Vitamin D

Biochemical action of Vitamin D

Vitamin D plays a significant hormonal role and is produced in the skin by UVB light in addition to being directly received from the diet. 7-dehydrocholesterol in the skin is transformed by ultraviolet B into vitamin D, which then develops into vitamin D. Vitamin D from the skin and diet is converted by the liver into 25-hydroxyvitamin D (25 OH D) and this can be used to measure vitamin D status. 1,25-dihydroxy vitamin D (1,25(OH)) is the biologically active form of vitamin D is generated in the kidneys and is regulated by parathyroid, calcium, and phosphorus levels. 1,25-dihydroxy vitamin D affects gene transcription by acting on the vitamin D receptor found in cells, increasing intestinal calcium and phosphorus absorption and encouraging calcium reabsorption in the kidneys. In the presence of vitamin D, this mechanism promotes calcium and phosphorus absorption.

• Cell differentiation, proliferation and growth: Vitamin D has the potential to combat cancer by inhibiting the proliferation of lymphocytes, keratinocytes, and other types of cells; vitamin D shapes cells by promoting the development of bone from stem cells.
• Regulation of calcium and phosphorus levels: PTH and vitamin D improve renal reabsorption, bone release, and absorption of calcium and phosphorus.
• Modelling and remodelling of bone: By increasing osteocalcin, estrogen production, and genistein synergy, vitamin D maintains normal calcium levels and improves bone health.

Vitamin D is available in various forms like tablets, capsules, oral solutions and injectable solutions.

• Tablets/ capsules are to be swallowed whole with water/liquid, as applicable.
• Topical Vitamin D is to be applied as directed by the doctor. It should be administered as a thin layer using a little amount of medicine (about the size of a pea), as applicable.
• Oral solutions are to be taken by mouth, as applicable.
• Injectable solutions are to be administered parenterally, as applicable.

• Vitamin D can be consumed as a supplement, has potential extraskeletal effects, and may be related to cancer, asthma, autoimmune disorders, cardiovascular and neurological conditions, and also to issues with pregnancy.
• Vitamin D is used as a supplement in stimulating insulin production modulates the function of activated T and B lymphocytes, prevents inflammatory bowel diseases, and affects myocardial contractility.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s)

Vitamin D is a supplement that benefits health in numerous ways.

• Deficiency states: Children with rickets have low vitamin D levels because of little sun exposure, a poor diet, or specific illnesses. It causes adult osteomalacia, which frequently manifests in chronic lower back pain. X-rays and serum 25(OH)D assays are used in the diagnosis. In case of inadequate vitamin D metabolism, high therapy dosages carefully supervised potential toxicity.
• Pregnancy and lactation supplementation: Pregnancy affects the development of the musculoskeletal system, nervous system, and fetal and neonatal growth in various ways. Since newborns depend on prenatal storage for their vitamin D needs, breast milk is insufficient. Therefore vitamin D supplementation is essential during lactation.
• Children: Supplementing with D2 or D3 at 1000–2000 IU/day for babies and up to 4000 IU/day for children older than a year is the most common recommendation.
• Bone health and osteoporosis: For optimal bone health, thereby reducing the risk of falling, and to prevent or cure osteoporosis, individuals should get the appropriate quantities of vitamin D and calcium from food and supplements.
• Type 2 diabetes mellitus (T2DM): By increasing the production of insulin through receptors on pancreatic beta cells and lowering peripheral insulin resistance through receptors in the muscles and liver, vitamin D impacts how glucose is metabolized. By affecting insulin signalling, pancreatic beta-cell function, inflammation reduction, and glucose metabolism, it may affect type 2 diabetes. In people with mild T2DM and non-diabetics who are deficient in vitamin D, supplementation increases insulin secretion; however, it has minimal effect in people with severe T2DM. When administered intravenously, vitamin D improves insulin sensitivity in women with gestational diabetes by significantly lowering fasting glucose and insulin levels.
• Hypoparathyroidism: Vitamin D helps balance calcium, phosphorus, 25(OH)D, and PTH levels; it has been proven beneficial in treating hypoparathyroidism when combined with calcium.
• Depression: Vitamin D has been linked to several cognitive processes and depressive brain regions that contain vitamin D receptors in their neurons and glial cells. The possible advantages of vitamin D supplementation for treating and preventing depression haven't been studied, though. For those at risk of depression and other mental problems, treating vitamin D deficiency through solar exposure, dietary sources, or supplements may be a simple and affordable way to improve mental health.
• Cancer: Vitamin D may be able to inhibit the growth of breast cancer cells as well as regulate the proliferation of healthy breast cells.
• Asthma In Children: The effects of vitamin D supplementation on asthma episodes, symptoms, and lung function in both children and adults with asthma have been investigated in a number of clinical trials.

