Vitamin-D Deficiency: Health Implications and Therapeutic Approaches
Anugya Abhiti*, Musaratafrin Saiyed
Department of Pharmacology, A. R. College of Pharmacy and G. H. Patel Institute of Pharmacy,
Vallabh Vidyangar, Anand, Gujarat, 388120.
*Corresponding Author E-mail: anugya1901@gmail.com
ABSTRACT:
Vitamin D deficiency, or Hypovitaminosis-D, is defined by 25(OH)D levels below 20 ng/mL, assessed via the 25-hydroxy vitamin D blood test. Major sources of vitamin D include sunlight, with limited sun exposure, skin complexion, dietary habits, and certain medical conditions contributing to deficiency. Notably, nearly half of the global population is affected, leading to increased mortality and various health issues. In India, vitamin D deficiency ranges from 40% to 99%, affecting diverse demographics, including the elderly, obese, nursing home residents, and hospitalized patients. Causes include poor sun exposure, specific diets, malabsorption syndromes, and certain medications. Vitamin D deficiency can lead to a host of health problems such as weakened immune function, fatigue, bone and muscle pain, osteoporosis, and mental health issues like depression. Specific conditions such as rickets in children and osteomalacia in adults are also linked to severe deficiency. Diagnosis is through blood tests measuring 25(OH)D levels, and treatment involves vitamin D supplementation. Management strategies include increasing sun exposure, consuming vitamin D-rich foods, and possibly using UV-B light therapy. Public health measures such as food fortification, awareness programs, and accessible testing facilities are recommended to address this widespread deficiency. Effective implementation and monitoring of these strategies are essential to reduce the global burden of vitamin D deficiency.
KEYWORDS: Hypovitaminosis, Vitamin deficiency, Risk factors, Consequences.
INTRODUCTION:
Vitamin D deficiency, also referred to as "Hypovitaminosis-D, " is characterized by a 25(OH)D level below 20ng/ml. Accurate assessment is achieved through the 25-hydroxy vitamin D blood test, with levels between 20ng/mL to 50ng/mL considered adequate for good health.1,2
The primary source of vitamin D is exposure to natural sunlight, making insufficient sunlight exposure the leading cause of deficiency. Using sunscreen with a Sun Protection Factor (SPF) of 30 or above can greatly diminish the skin's ability to produce vitamin D, typically by over 95%. Factors such as skin complexion, limited sunlight exposure, sunscreen use, dietary habits, and low intake of vitamin D fortified foods contribute to this deficiency, along with conditions like fat malabsorption syndromes and certain medications.3-5
In nephrotic syndrome, vitamin D deficiency may develop because vitamin D binding protein is lost through the urine. Additionally, certain medications, such as anticonvulsants and antiretrovirals, can enhance the catabolism of vitamin D metabolites, increasing the risk of deficiency. Disorders like sarcoidosis, tuberculosis, chronic fungal infections, some lymphomas, and primary hyperparathyroidism also elevate the metabolism of vitamin D metabolites, further increasing the risk of deficiency.5-8
Around half of the world's population experiences vitamin D deficiency, impacting roughly 1 billion individuals regardless of ethnicity or age. Lifestyle factors like reduced outdoor activities and environmental factors like air pollution contribute to this widespread insufficiency by limiting exposure to sunlight, necessary for UV-B-induced vitamin D production in the skin.9
The widespread occurrence of vitamin D deficiency is a major public health issue, as it independently heightens the risk of overall mortality in the general population. Emerging research suggests that current recommendations for vitamin D intake may need revision to effectively prevent chronic diseases.9
With the rising numbers of individuals experiencing vitamin D deficiency, research on the vital role of this hormone in overall health and disease prevention is gaining prominence. Given the limited dietary sources of vitamin D, supplementation is often recommended to meet suggested daily intake and tolerable upper limit levels, especially across all age groups.9
EPIDEMIOLOGY OF VITAMIN-D DEFICIENCY:
Vitamin D deficiency poses a significant global public health concern, with prevalence rates in India ranging from 40% to 99%, as indicated by various studies, with a majority reporting figures between 80% and 90%.10 According to a 2021 report, approximately 76% of Indians exhibit vitamin D deficiency or insufficiency. This statistic was derived from a study encompassing 4, 624 subjects across 229 sites within 81 cities across India.11
Vitamin D deficiency is especially common among certain demographic groups, such as older adults, individuals with obesity, nursing home residents, and hospitalized patients. Regardless of latitude and age, the prevalence of vitamin D deficiency is 35% higher among obese individuals compared to non-obese counterparts.12
In the United States, an estimated 50% to 60% of nursing home residents and hospitalized patients experience vitamin D deficiency. This issue is often seen in individuals with higher levels of skin melanin and those who frequently cover their skin, a common practice in Middle Eastern regions. In Asian nations, the highest prevalence of vitamin D deficiency was observed in Pakistan, followed by Bangladesh, India, Nepal, and Sri Lanka, respectively.12
