Review Article

Jan - Feb 2018  |  Vol: 4  |  Issue: 1
Vitamin D: Deficiency, Emerging Roles in Various Diseases, Metabolism, Supplementation, Treatment Strategies, Serum Levels and Dosage Recommendation

Sagar Kishor Savale*

*Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India

 

* Corresponding author,

Mr. Sagar Kishor Savale,

Department of Pharmaceutics,

R. C. Patel Institute of Pharmaceutical

Education& Research, Shirpur, 425405,

 Maharashtra, India.Mobile No: 9960885333,

Email ID: avengersagar16@gmail.com

 

 

ABSTRACT

Objective: Vitamin D has been found to be useful for a number of conditions. Various studies have found it useful in different disorders to varying degree. It is being prescribed very frequently in clinical practice. So, we decided to conduct review to clarify its role in prevention and treatment of different disorders. We found vitamin D to be efficacious in conditions like cardiovascular diseases, diabetes mellitus, osteoporosis; but its role in treatment of certain conditions like multiple sclerosis, cognition needs to be assessed further studies. Method: Various reports were taken from review or research articles published in journals, data from various books and other online available literature. Conclusion: The discovery that most tissues and cells in the body have a vitamin D receptor andthat several possess the enzymatic machinery to convert the primary circulating formof vitamin D, 25-hydroxyvitamin D, to the active form, 1,25-dihydroxyvitamin D, hasprovided new insights into the function of this vitamin. Great interest is the roleit can play in decreasing the risk of many chronic illnesses, including common cancers,autoimmune diseases, infectious diseases, and cardiovascular disease.

Keywords:Vitamin D Deficiency, cancer, cardiovascular, vitaminD3, diabetes mellitus, Multiple Sclerosis.

 

 

Introduction

Vitamin D is a prohormone that is essential for normal absorption of calcium from the gut and for growth, development and maintenance of skeletal system. Vitamin D Deficiency (VDD) is associated with rickets in growing children and osteomalacia in adults. Vitamin D is primarily synthesized in the skin after exposure to ultraviolet radiation (UVR), and <10% of vitamin D is derived from dietary sources.

 

 

Various factors such as traditional dressing, lifestyle and low sunlight exposure may prevent a large proportion of the population from synthesizing healthy amounts of vitamin D in the body. It has been estimated that worldwide about 1 billion people suffer from VDD. According to various scientific evidence published earlier there is a widespread prevalence of varying degrees (50- 90%) of VDD with low dietary calcium intake amongst Indian population. Apart from its conventionallyunderstood role in bone health and calcium homeostasis, vitamin D is believed to have an effect on body’s endocrine system, immune system, cardiovascular system, neuropsychological functioning, neuromuscular performance and is also believed to act as a potent antioxidant protecting against free radical damage, as well as being an inducer of cellular differentiation, protecting against carcinogenesis. In recent years, significant relationships have been documented between VDD and development of non-communicable diseases, notably cardiovascular diseases and diabetes, as well as their predisposing factors, such as obesity and insulin resistance. Vitamin D also has an important role in glucose and insulin metabolismVitamin D, also known as sunshine vitamin, until recently was known mainly for its effect on musculoskeletalsystem. However as more research has been carried out about the pivotal role it plays in functioning of several other organsystems, now there is abundant literature available regarding its vital role in prevention of various spectra of diseases. Hereis brief evidence based review of the various diseases in which role of this vitamin has been tested and proven (Nieves et al., 1994; Zittermann et al., 2003; Singh et al., 2014).

