Vitamin D, often termed the “sunshine vitamin”, is a fat-soluble secosteroid with unique biosynthetic properties and a wide spectrum of physiological functions. Unlike most micronutrients, it can be synthesised endogenously through dermal exposure to ultraviolet B (UVB) radiation; however, geographic, seasonal, cultural, and lifestyle factors frequently limit cutaneous synthesis, making dietary intake and supplementation essential to maintain adequate serum levels. Historically recognised for its critical role in calcium homeostasis and skeletal development, vitamin D has more recently been identified as a pleiotropic agent involved in immune regulation, cardiovascular health, metabolic function, mental well-being, and genomic stability. Complementing these benefits, omega-3 fatty acids (polyunsaturated fats) essential for maintaining cellular structure and providing metabolic energy, exert their own distinct yet synergistic effects on human health. While vitamin D functions primarily as a hormonal regulator of physiological systems, omega-3s serve as foundational components of cell membranes and are notable for their anti-inflammatory properties. Together, these nutrients contribute to the maintenance of heart, brain, bone, and immune health, with emerging evidence suggesting that their combined action may enhance disease prevention. This essay synthesises current scientific evidence on the health benefits of vitamin D, drawing on clinical trials, epidemiological data, and mechanistic studies, and further explores their potential for integration into public health strategies, while identifying key limitations and avenues for future research.
Vitamin D exists predominantly in two forms: ergocalciferol (D₂), derived from plant sources, and cholecalciferol (D₃), synthesised in the skin and found in animal-based foods. Both forms are converted in the liver to 25-hydroxyvitamin D [25(OH)D], the primary circulating form and biomarker of vitamin D status. Subsequent hydroxylation in the kidneys produces the hormonally active calcitriol [1,25(OH)₂D], which exerts its biological effects via the vitamin D receptor (VDR), a nuclear receptor expressed in diverse tissues including the intestines, bones, kidneys, immune cells, and central nervous system.
This widespread expression of VDR accounts for vitamin D’s multifaceted physiological roles. It regulates calcium and phosphate homeostasis, essential for bone mineralisation; modulates both innate and adaptive immune responses; influences cell proliferation and differentiation; and contributes to neuromuscular function. These pleiotropic effects provide a mechanistic basis for the broad array of health outcomes associated with adequate vitamin D status.
The most extensively validated benefit of vitamin D pertains to skeletal health. By promoting intestinal absorption of calcium and phosphate, vitamin D ensures adequate mineral supply for bone formation and maintenance. Deficiency leads to rickets in children and osteomalacia in adults, conditions characterised by bone softening and deformities. Moreover, vitamin D insufficiency in older adults contributes to osteoporosis and increased fracture risk. A comprehensive meta-analysis by Bolland et al. (2014) demonstrated that vitamin D, particularly when co-administered with calcium, significantly reduces the risk of hip and non-vertebral fractures in institutionalised elderly populations. This evidence underpins current clinical guidelines advocating supplementation for bone health in at-risk groups.
Vitamin D’s immunomodulatory properties are increasingly recognised. It enhances the microbicidal activity of macrophages and monocytes while attenuating pro-inflammatory cytokine production. Observational studies have consistently linked low 25(OH)D levels with heightened susceptibility to respiratory tract infections. Notably, Martineau et al. (2017), in a large-scale randomised controlled trial published in BMJ, found that vitamin D supplementation reduced the risk of acute respiratory infections, particularly among individuals with baseline deficiency. The COVID-19 pandemic further intensified interest in this domain, although definitive evidence regarding its protective efficacy against SARS-CoV-2 remains inconclusive and warrants further investigation.
Vitamin D may influence cardiovascular physiology through modulation of endothelial function, renin-angiotensin system activity, and systemic inflammation. Epidemiological data suggest an inverse association between serum 25(OH)D levels and risk of hypertension, myocardial infarction, and stroke. However, interventional trials have yielded equivocal results. The VITAL trial (Manson et al., 2019), encompassing over 25,000 participants, found no significant reduction in major cardiovascular events with vitamin D supplementation in the general population. Nonetheless, subgroup analyses suggest that individuals with low baseline vitamin D status may derive cardioprotective benefits, highlighting the need for stratified research designs.
