Vitamin D is a fat-soluble vitamin and prohormone that plays a fundamental role in calcium and phosphate homeostasis, skeletal development, and bone remodeling. Through its active metabolite, calcitriol (1,25-dihydroxyvitamin D), vitamin D regulates intestinal calcium absorption, maintains normal serum calcium concentrations, and supports healthy bone mineralization.
Vitamin D deficiency remains a significant global health concern, particularly among older adults, individuals with limited sun exposure, people with darker skin pigmentation, and patients with malabsorption disorders. Adequate vitamin D status is essential for preventing rickets in children, osteomalacia in adults, and contributing to overall musculoskeletal health.
What is Vitamin D?
Vitamin D refers to a group of fat-soluble secosteroids responsible for maintaining calcium and phosphate balance within the body.
The two major forms are:
Vitamin D2 (Ergocalciferol)
Vitamin D2 is a synthetic or plant-derived form commonly used in dietary supplements and fortified foods.
Vitamin D3 (Cholecalciferol)
Vitamin D3 is the naturally occurring form produced in the skin following exposure to ultraviolet B (UVB) radiation. It is also found in certain foods and dietary supplements.
Although both forms can raise serum vitamin D levels, some studies suggest that vitamin D3 may be more effective at maintaining circulating 25-hydroxyvitamin D concentrations over time.
Sources of Vitamin D
Vitamin D can be obtained from three primary sources:
Sunlight Exposure
Ultraviolet B (UVB) radiation converts 7-dehydrocholesterol in the skin into previtamin D3, which is subsequently transformed into vitamin D3.
Factors affecting cutaneous vitamin D synthesis include:
- Geographic latitude
- Season of the year
- Skin pigmentation
- Sunscreen use
- Age
- Duration of sun exposure
Dietary Sources
Natural food sources include:
- Fatty fish (salmon, mackerel, sardines)
- Cod liver oil
- Egg yolks
- Beef liver
- Fortified dairy products
- Fortified cereals
Dietary Supplements
Vitamin D supplements are available as:
- Vitamin D2 (ergocalciferol)
- Vitamin D3 (cholecalciferol)
Supplementation is often necessary for individuals with inadequate sunlight exposure or increased risk of deficiency.
Vitamin D Metabolism
Vitamin D obtained from sunlight, food, or supplements is biologically inactive and requires activation through two hydroxylation steps.
Step 1: Hepatic Conversion
In the liver, vitamin D undergoes hydroxylation to form:
25-Hydroxyvitamin D [25(OH)D]
Also known as calcidiol, this is the major circulating form of vitamin D and the best indicator of vitamin D status.
Step 2: Renal Conversion
In the kidneys, 25(OH)D is converted by the enzyme 1-alpha-hydroxylase into:
1,25-Dihydroxyvitamin D [1,25(OH)2D]
Also known as calcitriol, this is the biologically active hormone responsible for the physiological effects of vitamin D.
Regulation of Vitamin D Activation
The activity of renal 1-alpha-hydroxylase is primarily regulated by:
Parathyroid Hormone (PTH)
Low serum calcium stimulates PTH secretion, which enhances the conversion of 25(OH)D to calcitriol.
Low Serum Phosphate
Hypophosphatemia also stimulates calcitriol production.
Other Hormonal Influences
Additional hormones involved include:
- Estrogen
- Prolactin
- Growth factors
When PTH levels are low and phosphate concentrations remain elevated, 25(OH)D may be converted into inactive metabolites rather than calcitriol.
Physiological Functions of Vitamin D
Enhancement of Calcium Absorption
Vitamin D increases calcium absorption from the small intestine, helping maintain adequate serum calcium concentrations.
Without sufficient vitamin D, only a limited proportion of dietary calcium is absorbed efficiently.
Phosphate Absorption
Vitamin D enhances intestinal phosphate absorption, which is essential for bone mineralization.
Bone Remodeling
Vitamin D acts together with parathyroid hormone to regulate bone turnover.
Its effects include:
- Stimulation of osteoclastic bone resorption when calcium demand is increased
- Promotion of bone mineralization
- Support of osteoblast function
Maintenance of Neuromuscular Function
Vitamin D contributes to:
- Muscle strength
- Neuromuscular coordination
- Reduction of fall risk in older adults
Target Organs of Vitamin D
The primary target organs include:
Small Intestine
Vitamin D increases absorption of:
- Calcium
- Phosphate
Bone
Vitamin D regulates:
- Bone remodeling
- Mineralization
- Calcium mobilization when required
Kidney
Vitamin D contributes to calcium and phosphate conservation through renal mechanisms.
Vitamin D Deficiency
Vitamin D deficiency develops when vitamin D intake, synthesis, absorption, or activation becomes insufficient to meet physiological demands.
