Low vitamin D status is becoming more common worldwide. The prevalence of vitamin D deficiency (VDD) was found to be 28.9 % and vitamin D insufficiency (VDI) 41% in a subset of 26,010 US adults surveyed as part of the ongoing National Health and Nutrition Examination Survey (NHANES) 2001-2010. Those who were African American, less educated, of lower socioeconomic status, smokers, physically inactive, obese and infrequent milk consumers demonstrated a higher prevalence of VDD and VDI. ¹ Worldwide, many countries report a high prevalence of low vitamin D status. The percentage of individuals with VDD or serum 25(OH)D <30 nmol/L (or 12 ng/ml) is estimated to be 7.4% in Canada, ² 13% in Europe³ and as high as >20% of the population in India, Tunisia, Pakistan and Afghanistan. ^3,4 However, certain populations are more at risk for becoming deficient than others. For example, individuals with chronic diseases especially of the liver, kidney and heart, anyone with diseases that lead to malabsorption such as Crohn’s disease, hospitalized patients, and anyone with reduced exposure to sunlight. ^5,6 Older adults, individuals with existing conditions, obese individuals, diabetics and those taking certain medications are particularly at risk. Older adults, especially those that are institutionalized, are at increased risk due to decreased sun exposure, decreased ability to synthesize vitamin D in the aging skin, ⁷ decreased intake and possibly a greater number of medications. Medications such as antiseizure medications, glucocorticoids, rifampin and supplements such as St. John’s Wort may increase the risk of vitamin D deficiency. ⁸ 

Vitamin D is a fat soluble vitamin that humans get from the diet, sunlight and supplements. It is not a single compound but is a family of similar compounds with slightly different side chains. There are two major forms of vitamin D: vitamin D2 and D3. Vitamin D2 or ergocalciferol is the most common form and an important dietary source that is synthesized by plants and also used to fortify foods like milk, orange juice and cereals. Most mammals can convert vitamin D2 to vitamin D3. Vitamin D3, also called cholecalciferol, is the form that can be made by the human body from cholesterol and is naturally found in cod liver oil, oily fish, and is often found in dietary supplements. D3 is the active part of 1,25-dihydroxycholecalciferol (1,25(OH)2D), which is responsible for the biological functions of vitamin D. ¹ 

With no supplementation, about 80% of vitamin D3 is synthesized in the skin and 20% is obtained from the diet. With regular sun exposure, a healthy diet, and healthy kidneys, many people can make the vitamin D they need. However, most people are not regularly exposed to the sun and diets vary. The absorption of Vitamin D from food sources is dependent upon the presence of long chain fats and bile salts. Dietary vitamin D first goes to the liver then the kidney converts it to its active form and distributes the active form throughout the body. Because it is synthesized and released from , the kidneys, and the fact that there are vitamin D receptors in many tissues makes vitamin D a “hormone-like” vitamin. ¹ 

Vitamin D is delivered throughout the body on vitamin D binding protein and must bond with a vitamin D receptor (VDR) to enact its biological effects. These receptors are located throughout the body and explain why vitamin D is important for so many functions in the body. ² For example, VDR has been found in cells of the intestinal epithelium, renal tubules, parathyroid gland cells, skin (keratinocytes), mammary epithelium, pancreas (beta islet cells), pituitary gland, skeleton (osteoblasts and chondrocytes), immune system (monocytes, macrophages, and T-lymphocytes), and germ tissues. The tissues with the highest VDR content are intestine, kidney, parathyroid gland, and bone, all of which are associated with maintenance of calcium homeostasis. ³ 

Vitamin D was first known for its role in bone development and maintenance. It plays a key role in the metabolism of calcium and phosphorus, two important minerals for bone integrity. Vitamin D stimulates the cells of the small intestine to produce a calcium binding protein called calbindin, which increases calcium absorption. When blood calcium levels decline, vitamin D stimulates the production of calbindin to increase calcium absorption from food. In addition, when blood levels of calcium fall, vitamin D stimulates the kidneys to conserve calcium by decreasing urinary excretion. Vitamin D has many other important functions. It plays a key role in maintaining immune health, oral health, muscle health and strength, for regulating gene transcription and promoting protein synthesis. ¹ These functions have received more research attention in recent years due to the findings that vitamin D receptors (VDR) and the vitamin D activating enzyme 1-α-hydroxylase (CYP27B1) are found in many cells outside the bone and kidney including the muscles, the intestine and some immune cells. This suggests the biologically active form of vitamin D, 1,25(OH)2D, can influence immunity and health in multiple ways. ^1-3 

While calcium is often associated with bone health, it is important to remember that vitamin D is also essential for healthy bones. In fact, the U.S. Food and Drug Administration (FDA) has authorized health claims that describe the relationship between vitamin D, calcium and osteoporosis risk [1]. For example, the FDA authorized health claim 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 [1]. Around the world, vitamin D is recognized for bone health and other non-U.S. government authorities, like Health Canada and the European Food Safety Authority (EFSA), also have authorized health claims,[1] including:

• Vitamin D contributes to and helps develop/maintain/build strong bones and teeth [2-7]
• Vitamin D helps with absorption/use of calcium/phosphorus and maintenance of blood calcium levels [2, 8]
• Vitamin D and calcium may reduce the risk of developing osteoporosis when combined with healthy diet and regular exercise [2]
• Vitamin D and calcium may reduce the loss of bone mineral (a risk factor for osteoporotic bone fractures) in post-menopausal women [9]

How Does Vitamin D Work in Bone Health?