Vitamin D receptors are expressed in brain regions involved in mood regulation and cognition, suggesting a neurobiological role for the vitamin. Low vitamin D status has been associated with increased risk of depression and cognitive decline. A systematic review by Spedding et al. (2018) found that vitamin D supplementation ameliorated depressive symptoms, particularly in individuals with deficiency. However, the heterogeneity of study designs and potential confounding variables necessitate cautious interpretation. Further placebo-controlled trials with standardised outcome measures are needed to clarify causality.
Vitamin D’s influence on cellular proliferation, differentiation, and apoptosis has spurred interest in its potential anti-carcinogenic effects. Epidemiological studies have reported inverse correlations between vitamin D levels and incidence of colorectal, breast, and prostate cancers. The VITAL trial, however, reported no significant reduction in overall cancer incidence. Yet, a secondary analysis indicated a potential decrease in cancer-related mortality among those receiving supplementation, suggesting a role in prognosis rather than prevention. These findings, while promising, demand further long-term investigations to elucidate underlying mechanisms and clinical relevance.
Vitamin D may modulate glucose metabolism by enhancing pancreatic β-cell function and insulin sensitivity. Observational studies have linked low vitamin D levels with increased risk of type 2 diabetes. Interventional evidence remains inconsistent; however, a 2019 study in Diabetes Care (Pittas et al.) showed that high-dose vitamin D supplementation reduced the progression from prediabetes to diabetes in individuals with baseline insufficiency. These findings underscore the potential for targeted supplementation in metabolically vulnerable populations, though broader efficacy remains to be established.
A novel dimension of vitamin D’s benefits pertains to its role in cellular ageing. Recent data from the VITAL trial sub-study (Zhu et al., 2025) demonstrated that daily supplementation with 2,000 IU of vitamin D₃ over four years preserved leukocyte telomere length by approximately 140 base pairs relative to placebo, equating to a biological age delay of around three years. As telomere attrition is a hallmark of cellular ageing and genomic instability, these findings suggest a potential geroprotective effect. Mechanistically, vitamin D may regulate genes involved in oxidative stress, inflammation, and DNA repair via VDR-mediated transcriptional control. Such effects were independent of demographic variables and were not replicated by concurrent omega-3 supplementation, highlighting vitamin D’s unique role in modulating telomere dynamics. These insights open new avenues for research into nutritional interventions aimed at promoting healthy ageing.
Emerging research highlights a biologically plausible and clinically relevant synergy between omega-3 polyunsaturated fatty acids (PUFAs) and vitamin D, particularly in the domains of immune regulation, neurocognitive function, and cardiovascular health. While each nutrient exerts distinct physiological effects, their co-supplementation may yield additive or even synergistic benefits through intersecting molecular pathways and complementary anti-inflammatory actions.
Mechanistically, both vitamin D and omega-3 fatty acids modulate immune responses, albeit via different targets. Vitamin D primarily acts through the vitamin D receptor (VDR), influencing gene transcription in immune cells and promoting a shift from pro-inflammatory Th1 and Th17 responses toward anti-inflammatory Th2 and regulatory T cell profiles (Martineau et al., 2017). Omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors to specialised pro-resolving mediators (SPMs) such as resolvins and protectins, which actively terminate inflammation and promote tissue repair (Calder, 2020). Recent in vitro studies suggest that vitamin D may enhance the biosynthesis of SPMs by upregulating 15-lipoxygenase expression, thereby amplifying the anti-inflammatory potential of omega-3s (Zhang et al., 2021).
