Symptoms and treatment of VitaminD deficiency.

by

Dr Jawad Amjad

TABLE OF CONTENT

Vitamin D

Basic facts about Vitamin D

Vitamin D deficiency

UVB-related deficiency

Medical/physical condition-related deficiency

UV lamp in Vitamin D formation

Vitamin D as a treatment or prevention of different conditions

Vitamin D… Did you know?

Useful Links – Support Groups

References

Disclaimer

Vitamin D

Vitamin D is a group of fat-soluble prohormones. It obtained its name after the discovery of the antiarthritic effect of cod liver oil in the early part of the 20th century. The vitamin found in cod liver oil was designated “D” following Vitamin A, B and C, which had been discovered earlier.

Basic facts about Vitamin D

The metabolism of Vitamin D

The metabolism of vitamin D in the human body can be summarized as illustrated in the figure below,

The two major biologically inert precursors of vitamin D are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) [1,2]. Vitamin D3 is formed when 7-dehydrocholesterol in the skin is exposed to solar ultraviolet B (UVB, 290-320 nm), and then converted to previtamin D3. In a heat-dependent process, previtamin D3 is immediately converted to vitamin D. Excess UVB transform previtamin D3 into biologically inactive metabolites, tachysterol and lumisterol. Vitamin D2 is plant derived, produced exogenously by irradiation of ergosterol, and enters the circulation through diet [3].

Both vitamin D precursors resulting from exposure to the sunshine and the diet are then converted to 25-hydroxyvitamin D [25(OH)D] ( calcidiol) when they enter the liver [4]. 25 (OH)D is the major circulating form of vitamin D and is used to determine vitamin D status. In order to be biologically active, additional hydroxylation in the kidneys is needed to form active 1,25- dihydroxyvitamin D [1,25(OH)2D] (calcitriol) [5].

Sources of Vitamin D

In general, humans obtain vitamin D through dietary intake and exposure to sunlight. A list of vitamin D content in different sources is shown in Table.1,

Vitamin D deficiency

Vitamin D status

Vitamin D deficiency occurs when people do not have an appropriate dietary intake or exposure to UVB rays. It is universally accepted that the circulating level of 25-hydroxyvitamin D (25 (OH)D, produced in liver) should be used as an indicator of vitamin D status due to its ease of measurement, long half-life in circulation (approximately 2 or 3 weeks), and the correlation of its level with clinical disease states [3,6,7]. Different vitamin D status is shown in table.2

How much vitamin D do we need?

In 1997, the institute of Medicine of the US National Academy of Sciences recommended new adequate intakes for vitamin D as 200 IU for children and adults up to 50 years of age, 400 IU for adults 51 to 70 years of age, and 600 IU for adults 71 years of age or older [8]. However, a great number of researches revealed that without adequate sun exposure, children and adults require approximately 800 to 1000 IU per day [9-12] .

The prevalence of vitamin D deficiency

Vitamin D deficiency has already become a largely unrecognized global epidemic. Several studies showed that 40 to 100% of U.S. and European elderly men and women still living in the community (not nursing homes) are deficient in vitamin D [15]. In Europe , where very few foods are fortified with vitamin D, children and adults would appear to be at especially high risk [16-18]. A study of middle aged British adults showed that 60% are vitamin D insufficient, and the number rose to 90% during winter and spring [19].

Causes of vitamin D deficiency

There are many causes of vitamin D deficiency. Generally, they can be divided into two groups: UVB-related deficiency and medical/physical condition -related deficiency as figure.2 shows below:

UVB-related deficiency

The elderly

The elderly, due to the decreased presence of skin 7-dehydrocholesterol which is the precursor for UVB synthesis of vitamin D, are particularly at risk of vitamin D deficiency. Moreover, reduced mobility or institutionalization that discourages sun exposure, reduced renal production of 1,25-dihydroxyvitamin D as well as decreased intake of fortified foods pose great difficulties in vitamin D formation in body [20,21].

Dark skin

People with dark skin have great amounts of melanin in their epidermis. Melanin competes with 7-dehydrocholesterol for absorption of UVB photons. Therefore, people of color are less efficient in producing vitamin D than are whites. It is reported that a person with skin type 5/6 (dark skin) requires 10-50 times the exposure to sunlight to produce the same amount of vitamin D as does a white person with skin type 2/3 [22]

Season, latitude, and the time of day

It has been known that ozone layer can absorb UVB radiation above 290 nm which is responsible for generating previtamin D3. Zenith angle, defined as the angle of the sunlight reaching the Earth’s surface, decides the thickness of ozone layer which sunlight needs to penetrate. The thicker the ozone layer is, the fewer amounts of UVB photons can reach the earth, thus few previtamin D3 can be produced. Zenith angle is dependent on factors such as time of day, season of the year, and latitude. Thus those factors have great effect vitamin D production [23,24]. For example, residents of Boston (42 N), Edmonton, Canada (52 N) and Bergen, Norway (61 N) can not produce sufficient quantities of vitamin D in their skin for 4, 5, and 6 months, respectively [25].

