Vitamin D3 (cholecalciferol) is the best form of vitamin D for absorption, consistently outperforming vitamin D2 (ergocalciferol) in raising and maintaining serum vitamin D levels. In the UK, where vitamin D deficiency remains a public health concern—particularly during autumn and winter—understanding which supplement form offers superior bioavailability is essential. Clinical evidence demonstrates that vitamin D3 has a higher binding affinity for vitamin D-binding protein, resulting in a longer half-life and more efficient conversion to the active form measured in blood tests. This article examines the scientific evidence behind vitamin D absorption, practical factors affecting uptake, and NHS-aligned guidance for optimal supplementation.

Understanding Vitamin D Forms and How They Work

Vitamin D is a fat-soluble vitamin essential for calcium absorption, bone health, immune function, and numerous physiological processes. In the United Kingdom, vitamin D deficiency remains a public health concern, particularly during autumn and winter months when sunlight exposure is limited. Understanding the different forms of vitamin D available is crucial for making informed decisions about supplementation.

The two primary forms of vitamin D used in supplements and fortified foods are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D2 is derived from plant sources and fungi, produced when ergosterol is exposed to ultraviolet light. Vitamin D3, conversely, is synthesised in human skin upon exposure to UVB radiation and is also found naturally in animal-based foods such as oily fish, egg yolks, and liver. Both forms undergo conversion in the body to become biologically active.

Once ingested or synthesised, both vitamin D2 and D3 are transported to the liver, where they are hydroxylated to form 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. This is the major circulating form measured in blood tests to assess vitamin D status. Subsequently, 25(OH)D travels to the kidneys and other tissues, where it undergoes further hydroxylation to produce 1,25-dihydroxyvitamin D [1,25(OH)2D], or calcitriol, the active hormonal form that regulates calcium homeostasis and exerts effects on gene expression.

In the UK, vitamin D medicines are regulated by the MHRA, while most over-the-counter vitamin D supplements are regulated as food supplements by the Food Standards Agency and Office for Product Safety and Standards. The NHS recommends that adults and children over 4 years consider taking 10 micrograms (400 IU) of vitamin D daily during autumn and winter. People with limited sun exposure or darker skin tones may need supplements year-round. Children aged 1-4 years should take 10 micrograms daily throughout the year, and breastfed infants should receive 8.5-10 micrograms daily unless they consume more than 500ml of infant formula.

Which Form of Vitamin D Is Best Absorbed by the Body?

Clinical evidence consistently demonstrates that vitamin D3 (cholecalciferol) is more effective than vitamin D2 (ergocalciferol) at raising and maintaining serum 25(OH)D concentrations. Multiple randomised controlled trials have shown that vitamin D3 produces a greater and more sustained increase in circulating vitamin D levels compared to equivalent doses of vitamin D2. This difference becomes particularly pronounced with higher doses and longer supplementation periods, though the magnitude varies depending on dosing regimen and duration.

The superior efficacy of vitamin D3 relates to its pharmacokinetic properties. Vitamin D3 has a higher binding affinity for vitamin D-binding protein (DBP), the carrier protein that transports vitamin D metabolites in the bloodstream. This enhanced binding results in a longer half-life and more efficient conversion to 25(OH)D in the liver. Research suggests that vitamin D2 may be metabolised more rapidly and cleared from circulation faster than vitamin D3, contributing to its reduced potency.

Systematic reviews and meta-analyses published in peer-reviewed journals have concluded that vitamin D3 is more effective than vitamin D2 in raising serum 25(OH)D levels. However, it is important to note that both forms can effectively prevent and treat vitamin D deficiency when administered in appropriate doses. The choice between D2 and D3 may also be influenced by dietary preferences, as vitamin D2 is suitable for vegetarians and vegans, whilst D3 is typically derived from animal sources (though vegan D3 from lichen is now available).

UK clinical practice generally favours vitamin D3 (colecalciferol) over vitamin D2 (ergocalciferol) for supplementation and treatment of deficiency, as reflected in NICE Clinical Knowledge Summaries and the British National Formulary. For individuals requiring therapeutic doses to correct deficiency, vitamin D3 formulations are typically recommended by healthcare professionals due to their superior bioavailability and sustained effect on vitamin D status.