Causes of Vitamin D Deficiency
Inadequate Sun Exposure
Common among:
- Housebound individuals
- Nursing home residents
- Individuals living in northern latitudes
Poor Dietary Intake
Low consumption of vitamin D-rich foods may contribute to deficiency.
Malabsorption Disorders
Examples include:
- Celiac disease
- Crohn disease
- Chronic pancreatitis
- Bariatric surgery
Liver Disease
Impaired hepatic hydroxylation reduces calcidiol formation.
Kidney Disease
Reduced renal activation limits calcitriol production.
Medications
Certain drugs interfere with vitamin D metabolism, including:
- Phenytoin
- Phenobarbital
- Carbamazepine
- Other enzyme-inducing antiepileptic medications
Clinical Manifestations of Vitamin D Deficiency
In Children
Deficiency may cause:
- Rickets
- Delayed growth
- Skeletal deformities
In Adults
Manifestations include:
- Osteomalacia
- Bone pain
- Muscle weakness
- Increased fracture risk
In Older Adults
Vitamin D deficiency contributes to:
- Falls
- Frailty
- Osteoporosis progression
Assessment of Vitamin D Status
Best Laboratory Test
The preferred test for assessing vitamin D status is:
Serum 25-Hydroxyvitamin D [25(OH)D]
This marker reflects vitamin D obtained from sunlight, food, and supplements.
Why Not Measure Calcitriol?
Although calcitriol is the active hormone, it has a very short half-life and may remain normal despite vitamin D deficiency.
Therefore, serum 1,25-dihydroxyvitamin D is not routinely used to assess vitamin D stores.
Interpretation of Vitamin D Levels
Commonly accepted serum 25(OH)D concentrations are:
| Vitamin D Status | Serum 25(OH)D |
|---|---|
| Deficiency | <30 nmol/L (<12 ng/mL) |
| Insufficiency | 30–49 nmol/L (12–19 ng/mL) |
| Sufficiency | ≥50 nmol/L (≥20 ng/mL) |
| Potential Excess | >125 nmol/L (>50 ng/mL) |
Some experts advocate maintaining levels above 75 nmol/L, although consensus remains under discussion.
Recommended Daily Vitamin D Intake
Current recommendations for healthy individuals are:
Adults 19–70 Years
- 600 IU (15 mcg) daily
Adults Over 70 Years
- 800 IU (20 mcg) daily
Higher-Risk Individuals
Patients with deficiency, obesity, malabsorption, or limited sun exposure may require higher doses under medical supervision.
Populations at Increased Risk of Deficiency
High-risk groups include:
- Older adults
- Institutionalized individuals
- People with limited sun exposure
- Individuals with darker skin pigmentation
- Patients with chronic kidney disease
- Patients with liver disease
- Individuals taking anticonvulsant medications
- Patients with gastrointestinal malabsorption disorders
Vitamin D Toxicity
Vitamin D toxicity is uncommon and usually results from excessive supplementation rather than sunlight exposure.
Symptoms
- Hypercalcemia
- Nausea
- Vomiting
- Polyuria
- Kidney stones
- Confusion
Prevention
Patients should avoid prolonged use of high-dose vitamin D supplements without medical monitoring.
Key Clinical Takeaways
- Vitamin D is essential for calcium and phosphate homeostasis.
- The two major forms are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol).
- Vitamin D undergoes activation in the liver and kidneys to form calcitriol.
- Parathyroid hormone is the primary regulator of calcitriol synthesis.
- The principal target organs are the small intestine, bone, and kidneys.
- Serum 25-hydroxyvitamin D is the best marker of vitamin D status.
- A serum concentration of at least 50 nmol/L (20 ng/mL) is considered sufficient for most individuals.
- Deficiency is common in older adults, individuals with limited sun exposure, and patients with chronic disease.
- Appropriate supplementation and monitoring help prevent skeletal complications.
Conclusion
Vitamin D is a critical regulator of calcium metabolism, bone health, and musculoskeletal function. Through its active metabolite, calcitriol, it enhances intestinal calcium absorption and supports normal bone remodeling. Because deficiency remains common worldwide, healthcare professionals should understand vitamin D metabolism, risk factors, laboratory assessment, and evidence-based supplementation strategies. Measuring serum 25-hydroxyvitamin D remains the most reliable method for evaluating vitamin D status and guiding clinical management.
References & More
- Chauhan K, Shahrokhi M, Huecker MR. Vitamin D. [Updated 2023 Apr 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441912/
- Kaur J, Khare S, Givler A. Vitamin D Deficiency. [Updated 2025 Feb 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532266/
- Bikle DD. Vitamin D: Production, Metabolism, and Mechanism of Action. [Updated 2025 Jun 15]. In: Feingold KR, Adler RA, Ahmed SF, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278935/
- Blom, A., Warwick, D., & Whitehouse, M. R. (2018). Apley & Solomon’s system of orthopaedics and trauma (10th ed.). CRC Press
