Adequate vitamin D levels are necessary for muscle health, which is important for mobility, stability and posture [1-11]. As people get older, muscle weakness or muscle loss can increase the risk for frailty and falls, which can also lead to bone fractures [10, 12-14]. Vitamin D deficiency has been associated with increased falls and hip fractures in older adults [10, 12]. While fall risk involves many factors, including age, bone health, activity level, balance issues, underlying health conditions, and medication use [15-17], vitamin D is an important factor for reducing fall risk in older, vitamin D deficient populations because of its impact on muscle health [1-14]. 

How Does Vitamin D Work for Stability and Reducing Risk of Falls? 

Adequate muscle strength and mobility are associated with stability and a decreased risk of falling [1-10, 12-14, 18]. The role of vitamin D in reducing risk of falls starts with impacts on muscle strength and muscle metabolism. Vitamin D contributes to protein synthesis and muscle fiber metabolism, which is responsible for building and repairing muscle. Additionally, vitamin D is important for cell signaling processes and gene expression which contribute to the growth, development, function, and repair of muscle cells [5-8].  

Research on Vitamin D and Risk of Falls 

Evidence from human data, including observational data on vitamin D levels [13], interventional data [14, 16, 19-23], and meta-analyses of interventional data [6, 17, 18, 24-27], support an overall positive impact of vitamin D on stability, muscle health, and muscle function, which may impact the risk of falls, particularly for older adults who are vitamin D deficient or insufficient [17, 24, 25]. It should be noted that there have been inconsistent findings in vitamin D supplementation’s impact on fall risk [24, 28], resulting in conflicting recommendations [15, 17]. The inconsistent results might be attributed to some confounding factors, including differences in initial vitamin D status, dosing used, short study duration, and lack of individual dosing required to reach optimal levels [24].  

While more data is needed on vitamin D supplementation and falls [28], current evidence includes: 

• Vitamin D supplementation alone has a benefit of reducing fall risk in older adults with vitamin D levels lower than 50 nmol/L [25]. The combination of vitamin D with calcium supplementation in this study involving older, vitamin D deficient adults reduced fall risk by 12% [25].  
• Some studies suggest that consistent daily intake of vitamin D is associated with reduced risk of falls for those who are vitamin D deficient [24]. Studies also suggest that vitamin D intake amounts are important to consider and that higher amounts (≥1000 IU daily) may not show improvements in risk of falls compared to a daily intake of 200 IU [16, 19, 22, 23]. Together, the data highlights the importance of steady daily intake to maintain optimal vitamin D levels. 
• In vitamin D deficient, elderly women, the combination of vitamin D and calcium supplementation reduced fall risk compared to calcium supplementation alone, which is partially attributed to improved balance control [14]. This suggests that vitamin D may impact fall risk through improved balance, muscle strength, and lower extremity function in this population [14]. 
• Vitamin D has been linked to improved muscle health and mobility in vitamin D deficient healthy adults and older women [6, 13, 20, 29]. 

• Individuals with conditions or chronic diseases impacting motor function or balance may also benefit from maintaining optimal vitamin D levels [21, 30]. 

Fall Risk 

According to the U.S. Centers for Disease Control and Prevention, falls are a leading cause of injury (fatal and non-fatal) among older adults who are 65 years or older [31]. Age-related decreases of muscle strength and skeletal muscle mass are some factors that can impact mobility and stability [8, 32, 33]. Older adults may not have sufficient knowledge about vitamin D, specifically relating to deficiency-associated risk of falls, which highlights the importance of educating the public [34]. While fall risk is associated with multiple factors [15-17], the role of vitamin D to support muscle health and potentially reduce risk of falls is one clear reason to maintain optimal vitamin D levels, particularly in advancing age. 

Cardiovascular health continues to be an important health topic for Americans [1, 2]. Vitamin D deficiency and insufficiency have been associated with increased cardiovascular disease (CVD) and CVD mortality [3-5] and increased risk of many cardiovascular-related conditions, including abnormal lipid profiles and hyperlipidemia [6-8], hypertension, coronary artery disease, heart failure, stroke, acute myocardial infarction, atrial fibrillation, and endothelial dysfunction [3-5, 9-18].  

While there are clear associations between low vitamin D levels and increased CVD risk, interventional studies have had inconsistent results with vitamin D supplementation [19-25]. Some researchers consider the varying baseline vitamin D status to be an important reason for the inconsistency in findings, which highlights the need for a personalized dosing regimen to reach optimal blood levels [20, 22, 26-28]. 

How Does Vitamin D Work in Cardiovascular Health? 

The role of vitamin D in cardiovascular health is proposed to start with the presence of vitamin D receptors (VDR) in heart cells (cardiomyocytes) and blood vessel cells (endothelial and smooth muscle cells) [10, 21, 22]. VDR regulate the expression of many genes in these cells, which could eventually impact the fibrosis (scarring) and contraction of heart muscles [10, 21, 22]. Vitamin D may also play a role in heart health by regulating renin [10, 21, 22] and parathyroid hormone levels [6, 12, 22], which are connected to blood pressure control and blood lipids. The impact of vitamin D on oxidative stress and inflammatory pathways may also play an important role in maintaining a healthy cardiovascular system [21]. 