Clinical evidence for this synergy is most robust in the context of cardiovascular and neuropsychiatric outcomes. The VITAL trial, a large-scale randomised controlled trial involving over 25,000 participants, included a 2×2 factorial design assessing both vitamin D₃ (2,000 IU/day) and marine omega-3 fatty acids (1 g/day). While neither intervention alone significantly reduced the incidence of major cardiovascular events in the general population, a secondary analysis revealed a significant reduction in myocardial infarction risk among individuals receiving both supplements concurrently, particularly in those with low baseline fish intake (Manson et al., 2019). This suggests a potential interaction effect, possibly mediated by combined modulation of endothelial function, systemic inflammation, and lipid metabolism.
In neurocognitive domains, co-supplementation has shown promise in ameliorating depressive symptoms and cognitive decline. A randomised trial by Kiecolt-Glaser et al. (2021) demonstrated that combined vitamin D and omega-3 supplementation significantly reduced markers of inflammation (e.g., IL-6, CRP) and improved mood scores in older adults, relative to either nutrient alone. These findings align with the shared capacity of both nutrients to cross the blood-brain barrier (BBB), influence neurotransmitter synthesis, and mitigate neuroinflammation; factors implicated in the pathophysiology of depression and neurodegeneration.
Furthermore, recent epidemiological data suggest that individuals with concurrent sufficiency in both vitamin D and omega-3 fatty acids exhibit a lower risk of all-cause mortality compared to those deficient in either or both nutrients (Zhao et al., 2022). This additive effect may reflect the broad systemic roles of these nutrients in maintaining cellular integrity, modulating oxidative stress, and supporting mitochondrial function.
Despite these promising findings, heterogeneity in study designs, baseline nutrient status, and outcome measures complicates interpretation. Future research should prioritise stratified analyses and mechanistic studies to delineate the contexts in which co-supplementation is most efficacious. Nevertheless, the current body of evidence supports the integration of both vitamin D and omega-3 fatty acids into preventive health strategies, particularly for populations at risk of inflammatory, cardiovascular, or neurodegenerative conditions.
Cutaneous synthesis of vitamin D is initiated when ultraviolet B (UVB) radiation (290–315 nm) from sunlight penetrates the skin and converts 7-dehydrocholesterol to previtamin D₃, which subsequently isomerises to vitamin D₃. Melanin, the primary determinant of skin pigmentation, acts as a natural photoprotective (sunscreen) agent by absorbing and scattering UV radiation. In individuals with darker skin, characterised by higher melanin content, this protective function significantly reduces the penetration of UVB rays into the epidermis, thereby diminishing the efficiency of vitamin D synthesis (Holick, 2007; Webb et al., 2018).
From an evolutionary perspective, variations in skin pigmentation are understood as adaptations to differing intensities of solar radiation across latitudes. Populations indigenous to equatorial regions evolved darker skin to mitigate the harmful effects of intense UV exposure, including DNA damage and folate degradation, while still producing adequate vitamin D due to abundant sunlight. Conversely, populations at higher latitudes, where UVB availability is lower, evolved lighter skin to optimise vitamin D synthesis under limited solar conditions (Jablonski & Chaplin, 2010).
However, in contemporary, globally mobile societies, this evolutionary adaptation poses challenges. Individuals with darker skin residing in high-latitude regions such as the UK are at increased risk of vitamin D deficiency, particularly during the winter months when UVB radiation is insufficient for cutaneous synthesis. Epidemiological studies consistently demonstrate lower serum 25(OH)D concentrations among ethnic minority groups in northern climates, underscoring the need for tailored public health strategies (SACN, 2016; Cashman et al., 2016).
This interplay between skin pigmentation, UVB exposure, and geography forms a critical context for understanding current recommendations for vitamin D intake and assessment.
In the UK, the Scientific Advisory Committee on Nutrition (SACN, 2016) recommends a daily intake of 10 micrograms (400 IU) for individuals aged four years and older, assuming minimal sun exposure. This intake aims to maintain serum 25(OH)D levels above 25 nmol/L, the threshold for deficiency. International bodies, such as the Endocrine Society, often advocate higher intakes, particularly for at-risk groups, including older adults, people with darker skin, those with limited outdoor exposure, and individuals living in high-latitude regions.