The importance of vitamin D for bone health and strength is well-supported [10-15]. Vitamin D helps the body absorb and use calcium and assists the cells that re-structure and build bone through bone remodeling and bone mineralization [10-17].

Balance is key for bone health; the structure or scaffold of bone relies on normal bone mineralization, which requires balanced levels of calcium and phosphorus [13]. This is where vitamin D plays a vital role, via helping the body absorb calcium and phosphorus in the gastrointestinal tract and re-absorb calcium from the kidneys to keep it from being removed as waste [10, 14]. This role of vitamin D is regulated through actions of parathyroid hormone (PTH) which creates a feedback loop to keep vitamin D, calcium, and phosphorus all working together in concert [10, 12, 16]. When vitamin D levels are too low, less calcium is absorbed in the gastrointestinal tract [12, 17], leading to increases in PTH which causes the body to pull too much calcium from the bones, resulting in weaker bones over time [12, 17].

When thinking about bones, it may be easy to think of them as static after childhood and adolescence. But even in adults, bones are in a constant process of change as they turnover and remodel [10, 15, 17-19]. Bone cells, like osteoblasts and osteoclasts, work together in complex processes to digest old bone and replace it with new bone [10, 17, 18]. When vitamin D levels are too low, there can be an imbalance in this turnover, leading to more breakdown and less mineralization of the bone [12, 17].

Research on Vitamin D & Bone Health

Numerous studies have demonstrated the role of vitamin D in bone health and maintenance [1-14, 16, 17, 20-31]. Its importance has been shown in different populations:

• Older adults: Aging can impact physiology and behaviors, which impacts vitamin D exposure and metabolism [23]. Vitamin D deficiency has been associated with hip fractures in older adults [28]. In women (≥65 years old) with osteoporosis in long term care facilities, as serum vitamin D levels increased, there were significant improvements in measurements of bone health and mobility performance [31].
• Post-menopausal women: Vitamin D insufficiency was associated with increased bone remodeling and low bone mass in post-menopausal women [24]. Vitamin D supplementation, with or without calcium supplementation, reduce PTH in postmenopausal women [27].
• Individuals with obesity: Obese adults generally have lower serum vitamin D levels which could impact their specific dosing needs, and particularly following bariatric surgery, bone density and microarchitecture can deteriorate [26].
• Individuals with low vitamin D: Vitamin D intake is especially important for individuals with low serum vitamin D [13, 23, 27, 29, 30, 32, 33] and vitamin D supplementation may benefit bone mineral density over time in these individuals [13, 23, 29, 30].

Some clinical studies have found mixed results for bone mass density and risk of fractures [33, 34]. These results may be attributed to participants with sufficient vitamin D levels, or other factors impacting vitamin D levels, like sun exposure, dietary intake, and genetics [13, 14, 23, 27, 32, 33]. It is very important for individuals to know their personal vitamin D level as supplementation may be especially critical for people who have low or insufficient vitamin D levels [23, 27, 32, 33].

Bone Health Risk

According to the U.S. Department of Health, it is estimated that over 43 million people in the United States have low bone mass, which increases the risk for osteoporosis [35]. It is clear that severe vitamin D deficiency results in osteomalacia [30], but even vitamin D insufficiency may contribute to development of osteoporosis [10, 11]. Maintaining an ideal vitamin D level throughout the life span is important to ensure proper calcium absorption and bone health overall.

Adequate vitamin D levels are necessary for muscle metabolism and muscle protein synthesis [1-4]. Vitamin D deficiency can cause muscle pain and weakness [2-4], which may impact mobility, stability, and posture. The European Food Safety Authority (EFSA) has authorized the following health claims[1] relevant for muscle health:

• Vitamin D contributes to the maintenance of normal muscle function [3].
• Vitamin D helps to reduce the risk of falling associated with postural instability and muscle weakness. Falling is a risk factor for bone fractures among men and women 60 years of age and older [5].

How Does Vitamin D Work in Muscle Health?

The role of vitamin D in muscle health starts with protein synthesis and muscle fiber metabolism to build up muscle [6-8]. Studies in muscle cells show that vitamin D plays important roles in cell signaling processes and gene expression that contribute to the growth, development, and function of muscle cells [6, 7, 9]. Further, vitamin D contributes to the cellular function and repair of muscle cells [6].