Research on Vitamin D and Cardiovascular Health 

There is a link between vitamin D levels and cardiovascular health outcomes [3-5, 9-18]. Evidence from human data suggests a vital role of vitamin D in cardiovascular health [3-8, 11-15, 29, 30]. Specifically, vitamin D supplementation appears to have an overall positive impact on individuals at higher risk of cardiovascular disease or with low serum vitamin D levels [4, 11-15, 29, 30]. Research highlights include: 

• Vitamin D supplementation may be particularly important for individuals taking statins or other cardiovascular medications [30], those with deficient or insufficient vitamin D levels [4, 11, 13], older adults [15], and high-risk groups with CVD or other risk factors [4, 7, 12-14, 29]. 

• In a high-risk group of African American men with vitamin D deficiency, vitamin D supplementation increased vitamin D serum levels, decreased intact parathyroid hormone, and improved cardiovascular biomarkers of vascular function [13]. 

• In individuals with hypertension and low vitamin D levels, correcting vitamin D levels with supplementation improved cardiovascular health parameters, including total cholesterol and LDL cholesterol levels [29]. 

• Increasing vitamin D levels through supplementation improved lipid levels in individuals with low vitamin D levels and hypercholesterolemia [31] or hypertension [29].  

As a greater percentage of the population lives longer, more people have become interested in nutritional strategies that support healthy aging. Healthy aging refers to the maintenance of physiological function and quality of life as individuals age [1]. Researchers are looking for ways to measure biological aging rather than chronological aging. Chronological aging refers simply to measuring age by the passage of time, whereas biological aging ascribes an age that is reflective of the cumulative physiological and molecular changes that occur within cells and tissues, which may progress more quickly or slowly than chronological age. Molecular endpoints, such as telomere length and DNA methylation levels, have been examined as a way to evaluate biological, rather than chronological, aging. Vitamin D is a nutrient of interest in the context of these biomarkers and the broader concept of healthy aging. Of course, healthy aging also encompasses qualities such as resilience against disease and preservation of physical and cognitive performance. These qualities are heavily dependent on muscle mass and function, as well as cognitive performance. Beyond its well-known role in calcium homeostasis, vitamin D has been investigated for potential influence on cellular aging, muscle preservation, and cognitive function.

Telomeres and Methylation

Telomeres are repeating sequences of DNA that are positioned at the end of DNA and prevent its degradation [2]. They represent a cell’s replication potential and generally decrease in size with increased age. The methylation of DNA can regulate gene expression, and a computational model examining the methylation pattern on specific DNA regions has been used to describe biological age. Observational and interventional studies have examined whether there is a connection between vitamin D and these aging biomarkers.

In young adults, studies have not reported an association between serum vitamin D levels and increased telomere length [3, 4]; however, findings are different for older adults. In a randomized, double-blind, placebo-controlled study in China, 1,054 participants (females: >55 years old, males: >50 years old) consumed either vitamin D (2000 IU/day), omega-3 fatty acid (1 g/day), or placebo for 4 years. Leukocyte telomere length was measured at baseline and at the end of the study period [5]. At the end of the study, leukocyte telomere length was significantly greater in the vitamin D group compared to the placebo. In another randomized, double-blind, placebo-controlled study in China, 183 participants (age 65+ years) with mild cognitive impairment received either 800 IU/day of vitamin D or placebo for 12 months [6]. At the end of the study period, leukocyte telomere length was significantly greater in the treatment group compared to the placebo. Similar findings were reported in a randomized, double-blind, placebo-controlled study on post-menopausal women provided 50,000 IU/week for 8 weeks [7]. In all studies examined, telomere length elongated or, at least, did not decrease in the vitamin D cohort compared to placebo, suggesting that the intervention contributed to the improvement of this biomarker.

Studies looking at the influence of vitamin D on methylation patterns have also been conducted. In a randomized, double-blind, placebo-controlled study, 70 overweight or obese African Americans with serum vitamin D levels below 50 nmol/L received either 0, 600, 2,000, or 4,000 IU/day of vitamin D for 16 weeks [8]. DNA methylation patterns were examined at baseline and at the completion of the study period. Both the 2,000 and 4,000 IU/day dose groups had altered DNA methylation patterns that were associated with decreased biological aging compared to placebo. Another study examined biological aging via DNA methylation in 777 older adults who received vitamin D and/or omega-3 and/or exercise therapy over a three-year period. Results showed that vitamin D supplementation (2,000 IU/day) alone did not significantly slow biological aging [9]. However, when combined with omega-3 (1 g/day) and exercise, vitamin D contributed additive benefits to the methylation-associated biological aging endpoints. These results suggest that vitamin D may enhance the impact of other interventions on aging biomarkers. A similar conclusion was found in a cohort study that examined DNA methylation patterns in 274 healthy elderly individuals from Southwest Sweden [10]. In the study, while vitamin D intake (levels not detailed) alone showed a modest impact on DNA methylation, the combination of vitamin D supplementation and high physical activity significantly and positively altered methylation in certain genes, including the vitamin D receptor and cancer-related pathways.

The use and understanding of these novel metrics for aging are currently in development. Furthermore, as expected, not all studies show an effect of vitamin D on telomere or methylation patterns in older individuals [11]. However, taken together, the data support examining vitamin D at the cellular level to identify new mechanisms through which it shapes aging biology.