Vitamin D and Diabetes Mellitus: Vitamin D3 is the active form of Vitamin D. Receptors to this active form have nowbeen found in beta cells of pancreas. Vitamin D plays a role in functioning of beta cells of pancreas by binding of activeform of Vitamin D to its receptor on beta cells. Vitamin D deficiency has been proposed to predispose to development ofboth types 1 as well as type 2 diabetes mellitus. Lots of research studies have been carried out to identify its role inpathogenesis as well as in the treatment of diabetes.Several studies point to a link between deficiency of this vitamin in early life & later onset of Type I diabetes. Vitamin D supplementation during infancy, regular vs. none, followed the children up to 14 yrs. They found that relative risk 0.12 of later onset of type 1 diabetesin infants who were given regular Vitamin D compared to the one who were not given any supplementation. Vitamin Ddeficiency may predispose to glucose intolerance, altered insulin secretion & Type 2 diabetes mellitus. There are Vitamin Dreceptors & Vitamin D binding protein in pancreatic tissue and they are related to glucose intolerance and insulin secretion.Studies showed a consistent association between low Vitamin D status, calcium daily intake and prevalence of Type 2diabetes or metabolic syndrome. Vitamin D intake group as compared to lower intake. Thus, the available literature clearly proves the important role ofvitamin D in the prevention as well as treatment of Type 1, type 2 as well as gestational diabetes (Pittas et al., 2010).

Tuberculosis and vitamin D deficiency:vitamin D induce antibacterial peptides invitro that effectively inhibit tuberculosis (TB). Early studies in 1985 showed that vitamin D treatment of murine and humanmacrophages could potentiate the effects of IFN-γ to inhibit TB in vitro. Till recently Vitamin D deficiency wasconsidered uncommon in India. Following an original observation of Vitamin D deficiency in patients with Tuberculosis acontrolled study was done to verify that in Kerala. Vitamin D levels in patients with recently diagnosed activeTuberculosis and matched healthy controls were compared. Adequacy of dietary intake of Vitamin D and adequacy sunexposure was studied in the two groups. This study concluded that Vitamin D deficiency was present in all patients withtuberculosis. Deficiency was also noted in healthy controls even though the level was higher compared to patients. Theincidence of TB is higher among subjects with relatively low serum vitamin D levels, such as the elderly, uremic patients,and Asian immigrants in the U.Kvitamin D levels areassociated with higher risk of active tuberculosis. Since Vitamin D has a role in cell mediated immunity?Its deficiencycould be one of the causes for the infection. This has been supported by epidemiologic data which suggest that low vitaminD is associated with TB severity or susceptibility. Genes also probably contribute to this as shown by a meta- analysis showing a positive association between VDR polymorphisms and host susceptibility to tuberculosis. Patients with untreated TB, particularly those from a temperate climate, have lower serum vitamin D levels than healthy subjects.Recently, a double blind, randomized and placebo controlled trial used three high- dose (1,00,000 I.U.) vitamin Dsupplements in Tuberculosis patients. The study showed no beneficial effect in clinical outcome or mortality inTuberculosis. Another recent report in patients on dialysis showed no correlation between vitamin D supplementation anddecreased risk of Tuberculosis infection. So, in spite of several studies supporting role of vitamin D in body defenceagainst tuberculosis, evidence from large scale placebo controlled trials is lacking. And, there is not adequate informationavailable to claim vitamin D as an anti-infective agent. Hence, as of today, vitamin D cannot be recommended forprevention or as part of treatment of tuberculosis (Mesliniene et al., 2013).