Sunscreen users

Sunscreens can efficiently absorb UVB radiation. This dramatically prevents the interaction of UVB with 7-dehydrocholesterol, the process of previtamin D3 generation. It has been shown that when used properly, a sunscreen with an sun protection factor of 8 reduces the production of previtamin D3 by 95%, and 99% by a sun protection factor of 15 [26,27].

Medical/physical condition-related deficiency

Fat malabsorption

As a fat-soluble vitamin, vitamin D requires the presence of dietary fat in the gut for absorption. Certain pathological conditions, such as Crohn’s disease, cystic fibrosis, celiac disease, surgical removal of part of the stomach or intestines are associated with fat malabsorption thus leads to vitamin D deficiency. For example, cystic fibrosis (CF) patients suffer from pancreatic exocrine insufficiency. This result in malabsorption of fat-soluble vitamins, including vitamin D. CF patients, depending on the degree of exocrine insufficiency, absorb approximately 50% less vitamin D compared with what normal people absorb [28].

Anticonvulsant use

Anticonvulsants, also called antiepileptic drugs, have been used to treat epileptic seizures and bipolar disorder. It is well recognized that long-term use of some antiepileptic drugs, including phenobarbital, phenytoin, and carbamazepine and antimicrobial agent rifampicin ( RIF ), can result in osteomalacia [29-33]. The induction of the catabolism of 1,25-dihydroxyvitamin D from these drugs is thought to contribute to this deleterious side effect.

Chronic kidney disease

In order to become biological active vitamin D, the kidneys play an important role in the transforming process. Chronic kidney disease such as patients with stage 4 or 5 chronic kidney disease, as well as those requiring dialysis, are unable to make enough 1,25-dihydroxyvitamin D which has a direct effect in inhibiting parathyroid hormones expression [34,35]. Thus 1,25-dihydroxyvitamin D3 intake is needed to maintain calcium level in blood as well as control parathyroid hormones levels.

Obesity

It has been known for a long time that obese people are prone to be vitamin D deficient since they have lower 25-hydroxyvitamin D level [36-39]. A number of studies proved that vitamin D3 precursor 7-dehydrocholesterol in the skin of obese people were not significantly different from non-obese people [40, 41]. One explanation was that the subcutaneous fat, which is known to store vitamin D, sequestered more of the cutaneous synthesized vitamin D, which results in less release of vitamin D from the skin into the circulation in the obese subject than non-obese subject [42].

UV lamp in Vitamin D formation

Why and how a UV lamp can help boost vitamin D (fundamental theory)

Ultraviolet (UV) rays are electromagnetic waves with wavelength of between 400nm and 10nm. UV can be divided into three components according to wavelength: UVA (320-400 nm), UVB (290-320 nm), and UVC (100-290 nm). They have different skin penetration, and generate different biological effect.

UVB plays a key role in vitamin D formation. It is absorbed by the epidermal layer, where the highest concentration of 7-dehydrocholesterol exist. Th e absorption of UVB in the epidermal layer , as is shown in figure.1, is marked as the first step of vitamin D formation process. UV lamp irradiates UVB thus has the same effect of vitamin D production as sunshine (see figure.3). One advantage of UVB exposure in formation of vitamin D is that UVB exposure does not result in excessive production of vitamin D, which causes risks of intoxication. This can be explained that the previtamin D3 that is formed and the thermal isomerization product vitamin D3 that does not go into the circulation , absorb UVB radiation and isomerize to several photoproducts which have little activity on calcium metabolism [43].

The efficiency of UVB in boosting Vitamin D

Several studies have proved the effect of UV lamp in boosting vitamin D content. For example one study on elderly living in residential nursing home showed that daily exposure to UVB radiation from UV lamp can help improve vitamin D status [44]. Another 12-week investigation conducted in nursing home demonstrated that a few minutes per day of UVB irradiation generated the same effect of oral vitamin D3 intake [45]. For people who can not absorb vitamin D supplement efficiently, UV lamp has been proved as a good alternative to keep (maintain) vitamin D status. A recent study using UV lamp in treatment of vitamin D deficiency , resulted from cystic fibrosis (CF) showed that serum 25(OH)D level increased from 21 ng/ml to 27 ng/ml over 8 weeks (figure.4) [46].

Choice of wavelength

It has been found that optimum wavelength for the production of vitamin D was between 295 and 300 nm. This narrow range is sometimes referred to as D-UV [47]. One concern associated with this waveband is the erythema effect, which is result of cell irritation and destruction caused by ultraviolet radiation. In UVB region, the wavelength between 290 and 297 nm has the greatest erythema effect on human body with a steep decrease above 297 nm [48]. Therefore UVB tube with spectrum feature of minimal irradiance from 290 to 297 nm should always be chosen in treating vitamin D deficiency.

