VITAMIN D AND HEALTH: BONES AND BEYOND

Introduction

Vitamin D also called as vitamin D3 or ‘cholecalciferol’; is a fat-soluble vitamin. Human beings are dependent on the sun exposure to fulfill their needs of vitamin D. It is uv-B radiation that are being absorbed by 7-dehydrocholesterol present in the skin that aids in converting previtamin D3 to vitamin D3. Vitamin D is essential for the development of bones and also to enhance calcium and phosphorus uptake from the intestine. It assists in the oscillation of calcium ions between bone and blood. It is therefore vitamin D is essential component for all age groups; during infant to childhood stage it plays an essential role in bone development or else its deficiency results in bone deformation and rickets. In adults its deficiency results in softness of bone leading to osteomalacia. (Goldman, 2004).

Vitamin D3 once formed goes into circulation and is converted to 25 hydroxyvitamin D3 in liver, again released in circulation and subsequently converted to the active form of vitamin D, 1, 25- dihydroxyvitamin D3 in kidney. It is observed that Vitamin D deficiency remains unrecognized and therefore its insufficiency is taking a shape of epidemic among children and adults in United States.

Various research studies have been carried out throughout the world to conclude that vitamin D plays an imperative role not only for the bone health but also for various kinds of cancers, diseases related to heart, multiple sclerosis, in type I diabetes, also in various autoimmune diseases encompassing rheumatoid arthritis. Therefore, maintenance of suitable blood concentration of 25-hydroxyvitamin D (30 ng/ml) is very essential. As vitamin D is essential for enhancing intestinal calcium absorption, it’s appropriate level in the blood is also necessary for the formation of extrarenal 1?- hydroxylase which plays an imperative role in the formation of 1, 25- dihydroxyvitamin D3 (Holick, 2004).

Production and fate of Vitamin D

When an individual is exposed to sunlight previtamin D3 and also vitamin D3 forms photoproducts which are biologically inert. Vitamin D intake through diet or that formed in the skin with the help of sunlight come into the blood circulation, it reaches liver where it is metabolised to 25(OH)D3 by vitamin D 25-hydroxylase (25-OHase).  25(OH)D3 is again released in the circulation, it reaches kidney and get converted to 1,25(OH)2D3 in presence of enzyme 25(OH)D3 1 -hydroxylase (1-OHase). The renal production of active form of vitamin D is regulated by a variety of features encompassing serum phosphorus (Pi) and PTH. The active form of vitamin D (1,25(OH)2D) is now capable of managing the calcium metabolism. It is observed that the enzyme  25(OH)D 24-hydroxylase (24-OHase) enzyme which plays a crucial role in generating the active form of vitamin D, works on threshold mechanism to keep the check on the production of 1,25(OH)2D3 and if it is produced in higher quantity, the enzyme aids in the degradation of active vitamin D (Holick, 2004).

Further, it is also documented that 1,25(OH)2D can depress the activity of 1 -OHase, and the parathyroid hormone (PTH) can stimulate this activity. Many extrarenal tissues also express the 1 -OHase, these encompass tissues of bone osteoclasts, tissues of skin, macrophages, placenta, tissues of colon, tissues of brain, tissues of prostate, endothelial tissue, and glandular tissues of parathyroid. Extrarenal formation of 1,25(OH)2D3 might participate in the differentiation and proliferation of cell and also in immune response. Consequently, 1,25(OH)2D3  is essential for various physiological processes apart from its well-known function in calcium metabolism. In contrast to renal 1 -OHase, extrarenal 1 -OHase does not respond to stimulation by PTH. Furthermore, 1 -OHase may vary in expression with the physiologic state of a tissue as well as with disease progression (DeLuca, 2004).

Food incorporating Vitamin D

There are various resources of vitamin D, this encompass pure form of Cod liver oil, cooked form of Salmon, Mackerel, Tuna fish and Sardines canned in oil, sardines, margarine fortified, bran flakes, eggs, lamb liver.Fortified foods include milk and milk products especially cheese, orange juice and some breads and cereals (Vitamin D sources- Foods with Vitamin D).