Vitamin D and Multiple Sclerosis: Vitamin D is important for normal immune response of the body. It affects thegrowth and differentiation of immune-modulator cells like T and B lymphocytes, antigen presenting cells like macrophages,dendritic cells. This action has implications for a variety of autoimmune diseases including rheumatoid arthritis, systemiclupus erythematosis, type 1 DM, inflammatory bowel disease, and Multiple Sclerosis.Vitamin D supplementation mayhelp prevent the development of MS and may be a useful addition to therapy. Higher serum vitamin D levels areprotective against MS as shown by a case-control study which showed that for every 10-nmol/L increase of serum vitaminD level the odds of MS was reduced by 19% in women. Several other studies have supported the finding that lower level of vitamin D in MS patients are associated with more severe disability. Lower levels during relapses have also been reportedin patients with relapse-remitting MS. A large observational study in the United States that followed the Nurses’ HealthStudy involving women and the Nurses’ Health Study II involving women found that vitamin Dsupplementation in the form of a multivitamin seemed to lower their MS risk by 40%. However, several methodologicalweaknesses in study design made the results inconclusive. Vitamin D supplementation at appropriate dosage has beenshown to reduce gadolinium-enhancing lesions on magnetic resonance imaging without causing hypercalcemia,hypercalciuria, or other complication. Support for vitamin D supplementation in MS patients is also given by A Finnishstudy which found that, compared with patients without MS, patients with MS had lower serum vitamin D levels during thesummer. Vitamin D deficiency is associated with worse clinical course of multiplesclerosis, with more frequent relapses and disease exacerbations. A link between dietary intake of vitamin D and theincidence of MS has also been suggested. The Atlantic coastal areas of Norway have a lower incidence of MS than the restof Scandinavia, which is thought to be due to the high amount of vitamin D from fish in the local diet. So, the measuresto increase blood levels of vitamin D either by diet or supplementation may be used to improve the course and prognosis ofmultiple sclerosis (Pittas et al., 2010; Kaulgud et al., 2013).

The Role of Vitamin D in Cancer Prevention: Role of vitamin D is being researched by studies around all over. Morethan 1000 laboratory and epidemiological studies have been published concerning the association between vitamin D and itsmetabolites and cancer. Emphasis is being paid on vitamin D in cancer prevention and treatment because of the easyavailability and low cost of this molecule in addition to its positive results from lots of studies. The evidence suggests thatefforts to improve vitamin D status could result in less cancer incidence and mortality at low cost, with few or no adverseeffects. Raising serum vitamin D to appropriate level can prevent approximately 58,000 new cases of breast cancer and49,000 new cases of colorectal cancer each year. vitamin D incrementof 25 nmol/L was associated with a 17% reduction in total cancer incidence, a 29% reduction in total cancer mortality, and a43% and 45% reduction in incidence and mortality, respectively, of digestive-system cancers. Digestive system cancerincidence as well as mortality in men has been found to be associated with low levels of vitamin D. Vitamin Dsynthesis and serum vitamin D levels are inversely correlated with latitude and directly with sunlight, consistent withhigher incidence or mortality rates for colon and breast cancer, Thereare also north–south gradients for ovarian and prostate cancer(Singh et al., 2014).

Vitamin D and colon cancer: Relation between vitamin D deficiency and colon cancer has been subjected to variousstudies. Individuals with low circulating vitamin D levels have been shown to be at increased risk of colon cancer in variousstudies several epidemiological studies like Western Electric Cohort Study, the Nurses’ Health Study, and the Male HealthProfessionals’ Follow-Up Study have reported higher risk of colon malignancy in individuals consuming lower amounts ofvitamin D. Both human and animal studies interventional as well as non-interventional support protective notion thatvitamin D can reduce the risk of colon cancer related to high dietary fat intake. Daily intake of 1000–2000 IU/day ofvitamin D3 could reduce the incidence of colorectal without any significant risk. Population serum vitamin D level of 40to 60 ng/mL has been found to be adequate to obtain various health benefits of this vitamin, which is obtained from intakeof approximately 2000 IU per day of vitamin D3 (Basha et al., 2010; Belenchia et al., 2013).

Vitamin D and breast cancer: Western-style diet, which contains low calcium and vitamin D and increased fat contenthas been found to induce hyper-proliferation and hyperplasia in mammary gland and colonic epithelium in short-termstudies; dietary calcium supplementation inhibited those changes. Breast cancer death rates tend to be lower in areas withbetter sunshine. Women with lower serum Vitamin D levels (< 75nmol/l) have been found to have higher risk of breastcancer than those in whom vitamin D levels are in normal range. Lower vitamin D levels have also been associated withfaster progression of metastatic breast cancer. Several epidemiologic and experimental studies have now suggested thathigh dietary fat and decreased calcium and vitamin D intake have associations with mammary gland carcinogenesis (Svoren et al., 2009).

