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Nonclassical Actions of Vitamin D

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Nonclassical Actions of Vitamin D

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Vitamin D is a nutrient as well as a hormone. Apart from its classical actions, several novel actions of vitamin D have also been found. Read further.

Written by

Dr. Asna Fatma

Medically reviewed by

Dr. Kaushal Bhavsar

Published At July 15, 2022
Reviewed AtJune 29, 2023

Introduction:

Vitamin D is a fat-soluble vitamin as well as a hormone that our body produces. Vitamin D is mostly produced in the skin from sunlight, and some amount of it is absorbed from food. About ten percent of the total vitamin D is absorbed from the diet. The primary function of vitamin D is to increase the intestinal absorption of calcium, magnesium, phosphate, etc. Studies suggest that vitamin D also helps in controlling infections and reducing inflammation along with fighting cancer cells.

Vitamin D is a group of compounds, and the most important compounds in this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D plays a crucial role in calcium homeostasis and metabolism. Since vitamin D can be synthesized by most mammals from sunlight, it is not necessarily a hormone. In fact, it can be classified as a hormone. Cholecalciferol is converted into calcifediol which is further hydroxylated by the kidneys and some immune cells to form calcitriol. It is the biologically active form of vitamin D, and this calcitriol circulates in the blood in the form of a hormone.

How Is Vitamin D Produced?

Apart from being absorbed from a healthy diet, vitamin D is photochemically produced in the skin when it is exposed to sunlight. The skin consists of two primary layers; the dermis (inner layer) and the epidermis (outer and thinner layer). Vitamin D is produced in the keratin-producing cells (keratinocytes) present in the epidermis. The keratinocytes present in the stratum basale and stratum spinosum of the epidermis produce vitamin D.

What Is the Mechanism of Action of Vitamin D?

Whether ingested as a supplement or photosynthesized in the skin, vitamin D is carried to the liver via blood, where it is converted into the prohormone calcifediol. This circulating calcifediol is then hydroxylated into calcitriol (the biologically active form of vitamin D) by the kidneys.

What Are the Nonclassical Actions of Vitamin D?

Apart from the general functions associated with calcium absorption and metabolism, there are several other functions carried out by vitamin D. The nonclassical actions of vitamin D can be broadly classified into three groups:

  1. Regulation of hormone secretion.

  2. Regulation of immune function.

  3. Regulation of cellular proliferation and differentiation.

There may be more nonclassical actions of vitamin D apart from the ones mentioned above.

1. Regulation of Hormone Secretion: Vitamin D has the ability to regulate hormone secretion, which plays a key role in maintaining normal bone mineral homeostasis. The hormones affected by vitamin D are:

  • Parathyroid Hormone: Vitamin D inhibits the production and secretion of parathyroid hormone. Vitamin D also prevents the proliferation of parathyroid glands. The thyroid gland contains a negative vitamin D response element (a type of DNA sequence) through which it exerts suppression. The active form of vitamin D represses the parathyroid gene transcription and blocks parathyroid principal cell hyperplasia (enlargement due to an increased rate of reproduction of cells). Therefore, when the vitamin D concentration is low in the body, calcium absorption in the intestine also diminishes, leading to low calcium levels in the blood. As a result, the parathyroid gland becomes overactive and produces more parathyroid hormone. Therefore, vitamin D is an integral tool for treating secondary hyperparathyroidism in patients with renal diseases.

  • Insulin: Several studies have shown a link between vitamin D deficiency and insulin resistance. Vitamin D plays a vital role in developing insulin resistance and the pathogenesis of type 2 diabetes mellitus. Vitamin D affects insulin sensitivity and beta-cell functions. Vitamin D reduces insulin resistance due to its effect on calcium and phosphorus metabolism and through the regulation of insulin receptor genes. A number of studies have shown that vitamin D supplements have increased insulin sensitivity.

  • Fibroblast Growth Factor-23 (FGF23): Fibroblast growth factor 23 is primarily produced in the bones by the osteoblasts and osteocytes (bone-forming and bone-resorbing cells). FGF23 also plays a crucial role in vitamin D metabolism; it inhibits vitamin D production by the kidneys, thus forming a feedback loop. This feedback loop helps maintain a balance in these hormones' levels.

2. Regulation of Immune Function: The active form of vitamin D to regulate the body's immunological response has been discovered. Vitamin D is essential in regulating innate and adaptive immunity, influencing multiple clinical conditions. Innate immunity is the body's defense response with which an individual is born. In contrast, adaptive immunity results from exposure to a disease organism that triggers the immune system to form antibodies against that disease.

3. Regulation of Proliferation and Differentiation: Vitamin D affects cellular proliferation by modulating various processes, including apoptosis (physiologic and programmed death of a cell in an organism), cell cycle progression, and differentiation in a cell-specific manner. The anti-proliferative and pro- differentiation actions of vitamin D are also beneficial in preventing cancer to an extent. Studies have reported that vitamin D has been found to have several actions that might slow or prevent cancer cell growth. To prevent cancer, vitamin D promotes cell differentiation, decreases the growth of cancer cells, stimulates apoptosis, and reduces tumor blood vessel formation.

What Are the Other Functions of Vitamin D?

There are a few other nonclassical actions of vitamin D, including:

  • Xenobiotic (substance that is synthetic or foreign to the body) detoxification.