Muscle Mass and Function

As discussed in the “Vitamin D and Muscle Health” section, the maintenance of muscle mass and function is becoming a recognized component of healthy aging, as it supports mobility, metabolic health, and resilience against age-related decline. Skeletal muscle plays a role in glucose regulation, bone density, and immune function, all of which can deteriorate with aging [12]. Loss of muscle mass, known as sarcopenia, is associated with increased frailty and chronic disease. Muscle preservation through physical activity and nutrition interventions, such as vitamin D consumption, may positively contribute to this aspect of healthy aging.

Several epidemiological studies suggest that higher serum vitamin D levels are associated with greater muscle strength and function [13-15]. For example, elderly individuals (average age: 81 years) in long-term care facilities showed a correlation between higher serum vitamin D levels and gait speed, a characteristic of muscle function, after adjusting for covariates such as age, weight, and other medical history [16]. A study examining the strength and mobility of older individuals in Italy found a correlation between serum vitamin D levels and grip strength as well as the short performance physical battery [17]. Specifically, individuals with serum vitamin D levels below 25 nmol/L and 50 nmol/L performed worse in the battery and grip strength test, respectively, than those with higher vitamin D levels. Another study that examined serum levels of vitamin D in the elderly noted the lowest vitamin D levels was correlated with the most sway with walking, lowest quadricep strength, and slower reaction time [18]. However, residual confounding is possible; therefore, randomized controlled trials are preferred to determine causation.

A number of interventional studies utilizing vitamin D alone or with other ingredients have been performed. A systematic review and meta-analysis showed that the consumption of whey and vitamin D by older individuals with sarcopenia or healthy older individuals increased muscle strength and physical function improvements, even without resistance training, compared to controls [19]. The addition of vitamin D to the whey intervention enhanced lean muscle mass gains, muscle strength, and physical function compared to whey ingestion alone, suggesting that the presence of vitamin D may contribute an additive effect to therapies. A systematic review and meta-analysis of 792 older adults (aged ≥65 years) found that vitamin D supplementation combined with resistance training enhanced muscle strength gains beyond those achieved through resistance training alone[20]. Another systematic review and meta-analysis using whey protein powder, leucine, and vitamin D as an intervention for frail individuals showed a statistically significant increase in hand grip strength, short physical performance battery scores, and increased muscle mass [21].

Emerging evidence suggests that the muscle-related benefits of vitamin D supplementation may plateau beyond certain serum levels. In a randomized clinical study examining muscle strength and function in grip strength, walking endurance, and a physical performance battery in 260 elderly black women with vitamin D levels between 25-60 nmol/L, vitamin D supplementation to produce serum vitamin D levels > 75 nmol/L provided no additional benefit than baseline [22]. Additionally, other studies do not find a correlation between serum vitamin D levels and muscle strength or function [23, 24].

Other Healthy Aging Endpoints

Other characteristics that exemplify healthy aging include maintaining cognitive abilities and minimizing chronic diseases.

A longitudinal study from the Women’s Healthy Ageing Project examined the relationship between midlife serum vitamin D levels and cognitive performance a decade later in 252 women aged 55–67 [25]. Participants with vitamin D levels above 25 nmol/L demonstrated significantly better executive function at baseline and in the 10-year follow-up. No associations were found with verbal episodic memory. Notably, the study adjusted for multiple covariates, including age, education, BMI, physical activity, depression, vascular risk factors, supplementation, and APOE4 genotype. Findings suggest that vitamin D sufficiency in midlife may offer neuroprotective benefits, especially for executive function. Furthermore, the effects were most pronounced at the threshold of severe deficiency (≤25 nmol/L), supporting a nonlinear relationship between vitamin D and cognition. These results suggest early vitamin D repletion in aging women to preserve cognitive health.

In a randomized, double-blind, placebo-controlled study, 183 Chinese participants (age 65+ years) with mild cognitive impairment received either 800 IU/day of vitamin D or placebo for 12 months [6]. Statistically significant changes in measured cognitive markers, including full scale intelligence quotient, information, digit span, vocabulary, block design, and picture arrangement scores, were improved in the vitamin D group compared to the placebo.

Although vitamin D’s role in cognitive health appears promising, studies examining its ability to prevent cognitive decline have yielded inconsistent results, with some trials showing no significant benefit [26, 27]. Key limitations include suboptimal dosing and the absence of baseline serum 25(OH)D assessment in several studies. Although serum vitamin D deficiency has been associated with a number of chronic health conditions [28], future research should explore higher doses, longer interventions, and populations with cognitive impairment.

Conclusion

Observational and interventional studies indicate that better vitamin D status is generally associated with more favorable markers of biological aging and age-related outcomes, though the strength and consistency of this evidence vary. While low serum vitamin D levels are consistently associated with accelerated aging and poorer outcomes, supplementation benefits appear most pronounced in individuals with deficiency, particularly at levels below 25 nmol/L. The evidence remains mixed, with some randomized trials showing modest or conditional effects. Given the growing public health interest in strategies to extend health span, further research is warranted to establish vitamin D’s role in a comprehensive approach to healthy aging.

Adequate vitamin D plays a vital role in pregnancy [1]. As discussed in the previous series for bone, muscle, and cardiovascular health, vitamin D is essential for bone and musculoskeletal growth, and plays a role in blood pressure regulation [2]. Vitamin D is also involved in glucose metabolism, and all of these functions impact the health outcomes of pregnant women and their offspring [2]. 