Vitamin D status is best assessed via serum 25(OH)D concentrations, with commonly accepted thresholds categorising levels as deficient (<25 nmol/L), insufficient (25–50 nmol/L), or sufficient (>50 nmol/L). These benchmarks inform clinical decision-making and public health policy regarding supplementation and fortification strategies.
Vitamin D deficiency constitutes a significant global public health concern, particularly in regions with limited sunlight exposure. In the UK, the NHS recommends universal supplementation during autumn and winter, and year-round for vulnerable populations such as pregnant women, infants, and the elderly (NHS, 2022). Fortification of staple foods, a strategy adopted in several countries, offers a population-level approach to addressing widespread deficiency. However, effective public health interventions must also account for sociocultural practices, skin pigmentation, and lifestyle factors that influence vitamin D synthesis and intake. Educational campaigns, routine screening in high-risk groups, and targeted supplementation programmes are essential components of a comprehensive public health strategy.
Vitamin D is a vital micronutrient that exerts profound effects on skeletal integrity, immune competence, metabolic function, neuropsychiatric health, and cellular ageing. While the evidence base is most robust for its role in bone maintenance and infection prevention, emerging data point to broader systemic benefits, including potential contributions to cardiovascular health, diabetes mitigation, cancer mortality reduction, and telomere preservation. Nevertheless, inconsistencies in trial outcomes, heterogeneity in methodologies, and the multifactorial nature of many health outcomes necessitate cautious interpretation.
Given the high global prevalence of vitamin D insufficiency and its association with adverse health outcomes, public health interventions centred around supplementation, food fortification, and education are both warranted and urgent. Future research should prioritise well-powered, stratified, and longitudinal studies to delineate optimal dosing strategies, mechanistic pathways, and population-specific responses. In doing so, vitamin D may be further harnessed not only as a preventive nutrient but as a strategic component in the promotion of healthy ageing and the mitigation of chronic disease burden.
Vitamin D is an essential fat-soluble vitamin that plays a critical role in calcium absorption, bone health, immune function, and overall wellbeing. There are two primary forms relevant to human nutrition: vitamin D₂ (ergocalciferol) and vitamin D₃ (cholecalciferol). While both forms can be used in fortified foods and supplements, they differ in origin, bioavailability, and suitability for certain diets.
Sources: Vitamin D₂ is primarily derived from plant-based organisms, particularly fungi. Key sources include:
Dietary Suitability:
Bioavailability:
Sources: Vitamin D₃ is the form produced naturally in human and animal skin upon exposure to UVB radiation. It is typically found in animal-derived foods, including:
Supplemental Sources:
Dietary Suitability:
Bioavailability:
In conclusion, both forms of vitamin D have roles in supporting health, but their sources and efficacy differ. Individuals should select the form that aligns best with their dietary preferences and health needs.
Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained through the diet, as humans lack the enzymatic capacity to synthesise them de novo. The three principal omega-3 fatty acids relevant to human health are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These differ in structure, physiological function, and dietary origin. While ALA is predominantly found in plant-based sources, EPA and DHA are largely derived from marine organisms. However, select terrestrial animal products, such as omega-3-enriched eggs and grass-fed or fortified beef, can contribute modest but meaningful quantities of long-chain omega-3s. Understanding the distribution, bioavailability, and dietary suitability of these fatty acids is critical for both nutritional adequacy and therapeutic application.
Sources: ALA is the primary plant-based omega-3 fatty acid and serves as a metabolic precursor to EPA and DHA, although conversion efficiency in humans is limited (<10%). Major dietary sources include:
Dietary Suitability:
ALA-rich foods are inherently plant-derived and thus suitable for both vegetarians and vegans. They represent the principal omega-3 source in plant-based diets.
Bioavailability and Conversion:
While ALA is readily absorbed, its endogenous conversion to EPA and DHA is inefficient and influenced by factors such as sex, age, and overall dietary composition. Women of reproductive age may have slightly higher conversion rates, potentially due to oestrogen-mediated enzymatic activity.