Vitamin D and Cardiovascular diseases: Vitamin D deficiency has been associated with cardiovascular diseases.Several mechanisms have been proposed to explain how vitamin D could affect CVD risk. Probable mechanisms are- due toeffect of vitamin D on vascular smooth muscle cell proliferation, inflammation, vascular calcification, and blood pressurethrough the RAS. Third National Health and Nutrition Examination Survey data analysis showed an inverse associationbetween vitamin D levels and blood pressure. In this study, during 4 years of follow-up, men and women who had plasmavitamin D levels less than 15 ng/mL were 3 times as likely to have a new diagnosis of hypertension in the next 4 yearscompared with those with vitamin D levels greater than 30 ng/mL.Various study reports have linked vitamin D deficiency to such cardiovascular conditions as hypertension, diabetesmellitus, obesity and the metabolic syndrome, left ventricular hypertrophy, heart failure, coronary heart disease, renaldisease, and mortality. In small clinical trials, vitamin D supplementation has promoted reductions in blood pressure,left ventricular hypertrophy, and inflammatory cytokines. Regression of LV hypertrophy inhaemodialysis patients treated with vitamin D. lowcirculating level of vitamin D may predict a higher risk of cardiovascular disease death. In this study, subjects in the highestquintile of serum vitamin D level had less than half the risk of cerebrovascular death as those in the lowest quintile.Among participants in the Framingham Offspring Study cohort, vitamin D deficiency was associated with an increasedrisk of CVD. The association was observed only in hypertensive subjects, not in those without hypertension. In the HealthProfessionals Follow-up Study, men with a high circulating level of vitamin D had half the risk of myocardial infarction asmen with vitamin D insufficiency. Vitamin D deficiency is associated with increased mortality rates in the setting ofchronic kidney disease, and repleting vitamin D in such patients improves outcomes. Yadav and collegues, in their studyon chronic kidney disease patients, found Vitamin D deficiency to be correlating with preclinical atherosclerotic changes.There is also emerging evidence that treatment with vitamin D analogues reduces mortality in haemodialysis patients. Lowervitamin D levels have been observed in individuals with acute myocardial infarction, stroke, heart failure,andcardiovascular disease, peripheral arterial disease in several small cross sectional studies.Though many studies have highlighted the protective role of vitamin D in prevention of cardiovascular diseases,there is no unanimity. Hsia and colleagues recently reported that use of calcium and vitamin D supplements was notassociated with a reduction in cardiovascular events in the Women Health Initiative (Jeffrey et al., 2010).

 