Maternal supply of vitamin D is the only source for the developing fetus [3], and vitamin D levels in the infant, once born, depend on the maternal levels during pregnancy and lactation[4]. Despite its importance at all stages of pregnancy [2], maternal vitamin D levels decline progressively during pregnancy due to fetal development needs [5]. 

The two major concerns with vitamin D deficiency during pregnancy are neonatal hypocalcemia (low calcium concentration in the blood of the infants) [6, 7], and nutritional rickets (weak or soft bones in the infants) [7]. Vitamin D deficiency has been associated with additional adverse outcomes, such as altered glucose homeostasis/insulin resistance [2, 8], gestational diabetes [1, 3, 6-9], pre-eclampsia [1, 3, 6-10], miscarriages [10], and preterm birth [3, 6, 7, 9] for the mother, and low birth weight [2, 7, 8], growth restriction [3, 6, 10], respiratory tract infection [8], and later development of childhood asthma and wheeze for the infant [3, 6, 9, 11]. 

According to the American College of Obstetricians and Gynecologists (ACOG), vitamin D deficiency is common during pregnancy, with high-risk groups being: vegetarians, women with limited sun exposure, and ethnic minorities, especially those with darker skin [12]. Although research in this area is ongoing, vitamin D levels are important to consider during pregnancy.  

Research on Vitamin D and Maternal/Fetal Health 

Research suggests a positive impact of vitamin D supplementation on neonatal growth outcomes, especially birth weight (as detailed in the bullets below) [5, 13-18]. However, regarding preterm birth and maternal health outcomes like gestational diabetes and preeclampsia, there have been inconsistent results [1, 9, 18-20]. Study reviewers have noted that variations in supplementation dose and frequency, sample size, and baseline vitamin D levels, along with inconsistency in testing vitamin D levels and accounting for environmental factors that impact an individual’s vitamin D level could lead to conflicting results between studies [1, 7, 13]. 

While more research is needed, the overall evidence indicates that vitamin D levels and vitamin D supplementation during pregnancy warrants attention [5, 13], particularly for pregnant women at risk for vitamin D deficiency [12]. Research highlights on vitamin D supplementation during pregnancy include: 

• Maternal vitamin D supplementation has positive effects on fetal health measurements (birthweight and head circumference) [16], and is associated with increased birth length [17] and improved infant growth [14]. 

• Maternal vitamin D supplementation reduced the risk of low birth weight [16, 18] and being small for gestational age (SGA) [14, 16, 18] (defined as a birth weight of less than the 10th percentile for gestational age [21]). 

• In a randomized, placebo-controlled trial, improved bone formation response at 4-5 years of age were observed in children who were born with maternal vitamin D supplementation [15]. 

Most days we go about our routines completely unaware that our immune systems are always working, recognizing, fighting and adapting to foreign invaders that might be bacteria, viruses, fungi… .anything foreign to our bodies. However, in 2020 we likely became more aware than ever of the importance of our immune systems in health, well-being and survival. But what exactly is the immune system? Well, it is quite complex and impacts many aspects of illness and health. One researcher said it well, “The main functions of body’s immune system are to protect the host against infection from pathological microorganisms, to clear damaged tissues, and to provide constant surveillance of malignant cells that grow within the body. Additionally, the immune system develops appropriate tolerance to avoid unwanted response to healthy tissues of self or harmless foreign substances. There is considerable heterogeneity (differences) among individuals in the vigor of their immunological function, largely owing to factors such as genetics, environment, lifestyle, nutrition, and the interaction of these factors.” ¹  

Vitamin D has profound effects on the immune system and has antibacterial and antiviral effects. ² Vitamin D deficiency is associated with an increased risk of developing viral and bacterial infections. ^3,4 The connection between vitamin D and immunity was first reported when it was identified that important immune cells like macrophages and dendritic cells, referred to as “antigen-presenting” cells, actually make the active form of vitamin D. Further studies demonstrated that epithelial cells like those found in skin, lung and the intestinal lining also convert vitamin D to its active form. This suggested that these cells could be influenced by vitamin D, which may be very important in respiratory diseases. ² Overall, there are two parts to the immune system: the innate and adaptive immune responses which will be discussed below. The evidence is stronger for the role of vitamin D in the innate immune system, but promising for adaptive immune system function as well. ⁵ It is important to note that innate and adaptive immunity overlap and work together. For example, vaccines have been developed based on what scientists have learned about the complexities of our immune systems. Vaccines are designed to initiate an innate immune response, which then activates an antigen specific adaptive immune response. ⁶ It is important to clarify the difference, first let’s discuss innate immunity. 

The adaptive immune system is also called the acquired immune system. It is the body’s second defense against infection. Unlike the innate immune system, it fights against pathogens or antigens very specifically, but it takes longer to develop. It is activated by exposure to pathogens, and it is able to learn about the pathogen and adjust the immune response accordingly. It can be thought of as an immunological memory. It is the type of memory that is created by vaccines so that exposure to a specific pathogen causes our immune system to recognize and specifically target it. ¹ 1,25(OH)2D has an inhibitory, anti-inflammatory, effect on the adaptive immune system. ² When cells of the adaptive immune system, called T and B cells, are activated by pathogens, the number of VDR on their surfaces is increased, which then upregulates up to 500 vitamin D responsive genes that influence the adaptive immune cell response. This is thought to play a protective role in autoimmune disorders and to decrease the inflammatory response. ^3,4

