Vitamin D insufficiency


Vitamin d insufficiency and obesity are pandemic disease. The concentration of 25 hydroxy vitamin - d are considered as the best indicator of total body vitamin d stores. Activated vitamin-d may influence the mobilization of free fatty acids from the adipose tissues as well as metabolism of fat cells. Obesity associated vitamin-d insufficiency is likely due to the decreased bio availability of vitamin-d3 for cutaneous and dietary sources because of its deposition in the body fat compartments. The synthesis of vitamin-d is dependent upon the radiation in the ultra violet –B range of sunlight.


Vitamin D deficiency, a pandemic health problem, is a major cause of rickets in infants and toddlers and of osteopenia in adolescents [1–6]. The production of vitamin D in the skin depends on sunshine exposure, latitude, skin-covering clothes, the use of sun block, and skin pigmentation. Although the Mediterranean region generally has a sunny climate, higher rates of hypovitaminosis D are seen in European and Mediterranean countries. Vitamin D deficiency is especially common in the Middle East because of the prevalence of wearing skin-covering clothes and because of staying out of the sun.

Besides acting as a regulatory hormone in calcium metabolism, noncalciotropic effects of vitamin D such as cellular differentiation and replication in many organs have been found. Vitamin D is also critical in glucose homeostasis and insulin secretion via its endocrine mechanisms, besides its autocrine and paracrine role in adipocytes. Insulin resistance plays a major role in obesity, and as a population gets heavier at younger ages, the age of onset of non-insulin-dependent diabetes mellitus also decreases . Regrettably, obesity and adiposity is an emerging trend in the industrialized world it is a result of a limited exercise, a sedentary lifestyle, and replete diets with high-calorie, low-nutrient foods.

Why do we need vitamin D?

Your body must need vitamin D to absorb calcium and promote bone growth. Too little vitamin D results in soft bones in children (rickets) and fragile, misshapen bones in adults (osteomalacia). We also need vitamin D for other important body functions. Adequate vitamin D intake is important for the regulation of calcium and phosphorus absorption, maintenance of healthy bones and teeth, and is suggested to supply a protective effect against multiple diseases and conditions such as cancer, type 1 diabetes and multiple sclerosis. Vitamin D has multiple roles in the body, helping to:

  • Maintain the health of bones and teeth
  • Support the health of the immune system, brain and nervous system
  • Regulate insulin levels and aid diabetes management
  • Support lung function and cardiovascular health
  • Influence the expression of genes involved in cancer development.

It controls the problems of obesity ,because it is a fat soluble vitamin in it.

Vitamin D and Obesity


Vitamin D3 (cholecalciferol) is taken in the diet (from fortified dairy products and fish oils) or is synthesized in the skin from 7-dehydrocholesterol by ultraviolet irradiation. The vitamin D produced by 7-dehydrocholesterol depends on the intensity of UV irradiation which varies with season and latitude.

Sunscreen and clothing have been reported to prevent the conversion of 7-dehydrocholesterol to vitamin D3 . In order to be biologically active and affect mineral metabolism and to have effects on numerous other diverse physiological functions including inhibition of growth of cancer cells and protection against certain immune mediated disorders, vitamin D most be converted to its active form.

Vitamin D is transported in the blood by the vitamin D binding protein (DBP, a specific binding protein for vitamin D and its metabolites in serum) to the liver. In the liver vitamin D is hydroxylated at C-25 by one or more cytochrome P450 vitamin D 25 hydroxylases (including CYP2R1, CYP2D11 and CYP2D25), resulting in the formation of 25-hydroxyvitamin D3 (25(OH)D3).

It has been suggested that CYP2R1 is the key enzyme required for 25 hydroxylation of vitamin D since a homozygous mutation of the CYP2R1 gene was found in a patient with low circulating levels of 25(OH)D3 and classic symptoms of vitamin D deficiency.

25(OH)D3, the major circulating form of vitamin D, is transported by the DBP to the kidney. In the kidney, magalin, a member of the LDL receptor superfamily, plays an essential role in endocytic internalization of 25(OH)D3.