Vitamin D supplementation may be administered orally, or the skin can make it via UV exposure and parenterally.

• Orally: When Vitamin D supplements are taken orally, it is best to take them along with a fat-containing meal to promote optimal absorption due to their lipophilic nature.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

• Topically: Vitamin D supplements are applied topically to improve the health of your skin.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

• Parenterally: When Vitamin D supplement is administered parenterally, intramuscular is the best route of administration.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablet: 400IU (10mcg), 2000IU (50mcg)
• Capsule: 50,000IU (1.25mg)
• Oral solution: 8000IU/mL (200mcg/mL)
• Injections: 100,000 IU/mL, 300,000 IU/mL, 600,000 IU/mL

Dosage Adjustment for Adult Patients

Osteoporosis

Prophylaxis and treatment

>50 years: 800-1000 IU (20-25 mcg) PO once daily with calcium supplements

Hypoparathyroidism

50,000-200,000 IU (0.625-5 mg) PO once daily with calcium supplements

Vitamin D-Resistant Rickets

12,000-500,000 IU (0.3-12.5 mg) PO once daily

Familial Hypophosphatemia

10,000-60,000 IU (0.25-1.5 mg) PO once daily with phosphate

Vitamin D supplementation is available in the form of tablets, capsules and injections.

• The advantages of Vitamin D are countered by any meal or drink that contains caffeine, including coffee, tea, chocolate, and soda.
• Limit alcoholic beverages.
• Stay within your daily calorie needs.

Recommended Daily Allowance (RDA)

If a person receives little sunlight, the ICMR only recommends 400 IU (10 mcg) of vitamin D; otherwise, sunlight is sufficient to meet the requirement. As a result of the pandemic nature of the deficit, it is necessary to take a suitable amount of supplements. However, 1000–2000 IU per day appears to be safe.

Upper Tolerable Intake (UTL):

For adults, it is set at 4,000 IU (100 mcg).

The dietary restriction should be individualized as per patient requirements.

• Hypersensitivity to vitamin D.
• Hypercalcaemia.
• Not to be taken for sarcoidosis or hyperparathyroidism without medical supervision.
• Possible interference with the action of calcium channel blockers.
• High doses of Vitamin D require medical supervision in patients with arteriosclerosis and heart disease.
• High doses capable of inducing hypercalcaemia may precipitate arrhythmias in patients taking Digitalis.
• When treating hypoparathyroidism, concomitant treatment with intravenous calcium, parathyroid hormone, and/or dihydrotachysterol may also be required.
• The presence of tartrazine in some products may cause allergic reactions.

The treating healthcare must closely keep a watch and monitor for signs and symptoms like prolonged nausea, vomiting, or stomach discomfort. It is recommended to discontinue vitamin K in case of allergies.

Due to its fat-soluble nature, vitamin D is not easily eliminated from the body; thus, it is essential to follow the recommended dosage since exceeding it may result in difficulties.

Precaution should also be taken with sun exposure to prevent skin damage.

Vitamin D is generally well-tolerated.

The adverse reactions related to Vitamin D can be categorized as-

• Common: Gastrointestinal distress, including nausea, dry mouth, vomiting and constipation.
• Less common: Arrhythmias, hypercalcemia, arterial calcification, arrhythmia
• Rare: Nephrotoxicity, manifesting as polyuria, polydipsia and nocturia.