Factors That Affect Vitamin D Absorption

Vitamin D absorption is influenced by multiple physiological, dietary, and pharmaceutical factors that can significantly impact the effectiveness of supplementation. As a fat-soluble vitamin, vitamin D requires dietary fat for optimal absorption in the small intestine. Research suggests that taking vitamin D supplements with a meal containing fat can enhance absorption compared to taking them on an empty stomach. Even a modest amount of fat appears sufficient to improve bioavailability.

Gastrointestinal conditions that impair fat absorption can substantially reduce vitamin D uptake. Patients with coeliac disease, Crohn's disease, ulcerative colitis, chronic pancreatitis, or those who have undergone bariatric surgery may experience malabsorption. Conditions affecting bile production or secretion, such as cholestatic liver disease or biliary obstruction, also compromise vitamin D absorption since bile salts are essential for emulsifying fat-soluble vitamins. These individuals often require higher supplementation doses and regular monitoring of serum 25(OH)D levels.

Body composition plays a significant role in vitamin D status. Obesity is associated with lower circulating 25(OH)D concentrations, likely due to sequestration of vitamin D in adipose tissue and volumetric dilution. Individuals with a higher body mass index may require higher doses to achieve adequate serum levels, and monitoring may be needed under clinical guidance. Conversely, age-related changes in skin synthesis capacity and reduced renal conversion efficiency mean that elderly individuals may also need higher supplementation doses.

Medication interactions can affect vitamin D metabolism and absorption. Certain drugs, including some anticonvulsants (phenytoin, carbamazepine), glucocorticoids, and medications that interfere with fat absorption (such as orlistat or cholestyramine), can reduce vitamin D bioavailability or accelerate its catabolism. Patients taking these medications should discuss appropriate supplementation strategies with their GP or pharmacist. Regular monitoring may be warranted to ensure therapeutic vitamin D levels are maintained.

How to Take Vitamin D for Maximum Absorption

To optimise vitamin D absorption and maintain adequate serum levels, several practical strategies should be considered. Timing and dietary context are particularly important. Taking vitamin D supplements with a meal containing some fat maximises absorption. Research indicates that absorption is enhanced when vitamin D is consumed with foods containing healthy fats such as avocado, nuts, olive oil, oily fish, or full-fat dairy products. There is no evidence that time of day affects absorption, so the focus should be on consistency and taking the supplement with food.

Dosage and formulation considerations are equally important. Public Health England recommends that adults and children over 4 years consider taking a daily supplement containing 10 micrograms (400 IU) of vitamin D, particularly during autumn and winter. Individuals with limited sun exposure or darker skin tones may need supplements year-round. Children aged 1-4 years should take 10 micrograms daily throughout the year, and breastfed infants should receive 8.5-10 micrograms daily unless they consume more than 500ml of infant formula. Vitamin D is available in various formulations including tablets, capsules, oral sprays, and liquid drops. Liquid formulations may offer advantages for individuals with swallowing difficulties or malabsorption issues, though there is limited evidence that they are inherently better absorbed than tablets when taken with food.

Consistency and monitoring are key to maintaining optimal vitamin D status. Daily, weekly, or monthly regimens providing an equivalent total dose are all acceptable in UK practice, though very high single bolus doses should be avoided, particularly in older adults. If you are taking therapeutic doses to correct deficiency, this should be under clinical supervision. UK treatment regimens typically involve a total loading dose of approximately 300,000 IU over 6-10 weeks, followed by a maintenance dose. Your GP may arrange follow-up blood tests to assess response and adjust dosing if clinically indicated.

Safety considerations should not be overlooked. The tolerable upper intake level for adults is 100 micrograms (4,000 IU) daily, and this should not be exceeded without medical supervision. Vitamin D toxicity is rare and usually associated with substantially higher intakes over prolonged periods. Symptoms of toxicity include hypercalcaemia, nausea, weakness, and kidney problems. Be careful not to take multiple vitamin D-containing products concurrently (such as multivitamins and separate vitamin D supplements). Always follow dosing recommendations from your healthcare provider, and contact your GP if you experience unusual symptoms whilst taking vitamin D supplements. Individuals with certain medical conditions, including sarcoidosis, hyperparathyroidism, or kidney disease, should seek medical advice before commencing supplementation. If you suspect an adverse reaction to a vitamin D medicine, you can report this through the MHRA Yellow Card scheme.

Frequently Asked Questions