Vitamin D deficiency, measured as 25-hydroxyvitamin D (25(OH)D) levels, has reached epidemic levels among South Asian populations residing in Western countries, with severe deficiency (<12.5 nmol/l) observed in 27–60% of individuals, varying by season.13
In the United States, vitamin D deficiency affects 47% of African American infants and 56% of Caucasian infants, while the prevalence exceeds 90% among infants in Iran, Turkey, and India.14
Interestingly, despite ample sunshine in tropical countries like India, vitamin D deficiency remains widespread. Community-based studies conducted over the past decade on apparently healthy individuals in India have revealed a prevalence ranging from 50% to 94%.14
The community-based Indian studies of the past decade done on apparently healthy controls reported a prevalence ranging from 50% to 94%.15
Additionally, vitamin D deficiency is widespread among pregnant and breastfeeding women throughout India. The vitamin D status of these mothers closely correlates with that of their neonates and exclusively breastfed infants, with similar patterns observed in both rural and urban areas.14,16
Despite being a rich source of vitamin D, fish consumption is notably higher among residents of Bengal in eastern India compared to other regions. However, it is surprising that their vitamin D status remains poor, similar to the rest of the country. Even young, healthy soldiers and athletes, despite having adequate calcium intake, sufficient sun exposure, and regular exercise routines, have been found to have vitamin D deficiencies. A study conducted on resident doctors from both eastern and western regions of India showed that most of them were deficient in vitamin D. This deficiency was also common among healthcare professionals nationwide. Clearly, the nationwide prevalence of vitamin D deficiency is evident.14
ETIOLOGY AND RISK FACTORS OF VITAMIN D DEFICIENCY:
The factors contributing to this include skin complexion, limited sunlight exposure, use of sunscreen, dietary habits in India, and a low consumption of Vitamin D fortified foods. As many Indians follow a vegetarian diet, they often miss out on Vitamin D rich foods, which are primarily derived from animal sources. All the above-mentioned factors can be a cause in urban population.10
Despite having ample sunlight exposure due to their outdoor occupations, rural populations still exhibit low Vitamin D levels. This deficiency can be attributed to their diet, which is high in phytates and low in calcium. Phytates are known to hinder calcium absorption in the intestines. Hence, low dietary Calcium increases the catabolism of 25(OH) D and increases the inactive metabolites with the resultant reduction in 25(OH)D concentrations.10
Vitamin D deficiency can occur due to following causes:
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 lead to vitamin D deficiency. Lower vitamin D intake orally is more prevalent in the elderly population.8
Decreased sun exposure:
Approximately half to ninety percent of vitamin D is obtained through skin absorption from sunlight, with the remainder sourced from dietary intake. To prevent vitamin D deficiency, experts recommend exposing at least 40% of the skin to sunlight for about twenty minutes daily. As people age, the ability of the skin to synthesize vitamin D decreases. Individuals with darker skin tones tend to have lower levels of cutaneous vitamin D production. Those who are institutionalized or undergo prolonged hospital stays may experience reduced sun exposure, contributing to vitamin D deficiency. Consistent use of sunscreen also diminishes effective sun exposure.8
Decreased endogenous synthesis:
Individuals with chronic liver disease such as cirrhosis can have defective 25-hydroxylation leading to deficiency of active vitamin D. Defect in 1-alpha 25-hydroxylation can be seen in hyperparathyroidism, renal failure and 1-alpha hydroxylase deficiency.8
Increased hepatic catabolism:
Medications such as Phenobarbital, Carbamazepine, Dexamethasone, Nifedipine, Spironolactone, Clotrimazole, and Rifampin induce hepatic p450 enzymes which activate metabolism of vitamin D.8
End organ resistance:
End organ resistance to vitamin D can be seen in hereditary vitamin D resistant rickets.8
Age:
Ability of skin to synthesize vitamin D reduces with increasing in age.16
Mobility:
People who are home bound or are rarely outside (for example, people in nursing homes and other facilities) are not able to use sun exposure as a source of vitamin D.16
Skin colour:
Dark-colored skin is less able to make vitamin D than fair-colored skin.16
Human breast milk:
Breast milk naturally contains a limited amount of vitamin D, and infant formulas similarly provide only a small quantity of this essential nutrient. Consequently, infants, particularly those exclusively breastfed, may face a risk of inadequate vitamin D intake.16
Cystic fibrosis, Crohn's disease, and celiac disease:
These diseases do not allow the intestines to absorb enough vitamin D through supplements.16
Weight loss surgeries:
After weight loss surgeries that reduce stomach size or bypass part of the small intestine, individuals may find it challenging to ingest adequate amounts of essential nutrients, vitamins, and minerals. Regular monitoring by healthcare professionals is crucial, along with lifelong supplementation of vitamin D and other necessary nutrients.16