Generally, there are two types of UVB tube for medical purpose s : UVB-broadband and UVB-narrowband. Compared with UVB-broadband, narrowband is a relatively new development. Nonetheless it is now used widely in UK , continental Europe, and increasingly in the USA [49,50]. The great advantage of narrowband over broadband is that it covers less erythema area than the latter. Thus in theory narrowband is safer to human body than broadband.

Vitamin D production

The production of vitamin D depends on three factors: UV lamp power output, exposure duration, and body exposure area (see figure.5). In theory, the higher the power output, the longer the exposure duration, the larger the body exposure area, the higher vitamin D production.

With power output and exposure duration, UV radiation can be calculated. Limitations should be put on this parameter for safety considerations . Minimal erythema dose (MED) is defined as the minimum amount of UVB radiation that produces redness 24 hours after exposure. It is used when using UVB to treat psoriasis in order to minimise the potential for developing erythema. Thus UVB radiation should not exceed one MED, in other words, exposure (treatment) duration should be well controlled.

Vitamin D as a treatment or prevention of different conditions

Vitamin D deficiency has been found in a serial of diseases. The long-known examples include osteoporosis and osteomalacia, in which cases vitamin D deficiency results in Ca malabsorption. More recently, vitamin D deficiency is associated with a wider range of conditions such as cancer, hypertension, and diabetes to name a few. Although whether vitamin D deficiency is the direct cause of these conditions needs further investigation, yet vitamin D supplementation provides as a good prevention or treatment of these diseases. Table 3 summarizes the usage of vitamin D in major conditions. More conditions can be found in the scale bar in figure.5

Particular target groups – People who can not take vitamin D orally

As it can be seen from Figure.1, vitamin D can either be taken from diet in Gastrointestinal Tract (GI Tract) or formed by interaction with sunlight in skin. However, people with abnormalities in their GI tract can not absorb vitamin D through GI as it is illustrates in figure.6. Thus a UV lamp, which can help the formation of vitamin D through skin, is their major source of vitamin D.

These conditions include:

* Gastric bypass surgery

* Inflammatory bowel disease

* Bowel resection

* Cystic Fibrosis

Gastric bypass surgery

Gastric bypass surgery (GBP) is used to treat severe obesity. As the rate of obesity continues to rise in recent years, the demand for this surgery continues to increase. In GBP, the sites of duodenum and proximal jejunum, which are the preferential sites for the absorption of calcium, are bypassed. The remaining small intestine can only absorb calcium through a less efficient mechanism. A number of studies showed that people who underwent GBP suffered from calcium and vitamin D deficiency which resulted in decreased bone mass [92] and more seriously, osteomalacia [93-95]. It is reported that gastric bypass patients who don’t take regular vitamin D supplementation consume only about 50% of the recommended daily requirements of vitamin D [96]. Recent study, however, showed that this deficiency can not be corrected by standard multivitamin supplementation. This can be explained as oral supplementation can not be absorbed efficiently as GI tract can not function properly. Therefore UV lamp provides an alternative in keeping normal level of vitamin D

Inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the large intestine and small intestine. Crohn’s disease (CD) and ulcerative colitis (UC) are the two major types of IBD. Vitamin D deficiency and decreased bone mineral density are highly prevalent in IBD, especially CD [97]. One study showed that the risk of hip fracture was increased by 86% in patients with CD and by 40% in patients with UC [98]. An updated investigation reported that malabsorption of vitamin K and D is probably the cause of decreased bone mineral density, which increases the risks of fracture [97]. Even dietary intake of these vitamins was above the adequate intakes in IBD patients, the deficiency still exists. This suggests that supplement could not be a good option of correcting vitamin deficiency in IBD. In this case, a UV lamp holds a promising implication by boosting vitamin D content relying on skin instead of bowel.

Bowel resection

A bowel resection is a surgical procedure in which a part of the large or small intestine is removed. Research revealed that vitamin D deficiency is common (38.1%) in patients with small intestinal resection and was accompanied by increased marker of bone resorption and decreased bone mineral density. UV lamp has been used in treating vitamin D deficiency in patients after undergoing bowel resection. It proved that UVB radiation is more efficient in improving vitamin D in treating a patient with only 2 feet of small intestine remaining after 2 bowel resections [99].

Cystic Fibrosis

Cystic fibrosis (CF) is the UK ‘s most common life-threatening inherited disease. CF affects the internal organs, especially the lungs and digestive system, by clogging them with thick sticky mucus. Osteoporosis and fracture are common in children and adults with CF. Despite oral supplements (400 to 800 IU daily), vitamin D deficiency is also common and is associated with sever demineralization at the lumbar spine and hip. Thus oral supplementation may not be an effective way of maintaining normal vitamin D stores in CF [100]. As it is in bowel resection, UV lamp has also been used for boosting vitamin D and demonstrated as an excellent alternative.

Want to find out more information on Vitamin D? Download our research booklet on Vitamin D here

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