What is the speciality in Vitamin D?

speciality in Vitamin D

Among the vitamins that are essential to the body, vitamin D plays a major role. It is a fat-soluble vitamin. Also, there are several water-soluble vitamins too. Have you ever wondered how these vitamins are synthesized or how they are absorbed inside the body? Well, let’s have a look at how vitamin D is synthesized and worked inside the body.

There are 5 members in the vitamin D family. They can also be called “vitamers”. In common all of them are secosteroids which can be simply explained as steroids with on broken bond. The 5 members of the family can be named vitamin D1, D2, D3, D4, and D5. Out of these,

  • Vit D1 is a compound that has ergocalciferol and lumisterol in a 1:1 ratio.
  • Vit D2 is a compound that is known as ergocalciferol as well. It is synthesized majorly by plants, invertebrates, and fungi.
  • Vit D3 is a compound that is also known as cholecalciferol. It is synthesized by the skin when exposed to UV rays of sunlight. When looking into depth, it is synthesized by the reaction of 7-dehydrocholesterol with UVB rays of the sunlight. Many animals including us, humans synthesize vitamin D3 via the skin.
  • Vit D4 is a compound that is also known as 22-dihydroergocalciferol.
  • Vit D5 is a compound which is also known as sitocalciferol and it is an analog created from 7-dehydrositosterol.

When we look deeply into the synthetic analogs of vitamin D, it has a complicated path. 22-oxacalcitriol is the first analog found to have a wider therapeutic window that 1,25dihydroxycholecalciferol. Calcipotriol is derived from calcitriol. Dihydrotachysterol is a synthetic form of vitamin D that many consider superior to natural D2 and D3. It is activated by the liver without passing through hydroxylation in the kidneys. Paricalcitol which is also known as 19-norD2 is also derived from calcitriol. Tacalcitol is a derivative of vit D3. Doxercalciferol (1α(OH)D2) is a prodrug and it has to be activated in vivo. It is less toxic than 1α(OH)D3 when administered chronically. Falecalcitriol (1,25(OH)2-26,27-F6-D3) is approved for secondary hyperparathyroidism in japan. Sounds complicated, isn’t it? Let’s see how we get them from our day-to-day food sources.

What are the food sources rich with vitamin D?

The recommended dose of vitamin D is indicated in Dietary Reference Intakes (DRI). Which is developed by the expert committee of NASEM. The values can differ according to your age, gender, and the disease conditions such as hepatic and kidney disorders.

0-12 months 10mcg (400IU)
1-13 years 15mcg (600IU)
14-18 years 15mcg (600IU)
19-50 years 15mcg (600IU)
Pregnancy and lactation women 15mcg (600IU)
51-70 years15mcg (600IU)
Above 70 years 20mcg (800IU)

Vitamin D2 is rich in plant products and vitamin D3 is rich in animal products. When considering the sources that are rich with it, some food items come into consideration.

  • Fish oil :
    • Cod liver oil contains 450IU, which is 75% of a person’s recommended daily dose
    • Herring contains 306IU per fillet which is 51% of a person’s recommended daily dose
    • Swordfish contains 706IU per piece which contains 117% of a person’s recommended daily dose.
  • Mushrooms
    • Raw mistake mushrooms contain 562IU per 50g which is 94% of a person’s recommended daily dose
    • Dried shiitake mushrooms contain 77IU per 50g which is 12% of a person’s recommended daily dose
    • UV exposed raw Portobello mushrooms contain 568IU per 50g, which is 95% of a person’s recommended daily dose
    • Uv exposed raw white mushrooms contain 523IU per 50g which is 87% of a person’s recommended daily dose.
  • Egg yolk (free-range chicken eggs are observed for having high amounts of vitamin D than farm eggs. 2 eggs contain 88IU which is 15% of a person’s recommended daily dose.
  • Fortified foods :
    • Milk
    • Orange juice
    • Cereals

How is vitamin D metabolized inside the body?