Obesity:
Individuals with a body mass index (BMI) over 30 tend to have reduced levels of vitamin D. This is because adipose (fat) tissue can sequester vitamin D, hindering its release into the bloodstream. Vitamin D deficiency is more likely in obese people. Obesity often makes it necessary to take larger doses of vitamin D supplements in order to reach and maintain normal D levels.16
Kidney and liver diseases:
These conditions lead to a reduction in the enzyme necessary for converting vitamin D into its active form in the body. Inadequate levels of this enzyme are linked to a deficiency of active vitamin D.16
Breastfed Infants:
Vitamin D requirements cannot ordinarily be met by human milk alone, which provides < 25 IU/L to 78 IU/L.9
Older adults:
Due to aging, older individuals face an increased likelihood of vitamin D insufficiency. Factors contributing to this include reduced efficiency in synthesizing vitamin D through their skin, prolonged indoor activities, and potentially inadequate dietary intake of the vitamin.9
Pregnancy:
Beyond childhood, severe Vitamin D deficiency can occur in young women, including those who are pregnant, with higher risk with advancing age in a woman’s life cycle. There can be some Calcium loss during pregnancy through fetal demands and increased urinary Calcium excretion, which increases with advancing pregnancy. Throughout gestation, if a woman is Vit D deficient, it appears to impact fetal bone health more than maternal health.9
Males:
A lack of Vitamin D can initially cause men to feel fatigued and generally unwell. If not addressed, this deficiency may escalate to serious health conditions like cancer, Multiple Sclerosis, heart disease, stroke, and diabetes.17
SIGN AND SYMPTOMS OF VITAMIN D DEFICIENCY:
Vitamin D deficiency primarily remains asymptomatic. However, the deficiency can lead other symptoms such as:
Frequent infections or weakened immune system:
Vitamin D helps support the immune system. It plays a role in regulating immune function and inhibiting inflammatory reactions. It also helps in infections in the upper respiratory tract.18 Vitamin D influences the integrity of the airway epithelium, bronchial smooth muscles, and immune cells.19
Low levels of vitamin D have been linked to elevated inflammatory cytokines and a markedly higher susceptibility to pneumonia and viral upper respiratory tract infections. Additionally, vitamin D deficiency is correlated with a rise in thrombotic events, commonly seen in cases of COVID-19.20
Vitamin D 2is common among patients with Crohn's disease because of impaired conversion of vitamin D to its active metabolite, increased catabolism and increased excretion.21
Fatigue and muscle weakness:
Because vitamin D is key to bone health, an insufficient amount can cause bone and muscle weakness, because the capacity of the skin to synthesise the provitamin calcidiol (25-hydroxycholecalciferol) decreases.22
Bone, joint pain and fractures:
Sufficient vitamin D levels in the body play a crucial role in preserving bone strength by facilitating the absorption of calcium. This helps in enhancing bone mass and preventing bone loss. In contrast, a deficiency in vitamin D can lead to reduced bone mass and density, resulting in bone and joint pain. Patients who have experienced fractures often undergo testing to assess their vitamin D levels, tailored to their age and medical history.18
Osteoporosis worsening:
Vitamin D plays a crucial role in maintaining bone health by regulating bone mineral density and turnover. Insufficient levels of vitamin D can lead to reduced bone turnover and lower bone mineral density, potentially exacerbating conditions such as osteoporosis.23
Depression:
Lower levels of vitamin D have been linked to a heightened risk of depression. Vitamin D receptors are present in the brain, suggesting its potential protective role through anti-inflammatory mechanisms. Therefore, researchers suggest that individuals experiencing depression alongside severe vitamin D deficiency might find benefit in vitamin D supplementation.18 Depression is the leading cause of disability worldwide, affecting about 121 million people. Currently, the WHO has determined that depression is ranked fourth on the global burden of disease list.24
Muscular pain:
When vitamin D levels are low and the body not able to properly absorb Calcium and Phosphorus, there is an increased risk of bone pain, bone fractures, muscle pain and muscle weakness.25 Findings indicate that insufficient levels of vitamin D could contribute to muscular discomfort. Nociceptors, nerve cells that detect pain, possess receptors for vitamin D, implicating its role in pain perception. Moreover, vitamin D is thought to modulate pain signaling pathways within the body, potentially influencing chronic pain conditions. Clinical research suggests that supplementation with high doses of vitamin D might alleviate different forms of pain among individuals deficient in this vitamin.18
Weight gain:
Obesity is one risk factor for vitamin D deficiency. One study in adults found a possible link between low vitamin D status and both belly fat and increased weight, although these effects were more pronounced in men.18
Anxiety:
