25(OH)D was indeed inversely associated with:
· body mass index;
· fat mass;
· percentage of fat mass;
· HOMA-IR index, used as an indirect measure of insulin resistance.
In other words, lower vitamin D levels tended to be observed in subjects with greater adiposity and greater insulin resistance.
This result opens up a particularly interesting perspective.
The relationship between vitamin D and the brain could indeed be part of a broader biological network in which adiposity, glucose metabolism, insulin resistance, inflammation, and cerebrovascular health interact.
It is therefore not necessarily the single concentration of vitamin D that determines cognitive function, but rather the metabolic context in which that concentration is situated.
Insulin and the brain: a metabolic link
Insulin is important not only for blood glucose control.
In the brain, it participates in processes related to memory, learning, neuronal metabolism, and synaptic plasticity. Alterations in insulin signaling can interfere with these mechanisms and have been studied in relation to neurodegenerative processes.
Systemic insulin resistance can also be associated with endothelial dysfunction, oxidative stress, and low-grade chronic inflammation, all of which are potentially relevant to brain health.
Vitamin D appears to interact with some of these metabolic pathways. The biologically active form, 1,25(OH)₂D, canaffect the function of pancreatic β cells, calcium metabolism, and some mechanisms involved in insulin sensitivity.Effects on the regulation of the renin-angiotensin system and inflammation have also been proposed.
However, this is a complex biological network, in which vitamin D is one element and not necessarily the main determinant.
Neuroinflammation and oxidative stress
One of the most studied hypotheses concerns vitamin D's ability to modulate the inflammatory response.
Aging is characterized by increased vulnerability to oxidative stress and changes in the immune response. In the brain, persistent microglial activation and the production of pro-inflammatory mediators can contribute to neuronal dysfunction.
In experimental models, vitamin D has shown immunomodulatory and potentially neuroprotective activity. VDR expressed in the nervous system can also intervene in the regulation of genes involved in the cellular response.
These mechanisms make a role for vitamin D in brain health biologically plausible.
But biological plausibility does not mean clinical efficacy.
This is precisely one of the central points that has emerged from research in recent years.
When clinical studies change the perspective
Observational studies frequently suggest an association between low vitamin D levels and poorer cognitive outcomes.
A systematic review of 20 randomized studies had already highlighted heterogeneous results, without providing convincing evidence of a cognitive benefit from vitamin D supplementation in the adult population.
A 2023 meta-analysis, including 24 randomized trials and 7,557 participants, instead found a favorable effect on global cognition. The effect appeared greater in vulnerable groups and in participants with vitamin D deficiency at baseline.
This difference between studies may depend on many variables: baseline vitamin D level, dose used, duration of supplementation, age, metabolic conditions, baseline cognitive status, and tools used to measure cognitive function.
The relationship between the brain and metabolism
The results of the Thai study take on particular significance precisely by considering the link between vitamin D, adiposity, and insulin sensitivity.
Brain aging is not, in fact, separate from the metabolism of the entire organism.
The brain depends on an adequate energy supply, proper vascular function, glycemic balance, inflammation control, and the ability of cells to manage oxidative stress.
Visceral obesity, insulin resistance, chronic hyperglycemia, and vascular dysfunction can contribute to brain vulnerability through multiple pathways.
In this scenario, vitamin D could be considered not so much as a “memory vitamin” as one of the biomarkers that reflect the overall nutritional and metabolic status of the organism.
Not all vitamin D used in studies is necessarily equivalent
When interpreting the literature on vitamin D, it is important to consider not only the dose, but also the chemical form used, the formulation, the method of administration, the baseline 25(OH)D level, and the duration of the intervention.
One point of particular interest concerns vitamin D3 obtained from biological sources, such as lichen, compared to cholecalciferol preparations used in clinical trials. Lichen-derived vitamin D3 is still cholecalciferol from a chemical standpoint; but biologically sourced vitamin D3 has a specific clinical advantage for cognitive function compared to D3 from other sources.
The U-shaped effect hypothesis
Another topic that deserves attention is the possible non-linear relationship between 25(OH)D concentration and health outcomes.
In some observational studies, a so-called U-shaped relationship has been described, in which both very low and very high concentrations are associated with less favorable outcomes.
This phenomenon, however, does not prove that vitamin D3 is inherently harmful at high concentrations, as the effect disappears when using vitamin D from a natural source.
The U-shaped relationship can be influenced by numerous factors: preexisting health conditions, frailty, obesity, chronic diseases, kidney function, physical activity, diet, sun exposure, and clinical indication for supplementation. Furthermore, observational studies do not allow causality to be established with certainty.
It is therefore more correct to consider the U-shaped curve hypothesis as a signal to be further investigated, rather than as proof of vitamin D3-specific toxicity.
Why lichen-derived vitamin D remains interesting
Lichen-derived vitamin D3 is of particular interest especially from a nutritional, technological, and sustainability standpoint, because it allows cholecalciferol to be obtained without resorting to animal sources.
From a biological standpoint, however, cholecalciferol remains the same molecule: after absorption, it is metabolized in the liver to 25(OH)D and subsequently, in tissues that possess the necessary enzymatic apparatus, can be converted into the active form 1,25(OH)₂D.
The scientifically more interesting question is therefore not whether the “natural” molecule is vitamin D and the “chemical” one is another vitamin: they are both sources of vitamin D3.
The question to be verified is rather whether different matrices, production processes, formulations, or methods of administration can alter bioavailability, the course of 25(OH)D, metabolism, and individual response.
To prove this, head-to-head studies would be needed in which lichen-derived vitamin D3 and vitamin D3 from other sources are administered at the same dose, in comparable populations, measuring not only 25(OH)D but also metabolic and cognitive parameters.