• Antituberculosis drugs: Drugs like rifampicin and isoniazid have been found to cause vitamin D catabolism, which may show in the form of lower levels of metabolites. This could be an issue for people already at risk of inadequate vitamin D levels.
• Calcium channel blockers: Vitamin D supplementation may reduce the effectiveness of these drugs. Use with caution unless under medical supervision.
• Glucocorticoids: High doses of these medications directly prevent calcium absorption in the digestive system that is mediated by vitamin D. Calcium and vitamin D supplements should be considered while receiving long-term therapy with oral or inhaled corticosteroids.
• Ketoconazole: This drug reduces the conversion of vitamin D to its active forms. Increased vitamin D intake may be required with long-term drug use.
• Lipid-lowering drugs: Medications like colestipol and cholestyramine may inhibit the absorption of all fat-soluble vitamins. To prevent the interaction, take the dietary supplement at least an hour before or 4-6 hours after taking the medication.
• Mineral oil: Mineral oil impairs the absorption of all fat-soluble nutrients and may deplete oral intake of vitamin D sources—separate doses by at least 2 hours.
• Oestrogens: Vitamin D works synergistically with oestrogens to prevent bone loss. Interaction is beneficial.
• Orlistat: Orlistat has been shown to lower the absorption of some fat-soluble nutrients. Concurrent supplementation of a multivitamin with D is advised. Separate doses by a minimum of 4 hours either side of ingestion of orlistat.
• Phenytoin and valproate: The anticonvulsants induce catabolism of vitamin D through liver induction, and prolonged use is linked with an high risk of developing rickets and osteomalacia.

The common side effects of Vitamin D include the following:

• Confusion
• Vomiting
• Constipation
• Dry mouth
• Headache
• Hypercalcemia
• Lethargy
• Metallic taste
• Muscle or bone pain
• Nausea
• Sluggishness
• Arrhythmias

• Pregnancy:

Pregnancy category: C (ergocalciferol)

Research done on animals has demonstrated negative effects on the growing foetus despite the lack of human studies. If the advantages outweigh the hazards, use it with caution.

Daily doses of 4000 units/day are recommended for treatment in pregnancy.

• Paediatrics:

In the paediatric population, vitamin D is required for the absorption of calcium and maintaining of bone health.

Vitamin D supplements are the best way to help children get enough daily vitamin D.

Dosage Adjustment for Paediatric Patients

Vitamin D-Resistant Rickets

12,000-500,000 IU (0.3-12.5 mg) PO once daily

Familial Hypophosphatemia

40,000-80,000 IU (1-2 mg) PO once daily with phosphate supplements; may be reduced after the stage of growth is complete

• Geriatrics: There is a severe vitamin D deficiency among the elderly population.

Nutritional Supplementation

<70 years: 600 IU (15 mcg) PO once daily

>70 years: 800 IU (20 mcg) PO once daily

• Lactating mothers: Human milk typically contains vitamin D. Daily maternal vitamin D supplementation in the 400–2,000 IU (10–50 mcg) range results in insufficient milk concentrations to meet the infant's daily requirement for vitamin D while nursing exclusively. They are also inadequate to treat infants who already have vitamin D insufficiency.

Daily intake of 600 IU (15 mcg) of vitamin D for breastfeeding mothers.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Overdose of Vitamin D is Hypervitaminosis D. Symptoms include constipation, polydipsia, polyuria, and confusion.

There is no specific treatment in the event of an overdose. In the event of an overdose, the mainstay treatment is stopping the exogenous vitamin D supplementation by focusing on lowering calcium levels and treating the patient symptomatically, and supportive measures are instituted as required.

Adapted from

• Braun L, Cohen M. October 1, 2014.Herbs and Natural Supplements; 4^th Edition Vol-2. Australia. Elsevier.
• https://www.fssai.gov.in/upload/media/FSSAI_News_Vitamin_NDTV_02_07_2019.pdf
• reference.medscape.com/drug/drisdol-calciferol-vitamind-344417#10
• https://www.ncbi.nlm.nih.gov/books/NBK278935/
• https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
• https://www.ncbi.nlm.nih.gov/books/NBK557876/