Vitamin D deficiency has been associated with anxiety disorders. Research indicates that levels of Calcidiol, a type of vitamin D, are significantly lower in individuals experiencing anxiety and depression. Moreover, a study involving pregnant women suggests that maintaining sufficient vitamin D levels could potentially alleviate anxiety symptoms, enhance sleep quality, and mitigate the risk of postpartum depression.18
In children:
Symptoms of a vitamin D deficiency in children include: irritability, lethargy, bone pain or fractures, deformities of the teeth, developmental delays.17
COSEQUENCES OF VITAMIN D DEFICIENCY:
· Vitamin D deficiency resulting in abnormalities in metabolism of Calcium and Phosphorus and bone metabolism. Vitamin D deficiency causes a decrease in the absorption of dietary Calcium and Phosphorus, resulting in an increase in PTH (Parathyroid Hormone) levels.9
· The PTH-mediated increase in osteoclastic activity creates local foci of bone weakness and causes a generalized decrease in Bone Mineral Density (BMD), resulting in Osteopenia and Osteoporosis.9
· An inadequate Calcium–Phosphorus product causes a mineralization defect in the skeleton. In young children who have little mineral in their skeleton, this defect results in a variety of skeletal deformities classically known as rickets.9
· Vitamin D deficiency also causes muscle weakness; affected children have difficulty in standing and walking, whereas the elderly have increasing sway and more frequent falls, thereby increasing their risk of fracture.9
Rickets:
Rickets, a disorder impacting bone development in children, manifests with symptoms such as bone pain, stunted growth, and fragile bones prone to deformities. In adults, a comparable condition termed osteomalacia results in soft bone tissue. Vitamin D or calcium deficiency represents the primary cause of rickets, although genetic predisposition or conditions affecting nutrient absorption can also lead to its development.26
o Sign and Symptoms:
§ Pain or tenderness in the bones of the arms, legs, pelvis, or spine
§ Stunted growth and short stature
§ Bone fractures
§ Muscle cramps
§ Teeth deformities, such as: Delayed tooth formation, holes in the enamel, abscesses, defects in the tooth structure, an increased number of cavities
§ Skeletal deformities, including: An oddly shaped skull, bowlegs, or legs that bow out, bumps in the ribcage, a protruding breastbone, a curved spine, pelvic deformities.27
· Osteomalacia28, 29:
o Osteomalacia describes a disorder of “bone softening” in adults that is usually due to prolonged deficiency of vitamin D.
o Bone tissue consists of various cell types that play crucial roles in the dynamic process of bone remodeling. Osteoclasts, specialized in bone resorption, break down bone tissue by secreting collagenase. In contrast, osteoblasts are responsible for synthesizing and depositing the osteoid matrix, a collagen-rich scaffold that becomes mineralized with inorganic salts to form mature bone. This intricate process is regulated by hormonal signals, particularly parathyroid hormone (PTH) and calcitonin, which respond to serum calcium levels to maintain bone homeostasis.
o Sign and Symptoms
§ Pain in the legs, upper thighs, and knees
§ Weak, sore, and stiff muscles, especially in the trunk, shoulders, buttocks, and upper legs
§ Difficulty walking
§ Bones that can be sensitive to slight knocks
§ Muscle spasms
§ Pseudo-fractures of weight-bearing bones, such as the feet and pelvis
DIAGNOSIS OF VITAMIN D DEFICIENCY30
· A low vitamin D level can be diagnosed with a blood test called 25-hydroxyvitamin D or 25(OH)D (OH = hydroxy, D = vitamin D).
· Although definitions of vitamin D deficiency vary to some extent, most groups use the following values recommended by the National Academy of Medicine for adults:
o A normal level of vitamin D is defined as a 25(OH)D concentration ≥20 ng/mL (50 nmol/L).
o Vitamin D insufficiency is defined as a 25(OH)D concentration of 12 to 20 ng/mL (30 to 50 nmol/L).
o Vitamin D deficiency is defined as a 25(OH)D level less than 12 ng/mL (30 nmol/L).
o A “risk” of vitamin D toxicity is defined as a 25(OH)D level >100 ng/mL (>250 nmol/mL) in adults ingesting substantial amounts of Calcium.
o Most experts agree that levels lower than 20 ng/mL (50 nmol/L) are sub optimal for bone health.
TREATMENT OF VITAMIN D DEFICIENCY:
Vitamin D deficiency can be treated by vitamin D supplements. There are Two commonly available forms of vitamin D supplements are ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3).30
Vitamin D3 is preferred over vitamin D2 due to its superior ability to increase vitamin D levels effectively.
The recommended dosage of vitamin D varies depending on the severity of deficiency30:
· For individuals with 25-hydroxyvitamin D (25[OH]D) levels <12 ng/mL (30 nmol/L), treatment typically involves 50, 000 international units (1250 micrograms) of vitamin D2 or D3 orally, taken twice weekly for six to eight weeks, followed by daily supplementation of 800 to 1000 international units (20 to 25 micrograms) of vitamin D3 or more.
· Those with 25(OH)D levels between 12 to 20 ng/mL (30 to 50 nmol/L) generally require 800 to 1000 IU (20 to 25 micrograms) of vitamin D3 orally daily, although higher doses may be necessary. The optimal dose is determined by monitoring the individual’s 25(OH)D levels, adjusting the vitamin D dosage as needed to achieve normal levels, and maintaining therapy with 800 international units (20 micrograms) of vitamin D daily once normal levels are attained.
