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March 06, 2022 10 min read
Vitamin D is fat-soluble and plays a crucial role in calcium homeostasis and bone metabolism. Vitamin D deficiency can lead to rickets in children and osteomalacia in adults.
Although the fortification of milk with vitamin D in the 1930s was effective in eradicating rickets; subclinical vitamin D deficiency is still widely prevalent in both developed and developing countries with a worldwide prevalence of up to 1 billion. 
This subclinical vitamin-D deficiency is associated with osteoporosis, increased risk of falls and fractures. There are numerous conflicting studies demonstrating an association between vitamin D deficiency and cancer, cardiovascular disease, diabetes, autoimmune diseases, and depression. 
Vitamin D deficiency is a global public health issue with about 1 billion people worldwide being classified as deficient, while 50% of the population has vitamin D insufficiency. 
The prevalence of patients with vitamin D deficiency is highest in the elderly, obese patients, nursing home residents, and hospitalized patients. The prevalence of vitamin D deficiency was 35% higher in obese subjects irrespective of where they lived and their age. 
In the United States, about 50-60% of nursing home residents and hospitalized patients have vitamin D deficiency. 
Vitamin D deficiency may be related to populations who have higher skin melanin content and who use extensive skin coverage, particularly in Middle Eastern countries.
Vitamin D deficiency can result from several causes including:
1. Decreased dietary intake and/or absorption. Certain malabsorption syndromes such as celiac disease, short bowel syndrome, gastric bypass, inflammatory bowel disease, chronic pancreatic insufficiency, and cystic fibrosis may potentially lead to vitamin D deficiency. The elderly population is known to have a lower intake of vitamin D. 
2. Decreased sun exposure. About 50% to 90% of vitamin D is absorbed through the skin via sunlight while the rest comes from the diet. Twenty minutes of sunshine daily with over 40% of skin exposed is required to prevent vitamin D deficiency. Cutaneous synthesis of vitamin D declines with aging. In addition, dark-skinned people have less cutaneous synthesis of vitamin D. Decreased exposure to the sun as seen in individuals who are institutionalized, or have prolonged hospitalizations can also lead to vitamin D deficiency.  In addition; the effective dose of sun exposure is decreased in individuals who use sunscreens consistently.
3. Decreased endogenous synthesis. Individuals with chronic liver disease such as cirrhosis can have defective 25-hydroxylation leading to deficiency of active vitamin D.
4. Increased hepatic catabolism. Medications such as phenobarbital, carbamazepine, dexamethasone, nifedipine, spironolactone, clotrimazole, and rifampin induce hepatic p450 enzymes which activate degradation of vitamin D. 
5. End organ resistance. End organ resistance to vitamin D can be seen in hereditary vitamin D resistant rickets.
Below are some signs and symptoms of vitamin D deficiency:
Depression: A depressed mood may also be a sign of vitamin D deficiency. Recent evidence indicates a link between vitamin D deficiency and depression, particularly in older adults.
In one analysis, 65% of the observational studies found a relationship between low blood levels of vitamin D and depression. There is some data demonstrating that giving vitamin D to people who are deficient helps improve depression, including seasonal depression, which typically occurs during the colder months.
Anxiety: As with depression, there may be links between vitamin D deficiency and anxiety disorders. According to a recent review, levels of calcidiol, a form of vitamin D, was found to be lower in people with anxiety, as well as those with depression. 
A very recent investigation with pregnant women found that vitamin D levels could help reduce anxiety, improve sleep quality, and possibly help prevent postpartum depression. 
Weight gain: Obesity is actually the #1 risk factor for vitamin D deficiency. In addition; evidence also indicates that vitamin D deficiency may increase the risk of weight gain, too.
A recent longitudinal study utilizing both males and females found a possible link between low vitamin D status and both abdominal fat and increased weight. However, the effects were more prominent in men. 
Although there is other research confirming that vitamin D deficiency may be seen in obesity cases; further studies are needed to determine whether vitamin D could help prevent weight gain. 
Muscle pain: There’s some evidence indicating that vitamin D deficiency may be a potential cause of muscle pain in children and adults. 
For example, in a recent study 71% of people with chronic pain were found to be deficient in the vitamin. 
Interestingly the vitamin D receptor is found in nerve cells called nociceptors, which sense pain. According to one review, vitamin D may be involved in the body’s pain signaling pathways, which could play a role in chronic pain. 
Evidence also indicates that supplementing with high-doses of vitamin D may reduce various types of pain in people who are deficient. 
For instance, a fairly recent study including 120 children with vitamin D deficiency who had growing pains found that a single dose of the vitamin reduced pain scores by an average of 57%. 
Hair Loss: Hair loss is often attributed to stress which is certainly a common cause. However, when hair loss is severe, it may be due to a disease or nutrient deficiency.
Hair loss in women has been linked to low vitamin D levels, though there is very little research on this to date. In particular, research indicates that low vitamin D levels are linked to alopecia areata and may be a risk factor for developing the disease. 