As mentioned, the higher concentration of vitamin D influences the metabolic functions of the body, WHO has recommended intake dose of vitamin D by individuals belonging to different group. Up to the age of 50 years, during pregnancy and lactation the requirement is 200 IU/d, for the age group from 51-65 years it is 400 IU/D for the age of 65+ the requirement exceeds to 600 IU/d (Vitamin D sources- Foods with Vitamin D).

Considering the above data it is manifested that vitamin D is the most essential component for endorsing and preserving the health and vigor of bones as it directly affects the strength of bone in various skeletal and nonskeletal activities of the body encompassing cancers and depression (Lapp, 2009).

Symptoms of Vitamin D deficiency

Fall in plasma calcium and phosphate level, due to insufficient intestinal absorption, renders stimulation of  parathyroid hormone (PTH) secretion to restore serum calcium and bone resorption.

Rickets

In children, the deficient calcification of osteoid tissues result in bony deformities like bow leg, enlarged skull, spinal curvature, chest deformities and hepatosplenomegaly- characteristic features of Rickets. The reason is lack of appropriate bone tissue mineralization, causing soft bones and skeletal deformities. At-risk children are on prolonged exclusive breast feeding without supplementation of vitamin D. Additional risk factors includes vigorous use of sunscreens, and infants placed in daycares, with chances of sun exposure is reduced. Rickets is more prevalent in the children from Asia, Africa and Middle East (Davidson, 2002).

Osteomalacia

In adults decalcification and demineralization of bone leads to osteomalacia which is characterized by bone tenderness with pain and loss of bone density.

This disease is characterized by the aches and pains specifically in the lower back and thighs. Later on, it spreads to the arms and the rib cage.  This pain does not radiate to other areas. It is accompanied by the local tenderness in bones. Another cardinal feature is the weakness of the proximal muscles. This represents as a difficulty in climbing up stairs and getting up from a squatting position.

Due to the deformation of bones, lordosis is a common representation. While walking, the patient shows a waddling gate. Pathological fractures due to weight gain may occur. Despite all these typical signs and symptoms, sometimes chronic fatigue may be the only representing sign (Eisman, 1988).

Osteoporosis

According to an estimate, about more than 25 million adults in United States alone are having or are at risk of developing this disease. This disease is most often associated with an inadequate calcium intake, therefore vitamin D is essential for reducing calcium absorption

Osteoporosis epitomizes reduction in mass of bone, also reduces microarchitectural framework of bone and thereby weakens the tissues of bone and amplifying the risk of fracture. The incidence of osteoporosis and fractures related with osteoporosis raise with age in both males and females, displaying a decline in bone mass with age.

Osteoporosis has emerged as a major health issue in developed nations. It is a condition that depicts frequent fractures, and is expected to influence more of females than males at some stage in their lives. As the age progresses bones become tender leading to osteoporosis in older adults, post menopausal women, non ambulatory individuals and individuals on chronic steroid therapy. The natural rhythm of the body allows a constant remodeling of the bones. In post menopausal women, this ratio is disturbed resulting in a greater amount of bone absorption rather than bone remodeling (Goldman, 2004).

Calcium and Vitamin D

Calcium 500- 1000 mg daily and vitamin D supplements 20µg daily have an established role in  deterrence of elderly fractures, irrespective of whether or not BMD (Bone Mineral Density) values are reduced. This treatment is effective in reducing the danger of fractures related to hip fractures or other kind of fractures in community-living patients. (Davidson, 2002).

