Cholecalciferol, also known as vitamin D3 and colecalciferol, is a
type of vitamin D which is made by the skin, found in some foods, and
taken as a dietary supplement. It is used to treat and prevent
vitamin D deficiency and associated diseases, including rickets.
It is also used for familial hypophosphatemia, hypoparathyroidism that
is causing low blood calcium, and Fanconi syndrome. It is
usually taken by mouth.
Excessive doses can result in vomiting, constipation, weakness, and
confusion. Other risks include kidney stones. Normal doses are
safe in pregnancy. It may not be effective in people with severe
Cholecalciferol is made in the skin following UVB light exposure.
It is converted into calcifediol (25-hydroxyvitamin D) by the liver
and into calcitriol (1,25-dihydroxyvitamin D) by the kidney. One of
its actions is to increase the uptake of calcium by the intestines.
It is found in food such as some fish, cheese, and eggs. Certain
foods such as milk have cholecalciferol added to them in some
Cholecalciferol was first described in 1936. It is on the World
Health Organization's List of Essential Medicines, the most effective
and safe medicines needed in a health system.
available as a generic medication and over the counter. The
wholesale cost in the
Costa Rica is about 2.15 USD per 30 ml bottle of
10,000 IU/ml. In the United States treatment costs less than 25
USD per month.
1 Medical uses
Vitamin D deficiency
1.2 Other disease
2.2 Mechanism of action
3 Industrial production
5 Use as rodenticide
7 See also
9 External links
Vitamin D deficiency
Vitamin D deficiency
Cholecalciferol is a form of vitamin D which is naturally synthesized
in skin and functions as a pro-hormone, being converted to calcitriol.
This is important for maintaining calcium levels and promoting bone
health and development. As a medication, cholecalciferol may be
taken as a dietary supplement to prevent or to treat vitamin D
deficiency. One gram is 40,000,000 (40x106) IU, equivalently 1 IU is
0.025 µg. Dietary reference intake values for vitamin D
(cholecalciferol and/or ergocalciferol) have been established and
recommendations vary depending on the country:
In the US: 15 µg/d (600 IU per day) for all individuals (males,
female, pregnant/lactating women) between the ages of 1 and 70 years
old, inclusive. For all individuals older than 70 years, 20 µg/d
(800 IU per day) is recommended.
In the EU: 20 µg/d (800 IU per day)
In France: 25 µg/d (1000 IU per day)
Many question whether the current recommended intake is sufficient to
meet physiological needs. Individuals without regular sun exposure,
the obese, and darker skinned individuals all have lower blood levels
and require more supplementation.
The Institute of Medicine in 2010 recommended a maximum uptake of
vitamin D of 4,000 IU/day, finding that the dose for lowest observed
adverse effect level is 40,000 IU daily for at least 12 weeks, and
that there was a single case of toxicity above 10,000 IU after more
than 7 years of daily intake; this case of toxicity occurred in
circumstances that have led other researchers to dispute it as a
credible case to consider when making vitamin D intake
recommendations. Patients with severe vitamin D deficiency will
require treatment with a loading dose; its magnitude can be calculated
based on the actual serum 25-hydroxy-vitamin D level and body
There are conflicting reports concerning the relative effectiveness of
cholecalciferol (D3) versus ergocalciferol (D2), with some studies
suggesting less efficacy of D2, and others showing no difference.
There are differences in absorption, binding and inactivation of the
two forms, with evidence usually favoring cholecalciferol in raising
levels in blood, although more research is needed.
A much less common use of cholecalciferol therapy in rickets utilizes
a single large dose and has been called stoss therapy.
Treatment is given either orally or by intramuscular injection of
300,000 IU (7,500 µg) to 500,000 IU (12,500 µg =
12.5 mg), in a single dose, or sometimes in two to four divided
doses. There are concerns about the safety of such large doses.
A meta-analysis of 2007 concluded that daily intake of 1000 to 2000 IU
per day of vitamin D3 could reduce the incidence of colorectal cancer
with minimal risk. Also a 2008 study published in Cancer Research
has shown the addition of vitamin D3 (along with calcium) to the diet
of some mice fed a regimen similar in nutritional content to a new
Western diet with 1000 IU cholecalciferol per day prevented colon
cancer development. In humans, with 400 IU daily, there was no
effect of cholecalciferol supplements on the risk of colorectal
Supplements are not recommended for prevention of cancer as any
effects of cholecalciferol are very small. Although significant
correlations exist between low levels of blood serum cholecalciferol
and higher rates of various cancers, multiple sclerosis, tuberculosis,
heart disease, and diabetes, the consensus is that supplementing
levels is not beneficial.
Cholecalciferol is one of the five forms of vitamin D.
Cholecalciferol is a secosteroid, that is, a steroid molecule with one
Mechanism of action
By itself cholecalciferol is inactive. It is converted to its active
form by two hydroxylations: the first in the liver to form
25-hydroxycholecalciferol (calcifediol, 25-OH vitamin D3), and the
second in the kidney, to form 1,25-dihydroxycholecalciferol
(calcitriol, 1,25-(OH)2vitamin D3). All these metabolites are bound in
blood to the vitamin D-binding protein. The action of calcitriol is
mediated by the vitamin D receptor, a nuclear receptor which regulates
the synthesis of hundreds of enzymes and is present in virtually every
cell in the body.