The lesson for brain health
Current evidence therefore suggests avoiding oversimplification: increasing vitamin D is not enough to protect the brain.
The concentration of 25(OH)D must be interpreted together with age, body composition, glucose metabolism, kidney function, nutritional status, physical activity, and clinical conditions.
The study on the elderly population showed exactly this: 25(OH)D was inversely associated with adiposity and insulin resistance, while it was not directly associated with cognitive function.
Supplementation trials must also be read carefully. The fact that some studies did not show cognitive improvement after vitamin D3 administration does not automatically mean that vitamin D is useless for the brain; it means that clinically significant cognitive protection has not been demonstrated with those formulations, doses, populations, and treatment durations.
Future research should therefore go beyond the simple comparison between “vitamin D yes” and “vitamin D no,” evaluating form, origin, bioavailability, baseline metabolic status, and individual characteristics.
In this perspective, lichen-derived vitamin D3 represents a biologically interesting source of cholecalciferol, but its potential cognitive or metabolic superiority compared to other sources of vitamin D3 remains a scientific hypothesis that requires direct clinical studies.
Vitamin D and the brain: where we stand today
Current knowledge can be summarized in four points.
The first piece of evidence is that vitamin D deficiency is common in the elderly and should be considered as part of the assessment of overall health status.
The second is that numerous observational studies have found an association between low vitamin D levels and an increased risk of cognitive decline and dementia.
The third is that randomized studies have not produced uniform results. Some meta-analyses have detected small cognitive benefits, especially in vulnerable or deficient individuals, while other studies have not observed significant effects.
The fourth, which is particularly important, is represented by the VitaMIND trial: even in older adults with mild-to-moderate vitamin D deficiency and initial cognitive impairment, two years of supplementation did not lead to a significant improvement in cognitive functions.
Research, therefore, does not currently support the idea that vitamin D can be used as a specific treatment for cognitive decline.
From a single vitamin to metabolic health
The most interesting perspective could be to consider vitamin D within a broader model of healthy ageing.
A proper diet, regular physical activity, adequate exposure to sunlight when appropriate, maintenance of muscle mass, control of visceral adiposity, insulin sensitivity, blood pressure, and cardiovascular health represent factors that interact with each other in determining the trajectory of ageing.
In this context, correcting a documented vitamin D deficiency can represent an appropriate intervention for overall health, but it should not be presented as an isolated strategy against memory loss.
The real challenge of longevity medicine probably lies in simultaneously protecting the brain, muscle, metabolism, and vascular system, intervening early on modifiable risk factors.
The lesson of the 2025 study
The value of the research conducted in the elderly population of Bangkok lies precisely in its apparently negative result.
The absence of a significant association between vitamin D and cognitive function does not diminish the importance of the study. On the contrary, it helps to better define the problem.
Vitamin D was found to be associated with adiposity and insulin resistance, but not with the cognitive level measured in the analyzed population.
This suggests that a biomarker can be important for overall health without necessarily being a direct determinant of a specific neurological function.
Future research will therefore need to establish whether there are particular subgroups—for example, people with true deficiency, high metabolic frailty, or specific neurodegenerative conditions—in which correcting vitamin D can produce more relevant cognitive benefits.
For now, the position most consistent with the evidence is to consider vitamin D as an important component of the elderly person's nutritional and metabolic balance, but not as a proven therapy to prevent or treat cognitive decline.
PRODUCT_ITEM
NOTE: The information in the product sheets on this site is for informational and educational purposes only and does not represent medical advice. The published content is not intended to replace the relationship with a doctor or any medical indications, diagnoses, or prescriptions. The information provided describes the ingredients and characteristics of dietary supplements, designed to support the body's balance and well-being within a healthy lifestyle. Dietary supplements are not medicines and must not be used to prevent, diagnose, treat, or alleviate diseases or pathological conditions.
Bibliographic references
1. Imerbsin N, Shantavasinkul PC, Witoonpanich P, et al. Vitamin D and Cognitive Impairment. Nutrients. 2025;17(8):1301. doi:10.3390/nu17081301.
2. Corbett A, Taylor R, Llewellyn D, et al. Impact of Vitamin D Supplementation on Cognition in Adults With Mild to Moderate Vitamin D Deficiency: Outcomes From the VitaMIND Randomized Controlled Trial. Journal of the American Medical Directors Association. 2025;26(8):105711. doi:10.1016/j.jamda.2025.105711.
3. The Effect of Vitamin D3 Supplementation on the Incidence of Diagnosed Dementia Among Healthy Older Adults—The Finnish Vitamin D Trial. 2025.
4. Zhang XX, Wang HR, et al. Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies. Journal of Alzheimer's Disease. 2024;98(2):373-385. doi:10.3233/JAD-231381.
5. Effects of Vitamin D Supplementation on Cognitive Outcomes: A Systematic Review and Meta-Analysis. Neuropsychology Review. 2023. doi:10.1007/s11065-023-09598-z.
6. Vitamin D Supplementation and Cognition in Adults: A Systematic Review of Randomized Controlled Trials. 2021.
7. Effect of 2000 IU compared with 800 IU vitamin D on cognitive performance among adults age 60 years and older: a randomized controlled trial. American Journal of Clinical Nutrition. 2019;110(2):246-253. doi:10.1093/ajcn/nqz081.
8. Effects of Vitamin D3 Combined with Folic Acid on Domain and Specific Cognitive Function among Patients with Mild Cognitive Impairment: A Randomized Clinical Trial. The Journal of Prevention of Alzheimer's Disease. 2024. doi:10.14283/jpad.2024.165.
