Effects Of Vitamin D3 Supplementation On Lung Function Of Healthy Non-Smoking Young Iraqi Subjects

Background: There is an increasing evidence that vitamin D3 improves lung function in respiratory diseased subjects. Higher plasma vitamin D3 concentrations are also linked to better lung function in several communities. Objectives: To study the effects of single oral vitamin D3 supplementation (600 IU) on lung function in healthy non-smoking young Iraqi subjects.


INTRODUCTION
Pulmonary function tests are still the tools with which pulmonary diseases are identified (1) .They remain the most accurate means of quantifying the severity of diffuse lung diseases (2) .Spirometry is the basic pulmonary function test that is widely used to detect obstructive (3 and 4) and/or restrictive (5) lung diseases.Spirometric measurements include forced vital capacity (FVC), forced expiratory volume in first second (FEV 1 ) and forced expiratory volume ratio (FEV%) (2) .Interpretation of pulmonary function measurements is complicated by the fact that predicted values from the various published studies vary by as much as 20% for an individual subject.This is due to vast diversity of factors that affect the predicted normal spirometric values including age, height, gender, weight, muscular activity, race, ethnicity, cigarette smoking, occupation, residence, socioeconomic and nutritional status … (6) There is also evidence that diet can influence FEV 1 and vital capacity.In keeping with this, both the serum concentrations and the dietary intake of antioxidant nutrients such as vitamin C, vitamin E, beta-carotene, and selenium have been positively associated with lung function.
The dietary intake of magnesium is also associated with increased lung function and reduced airway reactivity.Low concentrations of vitamin D3 have been linked to many diseases including osteoporosis, hypertension, ischemic heart disease, type I diabetes, and cancer (7) .Vitamin D3 is synthesized in the skin following sunlight exposure, but concentrations of vitamin D3 can also be influenced by dietary intake.Vitamin D is converted to 25hydroxy vitamin D through the action of a hydroxylase in the liver, and this, in turn, is converted into 1,25dihydroxyvitamin D, the active metabolite, in the kidney.1,25-dihydroxy vitamin D has a number of actions that may be relevant to respiratory disease.It inhibits the formation of matrix metalloproteinases as well as fibroblast proliferation, and influences collagen synthesis (8) .These actions mean that 1,25-dihydroxy vitamin D could influence tissue remodeling.These observations raise the possibility that vitamin D3 could influence lung function (9 and 10) and that vitamin D3 deficiency could result in decline in lung function (11)   .Recently, evidence is presented that supplementation of high dose of vitamin D3 reduces exacerbations in chronic obstructive pulmonary disease (12) but further information are needed to explore the role of vitamin D3 in healthy lungs.

OBJECTIVES:
To study the effects of single oral vitamin D3 supplementation (600 IU) on lung function in healthy non-smoking young Iraqi subjects.

SUBJECTS AND METHODS
A total number of 110 subjects (52 males and 58 females) were initially included in the present research.They were, all, second year college students at the age of 20 years.Their heights were ranging from 155 cm to 178 cm.Unhealthy subjects were excluded no matter their diseases were respiratory or not.Subjects with history of respiratory illnesses were also excluded.All of participants claimed not to be smokers.All of the other subjects performed the forced expiratory maneuver during the first visit.Spirometric measurements including FVC, FEV 1 and FEV% were done with the use of a standardized spirometer produced by Vitalograph Medical Instrumentation Co. Ltd, Buckingham, England while measurements of height were done with a well calibrated scale.Spirometric measurements were done in sitting position after a period of resting time in order to achieve the steady state which means that the heart rate in consecutive minutes is changing by less than 3 beats per minute.With a clipped nose, the

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No.( 2) 2013 -3 -subject is instructed to inspire forcefully as much as possible and then to blow out through the fully and tightly encircled mouthpiece of spirometer as forceful and as quick as possible until no more air can be blown from the lungs.This is the right forceful expiratory maneuver which is allowed to be done in three trials with the best result to be recorded (6).
For the sake of better adjustments for any other factors that may affect the spirometric outcomes; the results on either far extremes were discarded.The remaining 82 subjects (38 males and 44 females) were divided into two main groups: Control group (CRL) and Vitamin D3 group (VTD).CRL group contained 42 subjects (18 males and 24 females) who didn't receive oral vitamin D3 supplementation.VTD group contained 40 subjects (20 males and 20 females) who received oral vitamin D3 supplementation which was provided as single dose of 600 IU vitamin D33 (devit3 manufactured by Deva).
Thirty days later, both groups performed the second visit spirometric maneuver as detailed above.Means and standard deviations were calculated for all parameters for the whole study population.Student's t-test was employed to compare the means of paired groups (first versus second visits) and statistical decisions were regarded significant when p values were less than 0.05.Graphs were drawn to clarify the results.