Click on icon in lower right corner to open. Click on genes, proteins
and metabolites below to link to respective articles. [§ 1]
Vitamin D Synthesis Pathway (view / edit)]]
Vitamin D Synthesis Pathway (view / edit)
^ The interactive pathway map can be edited at WikiPathways:
7-Dehydrocholesterol is the precursor of cholecalciferol. Within
the epidermal layer of skin,
7-Dehydrocholesterol undergoes an
electrocyclic reaction as a result of UVB light at wavelengths between
290 and 315 nm, with peak synthesis occurring between 295 and
300 nm. This results in the opening of the vitamin precursor
B-ring through a conrotatory pathway making previtamin D3
(pre-cholecalciferol). In a process which is independent of UV
light, the pre-cholecalciferol then undergoes a [1,7] antarafacial
sigmatropic rearrangement  and therein finally isomerizes to form
The active UVB wavelengths are present in sunlight, and sufficient
amounts of cholecalciferol can be produced with moderate exposure of
the skin, depending on the strength of the sun. Time of day,
season, and altitude affect the strength of the sun, and pollution,
cloud cover or glass all reduce the amount of UVB exposure. Exposure
of face, arms and legs, averaging 5–30 minutes twice per week, may
be sufficient, but the darker the skin, and the weaker the sunlight,
the more minutes of exposure are needed.
Vitamin D overdose is
impossible from UV exposure; the skin reaches an equilibrium where the
vitamin degrades as fast as it is created.
Cholecalciferol can be produced in skin from the light emitted by the
UV lamps in tanning beds, which produce ultraviolet primarily in the
UVA spectrum, but typically produce 4% to 10% of the total UV
emissions as UVB. Levels in blood are higher in frequent uses of
Whether cholecalciferol and all forms of vitamin D are by definition
"vitamins" can be disputed, since the definition of vitamins includes
that the substance cannot be synthesized by the body and must be
Cholecalciferol is synthesized by the body during UVB
The three steps in the synthesis and activation of vitamin D3 are
regulated as follows:
Cholecalciferol is synthesized in the skin from 7-dehydrocholesterol
under the action of ultraviolet B (UVB) light. It reaches an
equilibrium after several minutes depending on the intensity of the
UVB in the sunlight - determined by latitude, season, cloud cover, and
altitude - and the age and degree of pigmentation of the skin.
Hydroxylation in the endoplasmic reticulum of liver hepatocytes of
cholecalciferol to calcifediol (25-hydroxycholecalciferol) by
25-hydroxylase is loosely regulated, if at all, and blood levels of
this molecule largely reflect the amount of cholecalciferol produced
in the skin combined with any vitamin D2 or D3 ingested.
Hydroxylation in the kidneys of calcifediol to calcitriol by
1-alpha-hydroxylase is tightly regulated: it is stimulated by
parathyroid hormone and serves as the major control point in the
production of the active circulating hormone calcitriol
Cholecalciferol is produced industrially for use in vitamin
supplements and to fortify foods. As a pharmaceutical drug it is
called cholecalciferol (USAN) or colecalciferol (INN, BAN). It is
produced by the ultraviolet irradiation of 7-dehydrocholesterol
extracted from lanolin found in sheep's wool.
extracted from wool grease and wool wax alcohols obtained from the
cleaning of wool after shearing. The cholesterol undergoes a four-step
process to make 7-dehydrocholesterol, the same compound that is
produced in the skin of animals. The
7-dehydrocholesterol is then
irradiated with ultraviolet light. Some unwanted isomers are formed
during irradiation: these are removed by various techniques, leaving a
resin which melts at about room temperature and usually has a potency
of 25,000,000 to 30,000,000 International Units per gram.
Cholecalciferol is also produced industrially for use in vitamin
supplements from lichens, which is suitable for vegans.
Cholecalciferol is very sensitive to UV radiation and will rapidly,
but reversibly, break down to form sura-sterols, which can further
irreversibly convert to ergosterol.
Use as rodenticide
Rodents are somewhat more susceptible to high doses than other
species, and cholecalciferol has been used in poison bait for the
control of these pests. It has been claimed that the compound is less
toxic to non-target species. However, in practice it has been found
that use of cholecalciferol in rodenticides represents a significant
hazard to other animals, such as dogs and cats. "Cholecalciferol
produces hypercalcemia, which results in systemic calcification of
soft tissue, leading to renal failure, cardiac abnormalities,
hypertension, CNS depression, and GI upset. Signs generally develop
within 18-36 hr of ingestion and can include depression, anorexia,
polyuria, and polydipsia."
In New Zealand, possums have become a significant pest animal, and
cholecalciferol has been used as the active ingredient in lethal gel
baits and cereal pellet baits "DECAL" for possum control. The LD50 is
16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added
to the bait. Kidneys and heart are target organs.
The wholesale cost of cholecalciferol in
Costa Rica was 2.15 USD per
30 ml bottle of 10,000 IU/ml in 2015.
In the United States, treatment of vitamin D deficiency cost on
average less than 25 USD per month in 2015.
Vitamin D poisoning
Ergocalciferol, vitamin D2.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase, a kidney enzyme that
converts calcifediol to calcitriol.
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Vitamin D metabolism, sex hormones, and male reproductive function.
Pyridoxine#, Pyridoxal phosphate
‡Withdrawn from market
§Never to phase III
Cholestanes, membrane lipids: sterols
Types of Terpenes and Terpenoids (# of isoprene units)
Acyclic (linear, cis and trans forms)
Monocyclic (single ring)
Bicyclic (2 rings)
Iridoids (cyclopentane ring)
Iridoid glycosides (iridoids bound to a sugar)
Steroids (4 rings)
Pinene (β and α
Cholecalciferol (Vit D)
sap, resins, latex of many plants, e.g. rubber
Terpene synthase enzymes (many), having in common a
Terpene synthase N
terminal domain (protein domain)
Activated isoprene forms
Isopentenyl pyrophosphate (IPP)
Dimethylallyl pyrophosphate (DMAPP)
Vitamin D receptor modulators
Cholecalciferol (vitamin D3)
Ergocalciferol (vitamin D2)
Nuclear receptor modulators
Pharmacy and pharmacology port