Observational studies report consistent independent associations between low serum concentrations of 25-hydroxyvitamin D (the major circulating vitamin D metabolite) and susceptibility to acute respiratory tract infection. In an analysis of 25 studies, vitamin D supplementation reduced the risk of acute respiratory tract infection among over 11,000 subjects who were supplemented. Daily or weekly supplementation benefitted the subjects more than just a large single dose. Those that were most deficient benefitted the most. ¹

In addition to vitamin D’s role in acute COVID-19 outcomes, scientists are also investigating the potential connection between vitamin D and symptoms that persist or return after the initial acute COVID-19 infection. These health issues are often referred to as long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC) [1, 2]. Long COVID can cause various symptoms in different parts of the body, such as excessive fatigue and weakness, brain fog and mood changes, irregular heartbeats, pain and swelling, as well as symptoms similar to an acute COVID-19 infection that cannot be explained by an alternative diagnosis [1, 2]. These symptoms can be post-acute (generally persisting between 4-12 weeks after the acute infection) or longer (generally persisting beyond 12 weeks after the acute infection) [2].  

It is important to note that vitamin D and long COVID research is early stage, much is still unknown, and not all studies agree [3-5]. However, emerging observational data does suggest an association between long COVID and low vitamin D levels [4, 6-8]. For example, in small cohorts of COVID-19 survivors in Taiwan and Italy, low vitamin D levels were associated with higher occurrence of long COVID symptoms and delayed recovery from long COVID [6, 9, 10]. While more robust interventional research is needed, the preliminary data suggests that vitamin D levels may have an important role in post-COVID recovery [4, 6, 8]. More research on vitamin D supplementation is needed.  

Recent publications suggest that vitamin D has multiple mechanisms that may play a role in long COVID, including the following:  

• Neuroimmunological: Vitamin D supports the function of immune and neurological cells such as dendritic cells, macrophages, lymphocytes, cerebral endothelial cells, pericytes, neurons, astrocytes, and microglia and may have a protective role in these cells and tissues [2]. 
• Immune response: Micronutrient and vitamin D deficiencies are linked to a dysregulation of the host immune responses [2, 9, 10]. 
• Antimicrobial: Vitamin D plays a role in innate immunity, which is responsible for producing antimicrobial peptides in immune cells like macrophages and monocytes [2]. 
• Antioxidant system: Vitamin D acts as an antioxidant by reducing oxidative stress during the inflammation process and promoting cell survival [2, 9]. 
• Inflammation: Vitamin D has anti-inflammatory effects through inhibition of pro-inflammatory cytokine production and upregulation of the anti-inflammatory receptors [2]. 

Clinical research evaluating vitamin D supplementation and COVID-19 outcomes is ongoing and more evidence will help further elucidate the role for vitamin D in COVID-19 [3, 36]. 

Vitamin D goes through several transformations before the human body can use it [10, 23]. The first occurs in the liver where vitamin D is converted to 25-hydroxyvitamin D, also called calcidiol [25(OH)D] ^{10, 23}. The amount of 25(OH)D in the blood is a good indication of how much vitamin D the body contains ^{10, 23}. Vitamin D status is determined by measuring serum levels of 25(OH)D ^{10, 23, 24}. While multiple factors, like skin type and geographical location, can impact an individual’s vitamin D production from sun exposure ²⁵, it has been reported that serum vitamin D levels from sun exposure can range from 120-225 nmol/L (48-90 ng/mL) ^{25, 26}. While there is not complete agreement on the exact levels to define the vitamin D deficiency or insufficiency status ^{1, 9, 10, 23}, most experts agree that vitamin D levels below 25-30 nmol/L (10–12 ng/mL) indicate vitamin D deficiency ⁹. While vitamin D levels greater than 125-150 nmol/L (50–60 ng/mL) may be the lowest concentrations of possible concern ^{1, 9, 12}, vitamin D intoxication is not usually observed until 375 mmol/L (150 ng/mL) ²⁷ and the National Academy of Medicine (previously the Institute of Medicine (IOM)) and American Geriatrics Society (AGS) have identified levels of ≥500 nmol/L (≥200 ng/mL) for potential intoxication ^{1, 12, 13}. The variability in standardized definitions of vitamin D status is also seen in laboratory reference ranges for vitamin D testing ^28-30, which further highlights the importance that individuals speak with their healthcare provider about their personal status. As shown below, different organizations have varying interpretations of vitamin D status:

In 2011, the Endocrine Society Clinical Practice Guidelines defined vitamin D levels for deficiency as <50 nmol/L (<20 ng/mL) and insufficiency as 50–74 nmol/L (21–29 ng/mL) ¹⁶, however in the 2024 Guideline update, they no longer endorse specific 25(OH)D levels to define vitamin D sufficiency, insufficiency, and deficiency, because they now believe further clinical evidence is required ¹⁷.

