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It is officially summer in the northern hemisphere and, although COVID-19 is still a major concern in many parts of the world, progress has been made regarding vaccinations and reducing the positivity rate in several countries. We must not forget that it is still important to remain cautious in order to fully enjoy the warmer temperatures, but try to benefit from some safe outdoor activities! This is especially necessary if you have been in quarantine or lockdown for a large part of the year for one reason- vitamin D.

As you might have learnt at school, there is much more to laying out in the sun than getting a tan. In fact, one of the most crucial compounds in our bodies, vitamin D, is mainly synthesised from cholesterol with the action of UV light. A few foods such as oily fish, liver, egg yolks or fortified milk, contain vitamin D, but we do not eat enough of them to rely solely on this source. If you are interested in finding out about how we are able to produce this compound, its effects in the body and the consequences of having too much or too little vitamin D, keep reading!

Formation of vitamin D

There are two forms of vitamin D: D_{2} (ergocalciferol) and D_{3} (cholecalciferol). Only differing in their side chains, both have the same effects on the body once metabolised, but the former is more commonly found in artificial supplements, whereas the latter is the structure that our bodies make and can be found in other food sources.

We can make the active form of the vitamin thanks to several enzymes and the action of UVB light. Below you can see a diagram of the reactions involved in its synthesis.

The process begins with 7-dehydrocholesterol, a modified cholesterol (a steroid molecule that fortifies the cell membrane and can also be found in lipoproteins). The only difference is the presence of a second double bond at C7. This molecule undergoes a reaction under UV light which breaks open one of the rings (ring B), converting it into cholecalciferol, which is known as a pre-hormone. There is an additional step, a thermal isomerization reaction that transforms the molecule into a more linear structure.

Consequently, cholecalciferol is converted into 25-hydroxycholecalciferol in the liver, by 25-hydroxylase enzymes. Later on, in the kidney and other tissues, this compound is activated by further hydroxylations, leading to 1, 25-hydroxycholecalciferol. Lastly, another hydroxylase intervenes to form the active form of vitamin D (calcitriol), which can then be used in the cell’s metabolism. After three hydroxylations, the hormonal form of the vitamin is finally ready!

Molecular effects

This fat-soluble vitamin (meaning it is stored in adipocytes) is essential to regulate the amount of calcium and phosphate in the body. These minerals are necessary for bone growth and strength, which is why adequate amounts of them facilitate the formation of healthy bones. Other molecular effects of the vitamin include hormonal secretion and vasodilation.

Additionally, calcium is needed for a myriad of intracellular processes, namely those which involve secretion of a substance. Examples are muscle contraction and synapse in neurons.

On the other hand, phosphorus is one of the primary components of nucleotides. Recall that ATP, the main energy currency in the cell, is also a nucleotide and it relies on inorganic phosphate (PO^{-3}_{4}) to fuel almost every endergonic process in the body. These include the initial steps of glycolysis, cell movement, protein translation, active transport, etc.

The way that calcitriol maintains calcium levels is through three primary mechanisms. First of all, it increases the absorption of calcium across the length of the small intestine. Secondly, it stimulates the movement of calcium to bone to form osteoclasts (cells that break down bone tissue and are essential for the maintenance and repair of bone). Lastly, calcitriol acts in the kidneys to increase calcium reabsorption in the nephrons.

Less properly understood are the mechanisms by which the vitamin helps the absorption of phosphorus, but there seems to be negative feedback between low levels of phosphorous and increased production of calcitriol. You can read more about all the molecular effects of the vitamin here.

Insufficient vitamin: rickets

What happens if your vitamin D levels are below the recommended values (20 ng/mL-50 ng/mL)? If you are a child, you might develop rickets, a condition which causes bone malformation.

This was a very common disease in 17th century England and northern countries due to lack of exposure to sunlight in young children. Nowadays, it is rarer, but can occur if there are problems creating vitamin D.

If you are an adult, you might experience osteomalacia, which is a similar disease, also causing bone fragility and muscle pains. Other possible consequences of low vitamin D levels can include heart disease, high blood pressure, diabetes, infections, some types of cancer or even multiple sclerosis.

Excess vitamin: hypercalcemia

On the other side of the spectrum, you will find hypercalcemia, which is a disease caused by excessive levels of calcium in the blood. Remember that caclitriol helps the absorption of calcium and if there is too much of the vitamin, there will also be more calcium. This can cause bone weakness, kidney stones and even play a role in how your heart and brain work (including arrhythmias and neuropsychiatric conditions).


To sum up, vitamin D is a molecule that we can synthesise with help from the sun. The active form, calcitriol, is involved in many important processes, such as calcium and phosphorus homeostasis. These, in turn, promote proper bone growth and adequate intracellular communication, as well as facilitate crucial biochemical reactions. Some consequences of inadequate levels of this substance can cause rickets, osteomalacia (insufficiency) or hypercalcemia (excess).

Therefore, this summer, try to soak up some rays wherever you might be to allow your cells to synthesise this useful molecule. Important to note, though, is that while getting some sun is beneficial, too much sun without proper protection can cause diseases of the skin, including cancer (basal cell carcinoma, squamous cell carcinoma or melanoma). Most doctors recommend 10-15 minutes of sun exposure, several days a week to achieve healthy levels of vitamin D.


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Lilly Pubillones
Lilly Pubillones
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Trinity College Hartford

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