Reasons displaying insufficiency of vitamin D

1. Elevated pervasiveness of lactose intolerance causing undesirable effects with consumption of mild and dairy foods especially in African Americans.
2. Reduced ingestion of vitamin D- equipped food products, predominantly liquefied milk, milk products cereals, because of changing attitude towards health concern and fat intake.
3. Poor intake of calcium rich food encompassing poor intake of milk especially by the young women of reproductive age group thereby reduced concentration of vitamin D and calcium.
4. Augmentation in the use of sun block lotions along with the diminished exposure to sun to avert the chances of skin cancer is also one of the reasons of vitamin D insufficiency.
5. Human milk is meager in vitamin D, in the present era there is enhanced predominance in the duration of breast- feeding ensuing insufficient intake of vitamin D. thus causing low circulation of 25-hydroxyvitamin D concentrations among women.
6. Due to air pollution in industrial areas, the exposure to uv- radiation is reduced and also the poor dietary habits and availability of vitamin D equipped food makes the individual a victim of vitamin D deficiency.
7. In rare cases impaired absorption, enhances body requirement of vitamin D, or enhanced excretion or stringent practice of vegetarianism leads to vitamin D deficiency.
8. In some Arabian countries it is mandatory for women to long robes for religious purpose so their exposure to sun is reduced leading to insufficiency of vitamin D.

(Looker, 2002; Kreiter, 2000; Nesby-O’Dell, 2002).

Vitamin D and Bone Health (BMD, BMC, falls and fracture)

Vitamin D is responsible for forming and sustaining good health of bones by increasing absorption of calcium from intestine and depositing calcium in bones and maintains optimal BMD (Bone Mineral Density). Observation says that diminished absorption of calcium is related to vitamin D; thereby resulting in loss of bone or enhanced chances of osteoporosis (a situation depicting low BMD). Osteoporosis makes the bone fragile making the individual vulnerable to fractures (Cranneyet al, 2007).

It is reported by Holick (2006) that vitamin D deficiency causes various bone related anomalies like osteopenia, osteoporosis apart from osteomalacia, resulting in further weakening of muscles and hence exacerbating the risk of falls and fractures. Under such conditions the recommended dose must be increased to 1000 IU/d.

Recommendations for reducing fracture risk with vitamin D and calcium based on clinical studies

While giving the vitamin D supplements, mostly it is accompanied by calcium in order to obtain the desired results. According to a research study, it was concluded that the combined supplementation of both vitamin D3 and calcium in elderly patient aged 62-85yrs resulted in a decrease in the jeopardy of an individual’s falls, fractures, the bone loss within elderly population. The dose of vitamin D was given as 700-800 IU/day and calcium was given as 500-1200 IU/day.

It is now clearly understood the significance and pivotal role that vitamin D holds in retaining the good health of bone. A number of studies and surveys have been carried out, which strengthen this fact even more. Down here are discussed a few of such studies:

Skin Cancer and Vitamin D

People are now a-days much concerned about the sun exposure resulting in skin cancer. It is observed that chronic and extreme exposure to sunlight in childhood and early stages of life causing sunburns may culminate to increased risk for non-melanoma basal and squamous cell carcinomas (Veierod, 2003; Grodstein, 1995; Kennedy, 2003). Various research studies conclude that melanomas occur in the areas which are not exposed to sun indicating that the vitamin D3 is less synthesised; individuals apply sun protection creams which block UVB radiation responsible for the synthesis of vitamin D3 and the hence they may allow other sun radiations which may cause melanomas (Garland, 1993).

Noncalcemic Actions of Vitamin D

It is known that vitamin D3 interacts with nuclear receptor similar to steroid hormones. As soon as it enters the cell, it passes through the road map of microtubular network to the nucleus. In nucleus it binds with vitamin D receptor (VDR) and generates a complex to generate vitamin D responsive gene (Holick, 1999).

VDR is present in many tissues of body like small and large intestine, osteoblasts, T and B lymphocytes, ?-islets cells, brain, heart, skin, gonads, prostate, breast and mononuclear cells (Holick, 1999). Studies shows that when 1,25(OH)2D3 if nurtured with leukemic cells of human and mice origin, arrest the propagation and encourage to form grown-up macrophages (Tankaet al, 1982).

1,25(OH)2D3 has come up with antipropagation action that has been proved through clinical trials in psoriasis management. 1,25(OH)2D3 when topically applied, induced a noteworthy progress in various diseases like plaque thickness, scaling and erythema (Holick, 1998). Therefore, this has become the foremost treatment in psoriasis.

1,25(OH)2D3 is playing an imperative role in providing stimulus to the production of insulin (Lee, 1994), inflecting the activation of both B and T lymphocyte (Tsoukas, 1984), direct effect on myocardial contractility (Weishaar, 1987), effect on prevention of inflammatory bowel disease (Cantorna, 2000) and stimulate secretion of TSH.