In the proximal renal tubule 25(OH)D3 is hydroxylated at the position of carbon 1 of the A ring, resulting in the hormonally active from of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) which is responsible for most, if not all of the biological actions of vitamin D.

The cytochrome P450 monooxygenase 25(OH)D 1α hydroxylase (CYP27B1; 1α(OH)ase) which metabolizes 25(OH)D3 to 1,25(OH)2D3 is present predominantly in kidney. This enzyme is also found in extrarenal sites including placenta, monocytes and macrophages.

As with all mitochondrial P450 containing enzymes, during the 1α(OH)ase reaction electrons are transferred from NADPH to NADPH-ferrodoxinreductase through ferrodoxin. Inactivating mutations in the 1α(OH)ase gene result in vitamin D dependency rickets (VDDR) type 1 in spite of normal intake of vitamin D, indicating the importance of the 1α(OH)ase enzyme.

Type 1 vitamin D dependent rickets is characterized by growth failure, hypocalcemia, elevated PTH, muscle weakness and radiologic findings typical of rickets.

Mechanism Action

  • Calcium regulation in the human body.The role of vitamin D is shown in orange.
  • Liver hydroxylation of cholecalciferol to Calcifediol
  • Kidney hydroxylation of calcifediol to calcitriol
  • Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcifediol. Circulating calcifediol may then be converted into calcitriol, the biologically active form of vitamin D, in the kidneys. Following the final converting step in the kidney, calcitriol is released into the circulation. By binding to vitamin D-binding protein, a carrier protein in the plasma, calcitriol is transported to various target organs. In addition to the kidneys, calcitriol is also synthesized by monocyte-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders by stimulating the innate immune system.
  • Whether it is made in the skin or ingested, cholecalciferol is hydroxylated in the liver at position 25 (upper right of the molecule) to form 25-hydroxycholecalciferol (calcifediol or 25(OH)D). This reaction is catalyzed by the microsomal enzyme vitamin D 25-hydroxylase which is produced by hepatocytes. Once made, the product is released into the plasma, where it is bound to an α-globulin, vitamin D-binding protein.
  • Calcifediol is transported to the proximal tubules of the kidneys, where it is hydroxylated at the 1-α position (lower right of the molecule) to form calcitriol (1,25-dihydroxycholecalciferol and abbreviated to 1,25(OH)2D). This product is a potent ligand of the vitamin D receptor, which mediates most of the physiological actions of the vitamin. The conversion of calcifediol to calcitriol is catalyzed by the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, the levels of which are increased by parathyroid hormone (and additionally by low calcium or phosphate).

Food sources and skin synthesis

Vitamin D, synonym calciferol, often referred to as the ‘sunshine vitamin’, is essential for life in all higher organisms. It is a secosteroid hormone which exists in two forms: ergocalciferol (vitamin D2), found in fungi; and cholecalciferol (vitamin D3), found in vertebrates. Only a few foods contain appreciable amounts of vitamin D.

Vitamin D can also be synthesized in human skin in response to sunlight exposure and is the strongest factor influencing vitamin D status Solar ultraviolet-B (UVB) radiation (290–315 nm) initiates cutaneous synthesis of vitamin D by the photo conversion of 7-dehydrocholesterol to pre-vitamin D3. Then, over a period of 1–2 days at body temperature, pre-vitamin D3 isomerizes to D3; once formed, it is sterically unacceptable and ejected from the cell membrane into the extracellular space and then into circulation. It is important to note that prolonged exposure to UVB light does not increase pre-vitamin D3 production, but rather is photo degraded to biologically inert isomers.

Activation of vitamin D

Once in the circulation, due either to absorption of dietary vitamin D or skin synthesis, vitamin D (both D2 and D3 forms) is transported to the liver where it undergoes its first hydroxylation at carbon-25 via 25-hydroxylase, making 25(OH)D, or calcidiol, the major form of vitamin D circulating in the blood yet biologically inactive . For it to become active, 25(OH)D must undergo a second hydroxylation at carbon-1 by 1-α-hydroxylase, present primarily in the kidneys making 1,25-dihydroxyvitamin D [1,25(OH)2D] or calcitriol. Production of 25(OH)D is controlled via negative feedback by vitamin D, 25(OH)D and 1,25(OH)2D . In addition to the classical endocrine role of vitamin D involving renal synthesis of 1,25(OH)2D, numerous other tissues possess enzyme systems capable of hydroxylating 25(OH)D to produce the active form for intracrine and autocrine/paracrine functions.