Sources: EPA and DHA are long-chain omega-3 fatty acids with well-established roles in cardiovascular, neurological, and immune health. They are primarily found in marine organisms, including:
Supplemental Sources:
Dietary Suitability:
Bioavailability:
EPA and DHA from fish and algal oils are typically consumed in triglyceride or ethyl ester forms, both of which are efficiently absorbed. Co-ingestion with dietary fat enhances bioavailability. Compared to ALA, preformed EPA and DHA are more directly incorporated into cell membranes and utilised in the synthesis of specialised pro-resolving mediators (SPMs).
Although marine products remain the richest dietary sources of EPA and DHA. Certain land-based animal products particularly when produced under specific feeding regimens, can provide supplementary amounts of omega-3 fatty acids. These include free-range or omega-3-enriched eggs, as well as grass-fed or fortified beef. While their absolute omega-3 content is lower than that of fish, their contribution becomes relevant in populations with limited seafood intake.
Standard eggs contain modest amounts of omega-3s, primarily ALA, with trace levels of EPA and DHA. However, the omega-3 profile improves significantly in eggs from hens fed flaxseed, chia, or marine algae.
Bioavailability:
Omega-3s in eggs are present in the phospholipid and triglyceride fractions of the yolk, which are efficiently absorbed. Thus, omega-3-enriched eggs represent a practical, non-marine source of bioavailable long-chain omega-3s, particularly beneficial for omnivores with low fish intake.
The omega-3 content of beef is highly dependent on the animal’s diet. While beef is not a primary source of omega-3s, it can make a modest contribution to total intake.
Considerations:
Fortified beef may be marketed as “omega-3 enriched” and offers a functional food option for increasing long-chain omega-3 intake without the need for fish consumption.
| Food Source | ALA (mg/100 g) | EPA (mg/100 g) | DHA (mg/100 g) | Notes |
|---|---|---|---|---|
| Flaxseed oil | ~53,000 | 0 | 0 | Richest plant source of ALA; no EPA/DHA |
| Chia seeds | ~17,500 | 0 | 0 | High ALA; bioavailability affected by seed form |
| Walnuts | ~9,000 | 0 | 0 | Moderate ALA source |
| Oily fish (e.g. salmon) | ~100–300 | ~500–1,500 | ~700–1,500 | Marine standard for EPA/DHA |
| Algal oil (supplement) | 0 | ~100–300 | ~300–600 | Vegan source of preformed EPA/DHA |
| Free-range egg (1 large) | ~40–100 | ~10–30 | ~20–100 | Higher values in omega-3-enriched eggs |
| Grass-fed beef (100 g) | ~40–70 | ~5–20 | ~5–15 | Modest EPA/DHA; improved omega-6:3 ratio |
| Grain-fed beef (100 g) | ~15–30 | <5 | <5 | Low omega-3 content; high omega-6 |
| Fortified beef (100 g) | ~100–150 | ~20–50 | ~20–50 | Fortified via feed; may approach enriched egg levels |
Bioavailability: Omega-3 fatty acids from eggs and beef are efficiently absorbed, particularly when consumed with dietary fat. However, absolute EPA and DHA quantities remain markedly lower than those in marine sources.
Health Outcomes: Regular consumption of omega-3-enriched eggs or grass-fed/fortified beef can support cardiovascular and cognitive health, particularly in individuals who consume little to no fish.
Optimisation Strategies: For individuals aiming to enhance omega-3 status without marine products, a combined approach may provide a balanced and effective alternative:
ALA is a plant-based omega-3 fatty acid suitable for vegetarian and vegan diets, but its conversion to EPA and DHA is limited. Regular consumption of ALA-rich foods is recommended, particularly in populations avoiding marine products.
EPA and DHA are biologically active long-chain omega-3s found predominantly in marine organisms and some terrestrial animals. They are more effective than ALA in supporting anti-inflammatory and neuroprotective functions.
For individuals following plant-based diets, algal oil supplements offer a viable and bioequivalent source of DHA (and in some cases EPA), enabling adequate intake without reliance on animal-derived products.