· Individuals with 25(OH)D levels between 20 to 30 ng/mL (50 to 75 nmol/L) typically maintain adequate levels with daily oral supplementation of 600 to 800 international units (15 to 20 micrograms) of vitamin D3.
· Infants and children with 25(OH)D levels <20 ng/mL (50 nmol/L) usually receive 1000 to 2000 international units (25 to 50 micrograms) of vitamin D2 orally (depending on age) for two to three months.
· Children diagnosed with rickets, characterized by bone softening visible on X-ray, may require higher vitamin D doses and should be closely monitored by healthcare providers to ensure resolution of the condition.
Table 1: Recommended Vitamin D doses for the treatment and prevention of Vitamin D deficiency, per the Global Consensus30
Age range |
Daily treatment Vitamin D dose |
Bolus treatment Vitamin D dose |
Daily maintenance Vitamin D supplementation dose |
0–3 months old |
2000 IU (50mg) daily for 3 months |
Recommendation not available |
400 IU (10mg) daily |
3–6 months old |
2 000 IU (50mg) daily for 3 months |
Recommendation not available |
400 IU (10mg) daily |
6–12 months old |
2000 IU (50mg) daily for 3 months |
50 000 IU (1250mg) every 3 months |
400 IU (10mg) daily |
Greater than 12 months to 12 years old |
3000–6000 IU (75–150mg) daily for 3 months |
150 000 IU (3750mg) every 3 months |
600 IU (15 mcg) daily |
Greater than 12 years old |
6000 IU (150mg) daily for 3 months |
300 000 IU (7500mg) every 3 months |
600 IU (15 mcg) daily |
Side Effects of Vitamin D Supplements:
Common side effects associated with using vitamin D includes Arrhythmias, Confusion, Constipation, Dry mouth, Headache, High levels of Calcium in the blood (hypercalcemia), Lethargy, Metallic taste in the mouth, Muscle or bone pain, Nausea, Sluggishness, Vomiting.31
Dosages of Vitamin D should be given as Follows30:
· Adult and Pediatric Dosage Forms & Strengths
· 1 mcg = 40 international units (IU)
· Oral Solution: 8000IU/mL (200mcg/mL)
· Capsule: 50, 000IU (1.25mg)
· Tablet: 400IU (10mcg), 2000IU (50mcg)
Dosage Considerations31:
Vitamin D toxicity may last 2 months or more after therapy is discontinued. Adequate clinical response to vitamin D therapy is dependent on adequate dietary Calcium. In patients with rickets, the range between therapeutic and toxic doses is narrow in vitamin D–resistant patients; adjust dose based on clinical response to avoid toxicity.
Vitamin D as Nutritional Supplementation in Different Conditions:
Recommended daily allowance (RDA)
· For 19-70 years: 600 IU (15 mcg)/day
· For Pregnant or lactating women: 600 IU (15 mcg)/day
· Vitamin D to Prevent and Treat Osteoporosis:
· >50 years: 800-1000 IU (20-25 mcg) PO once daily with Calcium supplements
· Vitamin D to Prevent and Treat Hypoparathyroidism:
· 50, 000-200, 000 IU (0.625-5 mg) PO once daily with Calcium supplements
· Vitamin D to Prevent and Treat Vitamin D-Resistant Rickets
· 12, 000-500, 000 IU (0.3-12.5mg) PO once daily
Precautions for Vitamin D Supplements31:
· Ergocalciferol should be used cautiously in individuals with renal impairment, heart disease, kidney stones, or arteriosclerosis.
· Discontinue the medication if hypercalcemia develops in the patient.
· Some products containing tartrazine may trigger allergic reactions.
· Vitamin D toxicity can persist for more than two months after discontinuation of therapy.
· Limit intake in infants with idiopathic hypercalcemia.
· Exercise caution when using concurrently with cardiac glycosides.
· The effectiveness of vitamin D therapy depends on sufficient dietary calcium intake.
· Adults with a BMI over 30 kg/m˛ are at increased risk of vitamin D deficiency due to its storage in adipose tissue; higher than recommended daily doses may be necessary but require careful monitoring to prevent toxicity.
· Ergocalciferol supplementation may be necessary in renal impairment.
· In patients with rickets, adjusting the dose of vitamin D is crucial to maintain a balance between therapeutic benefits and avoiding toxicity, especially in vitamin D–resistant cases.
Available Marketed Preparation of Vitamin D32:
There are many types of vitamin D preparations are available, which are used in treatment of vitamin D deficiency or insufficiency.