Deficiency of Vitamin D and its association with to occurrence of autoimmune disorders and cancer

It is observed through various research studies that people living in higher latitudes get less exposure to sun, culminating in vitamin D deficiency and hence accounts for higher incidence of breast cancer mortality rate in north Europe (Grant, 2002).

Vitamin D and Autoimmune Diseases

Data from many animal and human studies shows that vitamin D prevents development of type I diabetes mellitus, rheumatoid arthritis, hypertension, cancers of colon, breast and prostate, Crohn’s disease, multiple sclerosis (Holick, 2004).

Vitamin D Supplementation

The required amount of vitamin D is difficult to be met from food alone. In some at-risk groups it becomes necessary to give vitamin D-fortified food, or expose them to sunlight. Various at risk groups for vitamin D inadequacy include:

1. Breastfed infants:

The human milk provides vitamin D with the concentration of 25 IU/L insufficient for the baby. The results of a recent review revealed that a majority of cases of nutritional rickets were found among young African American breastfed infants. According to the recommendations by AAP it is advised that the partially and exclusively breastfed infants should be supplemented with a daily dosage of 400 IU.

1. People with limited sun exposure:

These include:

1. People exclusively bound to stay in homes
2. Northern latitude inhabitants
3. Women wearing long robes for religious purposes
4. People with occupations preventing sun exposure

All such individuals must obtain the recommended daily supplemented dosage of vitamin D equivalent to 400 IU in order to prevent them from vitamin D deficiency diseases.

1. People with dark skin:

These individuals possess a larger amount melanin pigment. Having an excess of this pigment reduces the vitamin D generating ability of skin on sun exposure. It is also suggested in some studies that women of older age, with a darker skin relatively show higher possibility of developing deficiency of vitamin D. Yet, it is seen that the African Americans, possessing a darker skin, despite having a lower level of vitamin D than required, develop fewer osteoporotic fractures compared with the Caucasians (Eisman, 1988).

1. People with fat malabsorption:

Fat solubility of vitamin D demands a little fat in the diet to be absorbed well in the gut. Individuals having decreased vitamin D absorption capability need the its supplementation in order to meet its demands. Some of the diseases leading to fat malabsorption include:

1. Liver diseases
2. Cystic fibrosis and

1. Obese people:

Obese people also come under at risk individual’s group for vitamin D inadequacy. This is thought to be true for people with a BMI > 30. As their obesity increases, the level of vitamin D in their body decreases. This is because of an increase in the body fat. The reason behind is greater amount of subcutaneous fat sequester more of the vitamin and affect its release in to the circulation. BMI is inversely related with the peak serum concentrations of vitamin D, thus sometimes even the oral supplementation in such individuals causes sequestration of the vitamin into the larger fat pools of the body.

1. People with gastric bypass surgery:

Such individuals are prone to develop a deficiency of vitamin D because part of upper small intestine, where vitamin D gets absorbed is bypassed. Thus, they also require the oral supplementation of vitamin D.

1. Older adults:

Older adults come under the endangered groups in case of developing deficiency of vitamin D; because, with an increasing age, the skin loses its ability to synthesize vitamin D from sunlight. Also, there becomes a decreased ability to convert vitamin D in kidneys into live hormone.

Conclusion

Initially it was thought vitamin D is imperative only for preventing rickets in children or osteomalacia in adults or osteoporosis in elderly group or is responsible for bone health but now it is established fact that vitamin D is imperative for metabolic processes. Deficiency of vitamin D and reduced solar UVB exposure increases the risk of various widespread cancers or type I diabetes, various autoimmune disorders like multiple sclerosis and rheumatoid arthritis and schizophrenia. Various studies demonstrate that vitamin D has evolved as a vital and necessary hormone, which acts as a marker for the overall health and well being of an individual. It is therefore important to maintain normal vitamin D level of 75-125nmol/L. It is therefore mandatory that one must get the plasma levels of 25(OH)D checked and it should be part of routine checkups.

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