  • Oxidative stress reduction.

  • Neuroprotective functions.

  • Antimicrobial defense.

  • Immunoregulation.

  • Cardiovascular benefits.

Conclusion:

Vitamin D is a vitamin as well as a hormone that our body produces. Vitamin D is photosynthesized in the stratum basale and stratum spinosum of the epidermis layer of the skin when it is exposed to sunlight. And some amount of vitamin D is also ingested from food as a part of a healthy diet. The primary function of vitamin D has always been associated with its skeletal function. It has been known to be involved in the absorption of calcium, magnesium, and phosphate. Vitamin D helps in regulating the serum calcium and phosphate levels; it also helps in bone growth and reorganization through its actions on osteoblast (bone-forming cells) and osteocytes (cells responsible for bone resorption as well as bone-deposition). However, in recent times nonclassical or novel actions of vitamin D have been reported. These nonclassical actions of the vitamin include regulation of hormone secretion, regulation of both innate and active immunity, and regulation of cellular proliferation and differentiation.

Frequently Asked Questions

1.

What Is Vitamin D’s Non-skeletal Function?

Vitamin D is essential for many physiological functions, including the regulation of the immune system and the development and function of the adult brain.

2.

What Are Vitamin D’s Actions?

It has long been recognized that this fat-soluble vitamin aids in the body's absorption and retention of calcium and phosphorus, both of which are essential for bone development. Infections can be fought off and inflammation can be decreased with the help of vitamin D.

3.

What Are the Benefits of Vitamin D That Are Not Related to the Musculoskeletal System?

In order to sustain the majority of metabolic processes, bone mineralization, and neuromuscular transmission, vitamin D primarily serves to keep serum levels of calcium and phosphorus within the normal physiological range.

4.

What Should One Understand About Vitamin D for Skeletal and Non-skeletal Health?

Vitamin D is crucial for maintaining a healthy, mineralized skeleton and controlling calcium and phosphate metabolism. Additionally, the consequences of vitamin D deficiency include muscle weakness, a higher risk of falling, and chronic musculoskeletal pain.

5.

What Effect Does Vitamin D Insufficiency Have on the Musculoskeletal System?

The following are the effects of vitamin D insufficiency on the musculoskeletal system:
- Neuromuscular performance of muscles.
- Muscle size.
- Muscle strength.

6.

Is a Lack of Vitamin D Affect the Musculoskeletal?

Musculoskeletal health is impacted by vitamin D levels. Clinical symptoms of low vitamin D levels might include:
- Discomfort in the bones.
- Muscle weakness. 
- Low bone mass.
- Fractures. 
- Osteomalacia (it is an adult condition characterized by "bone softening" that is typically brought on by a consistent vitamin D deficit).
- Osteoporosis (it is a bone condition that manifests as a loss in bone mass and mineral density or a change in the composition and strength of bone). 
- Myopathy (myopathies are a diverse range of illnesses that predominantly affect the skeletal muscle structure).
 

7.

What Are the Fourteen Symptoms of Vitamin D Deficiency?

The following are the fourteen symptoms of vitamin D deficiency:
- Muscle aches.
- Painful bones.
- Fatigue impairs endurance.
- Problems with low moods. 
- Sweaty head.
- Hair loss.
- Wounds slowly recover.
- Dizziness.
- Heart issues.
- Weight gain.
- Infections that reoccur.
- Cognitive function impairment.

8.

Vitamin D Insufficiency Affects Which Organ?

Vitamin D insufficiency affects the following organs:
- Bone marrow.
- Colon. 
- Intestine.
- Kidney.
- Lung. 
- Prostate. 
- Retina. 
- Stomach.
- Uterus.

9.

What Is the Best Vitamin D Source?

The following are the best sources of vitamin D:
- Fatty fish meat. 
- Fish liver oils.
- Egg yolks. 
- Cheese. 
- Cow liver.
- Mushrooms.

10.

Which Vitamin D Is the Most Effective?

Vitamin D2 and D3 are both effective vitamin D pills. Vitamin D3 is the most regularly used vitamin D dietary supplement.

11.

What Is the Best Vitamin D for the Skin?

When exposed to sunshine, the body naturally produces vitamin D3 (also known as cholecalciferol). The activated form of vitamin D3 aids in skin renewal and other metabolic processes in the skin.

12.

Does a Lack of Vitamin D Create Neurological Problems?

Yes, neurodegenerative illnesses like multiple sclerosis, Alzheimer's disease, Parkinson's disease, and neurocognitive impairments may be brought on by low vitamin D levels.

13.

Can a Lack of Vitamin D Promote Hair Loss?

Yes, serum vitamin D levels promote non-scarring alopecias like telogen effluvium (it is excessive hair loss caused by hormonal changes, medicine, or metabolic stress in the telogen or resting stage), androgenetic alopecia (it is a condition that runs in the family and is brought on by an overactive reaction to androgens), alopecia areata (it is an autoimmune condition that may cause erratic hair loss), and trichotillomania (it is a mental illness in which a person obsessively pulls out or breaks their own hair).

14.

When Is the Optimum Time to Take Vitamin D?

Since vitamin D is a fat-soluble vitamin, it does not dissolve in water and is best absorbed in the bloodstream when consumed with foods that are high in fat.  Vitamin D pills should be taken with food to improve absorption, and the optimum time is earlier in the day.
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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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