As you already know Vit D3 can be synthesized by ourselves without taking it from outside food sources. It is interesting to know that we can make our vitamins. Let’s see how it happens. It is synthesized in the epidermis as an inactive vitamer and later metabolized in the liver to become activated. Under the irradiation of UV rays between 290-310 wavelength, the pre D3 is formed. Further irradiation of UV rays converts preD3 into luisterol and tachysterol.

 This product can be altered by the amount of melanin in the skin, the period you have been exposed to UV rays, and the intensity of the UV rays you expose to. As the production of preD3 reaches a maximum level, the biologically inactive lumisterol continues to accumulate with continued UV exposure. The formation of lumisterol is reversible which can be converted back to preD3 as preD3 concentration falls. (Luisterol ßà preD3) Therefore vitamin D toxicity never occurs even though you stand in the sun for too long.

But if you have got darker skin, the amount of preD3 produced can be reduced. Excess exposure to sunlight enhances your melanin pigmentation as well. This is also a mechanism that you won’t get toxicity. Because of this very reason the studies have been done in different countries, different climates, and different groups of people. And the results have shown way different levels of preD3 production from one another.

After the production of the preD3 by the skin, the next step happens in the liver. This step is common for both vitD3 as well as vitD2. As the first step, the hydroxylation of vitD2 and D3 to 250HD happens with the help of hepatic enzymes such as 25-hydroxylase and triol27-hydroxylase. Normally 250HD is the major form of them that circulates in the blood. 25-hydroxylase is a high-capacity low-affinity enzyme. The 1αOH derivatives of vitamin D are more rapidly hydroxylated than the parent compounds.

After the hydroxylation, 1,25(OH)D is produced from 25OHD by the enzyme 25OHD-1α hydroxylase. This product is the most potent form of vitamin D inside the body. The kidney is also in the business as the liver in the same importance. It produces the second most important product, 24,25(OH)2D. the enzyme responsible for this conversion is 25OHD-24 hydroxylase. In some tissues 24,25(OH)2D has shown a different biological effect from 1,25(OH)2D.

How is vitamin D transported inside the body?

There are two methods of transportation of vitamin D derivatives in the blood. And they are,

  • By binding to albumin proteins in the blood plasma.
  • As free particles in the plasma

A higher concentration (85-88%) of vitamin D transports in the blood by binding with the albumin proteins in the plasma. In a normal adult body, the concentration of vitamin D bound proteins (DBP) is approximately 4-8Mm. DBP has a high affinity for its metabolites such that under normal conditions only about 0.03% 25OHD and 24,25(OH)2D and 0.4% 1,25(OH)2D are free.

Some disease conditions such as nephrotic syndrome result from a reduced DBP level. Vitamin D intoxication can increase the concentration sufficiently to increase the free concentration of 1,25(OH)2D and also may cause hypercalcemia without necessarily raising the total concentration.

It is a fact that the cellular uptake is higher for the free-moving drugs than the protein-bound drugs. Certain tissues such as kidneys, placenta, and parathyroid gland express the megalin/cubilin complex which can transport vitamin D metabolites bound to DBP into the cell. However, in patients with liver diseases, the free concentration of 25OHD and 1,25(OH)2D are normal.

What is the mechanism of action of vitamin D in the body?

As you know, Vit D2 can be found in many food sources as well as dietary supplements. Vit D3 is adequately synthesized by our skin. Its principal function is the regulation of the calcium and phosphate concentrations in the blood. It enhances the efficacy of absorption calcium and phosphate by the small intestine. The 1,25-dihydroxy vitamin D made in the kidneys bind to endogenous vitamin D receptors. This binding results in many regulatory functions such as

  • Maintaining calcium balance
  • Regulation of parathyroid hormones
  • Promotion of the renal absorption of calcium
  • Increased intestinal absorption of calcium and phosphorous
  • Increased calcium and phosphorous mobilization from plasma to bones to balance the concentrations of the plasma calcium and phosphorous.

Calcitriol interacts with VDR in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from 10-15% to 80% gradually. Calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor Kb ligand which subsequently interacts with the receptor activator of nuclear factor Kb on immature preosteoclasts, maturing them to bone-resorbing osteoblasts. Mature osteoblasts function by removing calcium and phosphorous from bones to maintain blood calcium and phosphorous levels. Calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys.