Vitamin D and Neurological Disorders: VDD is associated with several neuropsychiatric disorders including dementia, Parkinson's disease, multiple sclerosis, epilepsy, and schizophrenia. Scientific evidence suggests that subjects who live at higher latitudes are at an increased risk of VDD and are also more prone to develop schizophrenia. An association between Vitamin D deficiency and neurological disorders was investigated among hospitalized patients to indicate its role in physiologic and pathological processes of the nervous system. The results indicated VDD (25OH (D) levels below 20 ng/ml) amongst 58.1% of the subjects. The mean serum 25OH(D) level was 11.6 ± 4.5 ng/mL. VDD was detected more frequently in patients suffering from ataxic syndromes (72.7%), Amyotrophic lateral sclerosis (66.7%), spine lesions (63.3%), polyneuropathies (63.0%), and stroke (62.6%). Neonatal vitamin D status and its association with risk of schizophrenia were examined in a case control study in Denmark. The quintiles for 25(OH)D3 in the control group were as follows: >19.7, 19.7 to 30.9, 31.0 to 40.4, 40.5 to 50.9, and <51 nmol/L. Compared with neonates in the fourth quintile those in each of the lower 3 quintiles had a significantly increased riskof schizophrenia (2-fold elevated risk). An association between vitamin D status and dementia was examined among elders (aged 65–99 years) receiving home care in the United States. The results indicated that mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL) and there was a higher prevalence of dementia among participants with 25(OH)D insufficiency (≤20 ng/mL) (30.5% vs 14.5%). In a study of vitamin D3 supplementation (oral dose of 40,000–200,000 IU bolus in order to normalize VDD, and then a daily maintenance dose of 2000–2600 IU) resulted in improved seizure control in patients with pharmacoresistant epilepsy. Among all patients, the median seizure reduction was 40%. An association of vitamin D with Multiple Sclerosis (MS) was determined in a case control study in India. Cases had significantly lower 25(OH)D levels than matched controls (p = 0.003) and VDD (< 50 nmol/l) was seen in a higher proportion of cases (71.8%) than controls (53.7%) (p = 0.01). The results of the study indicated that serum 25(OH)D showed an inverse relationship with MS. Vitamin D status and its association with depression were investigated among older primary care patients aged ≥60 years in the United States. Lower vitamin D levels were associated with depression. Subjects with depression had a lower 25(OH)D than the non-depressed group subjects (32.7 vs 35.0, P = 0.002). Those with severe VDD were twice as likely to have depression. Vitamin D levels in patients with Parkinson's disease (PD) and its relationship with severity of symptoms and signs were evaluated in Iran. The mean 25(OH)D3 concentration was lower in the PD population than in the normal group. Lower levels of 25(OH)D3 were associated with more severe postural instability and abnormal posture. A meta-analysis of six studies on the 25(OH)D status in Alzheimer's disease (AD) patients showed that AD patients had lower levels of 25(OH)D than healthy controls (Jeffrey et al., 2010).

 

Vitamin D Photobiology, Metabolism,Physiology, and Biological Functions

Vitamin D is unique among hormones because it can bemade in the skin from exposure to sunlight. VitaminDcomes in two forms. VitaminD2 is obtained from theUVirradiation of the yeast sterol ergosterol and is found naturallyin sun-exposed mushrooms. Vitamin D3 is synthesizedin the skin and is present in oil-rich fish such assalmon, mackerel, and herring; commercially available vitaminD3 is synthesized from the cholesterol precursor7-dehydrocholesterol naturally present in the skin or obtainedfrom lanolin. Both vitamin D2 and vitamin D3are used for food fortification and in vitamin D supplements.Vitamin D (D represents D2, or D3, or both) that isingested is incorporated into chylomicrons, which are absorbedinto the lymphatic system and enter the venousblood. Vitamin D that comes from the skin or diet is biologicallyinert and requires its first hydroxylation in theliver by the vitamin D-25-hydroxylase (25-OHase) to25(OH)D. However, 25(OH)D requires a furtherhydroxylation in the kidneys by the 25(OH)D-1_-OHase(CYP27B1) to form the biologically active form of vitaminD 1,25(OH)2D. 25(OH) 2D interacts with its vitaminD nuclear receptor, which is present in the smallintestine, kidneys, and other tissues. 1, 25(OH) 2Dstimulates intestinal calcium absorption. Without vitaminD, only 10 to 15% of dietary calcium and about60% of phosphorus are absorbed. Vitamin D sufficiencyenhances calcium and phosphorus absorption by 30–40%and 80%, respectively. 1, 25(OH) Dinteractswith its vitamin D receptor in the osteoblast to stimulatethe expression of receptor activator of nuclear factor _Bligand; this, in turn, interacts with receptor activator ofnuclear factor _B to induce immature monocytes to becomemature osteoclasts, which dissolve the matrix andmobilize calcium and other minerals from the skeleton. Inthe kidney, 1, 25(OH) 2D stimulates calcium reabsorptionfrom the glomerular filtrate.The vitamin D receptor is present in most tissues andcells in the body. 1, 25(OH) 2D has a wide range ofbiological actions, including inhibiting cellular proliferationand inducing terminal differentiation, inhibiting angiogenesis,stimulating insulin production, inhibitingrenin production, and stimulating macrophage cathelicidinproduction. In addition, 1, 25(OH) 2Dstimulatesits own destruction by enhancing the expression ofthe 25-hydroxyvitamin D-24-OHase (CYP24R) to metabolize25(OH) D and 1, 25(OH) 2D into water-soluble inactiveforms. There are several tissues and cells that possess1-OHase activity. The local production of1, 25(OH) 2D may be responsible for regulating up to 200genes that may facilitate many of the pleiotropic healthbenefits that have been reported for vitamin D (Chesney et al., 1989; Grady et al., 1991; Hidayat et al., 2010).