Fortified foods and supplements should be scrutinised for source and form, particularly by those adhering to dietary restrictions, as many omega-3-enriched products utilise fish oil unless explicitly labelled otherwise.
Balance and Health Outcomes an optimal dietary ratio of omega-6 to omega-3 fatty acids is essential. Modern Western diets often exhibit imbalances, with a ratio as high as 20:1, favouring omega-6, which may contribute to chronic inflammation and increased risk of cardiovascular disease (Simopoulos, 2002). Increasing omega-3 intake through fatty fish or supplements is commonly recommended to counteract this imbalance.
In conclusion, while oily fish and marine supplements remain the most concentrated sources of EPA and DHA, other dietary options such as omega-3-enriched eggs and grass-fed or fortified beef can provide complementary benefits. These terrestrial sources, though lower in absolute omega-3 content, offer favourable bioavailability and may improve the overall fatty acid profile of the diet. Their inclusion is particularly relevant for individuals with limited access to or preference against marine foods. When incorporated thoughtfully alongside plant-based ALA sources and, where appropriate, algal oil supplements, such foods can contribute to a nutritionally adequate and health-supportive omega-3 intake pattern.
1,25(OH)₂D (calcitriol): The hormonally active form of vitamin D, produced in the kidneys. It helps regulate calcium metabolism and affects many other bodily functions.
2×2 factorial design: A type of experimental study design in which participants are randomly assigned to one of four groups to test the individual and combined effects of two interventions. This allows for the assessment of interaction effects between treatments.
25(OH)D (25-hydroxyvitamin D): The main circulating form of vitamin D in the blood and the best indicator of vitamin D status.
15-lipoxygenase: An enzyme involved in the metabolism of polyunsaturated fatty acids. It catalyses the formation of precursors to SPMs, such as resolvins and protectins, and is upregulated by vitamin D in certain immune cells.
Algal oil: A plant-based oil derived from marine microalgae, used as a vegan source of the omega-3 fatty acids DHA and EPA. It is a sustainable alternative to fish oil with comparable bioavailability.
Apoptosis: A controlled process by which the body removes damaged or unnecessary cells; sometimes referred to as programmed cell death.
β-cells (beta cells): Cells located in the pancreas that produce insulin, a hormone essential for regulating blood sugar levels.
Bioavailability: The extent to which a nutrient is absorbed and used by the body. Higher bioavailability means the body can use more of the nutrient.
Biomarker: A measurable substance in the body, such as 25(OH)D, that indicates a biological condition or nutrient status.
Blood-brain barrier (BBB): A selective, semipermeable barrier formed by endothelial cells lining cerebral blood vessels. It protects the brain from harmful substances in the bloodstream while allowing essential nutrients and signalling molecules to pass through.
Bone mineralisation: The process of depositing minerals like calcium and phosphate into bone tissue, making it strong and rigid.
Calcitriol: See 1,25(OH)₂D.
Calcium/phosphate homeostasis: The regulation of calcium and phosphate levels in the body, essential for bone health and many cellular processes.
Cholecalciferol (vitamin D₃): The form of vitamin D produced in the skin when exposed to ultraviolet B (UVB) rays and found in animal-based foods and some supplements.
C-reactive protein (CRP): A protein produced by the liver in response to inflammation. CRP is commonly used as a clinical biomarker to assess the presence and intensity of systemic inflammation.
Cutaneous synthesis: The production of vitamin D₃ in the skin when exposed to UVB radiation. This is the primary natural source of vitamin D in humans.
Cytokines: Signalling proteins released by cells, especially in the immune system. They help regulate inflammation and immune responses.
Deficiency: A state in which the body does not have enough of a nutrient to maintain normal health and function.
Dermal synthesis: The production of vitamin D in the skin following exposure to sunlight, particularly UVB radiation.
Docosahexaenoic acid (DHA): A long-chain omega-3 fatty acid abundant in the brain and retina. DHA is critical for neuronal membrane fluidity, cognitive function, and visual development, and also contributes to anti-inflammatory signalling.
