Colecalciferol

What Does Colecalciferol Do?

Colecalciferol, or Vitamin D3, primarily treats and prevents vitamin D deficiency and related conditions such as rickets, osteomalacia, and osteoporosis. This fat-soluble vitamin is pivotal in maintaining calcium balance and bone metabolism. Off-label uses include cancer treatment, multiple sclerosis and autoimmune diseases.

How Does Colecalciferol Work?

Colecalciferol is administered orally and undergoes two hydroxylation processes, one in the liver and another in the kidneys, to form the biologically active form of vitamin D. Hydroxylation is a chemical process that introduces a hydroxyl group (-OH) into an organic compound, usually by replacing a hydrogen atom. 

By binding to the vitamin D receptor, it regulates gene expression involved in calcium and phosphate metabolism, maintaining normal serum calcium levels essential for bone mineralisation and muscle function. The kidneys further process it into the biologically active Vitamin D (1,25-dihydroxyvitamin D). This then binds to receptors in intestines, bones, kidneys and parathyroid glands, thus regulating genes responsible for calcium and phosphate metabolism. 

The consequence of this process is that calcium absorption from the gut is increased, whilst kidney excretion of calcium is decreased, allowing for normal calcium levels, which is essential for bone and muscle functions.

Drug Type and Category of Colecalciferol

Cholecalciferol is a type of vitamin D that is classified as a dietary supplement and medication. It falls under the following drug categories:

• Alimentary Tract and Metabolism (ATC code A)
• Bone Density Conservation Agents
• Calcium-Regulating Hormones and Agents
• Cholecalciferol, antagonists & inhibitors
• Cholestanes
• Cholestenes
• Cytochrome P-450 CYP2C8 Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors

What dosage of Colecalciferol should you be taking?

According to the NICE guidelines, the recommended dosage of Colecalciferol depends on the severity of deficiency:

Deficiency (serum 25-hydroxyvitamin D < 25>

• Loading dose: 20,000 units per day for 15 days (total 300,000 units), then 20,000 units per month as maintenance ⁴
• Alternative loading dose: 800-2000 units daily for 6-10 weeks ^1,3

Insufficiency (serum 25-hydroxyvitamin D 25-50 nmol/L):

• Loading dose: 800-2000 units daily for 6-10 weeks ^1,3
• Maintenance: 800-1000 units daily ^4,5

Adequate (serum 25-hydroxyvitamin D > 50 nmol/L):

• No treatment needed, consider over-the-counter supplements ⁵

For children, the loading dose is:

• Age 1-5 months: 3,000 units daily for 8-12 weeks
• Age 6 months-11 years: 6,000 units daily for 8-12 weeks 
• Age 12-17 years: 10,000 units daily for 8-12 weeks ¹

The maintenance dose for children is 400-600 units daily. ^1,2 For infants and young children, a daily supplement of 340-400 units is recommended to prevent deficiency. ¹

What are the side-effects of too much Colecalciferol?

The most common side effects of cholecalciferol at normal doses are usually mild and may include:

• Nausea/vomiting
• Constipation
• Loss of appetite
• Weight loss
• Weakness
• Metallic taste in mouth

These side effects are more likely to occur with overdose. Signs of vitamin D overdose include:

• Increased thirst and urination
• Mental/mood changes
• Unusual tiredness
• Irregular heartbeat
• Muscle or bone pain

A very serious allergic reaction is rare but can occur. Seek immediate medical attention if you experience symptoms like rash, severe dizziness, trouble breathing, or swelling of the face/tongue/throat. 

Most experts recommend not exceeding 4,000 IU of vitamin D per day to avoid potential side effects. Bear in mind, this level is significantly lower than the loading doses suggested by NICE. Always follow dosage instructions and consult your doctor if you have any concerns. Vitamin D levels should be monitored with lab tests while taking supplements.