 

Sources of Vitamin D

Amajor source of vitaminDfor most humans comes fromexposure of the skin to sunlight typically between 1000 hand 1500 h in the spring, summer, and fall. VitaminDproducedin the skin may last at least twice as longin the blood compared with ingested vitamin D.When an adult wearing a bathing suit is exposed to oneminimal erythemal dose ofUVradiation (a slight pinknessto the skin 24 h after exposure), the amount of vitamin Dproduced is equivalent to ingesting between 10,000 and25,000 IU. Avariety of factors reduce the skin’s productionof vitamin D3, including increased skin pigmentation,aging, and the topical application of a sunscreen.Analteration in the zenith angle of thesuncausedbyachangein latitude, season of the year, or time of day dramaticallyinfluences the skin’s production of vitamin D3. Aboveand below latitudes of approximately 33°, vitamin D3 synthesisin the skin is very low or absent during most of thewinter.Few foods naturally contain vitamin D2 or vitamin D3. In the United States and Canada, milk is fortified withvitamin D, as are some bread products, orange juices, cereals,yogurts, and cheeses. In Europe, most countriesdo not fortify milk with vitamin D because in the 1950s,there was an outbreak of vitamin D intoxication in youngchildren, resulting in laws that forbade the fortification offoods with vitamin D. However, Sweden and Finland nowfortify milk, and many European countries add vitamin Dto cereals, breads, and margarine.Multivitamin preparations contain 400-1000 IU of vitaminD2 or vitamin D3, whereas pharmaceutical preparationsin the United States contain only vitaminD2 (Chang et al., 2000; Talat et al., 2010).

Causes of Vitamin D Deficiency

The major source of vitamin D for children and adults isexposure to natural sunlight. Very few foodsnaturally contain or are fortified with vitamin D. Thus, themajor cause of vitamin D deficiency is inadequate exposureto sunlight. Wearing a sunscreen with a sunprotection factor of 30 reduces vitamin D synthesis in theskin by more than 95%. People with a naturally darkskin tone have natural sun protection and require at leastthree to five times longer exposure to make the sameamount of vitamin D as a person with a white skin tone. There is an inverse association of serum25(OH)D and body mass index (BMI) greater than 30kg/m2, and thus, obesity is associated with vitamin D deficiency. There are several other causes for vitamin Ddeficiency). Patients with one of the fat mal-absorptionsyndromes and bariatric patients are often unable toabsorb the fat-soluble vitamin D, and patients with nephroticsyndrome lose 25(OH)D bound to the vitaminD-binding protein in the urine. Patients on a wide varietyof medications, including anticonvulsants and medicationsto treat AIDS/HIV, are at risk because these drugsenhance the catabolism of 25(OH)D and 1, 25(OH)2D. Patients with chronic granuloma-forming disorders,some lymphomas, and primary hyperparathyroidism whohave increased metabolism of 25(OH)D to 1, 25(OH) 2Dare also at high risk for vitamin D deficiency (Cohen et al., 1986; Jeffrey et al., 2010).

 

 

 

 

Figure 1: Sources of Vitamin D2 and Vitamin D3

 

 

 

 

Figure 2: Biosynthesis and Structures: vitamin D, it’s 25-hydroxy metabolite, and its 1α, 25-hydroxy metabolite

 

Figure 3: Overview of vitamin D Metabolism

 

 

Figure 4: Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism.