DNA repair: The body’s natural process for correcting damage to its genetic material (DNA), which helps maintain genomic stability.
Eicosapentaenoic acid (EPA): A long-chain omega-3 fatty acid found in oily fish and marine oils. EPA serves as a precursor to anti-inflammatory compounds and plays a role in cardiovascular, immune, and mental health.
Endogenous synthesis: The body’s internal ability to produce a substance naturally, such as vitamin D in the skin.
Endothelial function: The performance of the inner lining of blood vessels, which influences blood flow and pressure regulation.
Epigenetic regulation:The control of gene activity without altering the DNA sequence, often through chemical modifications. Vitamin D may influence gene expression through epigenetic mechanisms.
Ergocalciferol (vitamin D₂): A form of vitamin D derived from plant sources and fungi, often used in fortified foods and vegan supplements.
Fat-soluble: Describes vitamins (like A, D, E, and K) that dissolve in fat and can be stored in the body’s fatty tissues.
Factorial design: A study design that allows researchers to test the effects of multiple interventions both independently and in combination, helping to identify potential interaction effects.
Fortification: The addition of nutrients to foods during manufacturing to improve their nutritional value, such as adding vitamin D to breakfast cereals or plant-based milk.
Free radicals: Unstable molecules that can damage cells, contributing to ageing and disease. Vitamin D may help reduce their harmful effects.
Geroprotective: Refers to something that protects against the biological processes of ageing, potentially slowing age-related decline.
Hydroxylation: A chemical reaction in the body that converts vitamin D into its active forms by adding hydroxyl groups (-OH). This occurs primarily in the liver and kidneys.
Incidence vs mortality: ‘Incidence’ refers to how often a disease occurs (new cases), while ‘mortality’ refers to the number of deaths caused by that disease.
Inflammation / pro-inflammatory: Inflammation is the body’s response to injury or infection. ‘Pro-inflammatory’ substances promote this process, which can be protective or harmful depending on the context.
Insulin sensitivity: How effectively the body responds to insulin. Higher sensitivity helps maintain normal blood sugar levels and reduces diabetes risk.
Interleukin-6 (IL-6): A pro-inflammatory cytokine produced by various cells in response to infection or injury. Elevated IL-6 levels are associated with systemic inflammation and have been linked to cardiovascular and neuropsychiatric disorders.
International Units (IU): A standard unit used to measure the potency of vitamins and other substances. For vitamin D, 1 microgram (µg) = 40 IU.
Isomerisation: A chemical process in which a molecule is transformed into another molecule with the same atoms but a different arrangement. In vitamin D metabolism, previtamin D₃ is isomerised to cholecalciferol.
Latitude effect (on UVB exposure): The phenomenon whereby UVB radiation decreases with increasing distance from the equator, due to the angle of sunlight. This affects the skin’s ability to produce vitamin D.
Leukocytes: Also known as white blood cells, they are part of the immune system and help defend the body against infections and foreign substances.
Leukocyte telomere length: A biomarker of biological ageing measured by the length of telomeres in white blood cells. Shorter telomeres are associated with increased disease risk and reduced lifespan.
Lichen: A symbiotic organism made up of fungi and algae or cyanobacteria. Some lichens are used to produce vegan-friendly vitamin D₃ supplements.
Macrophages / monocytes: Types of white blood cells involved in detecting, engulfing, and destroying pathogens and cellular debris.
Meta-analysis: A research method that combines data from multiple studies to draw a more comprehensive conclusion.
Micrograms (µg): A unit of weight equal to one millionth of a gram, commonly used to measure vitamin and mineral content.
Mitochondrial: Refers to structures in cells (mitochondria) that generate energy, often called the cell’s powerhouses.
Neuroinflammation: Inflammatory responses occurring within the central nervous system, often involving microglia and astrocytes. Chronic neuroinflammation is implicated in neurodegenerative diseases and mood disorders.
nmol/L (nanomoles per litre): A unit for measuring concentration of substances in the blood, such as 25(OH)D for vitamin D status.
Nuclear receptor: A type of protein inside cells that binds to hormones like vitamin D and influences gene activity.