Transport of vitamin D and its metabolites

Once generated, 1,25(OH)2D is then transported systemically or locally to nuclear VDR in target cells, followed by the subsequent generation of appropriate biological responses. Another key component of this system is the group-specific protein known as vitamin D-binding protein (DBP) which carries vitamin D and its metabolites to their sites of metabolism and various target organs . Although >99% of 25(OH)D circulates bound to DBP or other serum proteins, the general assumption is that biological activity involves unbound or ‘free’ fractions even though this component in serum is very small . This ‘free-hormone hypothesis’ has been proposed as a universal mechanism for cellular uptake of steroid hormones , though recent data challenge this assertion in vitamin D metabolism.

Storage and excretion of vitamin D and its metabolites

Vitamin D is fat soluble and has a half life of 4–6 weeks. Vitamin D can accumulate in the body, where it is distributed widely, but is primarily stored in adipose tissue and released slowly, so that higher doses of vitamin D lead to a long resident.

For example, doses of 50,000 IU have been shown to increase the half life to 90 days.

Both 25(OH)D and 1,25(OH)2D can undergo hydroxylation and oxidation to yield several metabolites that are related to deactivation and rapid clearance of 1,25(OH)2D. This is particularly true for the carbon-23 and -24 oxidations, which ultimately yield a biologically inactive water-soluble metabolite, 1-α-hydroxy-24,25,26,27-tetranor-23-COOH-vitamin .

Factors affecting vitamin D status

Several factors can influence vitamin D status. Any barrier to the penetration of UVB radiation into the skin epidermis and dermis is inversely correlated with circulating 25(OH)D.

These include: decreased solar zenith angle such as occurs during the winter months in temperate climates and at high latitudes year-round; the use of sunscreen or sunblock – even sun protection factor (SPF) as low as 7 can significantly block vitamin D production); high melanin skin pigmentation (which functions as a natural sunscreen) ; and cultural clothing practices where little/no skin is expose. Other factors associated with increased risk of vitamin D deficiency or insufficiency include avoidance of milk, fat mal absorption, and excess adiposity .

Signs and symptoms

can cause day-to-day health problems such as:

Obesity is diagnosed when your body mass index (BMI) is 30 or higher. Your body mass index is calculated by dividing your weight in kilograms (kg) by your height in meters (m) squared.

Diagnosis of vitaminD deficiency

Metabolic bone disease, prevention of falls and fractures, and treatment of secondary hypo thyoidism are the classic reasons to treat with vitamin D.

Nevertheless, the treatment of asymptomatic vitamin D deficiency is the most common reason to prescribe vitamin D. However, like all diagnoses, one must think of it before one can make it.

Then, like any diagnosis, the physician must confirm it or rule it out by means of history, physical examination and laboratory assessment.

The classic presentation of severe vitamin D deficiency is metabolic bone disease in adults and rickets – with or without hypocalcaemic tetany – in children, a subject recently Osteomalacia (unmineralised collagen matrix)presents after the epiphyseal plates fuse and can occur in adolescence.

Stress fractures – in otherwise healthy adolescents and adults – may indicate vitamin D deficiency.

Unexplained fractures in childhood may be rickets and not child physical abuse Radio-graphs of the wrist, alkaline phosphatase, and 25(OH)D level must be obtained before making life-altering – and false – accusations.

Vitamin D deficiency often presents with common, non-specific symptoms, such as muscular weakness – predominantly of the proximal limb muscles – a feeling of heaviness in the legs, chronic musculoskeletal pain, fatigue or easy tiring.

BMI Weight status
Below 18.5 Underweight
18.5-24.9 Normal
25.0-29.9 Overweight
30.0-34.9 Obese (Class I)
35.0-39.9 Obese (Class II)
40.0 and higher Extreme obesity (Class III)

RDA chart

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