 

 

 

Figure 5: Metabolism of 25-Hydroxyvitamin D to 1,25-Dihydroxyvitamin D for Non-skeletal Functions

 

 

 

Serum levels recommended

Based on the serum levels, Vitamin D deficiency can be classified into different groups. This is shown in table below (Bhalla et al., 1983; Sabherwal et al., 2010).

 

 

 

 

 

Table 1: Serum levels recommended

Classification

25 (OH) D level ( nmol/L)

Deficient

< 20

Insufficient

20-50

Optimal

50-125

High

125-225

Toxic

> 225

 

 

 

Dosage recommendation

In patients with documented vitamin D deficiency, a cumulative dose of at least 6 lakh units administered over several weeks is essential to replenish stores. According to mayoclinic, for type 2 diabetes patients, 400-5714 IU of vitamin D is recommended to be taken by mouth daily for 2 months to several years. According to KDOQI guidelines, in patients with chronic kidney disease, monthly intake of 50,000 IU orally is recommended. 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. So, exposure to sunlight is very simple and effective measure to prevent vitamin D deficiency. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing.

 

 

Table 2:Recommendation of vitamin D dosage in different age groups

0-1 yrs

400 IU/day

2000 IU/day or 50,000/week for 6weeks& 400-1000 IU/d maintenance

1-18 yrs

600 IU/day

2000 IU/day or 50,000/week for 6 weeks& 600-1000 IU/d maintenance

19-50 yrs

600 IU/day

6000 IU/day or 50,000/week for 8 weeks& 1500-2000 IU/d maintenance

51-70- yrs

600 IU/day

6000 IU/day or 50,000/week for 8 weeks& 1500-2000 IU/d maintenance

> 70 yrs

800 IU/day

6000 IU/day or 50,000/week for 8 weeks& 1500-2000 IU/d maintenance

Age group Vitamin D sufficient Vitamin D deficient

 

 

Vitamin D Treatment Strategies

Adequate sunlight exposure is the most cost-effective meansof obtaining vitamin D. Whole body exposure to sunlight hasbeen calculated to provide the equivalent of 10,000 IU vitaminD3. A 0.5 minimal erythema dose of sunlight (i.e., one halfthe dose required to produce a slight reddening of the skin) orUVB radiation to the arms and legs, which can be achieved in5-10 min on a bright summer day, has been calculated to bethe equivalent of 3000 IU vitamin D3. However, concernsregarding the association between sunlight and skin cancerand/or aging have limited this approach, perhaps to the extreme,although it remains a viable option for those unable orunwilling to benefit from oral supplementation. Current recommendationsfor daily vitamin D supplementation (200 IUfor children and young adults, 400 IU for adults 51-70 yr ofage, and 600 IU for adults >71 yr of age) are too low and do notmaintain 2S(OH)D at the desired level for many individuals.Studies have shown that for every 100 IU vitamin D, supplementationadministered, the 2S(OH)D levels rise by 0.5-1 ng/ml.(77.783S) even hundred to 800 IU seems to be the lower limitof vitamin D supplementation required to prevent fracturesand falls. Unfortified food contains little vitamin D, with theexception of wild salmon and other fish products such as codliver oil. Milk and other fortified beverages typically contain100 IU/X-oz serving. Vitamin D, is substantially less potentthan vitamin D, in part because it is more rapidly cleared.Therefore, if vitamin D, is used, it needs to be given at leastweekly. Toxicity caused by vitamin D supplementation has notbeen observed at doses <10,000 IU/d.