Observational study: A type of research where scientists monitor health outcomes without intervening, useful for identifying associations but not causation.
Omega-3 polyunsaturated fatty acids (PUFAs): A class of essential fatty acids characterised by the presence of multiple double bonds, with the first double bond located at the third carbon from the methyl end of the molecule. Omega-3 PUFAs, including EPA and DHA, are primarily derived from marine sources and are known for their anti-inflammatory and cardioprotective properties.
Osteomalacia: A condition in adults where bones become soft and weak due to inadequate vitamin D, often leading to bone pain and muscle weakness.
Osteoporosis: A condition where bones become porous and fragile, increasing the risk of fractures, especially in older adults.
Oxidative stress: A harmful condition caused by an imbalance between free radicals and antioxidants. It can damage cells and contribute to ageing and disease.
Placebo-controlled: A type of study where one group receives the treatment while another receives a placebo (inactive substance), allowing researchers to compare outcomes.
Pleiotropic: Describes a substance or gene that has multiple effects on different systems or functions in the body. Vitamin D is considered pleiotropic due to its diverse roles.
Prediabetes: A condition where blood sugar levels are elevated but not high enough to be classified as type 2 diabetes. It increases the risk of developing diabetes later.
Protectins: Another subclass of SPMs derived primarily from DHA. Protectins contribute to the resolution of inflammation and have been implicated in neuroprotection and immune regulation.
Randomised controlled trial (RCT): A high-quality experimental study where participants are randomly assigned to either the treatment or control group to test the effectiveness of an intervention.
Regulatory T cells (Tregs): A subset of T cells that modulate the immune response by suppressing excessive inflammation and maintaining immune tolerance, thereby preventing autoimmunity.
Renin-angiotensin system: A hormone system that regulates blood pressure and fluid balance. Vitamin D may help modulate this system.
Resolvins: A subclass of SPMs biosynthesised from EPA and DHA. Resolvins help terminate inflammatory responses and facilitate the return to tissue homeostasis without suppressing immune defence.
Rickets: A childhood disease caused by vitamin D deficiency, leading to soft, misshapen bones and skeletal deformities.
Secosteroid: A type of steroid-like compound with a broken ring in its structure. Vitamin D belongs to this group.
Serum: The clear liquid part of blood that remains after clotting. It is used in laboratory tests to measure substances like 25(OH)D.
Specialised pro-resolving mediators (SPMs): A group of bioactive lipid compounds derived from omega-3 fatty acids that actively promote the resolution of inflammation and tissue repair. Examples include resolvins, protectins, and maresins.
Stratified study: A study design that divides participants into subgroups (e.g. by age, sex, or vitamin D level) to analyse how different groups respond to a treatment.
Subgroup analysis: An analysis within a study that looks at specific groups of participants to see if results vary between them.
Supplementation: The practice of taking additional vitamins or minerals to improve nutritional intake.
Telomere: The protective end caps of chromosomes that prevent genetic material from deteriorating. They become shorter with age.
Telomere attrition: The gradual shortening of telomeres over time, associated with cellular ageing and reduced genomic stability.
T cell subsets (Th1, Th2, Th17, Tregs): Different types of helper T cells with specialised immune functions:
Ultraviolet B (UVB): A component of sunlight (wavelength 290–315 nm) that stimulates vitamin D production in the skin. UVB exposure varies with time of day, season, and latitude.
UV index: A standard measure of the strength of ultraviolet radiation from the sun at a particular place and time. Higher values indicate greater potential for skin damage and vitamin D synthesis.
Vitamin D receptor (VDR): A protein found in many cells that binds to calcitriol and helps regulate gene expression and cellular function.
Vitamin D₂ (ergocalciferol): A plant-derived form of vitamin D found in fungi and fortified foods. Suitable for vegetarians and vegans but less potent than D₃.
Vitamin D₃ (cholecalciferol): The form of vitamin D produced in human skin and found in animal products. It is more effective than D₂ at raising and maintaining vitamin D levels.