Research on Vitamin D and Muscle Health

There is a causal relationship between vitamin D levels and skeletal muscle health [9]. Evidence from human data supports an overall positive impact of vitamin D on muscle health, including [7, 9-19]:

• In healthy adults, whey protein when combined with vitamin D supplementation improved lean muscle, muscle strength and physical mobility. As these muscle health improvements in healthy adults were not seen with whey protein supplementation alone, it is thought that correcting low or deficient vitamin D level was key to supporting muscle strength [7, 12].
• In older Asian adults, low or deficient vitamin D levels have been associated with lower muscle health measures [15, 19].
• In women (aged 74-89 years old) living in long term care facilities, increases in serum vitamin D levels were associated with better gait speed [16], a measurement of mobility and muscle strength [20].
• Adolescents (aged 10-19 years old) with sufficient vitamin D levels had better grip strength measurements compared to their counterparts with vitamin D deficiency, suggesting a role of vitamin D for muscle health in adolescents [17].
• In mobility-limited, vitamin D deficient women (aged 73-83 years old), vitamin D supplementation improved measurements of skeletal muscle fiber [18].

Muscle Health Risk

According to the U.S. Center for Disease Control, muscle strength decreases with age [21]. Skeletal muscle mass can decrease by 30% by age 80 [9]. An analysis that included U.S. adults aged 50 or older, found the prevalence of low muscle mass to be 17-23% and the prevalence of low muscle strength to be 19% [22]. Another analysis of Americans aged 65 or older found that 47-55% had weak muscles as defined by their grip strength, with 55% having slow gait speed [23]. The role of vitamin D in muscle health is one clear reason to maintain an ideal vitamin D level throughout all life stages.

[1] Health claims have specific conditions for use (e.g., require specific minimum levels of vitamin D) and specific wording of the claim – refer to the authorizing text for requirements mandated by the regulatory agency.

Innate immunity is the human body’s first defense against infection. It includes physical barriers including the skin, mucus and lining of the lungs and intestines, as well as cells with receptors that quickly recognize pathogens. The role of Vitamin D in the regulation of this line of defense was initially discovered during research for the treatment of leprosy and tuberculosis. Vitamin D reinforces the barrier provided by epithelial cells, enhances the cell’s ability to produce 1,25 (OH)2D at the site of infection, increases other key defenses of innate immunity and decreases inflammatory markers. ¹ Vitamin D is known to prevent the overproduction of certain inflammatory agents, cytokines, and enhances the bacterial fighting ability of a class of immune cells, called macrophages. ²

Vitamin D goes through several transformations before the human body can use it. The first occurs in the liver where vitamin D is converted to 25-hydroxyvitamin D, also called calcidiol [25(OH)D]. The amount of 25(OH)D in the blood is a good indication of how much Vitamin D the body contains. Vitamin D status is determined by measuring serum levels of 25(OH)D. While there is not complete agreement on the exact levels to diagnose insufficiency, most experts agree that between 20 and 125 nmol/L is ideal for bone health. Levels higher than 150 nmol/L can be detrimental. Low concentrations of serum 25(OH)D (<30 nmol/L) are associated rickets and osteomalacia, conditions characterized by softened and weakened bone. Higher concentrations of serum 25(OH)D above the deficiency range, yet not sufficient, are associated with bone mineral depletion and susceptibility to fractures. ^1,2,3 The National Academy of Medicine-recommends the following: at risk of deficiency [serum 25(OH)D <30 nmol/L (<12 ng/mL)], at risk of inadequacy [serum 25(OH)D 30–49 nmol/L (12–19 ng/mL)], sufficiency [serum 25(OH)D 50–125 nmol/L (20–50 ng/mL)], and concentrations of possible concern [serum 25(OH)D >125 nmol/L (>50 ng/mL)]. ⁴ Vitamin D deficiency can be caused by many factors including 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. ^5-7 Vitamin D deficiency is 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. ^5-7

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 Institute of Medicine 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. ¹ Few people are able to obtain enough vitamin D from food sources alone, therefore supplementation is very important. ² 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 not deficient. As you read through the various studies and information regarding vitamin D, you will notice varying approaches to dosing individuals identified to be deficient. For many years it was common to provide what is called a bolus, or large single dose, it was easy and efficient, but it was determined to be less effective and to be associated with increased risk of falls and other issues. It then became more common to provide daily or weekly doses, and sometimes in individuals who are in intensive care or severely deficient, a large single dose is used along with daily or weekly supplementation. There is no agreed upon dose globally, recommendations typically range from 400-2000 IU/day and your doctor may recommend more. However, a common dose of 1000 IU or 25 μg of vitamin D3, has been identified to be safe and effective. ² 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 (or 20 ng/mL) in most healthy individuals, and 2000 IU is sufficient to achieve a level of at least 75 nmol/L (or 30 ng/mL). ³

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