What is vitamin D deficiency?

Vitamin D deficiency occurs when you don’t have a normal level of calcium and phosphorous for a prolonged time. This can be occurred by inadequate intake of food that are rich with it, malabsorption syndromes, hepatic disorders, kidney diseases, not enough exposure to sunlight, etc. the most common risk factors for vitamin D deficiency are known to be,

  • Having a dark skin/ high melanin pigmentation
  • Being elderly or old aged
  • Being overweight/ obese
  • Not taking adequate amounts of dairy products or fish
  • Living far from the equator where there is no enough sunlight around the year
  • Always using sunscreen when going outside/ staying indoors
  • Intestinal surgeries and malabsorption disorders
  • Living in high latitudes
  • Winter season
  • Air pollution
  • Medications such as antiepileptic, HAART, corticosteroids, rifampicin, st john’s wart
  • Liver failure
  • Renal failure
  • Hepatic and kidney diseases such as nephrotic syndrome
  • Intestinal malabsorption caused by,
    • IBD
    • Cystic fibrosis
    • Celiac diseases
    • Bile insufficiency
    • Gastric bypass surgery
    • Cholestyramine
    • olestra

Anyways how can you know if you are deficient in vitamin D? well, there are some symptoms that you have to be aware of. Those are, getting sick or infected often, fatigue, bone and back pain, depression, impaired wound healing, bone loss, hair loss, muscle pain, etc.

How can you get infected often with deficient vitamin D? It is very important in keeping your immune system strong. Even in viruses, bacteria, protozoan, and fungal infections, you can fight against it with a strong immunity by having vitamin D. also you can be chronic fatigue with headache and dizziness because of it. The levels under 20ng/ml are considered deficient. Also as the low levels of vitamin D in the blood, stimulates the resorption of calcium and phosphorous from the bones. Bone pain and lower back pain may be signs of inadequate vitamin D levels in the blood. Depression is also occurred by its deficiency. This has been proven by the studies of deficient people who live in countries that have seasonal changes. Slow wound healing is also a sign of vitamin D deficiency. As it plays an important role in calcium and phosphorous metabolism when a person is deficient in vitamin D the bone resorption occurs. And for this very reason, bone loss has occurred.

What are the disease conditions associated with vitamin D deficiency?

As vitamin D deficiency leads to loss of bone density, it can cause bone fractures. And also in adults, osteomalacia and osteoporosis are common. Osteomalacia and osteoporosis cause weak bones, bone pain, and muscle weakness. In children, vitamin D deficiency can lead to rickets conditions. In rickets condition, the bones become soft and bending. In addition to these diseases, researchers have shown that the conditions like diabetes, high blood pressure, cancer, and autoimmune conditions such as multiple sclerosis can occur.  Its deficiency is common in patients with Parkinson’s disease, Alzheimer’s disease, schizophrenia, depression, anxiety disorders, dementia, and older adults with cognitive decline. Also, vitamin D deficiency in infants can cause skeletal deformities.

  • Neuropsychiatric disorders
    • Schizophrenia
    • Major depressive disorder
    • Neurodegenerative disorders
  • Infections
    • Respiratory infections
    • COVID’19
    • Sepsis
    • Tuberculosis
  • Hypertension
  • Cardiovascular diseases
  • T2DM
  • Muscle pain
  • Proximal muscle weakness
  • Rickets
  • Osteomalacia
  • Osteoporosis
  • Osteoarthritis
  • Skin diseases
    • Epidermolytic ichthyosis
    • Autosomal recessive congenital ichthyosis
  • Allergic diseases
    • Asthma
    • Wheezing
    • Urticarial
    • Atopic dermatitis
  • Autoimmune diseases
    • RA
    • IBD
    • T1DM
    • MS
    • Psoriasis and P5A
    • Vitiligo
  • Cancers
    • Breast
    • Colon
    • Prostate
    • Etc.

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