Table No.1: Available Marketed Preparation of Vitamin D32
Preparations |
Brand name |
Dose |
Calciferol (vit D2) |
CALCIFEROL, DRISOL cap. |
As solution in oil, filled in gelatin capsules 25, 000 and 50, 000 IU caps. |
Cholecalciferol (vit D3) |
CALCIROL, CALCIBEST SACHET |
60, 000 IU in 1 g granules suspended in milk/water and taken at 3–4 weeks intervals, and then every 2–6 months. |
Calcitriol |
CALTROL, ROLSICAL, ROCALTROL 0.25 µg cap. |
0.25–1 µg orally daily or on alternate days |
Alfacalcidol |
ONE ALPHA, ALPHA D3, ALPHADOL 0.25 and 1 µg caps, ALFACAL 0.25, 0.5 µg caps. |
1–2 µg/day, children < 20 kg 0.5 µg/day. Repeated serum calcium measurements are essential. |
MANAGEMENT OF VITAMIN-D DEFICIENCY:
Pharmacological Management:
· The amount of vitamin D required to treat the deficiency depends largely on the degree of the deficiency and underlying risk factors.1
· Several preparations of vitamin D are available. Vitamin D3 (cholecalciferol), when compared with vitamin D2 (ergocalciferol), has been shown to be more efficacious in achieving optimal 25-hydroxyvitamin D levels, thus favoring vitamin D3 as a treatment of choice.1
· 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 to 2, 000 IU is recommended.28
· 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 (African Americans, Hispanics, obese, taking certain medications, malabsorption syndrome). Once serum 25-hydroxyvitamin D level exceeds 30ng/mL, 3000 to 6000 IU/day maintenance dose is recommended.28
· 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-hydroxyvitamin D level exceeds 30 ng/mL, 1000 IU/day maintenance treatment is recommended.28
· 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.28
· 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.45
· Adults less than 65 years of age who do not have year-round effective sun exposure should consume 600 to 800 international units of vitamin D3 daily to prevent deficiency.28
· Older adults 65 years of age or more should consume 800 to 1000 international units of vitamin D3 daily to prevent deficiency and to reduce the risk of fractures and falls.28
Non-Pharmacological Management:
· Habit to get exposure to sun or UV-B light:
o Many middle-aged adults face heightened risks of vitamin D deficiency owing to reduced sun exposure and heightened use of sunscreen. Studies indicate that achieving a serum level of 25-hydroxyvitamin D above 30 ng/ml requires a daily intake of at least 1000 IU, with recommendations potentially reaching 1500-2000 IU/day. Approximately 70% of vitamin D is synthesized through cutaneous production, with the remaining 30% obtained from dietary sources.34
· According to the Vitamin D Council, people with light colour skin need around 15 minutes in the sun, while people with dark colour skin might need an hour or more. So, need to develop a habbit to take atleast 15 minutes to 30 minutes sun bath by exposing legs, arm, abdomen and in early morning on regular basis.35
· Get more sun exposure at midday in the summer when the UV Index is greater than 3.
· If the UV index is not above 3 outdoors or can’t get outside, then artificial sources are next best source of vitamin D through UVB sunbeds or sunlamps.36
· Vitamin-D rich food supplements:
o Include Vitamin-D rich food in regular diet such as, flesh of fatty fish and fish liver oils, egg yolks, cheese, beef liver, Cod liver oil, Salmon, Swordfish, Tuna fish, Orange juice fortified with vitamin D, Dairy and plant milks fortified with Vitamin D, and fortified cereals.37, 38
VITAMIN-D LIGHT LAMP THERAPY: A NEW APPROACH FOR VITAMIN-D DEFICIENCY TREATMENT:
A Vitamin-D lamp is a lamp that emits UV-B light helping body to make vitamin D.38 A UV lamp that emits ultraviolet radiation similar to sunlight and thus produces vitamin D3 in the skin is an excellent alternative for patients who suffer from vitamin D deficiency due to fat malabsorption, especially during the winter months when natural sunlight is unable to produce vitamin D3 in the skin.40
Figure No.2: Vitamin-D Lamp Light
Light therapy is also used to treat other conditions, including: seasonal affective disorder (SAD), depression, sleep disorders, dementia.41 Instead, take a vitamin D supplement that offers up to 2000 IUs per day. Light therapy boxes that emit no harmful UV light can be useful for fighting seasonal affective disorder if their light reaches an intensity of 10, 000 lux. Different light therapy boxes that do utilize different types of UV light can be used under close medical supervision to treat severe eczema and psoriasis.42
Phototherapy and photochemotherapy are widely acknowledged as effective treatments for numerous cutaneous disorders, offering a favorable safety profile and well-documented side effect profiles. These modalities not only ensure patient convenience but also enhance treatment compliance and improve therapeutic outcomes. However, their administration necessitates adequate space for equipment, trained staff, and comprehensive patient education before commencement.43
THE WAY FORWARD TOWARDS VITAMIN D DEFICIENCY44:
· World Vitamin D Day, observed on November 2nd as part of Vitamin D Awareness Month, is an initiative promoted by the Vitamin D Council to raise awareness about the declining levels of vitamin D among people globally.