Low vitamin D levels can be caused by many factors including skin pigment, decreased intake, inadequate exposure to sunlight, living at high latitudes, winter season, having respiratory disease such as asthma, obesity, diabetes and even some medications can lead to deficiency ^{18, 19, 25, 32}. Low vitamin D levels are a major health concern because it has been linked to depression, fatigue, muscle aches, increased risk of respiratory infections, autoimmune disorders, osteoporosis, osteomalacia, osteoarthritis, increased risk of infection and some cancers ^{18, 19, 32}. For example, serum 25(OH)D levels of <30 nmol/L (<12 ng/mL) are associated rickets and osteomalacia, conditions characterized by softened and weakened bone ^{9, 24}. Serum 25(OH)D concentrations that are between 30–49 nmol/L (12–19 ng/mL) are associated with bone mineral depletion and susceptibility to fractures ^{10, 24}. And serum 25(OH)D between the 50-75 mmol/L (20-30 ng/mL) range have been associated with development of secondary hypothyroidism which can lead to decreased bone mineral density ^{27, 33}. Overall, serum 25(OH)D levels of <75 mmol/L (<30 ng/mL) have been associated with poor balance and decreased lower extremity function, higher fall rates, and lower bone mineral density in older adults ¹ as well as worse metabolic biomarkers (e.g., insulin and glucose ³⁴, blood lipids ³⁴), worse blood flow ³⁴, and higher risk of depression ³⁵, demonstrated in various populations.

Vitamin D comes from 3 potential sources: food, sunlight-dependent production in the skin and supplements. There are very few natural food sources; plants contain ergocalciferol (vitamin D2) and fatty fish (salmon, mackerel, sardines, cod liver oil) and some types of mushrooms (Shiitake), especially if sun-dried, contain cholecalciferol (vitamin D3). Because it is not easily obtained from food, manufacturers in many countries, including the US and Canada, have regulation that requires fortification of commonly consumed foods, such as milk, orange juice, other dairy products and cereals with vitamin D. Dietary supplements also contribute to intake and are of extra importance in the large population that is not regularly exposed to sunlight and/or who do not consume enough from food. ¹

One of the many unique characteristics of vitamin D is that the body can make it from sunlight. Cholesterol combines with ultraviolet rays from sunlight and is converted to a precursor form of vitamin D. Through a series of steps, it is ultimately converted to the active form of vitamin D. Even though humans can theoretically make all of the vitamin D they need, it is still advisable to consume vitamin D from food and/or dietary supplement sources because few people have sufficient exposure to sunlight. Anything that interferes with exposure to sunlight, especially UVB sunlight, can potentially impair sunlight-stimulated vitamin D production. UVB rays are not very strong at latitudes above 35 °N in the winter, so sufficient amounts of vitamin D cannot be made from sunlight exposure during the winter months at higher latitudes. Clothing, sunscreen and skin melanin levels also impair sunlight-induced vitamin D production. People with darker skin require longer exposure to the sun to make the same amount of vitamin D as individuals with less melanin. ¹ Because the use of sunscreen is critical important for skin health, it is important to consider sources of vitamin D beyond sunlight as well.

The National Academy of Medicine (NAM) (previously the Institute of Medicine (IOM)) recommends a dietary intake of vitamin D of 600 IU/day for all ages over 1 year (and for pregnant and lactating women), with increases to 800 IU/day for individuals over 71 years ³⁶. Few people are able to obtain enough vitamin D from food sources alone, therefore supplementation is very important ³⁷. How much to supplement is less clear and will vary based on vitamin D status. Deficient individuals will need a different supplemental strategy than those who are vitamin D insufficient or sufficient. An examination of the literature on vitamin D reveals varying approaches to dosing individuals identified to be deficient. For many years it was common to administer a bolus, or large single dose, of vitamin D due to the ease and efficiency. Over time, it became more common clinically to provide daily or weekly doses. However, for individuals who are in intensive care or severely deficient, a large single dose is sometimes administered alongside daily or weekly supplementation. While there is no agreed upon dose globally ^{9, 23}, recommendations typically range from 400-2000 IU/day and health care practitioners may recommend more based on an individual’s specific needs ⁹. A common daily dose of 1000 IU or 25 mcg of vitamin D3, has been identified to be safe and effective ³⁷. It has been reported that a daily vitamin D dose of 800 IU can achieve a target 25(OH)D level of at least 50 nmol/L (20 ng/mL) in most healthy individuals, and 2000 IU is sufficient to achieve a level of at least 75 nmol/L (30 ng/mL) ^{9, 18}. As discussed in the section “What blood levels of vitamin D should you maintain?”, while there is no overall consensus on the vitamin D level that is adequate or optimal, the current data suggests it is reasonable to strive for at least 75-125 nmol/L (30-50 ng/mL) ^{3, 8-11, 13, 15-17, 38}.

Vitamin D’s involvement in numerous biochemical processes means that it works in concert with many other vitamins, minerals, and proteins, including vitamin K. Vitamin K is a fat-soluble vitamin containing a methylated naphthoquinone nucleus [1]. It can be further specified as either vitamin K1 (phylloquinone) or vitamin K2 (menaquinone), depending on the compound’s aliphatic side chain [2, 3]. Vitamin K1 is found in leafy greens and vitamin K2 is found in fermented foods and animal products. Vitamin K2 can further be classified depending on the length of its associated chain. The most common vitamin K2 in the human diet is menaquinone-4 (MK4), with 4 units in its tail. There are also vitamin K2 molecules with longer chains, such as menaquinone-7 (MK7). While both vitamin K1 and K2 are involved at some level with vitamin D in the body, vitamin K2 has been the subject of more recent investigations and is therefore the predominant focus of this section.

How Do Vitamin D and Vitamin K2 Work Together?