Drug Interactions

There are 76 medications known to interact with cholecalciferol. Of these, 11 are major interactions, 64 are moderate interactions, and 1 is a minor interaction. ^5,7

Some of the most frequently reported interactions include:

• Hydrochlorothiazide
• Digoxin
• Carbamazepine
• Aspirin
• Statins like atorvastatin and rosuvastatin
• Antidepressants like duloxetine and sertraline
• Anticoagulants like apixaban and warfarin
• Proton pump inhibitors like esomeprazole and pantoprazole

Cholecalciferol can also interact with certain disease states, including:

• Hyperparathyroidism
• Sarcoidosis
• Tuberculosis
• Lymphoma
• Renal failure

Patients taking cholecalciferol should be monitored for signs of hypercalcemia, and dosages may need to be adjusted when taken with interacting medications. ^6,8 

Natural Alternatives to Colecalciferol

The main natural alternatives to cholecalciferol are:

1. Sunlight exposure: When your skin is exposed to UV-B radiation from the sun, it can produce its own vitamin D. This is the most natural way to boost vitamin D levels. ¹⁰
2. Fatty fish and seafood: These are among the foods highest in vitamin D, though exact vitamin content may vary. Good sources include:

• Rainbow trout (645 IU per 3 oz serving, 81% DV) ¹³
• Sockeye salmon (570 IU per 3 oz, 71% DV) ¹³
• Sardines (200 IU per can) ¹³

3. Mushrooms: Mushrooms are the only vegetarian source of vitamin D. When exposed to UV light, they produce vitamin D2 and some D3. ^10,13
4. Fortified foods: Many foods are fortified with vitamin D, including cow's milk, plant-based milks, infant formula, breakfast cereal, yogurt, margarine, and orange juice. ^10,13 However, the vitamin D in these is usually D2 rather than D3. 
5. Ergocalciferol (vitamin D2): This is a plant-derived form of vitamin D that is typically vegan-friendly. It is available as a supplement and behaves similarly to D3 in the body, though D3 is slightly more potent. ^10,11

So in summary, the most natural ways to get vitamin D are through sun exposure, eating fatty fish, and consuming UV-exposed mushrooms. Fortified foods and D2 supplements are also options, especially for vegetarians and vegans. Consulting with a healthcare provider to check vitamin D levels can help determine if supplementation is needed.

It is worth noting that Vitamin D and Vitamin K2 can work concurrently to improve bone density. Some people believe that Vitamin K can help the absorption of Vitamin D, although this is not robust. 

Interesting facts about Colecalciferol

Colecalciferol belongs to a group of secosteroids, characterised by a broken ring structure. Its chemical formula is C27H44O. Cholecalciferol was first described in 1936. In 2024, it was the 8th most prescribed drug in the UK. 

Approximately 20-30% of the UK population are low on Vitamin D, and this percentage is higher in darker skinned people. It’s not clear why that may be. Our hypothesis is that people are inside for longer periods of time, and there’s more concern about overexposure of sunlight due to the rise of skin cancer. 

Disclaimer

This article is generated for informational purposes only. It was created in September 2024. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References:

1. https://www.nhs.uk/medicines/colecalciferol/how-and-when-to-take-colecalciferol/
2. https://bnfc.nice.org.uk/drugs/colecalciferol/
3. https://www.nice.org.uk/bnf-uk-only
4. https://www.panmerseyapc.nhs.uk/media/2146/vitamind_adult.pdf
5. https://www.covwarkformulary.nhs.uk/docs/chapter09/CG019-Vitamin D Guidelines.pdf
6. https://www.drugs.com/drug-interactions/cholecalciferol.html
7. https://www.webmd.com/drugs/2/drug-6152/cholecalciferol-vitamin-d3-oral/details
8. https://www.drugs.com/drug-interactions/cholecalciferol,vitamin-d3.html
9. https://go.drugbank.com/drugs/DB00169
10. https://bnf.nice.org.uk/interactions/colecalciferol/
11. https://www.drugs.com/compare/cholecalciferol
12. https://www.stlukes-stl.com/health-content/medicine/33/000340.htm
13. https://www.webmd.com/diet/foods-high-in-vitamin-d3
14. https://driphydration.com/blog/vitamin-d-sources-natural-synthetic/