· The day emphasizes the importance of evaluating one’s vitamin D intake and taking preventive measures against deficiency, especially since sunlight exposure may not suffice for natural vitamin D synthesis at latitudes above 37°N during winter months.
· Optimal vitamin D levels are crucial year-round for maintaining overall health. This day serves to educate the public on the significance of sustaining adequate vitamin D blood levels.
· Despite India's tropical climate providing ample sunshine, the prevalence of vitamin D deficiency remains high. This necessitates targeted public health interventions to address the issue effectively.
· Strategies such as fortifying commonly consumed foods like milk, edible oils, yogurt, and cereals with vitamin D can play a pivotal role in mitigating deficiency risks. Legislation ensuring the inclusion of vitamin D fortified foods in public distribution systems is crucial, backed by sustained governmental support.
· Comprehensive educational programs are essential to raise awareness about vitamin D deficiency among both healthcare providers and the general public. Adequate investment in such programs is pivotal for their development and sustainability.
· Access to affordable vitamin D supplements at primary healthcare centers is critical for vulnerable populations such as pregnant women, lactating mothers, children, and the elderly.
· There is a need for revising the Recommended Dietary Allowance (RDA) for vitamin D in India to align with global standards and ensure adequacy.
· Implementing vitamin D fortification in school meal programs and promoting daily physical activity among schoolchildren can significantly contribute to ensuring adequate vitamin D levels in this age group.
· Affordable testing facilities for vitamin D levels should be made accessible to high-risk populations, including pregnant women, children, and the elderly, to facilitate timely diagnosis and intervention.
· Governmental support for research initiatives aimed at evaluating the impact of vitamin D supplementation and fortification strategies is essential for informed policy-making and public health improvement.
REFERENCES:
1. Daniel D. Bikle. Vitamin D: Production, Metabolism and Mechanisms of Action. Last Update: December 31, 2021.
2. Thacher TD and Clarke BL. Vitamin D insufficiency. Mayo Clinic Proceedings. 2011; 86(1): 50–60.
3. Ann Epidemiol. Vitamin D Status: Measurement, Interpretation and Clinical Application. 2009 Feb; 19(2): 73–78.
4. Mary Anne Dunkin. Vitamin D deficiency: 6 causes, common symptoms and health risks. WebMD, Available at: https://www.webmd.com/diet/guide/vitamin-d-deficiency July 28, 2020.
5. Matsuoka LY and Wortsman J and MacLaughlin JA and Holick MF. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab. 1987; 8.
6. Clemens TL and Henderson SL and Adams JS. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. 1982; 6.
7. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 81.
8. Zhou C and Assem M and Tay JC. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest. 2006; 116: 12. 14.
9. Rathish Nair and Arun Maseeh. Vitamin D: The “sunshine” vitamin. Apr-Jun 2012; 3(2): 118–126.
10. P. Aparna and S. Muthathal and Baridalyne Nongkynrih and Sanjeev Kumar Gupta. Vitamin D deficiency in India. 2018; 324 -330.
11. Ray S. Indians are vitamin D deficient. and no, it can't be fixed by Diet Alone. The Print. 202. Available from: https://theprint.in/opinion/indians-are-vitamin-d-deficient-and-no-it-cant-be-fixed-by-diet-alone/779535/ Accessed on:3 November 2022.
12. Grey A, Lucas J, Horne A, Gamble G, Davidson JS, Reid IR. Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J Clin Endocrinol Metab. 2005; 90: 2122–6.
13. Nair R and Maseeh A. Vitamin D: The "sunshine" vitamin. J Pharmacol Pharmacother. 2012 Apr, 26.
14. Pereira-Santos M and Costa PR. Obesity and vitamin D deficiency: a systematic review and meta-analysis. 2015 Apr, 9.
15. Omeed Sizar and Swapnil Khare “Vitamin D Deficiency. July 27, 2022.
16. Palacios C and Gonzalez L. Is vitamin D deficiency a major global public health problem. J Steroid Biochem Mol Biol. 2014 Oct: 138-45.
17. Balance Hormone Center. Vitamin B deficiency treatment for men. Norman, Available from: https://www.balancehormoneoklahoma.com/contents/men/vitamin-b-deficiency-treatment-for-men Accessed: 2022 Nov11.
18. Vitamin D deficiency symptoms: Signs and treatment. Medical News Today. MediLexicon International, Available from: http://www.medicalnewstoday.com/articles/vitamin-d-deficiency-symptoms#symptoms Accessed: 2022 Nov1.
19. Iqbal SF and Freishtat RJ. Mechanism of action of vitamin D in the asthmatic lung. J Investig Med. 2011; 59: 1200-2.
20. Weir EK and Thenappan T and Bhargava M and Chen Y. Does vitamin D deficiency increase the severity of COVID-19? Clinical Medicine. 2020; 20(4).