Vitamin D and K2 are co-factors involved in the production and functioning of essential proteins associated with calcium usage in the body, including matrix Gla protein (MGP) and osteocalcin. MGP can be secreted by endothelial cells and is one of many factors that modulate calcification within the cardiovascular system [4]. Calcification within the cardiovascular system is most associated with the hardening of plaque found along arterial walls, called atherosclerosis [4]. Calcified plaque can narrow or block arteries and lead to cardiovascular disease. Osteocalcin is secreted by bones and is involved in bone mineralization, which utilizes calcium and phosphorus to harden bones [3]. Vitamin D supports the production of these proteins by activating genes responsible for their production [5]. Adequate vitamin D intake also ensures optimal calcium absorption in the gastrointestinal tract [5]. Additionally, vitamin K2 activates MGP and osteocalcin through carboxylation, allowing them to perform their respective roles in calcium utilization [1].

Research on Vitamin D and Vitamin K in Skeletal and Cardiovascular System

The effects of ingesting vitamin D alone compared to vitamin D and vitamin K2 have been examined in various skeletal and cardiovascular clinical outcomes.

Decreased bone mineral density (BMD) is common in older adults, especially post-menopausal females, and can predispose individuals to the risk of bone fracture [5]. Intervention studies, most performed in post-menopausal women, have compared the effect of vitamin D alone to that of vitamin D and K2 on bone mineral density and other bone biomarkers. A study administering 375 µg/day of MK-7 for 3 years to Japanese post-menopausal women concurrently consuming 38 µg/day of vitamin D3 and 800 mg/day of calcium showed increased carboxylation of osteocalcin, a marker of bone quality. However, it did not show improved bone turnover, bone mineral density, or bone microarchitecture [6]. Other results have shown the use of vitamin K2 (both MK4 and MK7 forms), in addition to vitamin D, may induce greater BMD improvements than vitamin D alone [6-9]. A meta-analysis including 8 randomized controlled trials with a total of 971 male and female subjects of wide age range and examined the effects of vitamin K (either K1, K2, or unspecified) and vitamin D on bone quality [2]. Total BMD was significantly increased compared to baseline measurements when subjects supplemented with vitamin K2 (45-500 micrograms/day) concurrently with vitamin D. In summary, evidence supports utilizing vitamin D along with vitamin K2 to increase bone mineral density, especially in post-menopausal women, although more research is necessary.

Research has demonstrated the effects of vitamin D and K on cardiovascular health. Low vitamin D and vitamin K status have been associated with poorer cardiovascular health in older adults in observational prospective studies [3, 10]. Research examining the supplementation of vitamin D and K2 over two years compared to placebo showed progression of calcification significantly slowed in subgroups of male individuals taking statins and male individuals with higher coronary artery calcification scores [11]. Studies examining other aspects of cardiovascular endothelial health in association with vitamin D and K are limited, but results suggest increased elasticity, distensibility, and compliance of arteries with the use of vitamin D and K, which is indicative of improved cardiovascular health [12, 13]. Evidence suggests these nutrients have modest effects in reversing arterial calcification once cardiovascular calcification is advanced [11, 14]. Research examining this nutrient combination’s effects on cardiovascular health is emerging, and more research is needed.

Research highlights include:

• Research suggests vitamin D and K2 supplementation is superior to supplementation with vitamin D alone to support bone mineral density, especially in post-menopausal women [6-9].
• Research found individuals with cardiovascular disease who took statins or had higher coronary artery calcification scores were shown to benefit from combined vitamin D and K supplementation [11, 14].
• While there are some promising results of combined vitamin D and K supplementation to support cardiovascular health, further research is needed [11, 12].

Calcium is a critical nutrient for bone health, muscle function, and nerve signaling [1-3]. Approximately 99% of the calcium in the body is stored as a component of bones and teeth, which helps them maintain their structure [2]. A major 2024 publication examining data from the National Health and Nutrition Examination Survey (NHANES) of more than 80,000 participants throughout the United States (U.S.) found that approximately 45% of the population consume less than the estimated average requirement [4][1] for calcium recommended for their age group [5]. This and other studies indicate that calcium is a nutrient of concern, as intake often falls below the recommended dietary allowance [4][2] in much of the U.S. and global populations. Strategies that help individuals achieve safe and healthy levels of calcium is therefore essential [5, 6].

Vitamin D is a key regulator of calcium homeostasis in the body, working alongside calcium as an essential complementary nutrient [2]. Efficient absorption of ingested calcium in the intestinal tract depends on many factors, including vitamin D status [7]. Calcium absorption in the intestines occurs through both passive and active mechanisms. While some calcium is absorbed passively, sufficient vitamin D is required for active absorption, significantly enhancing the body’s ability to utilize dietary calcium [2]. Without adequate vitamin D, intestinal calcium absorption in humans is limited to approximately 10-15%, but when vitamin D levels are sufficient, absorption increases to 30-40% [8].

Once calcium is absorbed by the body, it is closely monitored and tightly controlled [2]. Most calcium is reabsorbed through the kidney, which can increase or decrease calcium reabsorption depending on signaling from vitamin D and parathyroid hormone, another factor that regulates calcium homeostasis [9]. Vitamin D deficiency or insufficiency can negatively impact calcium absorption [8].

Research on Vitamin D and Calcium Interactions

Randomized controlled trials and meta-analyses have examined the effects of vitamin D and calcium on bone health.