 

Future Directions

There needs to be an appreciation that unprotected sun exposure is the major source of vitamin D for both children and adults and that in the absence of sun exposure it is difficult, if not impossible, to obtain an adequateamount of vitamin D from dietary sources without supplementation to satisfy the body’s requirement. Concernsabout melanoma and other types of skin cancer necessitate avoidance of excessive exposure to midday sun. These observations strengthen the arguments for supplementation, especially for people living above 33° latitude. All available evidence suggests that children and adults should maintain a blood level of 25(OH) D above 20 ng/ml to prevent rickets and osteomalacia, respectively. However, to maximize vitamin D’s effect on calcium, bone, and muscle metabolism, the 25(OH) D blood level should be above 30 ng/ml. Numerous epidemiological studies have suggested that a 25(OH) D blood level above 30 ng/mlmay have additional health benefits in reducing the risk of common cancers, autoimmune diseases, type 2 diabetes, cardiovasculardisease, and infectious diseases. Few RCT have used an amount of vitaminDthat raises the blood level above 30 ng/ml, and thus there remains appropriate skepticism about the potential non-calcemic benefits of vitamin D for health. Concern was also raised by the IOM report that some studies have suggested that all-cause mortality increased when blood levels of 25(OH)D were greater than approximately 50 ng/ml. RCT that evaluate the effects of vitamin D doses in the range of 2000-5000 IU/d on non-calcemic health outcomes are desperately needed. There is no evidence that there is a downside to increasing vitamin D intake in children and adults, except for those who have a chronic granuloma- forming disorder or lymphoma (Adams et al., 1982; Rathored et al., 2012).

 

Conclusion

Vitamin D is essential for good health. Poor vitamin D status or low circulating concentrations of vitamin D metabolites have been associated with increased risk for numerous diseases, including osteoporosis, several types of cancer, diabetes, hypertension, metabolic syndrome, cardiovascular disease and neurological disorders. Regulation of bone and mineral metabolism is a characteristic vitamin D effect, but the identification of the vitamin D receptor (VDR) in almost all human cells suggests a role of vitamin D also in extra-skeletal diseases. It can be concluded that increased weight loss amongst obese individuals was associated with increase in serum vitamin D levels. Low serum vitamin D levels serve an important risk factor in the development of cancer, type 2 diabetes, cardio vascular diseases and neurological disorders. Amongst hypertensive patients vitamin D sufficiency was associated with decrease in systolic blood pressure. Thus there is a need to further investigate and establish the role of vitamin D deficiency with the reviewed and possible other co-morbidities.It is probably also beneficial for chronic pain. But its role in cognitive disorders,multiple sclerosis and tuberculosis requires further research. Because of the overall health benefits of this vitamin forvarious diseases, measures to prevent deficiency of this vitamin like exposure to sunlight, dietary supplementation need tobe encouraged in all the individuals.Calcitriol is a very potent steroid hormone and is, on a molar basis, the most effective vitamin D metabolite.Nevertheless, an adequate serum 25(OH) D level is also necessary to achieve full physiological vitamin D activity. Obviously, the serum 25(OH) D level and not the serum calcitriol level is the best indicator for vitamin D insufficiency, adequacy, or toxicity.Current estimations for an adequate oral intake are obviously much too low to achieve an optimal vitamin D status and thus to effectively prevent chronic vitamin D-dependent diseases.Vitamin D represents one of the most studied and discussed topics in the field of bone and mineral metabolism diseases worldwide. The metabolism of the hormone has been extensively clarified, particularly the role of the different enzymes involved, as well as the active and inactive metabolites and the vitamin D receptor. Taken together, these data have also allowed best investigating the pleiotropic and multiorgantargeted effects of vitamin D. In particular, several studies described the interrelationship between the hormone and the adipose tissue, both considering obesity as a predisposing condition to hypovitaminosis D and vitamin D as a cofactor in the pathogenesis of obesity. Moreover, direct and indirect effects of the hormone on the skeletal muscle tissue lead to a better understanding of the clinical features associated with vitamin D deficiency. As many efforts have been made in the understanding of vitamin D metabolism and functions, several mechanismsstill need to be covered, particularly in relation to many genetic factors involved. Additionally, notwithstanding the whole amount of data on the field, no consensus currently exists on definition and treatment regimen of hypovitaminosis D, mostly as far as particular conditions (such as obesity) and targeting functions (as muscle strength) are concerned.

 

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