Alopecia areata is an autoimmune disease characterized by severe hair loss from the head and other parts of the body. It’s connected with rickets, which is a disease that causes soft bones in children due to vitamin D deficiency. 
One study including people with alopecia areata showed that lower vitamin D blood levels tended to be associated with more severe hair loss. 
Other research where subjects applied a synthetic form of the vitamin topically for 12 weeks found a significant increase in hair regrowth in people with alopecia areata. 
Hair loss may potentially be a sign of vitamin D deficiency in female pattern balding or the autoimmune condition alopecia areata.
Bone loss: Vitamin D plays a crucial role in calcium absorption and bone metabolism. Many older people who are diagnosed with bone loss believe they need to take more calcium. However, they may be deficient in vitamin D as well.
Low bone mineral density is a sign that your bones have lost calcium and other minerals. This places older adults, especially women, at an increased risk of fractures. Research in middle-age menopausal or postmenopausal women shows a strong link between low vitamin D levels and low bone mineral density. 
Getting adequate vitamin D intake and maintaining blood levels within the optimal range may be a good strategy for protecting your bone mass and reducing your fracture risk.
Fatigue and tiredness: There can potentially be an array of reasons for feeling tired and fatigued, and vitamin D deficiency may be one of them. Unfortunately, it’s often overlooked as a potential cause. Evidence shows that very low blood levels of vitamin D can cause fatigue, thus having a severe negative effect on quality of life. 
Vitamin D can also have an impact on fatigue and sleep quality in children. In a study including 39 children, low vitamin D levels were associated with poor sleep quality, shorter sleep duration, and delayed bedtimes. 
Interestingly, evidence demonstrates that supplementing with vitamin D could reduce the severity of fatigue in people with a deficiency. 
It is not recommended to screen asymptomatic (i.e., no symptoms) individuals for vitamin-D deficiency, but high-risk individuals shall be evaluated. Vitamin D sufficiency or deficiency is evaluated by the measurement of serum 25-hydroxyvitamin D in serum.
Optimal levels of 25-hydroxyvitamin D are still controversial as there are substantial differences in mineral metabolism amongst different races. African Americans, for example, have higher bone density and low fracture risk compared to other races.
Furthermore, the effects of calcium and vitamin-D supplementation in the non-Caucasian population have not yet been completely evaluated or reported. The International Society for Clinical Densitometry and International Osteoporosis Foundation recommend minimum serum levels of 25-hydroxyvitamin D of 30 ng/mL to minimize the risk of fall and fractures in elderly individuals. 
There is a lack of data on the maximum safe upper level of serum 25-hydroxyvitamin D, however, at high levels such as above 100 ng/mL, there may be a potential risk of toxicity due to the secondary hypercalcemia. In patients that are diagnosed with vitamin-D deficiency, it is important to evaluate for secondary hyperparathyroidism and levels of parathyroid hormone and to also check serum calcium levels.
Several preparations of vitamin D are available. Vitamin D3 (cholecalciferol), when compared with vitamin D2 (ergocalciferol), has been shown to be more effective in achieving optimal 25-hydroxyvitamin D levels, thus favoring vitamin D3 as a treatment of choice. 
The severity of vitamin D deficiency is divided into mild, moderate, and severe. 
Prevention of Vitamin D deficiency
Adults under 65 years of age who do not have year-round effective sun exposure should aim to consume 600-800 IU of vitamin D3 daily to prevent deficiency. Older adults 65 years of age or more should aim for 800-1000 IU of vitamin D3 daily to prevent deficiency and to reduce the risk of fractures and falls.
Management of Vitamin D deficiency
The amount of vitamin D required to treat the deficiency depends largely on the degree of the deficiency and underlying risk factors.
Initial supplementation for 8 weeks with Vitamin D3 either 6,000 IU daily or 50,000 IU weekly can be considered. 
Once the serum 25-hydroxyvitamin D level exceeds 30 ng/mL, a daily maintenance dose of 1,000-2,000 IU is recommended.
A higher-dose initial supplementation with vitamin D3 at 10,000 IU daily may be needed in high-risk adults who are vitamin D deficient (i.e., African Americans, Hispanics, obese, taking certain medications, malabsorption syndrome). Once serum 25-hydroxyvitamin D level exceeds 30ng/mL, a maintenance dose of 3000-6000 IU/day is recommended.
Children who are vitamin D deficient require 2000 IU/day of vitamin D3 or 50,000 IU of vitamin D3 once weekly for 6 weeks. Once the serum 25(OH)D level exceeds 30 ng/mL, a maintenance dose of 1000 IU/day is recommended. According to the American Academy of Pediatrics, infants who are breastfed and children who consume less than 1 L of vitamin D-fortified milk need 400 IU of vitamin D supplementation.
Calcitriol can be considered where the deficiency persists despite treatment with vitamin D2 and/or D3. The serum calcium level shall be closely monitored in these individuals due to an increased risk of hypercalcemia secondary to calcitriol.
Calcidiol can be considered in patients with fat malabsorption or severe liver disease.
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