21. Raftery T and O'Sullivan M. Optimal vitamin D levels in crohn's disease: A Review. Proceedings of the Nutrition Society. 2014; 74(1): 56–66.
22. Venning G. Recent developments in vitamin D deficiency and muscle weakness among elderly people. BMJ. 2005; 330(7490): 524–6.
23. Lips P and van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Practice and Research Clinical Endocrinology & Metabolism. 2011; 25(4): 585–91.
24. Penckofer S and Kouba J and Byrn M and Estwing Ferrans C. Vitamin D and depression: Where is all the sunshine? Issues in Mental Health Nursing. 2010; 31(6): 385–93.
25. Yale Medicine. “Vitamin D deficiency” Yale Medicine, Available from:https://www.yalemedicine.org/conditions/vitamin-d-deficiencyAccessed: 2022 Nov 11.
26. NHS choices. Rickets and osteomalacia. NHS, Available from: https://www.nhs.uk/conditions/rickets-and-osteomalacia/#:~:text=Rickets%20is%20a%20condition%20that, symptoms%20of%20rickets%20and%20osteomalacia. Accessed: 2022 Nov11.
27. Cafasso J. Rickets: Symptoms, diagnosis, and treatments. Healthline Media, Available from: https://www.healthline.com/health/rickets#symptoms 2019.
28. Osteomalacia: Causes, symptoms, diagnosis, treatment, and more. Medical News Today, MediLexicon International, Available from: https://www.medicalnewstoday.com/articles/osteomalacia#symptoms Acessed: 2022Nov11.
29. Shwetha M. N, Nancy Chandra Priya. P. Knowledge regarding vitamin D deficiency among students. Asian J. Nursing Education and Research. 2019; 9(1): 66-68.
30. UpToDate. Patient education: Vitamin D deficiency (Beyond the Basics). Available from: https://www.uptodate.com/contents/vitamin-d-deficiency-beyond-the-basics#H10. Accessed: 2022Nov11.
31. RxList. Vitamin D: Supplement, uses, side effects, dosages, interactions, warnings. RxList, Available from: https://www.rxlist.com/consumer_vitamin-d/drugs-condition.htm Accessed: 2022Nov11.
32. Tripathi KD. Essentials of Medical Pharmacology. 7th ed., New Delhi: Jaypee Brothers Medical Publishers; 2019, 342.
33. Holick MF and Binkly NC. Evaluation, Treatment, and Prevention of Vitamin D deficiency. J Clin Endocrinol Metab. 2011; 1911-1930.
34. Bijan Iraj, Alireza Ebneshahidi. Vitamin D Deficiency, Prevention and Treatment. Int J Prev Med. 2012 Oct; 3(10): 733–736.
35. Timesofindia.com. The right way to get vitamin D from the sun. The Times of India. Times of India; 2020. Available from: https://timesofindia.indiatimes.com/life-style/health-fitness/health-news/the-right-way-to-get-vitamin-d-from-the-sun/photostory/77370069.cms Accessed: 2022 Nov1.
36. World Vitamin D November 2. Stop Vitamin D Deficiency. worldvitamindday.net. Available from: https://worldvitamindday.net/ Accessed on : 2022Nov13.
37. Vitamin D deficiency: Causes, symptoms and amp; treatment. Cleveland Clinic. Available from: https://my.clevelandclinic.org/health/diseases/15050-vitamin-d-vitamin-d-deficiency Accessed 2022Nov13.
38. Vitamin D (2022) The Nutrition Source. Available at: http://www.hsph.harvard.edu/nutritionsource/vitamin-d/ Accessed: October 22, 2022.
39. Linnea Zielinski. What is a vitamin D lamp and how does it work? Available from: https://ro.co/health-guide/vitamin-d-lamp/#:~:text=A%20vitamin%20D%20lamp%20is, seasonal%20affective%20disorder%20(SAD).
40. Chandra P and Wolfenden LL and Ziegler TR. Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: A case series. Photodermatology, Photoimmunology & Photomedicine. 2007; 23(5): 179–85.
41. Santos-Longhurst. Sun Lamp: Uses, treatments, and costs. Healthline Media, 2019 Available from: https://www.healthline.com/health/sun-lamp, Accessed 2022Nov13.
42. Janaki Jitchotvisut. Everything you need to know about using Vitamin D lamps to combat seasonal affective disorder. Insider, Jan 17, 2019.
43. Robert J. Sage and Henry W. Lim. UV-based therapy and vitamin D. Dermatologic Therapy. 2010; 23: 72–81.
44. Perry Holman. UV→D NOW Let the Sunshine back into your life! Nov 18, 2021.
Received on 06.07.2024 Revised on 21.09.2024 Accepted on 28.10.2024 Published on 18.12.2024 Available online on December 21, 2024 Asian J. Pharm. Tech. 2024; 14(4):363-372. DOI: 10.52711/2231-5713.2024.00058 ©Asian Pharma Press All Right Reserved
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