RESULTS
All of the second year college students were 20 years old (SD = 0).Males' average height was 175.18 cm ± 1.89 cm and females' average height was 162.8 cm ± 3.99 cm.In either sex; there were no significant differences between the means of heights of VTD and CRL groups.Table 1 shows the spirometric outcomes for VTD and CRL groups in the two visits and in either sex.

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No.( 2) 2013 -4 - Regarding FVC measurements; figure 1 illustrates that they were significantly higher (by about 120 ml) in the second than in the first visits for both VTD and CRL male groups (p<0.002 and p<0.05 respectively).Figure 2 illustrates that FVC measurements were also significantly higher in the second than in the first visits for both VTD (by about 80 ml) and CRL (by about 120 ml) female groups (p<0.002 and p<0.05 Regarding FEV 1 measurements; figure 3 illustrates that they were significantly higher (by about 130 ml) in the second than in the first visits for both VTD and CRL male groups (p<0.05).The same results are shown in figure 4 which illustrates that FEV 1 measurements were also significantly higher in the second than in the first visits for both VTD (by about 80 ml) and CRL (by about 90 ml) female groups (p<0.05 and p<0.04 respectively).

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No.( 2 While for FEV%; the results were different as shown in figure 5 which illustrate that there were no significant differences in FEV% between the first and the second visits for both VTD and CRL groups and in males.Again, figure 6 illustrate that there were no significant differences in FEV% between the first and the second visits for both VTD and CRL groups and in females.

DISCUSSION
Vitamin D3 deficiency was found to be associated with many diseases including osteoporosis, hypertension, ischemic heart disease, type I diabetes, and cancer and declined lung function (7- 12) .High dietary consumption of fruit, vegetables, oily fish and whole meal cereals was found to be associated with better lung function (13) .Higher prudent diet scores are associated with greater intakes of a range of micronutrients including vitamin D3 (14) but the protective effect of the 'prudent' pattern

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No.( 2) 2013 -7 -may not be due to a higher intake of vitamin D3 and is more likely to be explained by antioxidant nutrients in fruit, vegetables and whole grains or nutrients other than vitamin D3 in oily fish such as fatty acids.A higher intake of fruit and whole grains, of various antioxidants including vitamins C and E, beta carotene and selenium, and of fatty acids have all been linked to better lung function (15) .Controversy is still present in literature about the relationship between vitamin D3 plasma concentration and lung function.While some researches suggested a positive relationship (16 and 17) ; others not (18 and 19) .Present research, however, confirmed that FVC and FEV 1 measurements are increased by 80 -130 ml after vitamin D3 supplementation, but nearly the same increase was found in control group during the second visit without intake of vitamin D3 (though with lower levels of significance for FVC).This improvement in spirometric measurements may be attributed to the role of vitamin D3 or to other factors like the improved performance of spirometric maneuver by the young students.The mechanisms by which vitamin D3 levels might affect lung function are unclear.Potential explanations in diseased subjects include effects on respiratory infection risk (via both innate and adaptive mechanisms) and lung tissue remodeling (via matrix metalloproteinases and other pathways (20 and 21) .In apparently healthy subjects, however, there is no induction of tissue remodeling, innate or adaptive mechanisms.Furthermore, there is no vitamin D3 deficiency challenging our temperate climate population to be compensated.It is suggested that the role of vitamin D3 in the improvement of lung function must be comprehensively studied in respiratory diseased subjects.

Figure 1 :
Figure 1 : Differences in forced vital capacity (in liters) between first and second visits in CRL and VTD male groups.

Figure 2 :
Figure 2 : Differences in forced vital capacity (in liters) between first and second visits in CRL and VTD female groups.

Figure 3 :
Figure 3 : Differences in forced expiratory volume (in liters) between first and second visits in CRL and VTD male groups.

Figure 4 :
Figure 4 : Differences in forced expiratory volume (in liters) between first and second visits in CRL and VTD female groups.

Figure 5 :
Figure 5 : Differences in forced expiratory volume ratio (as a percentage) between first and second visits in CRL and VTD male groups.

Figure 6 :
Figure 6 : Differences in forced expiratory volume ratio (as a percentage) between first and second visits in CRL and VTD female groups.