A 2006 article describes The Women’s Health Initiative study which examined the effect of supplementation of vitamin D with calcium in 36,282 postmenopausal women between the ages of 50 and 79 years old [10]. Subjects either received an additional 1000 mg of calcium and 400 IU of vitamin D daily or they maintained their baseline consumption levels of the nutrients. Participants were followed for approximately 7 years. Supplementation significantly improved hip bone density. Those in the vitamin D and calcium supplementation group had a 12% reduction in hip fracture, 10% reduction in clinical spine fracture, and 4% reduction in total fractures, however, none of these measures of fracture achieved statistical significance. The study’s findings were confounded by participants in both groups who had previously taken dietary supplements, potentially leading to sufficient baseline calcium and vitamin D levels that diminished the observed effects.

A 2019 meta-analysis of six randomized controlled trials (RCTs) examining combined vitamin D (400–800 IU/day) and calcium (1,000–1,200 mg/day) supplementation found a statistically significant reduction in fracture risk. The combination lowered the risk of any fracture by 6% and hip fractures by 16% [3].

A 2014 Cochrane analysis of 53 RCTs, including 91,791 participants, examined the effects of vitamin D with or without calcium on fracture prevention in elderly (aged 65 years or more) in community, nursing homes, or hospital inpatient facilities [11]. Authors noted that there was high-quality evidence that a small reduction (relative risk reduction of 16%) in hip fracture risk and incidence of non-vertebral fractures took place with vitamin D and calcium co-supplementation.

A 2007 meta-analysis of 6 RCTs evaluating vitamin D supplementation with calcium showed a significant reduction in hip fracture risk compared to placebo/no treatment. The research was in postmenopausal women or men aged 50 years or older [12]. Most vitamin D levels in the examined studies were 700-800 IU, most calcium levels were 500-1000 mg/day, and all trials lasted for at least 24 months.

A 2007 meta-analysis of 29 randomized trials, involving 63,897 participants aged 50 and older, examined the effects of calcium and vitamin D supplementation over intervention periods ranging from one to eight years [13]. The main outcomes were fracture risk and bone mineral density. Both calcium alone and calcium combined with vitamin D significantly reduced fracture risk and bone loss. However, supplementation with at least 1,200 mg of calcium per day and 800 IU or more of vitamin D yielded even greater benefits. Additionally, older individuals, those with poorer bone health, and participants who adhered more closely to the study protocol experienced the most significant improvements.

Overall, these research publications highlight that:

• The majority of the evidence demonstrates that supplementation of vitamin D with calcium benefits bone health. However, some evidence is conflicting, and more studies are needed.

Scientific and Regulatory Opinions

The FDA authorized a health claim that recognizes that adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis in later life [14]. Vitamin D and calcium are also recognized by other non-U.S. government authorities, like Health Canada and the European Food Safety Authority (EFSA), which have also authorized health claims,[3] including:

• Vitamin D helps with absorption/use of calcium/phosphorus and maintenance of blood calcium levels [15, 16]
• Vitamin D and calcium may reduce the risk of developing osteoporosis when combined with healthy diet and regular exercise [16]
• Vitamin D and calcium may reduce the loss of bone mineral (a risk factor for osteoporotic bone fractures) in post-menopausal women [17]

The U.S. Preventive Services Task Force (USPSTF) recommended against daily vitamin D (<400 IU) and calcium (<1000 mg) in healthy menopausal women, as evidence was lacking in studies utilizing lower dose levels of these nutrients. [18]. No recommendation has been proposed by the USPSTF for other healthy individuals or for individuals with osteoporosis, osteopenia, a history of fracture due to osteoporosis, or an increased risk of falls. The USPSTF has not performed an examination of the effects of vitamin D supplementation on individuals who are vitamin D deficient or insufficient.

Safety Considerations

Some authors and scientific bodies have noted the potential for increased risk of kidney stones with the intake of vitamin D and calcium, although the magnitude of the issue was deemed as small [10, 11, 18].

Several systematic reviews and meta-analyses have evaluated the effects of combined vitamin D and calcium supplementation on cardiovascular outcomes [19-22]. Calcium supplementation, with or without vitamin D, did not significantly impact cardiovascular disease (CVD) risk [21], and co-supplementation with vitamin D did not alter coronary heart disease (CHD) risk either [22]. However, a recently published trial reported a slight increase in CVD mortality, though not CVD risk, among postmenopausal women receiving calcium and vitamin D over a follow-up period of 20+ years [23]. This increase was observed only during long-term follow-up, not during the trial’s 7-year intervention period. Since vitamin D supplementation alone was not associated with increased CVD risk or mortality [24], it has been suggested that calcium-related cardiovascular effects, if any, may take time to emerge. The underlying mechanism remains unclear, and further research is needed to verify these findings in other populations.

Toxicity is rare, and vitamin D is very safe at wide ranges of intake. However, growing consumer awareness of vitamin D has led to increased supplementation and intake making potential toxicity more of a possibility. In addition, there have been global public health campaigns to fortify common foods like dairy products, which increases total vitamin D consumption. High concentrations of serum 25(OH)D or free 1,25(OH)2D, when serum 25(OH)D exceeds 375 nmol/l (or 150 ng/ml), causes high calcium in the blood and urine and is typically associated with high calcium intake or genetic abnormalities in vitamin D metabolism. Vitamin D is a fat soluble vitamin so if levels increase to toxic levels, they will stay elevated for up to 18 months. Therefore, although it is very rare and one would have to consume a lot of vitamin D to reach toxic levels, it is advisable to stay within recommended intake ranges or follow the doses recommended by your healthcare practitioner. ¹