EFFECT OF VITAMIN D SUPPLEMENTATION ON CARDIOVASCULAR AUTONOMIC FUNCIONS IN SUBJECTS IN HIGH ALTITUDE : A RANDOMIZED CONTROL TRIAL

Objectives:

 1.       To estimate the Vitamin D levels in the serum of soldiers prior to induction to heights of more than 15000 ft and post de-induction, after a period of stay for 3 to 4 months.

 2.       To assess the Cardiovascular Autonomic functions in the same group of soldiers prior to induction and post de-induction, after a period of stay for 3 to 4 months.

 3.       To compare the Cardiovascular Autonomic functions with an intervention of calcium + Vitamin D supplementation

  Relevance :

 1.       Vitamin D belongs to the family of fat soluble vitamins and is a hormone concerned primarily with bone and also having anti-inflammatory and immune-modulating actions. Indians have been known to have low levels of vitamin D in the blood and deficiency state has been seen in the paramilitary personnel also. The levels of vitamin D are adversely affected by a diet poor in vit D, presence of phytates in the diet, lack of vit D supplementation, lack of exposure to sunlight, and relative lack of physical exercise. These all occur in the soldiers at high altitude. Further, Vitamin D body reserves last for three weeks only. The soldiers often present with complaints of muscle pain and soreness, bone pain, and frequent infections.

 2. Hypobaric hypoxia in High Altitude leads to sympathetic nervous activation as an adaptive response by the cardiovascular system. The sympathetic over activity diminishes with acclimatization. However in certain individuals, the sympathetic nervous remains overactive leading to hypertension and cardiovascular disorders.

 3.       There have been very studies showing the effect of vitamin D supplementation on the modulation of sympathetic nervous system. The mechanism behind this modulation is unknown. This modulation can ameliorate the rise in blood pressure and heart rate of individuals that can occur as a consequence of prolonged stay in High Altitude areas and help in planning the prevention of cardiac diseases. The clear effect on the autonomous nervous system of vitaminâ€D and the absence of side effects of vitaminâ€D supplementation in general opens for the present study to be carried out in soldiers posted to High Altitude areas in excess of 15000ft (Siachen Glacier).

Technical Appreciation :

 1.       Vitamin D belongs to the family of fat soluble vitamins and is a hormone concerned calcium and bone metabolism. In the recent past studies have revealed an anti-inflammatory and immune-modulating action of vitamin D (1). Vitamin D deficiency is prevalent in epidemic proportions all over the India. The prevalence, as noted by various studies ranges between 70 to 100 % (2,3,4). This deficiency of vitamin D is plays an important role in rickets, osteoporosis, cardiovascular disease, diabetes and cancers. In addition the subclinical deficiency of vitaminD is assumed to play a role in the prevalence of non-specific lower back pain, muscle weakness, muscle cramps, depression, tibial tenderness, and predisposition to infectious                                          diseases. The prevalence of vitamin D deficiency was also seen in sportspersons and college going students, who are expected to have a lifestyle characterized by exposure to sun, good diet and moderate to high level of physical activity (5). The Indian army soldiers deployed at high altitude areas may be affected by vitamin D deficiency due to lack of exposure to sunlight, due to cold weather, increased skin pigment and the requirement to be well clothed (6). Vitamin D levels < 21 ng/mL was associated with increased risk of hypertension, diabetes, obesity and high triglyceride (7)which are the factors associated with increased cardiovascular mortality.

 2.       Acute hypoxia is a potent activator of sympathetic activity via decrease in partial pressure of oxygen and arterial oxygen contents. The sympathetic nervous system activation is an acute adaptive response of cardiovascular system. Several studies found that within the first hour of exposure to hypoxia there is a decrease in total peripheral resistance and reduction in blood pressure(8,9). Gradually the acclimatisation of the individual takes place which increases the oxygen delivery to the tissues hence the strength of hypoxia diminishes leading to overpowering of the sympathetic nervous system in increasing the blood pressure. Studies have also found that the same phenomenon of sympathetic vasoconstriction raised blood pressure and peripheral resistance during high altitude acclimatization(10). Various studies indicate that blood pressure increases during the first week or two at high altitude(11,12). Further sustained hypoxia may leads to chronic sympathetic hyperactivity which subsequently follows down-regulation of adrenergic receptors and reduction in blood pressure (13).

 3.       It has also been found that hypertension at high altitude does not occur in all the individuals, rather only some percentage of people ascending to high altitude are affected. It can be inferred from this that the sympathetic activation in these people which generally starts diminishing after acclimatisation has remained overactive causing hypertension.

 4.      Studies showing the effect of vitamin D supplementation on ameliorating autonomic Function are very few. A study conducted in Denmark in 2014 concluded that supplementation of vitamin D and calcium in normal youngsters with low Sâ€25[OH]D can modulate the sympathetic nervous system giving rise to alterations in blood pressure and heart rate (14). The mechanism behind the modulation of the response from the sympathetic nervous system is unknown, but is in line with animal studies (15, 16, and 17). This clear effect on the autonomic nervous system of vitaminâ€D supplementation warrants for further studies on the impact of low or normal circulating levels of vitaminâ€D on cardiovascular autonomic functions.

          This study will generate data to find out the effect of Vitamin D supplementation on Cardiovascular Autonomic Functions in soldiers posted in High Altitude areas. Based on the results, it can be recommended that Vitamin D supplementation prior to induction can be effective to keep the soldiers healthy.

 References:

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 2.       Ritu G, Ajay Gupta. Vitamin D deficiency in India: Prevalence, casualties and interventions. Nutrients 2014; 6:   729-75.

 3.       Goswami R, Gupta N, Goswami D et al. Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr 2000; 72: 472-75.

 4.       Tandon N, Marwaha R K, Kalra S et al. Bone mineral parameters in healthy young Indian adults with optimal vitamin D availability, Natl Med J  India 2003; 16: 298-02.

 5.       Marwaha R K, Puri S, Tandon N et al. Effects of sports training and nutrition on bone mineral density in young Indian healthy females. Indian J Med Res 2011; 134:307-13.

 6.       Clemens T L, Adams J S, Henderson S L et al. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet 1982; 1: 74-76.

 7.       Martins D, Wolf M, Pan D et al. Prevalence of cardiovascular risk factors and the serum levels of 250hydroxyvitamin D in the United States. Arch Intern Med 2007; 167: 1159-65.

 8.        LEVINE, BD. Effect of high-altitude exposure in the elderly : The Tenth Mountain Division study. Circulation

 9.        Rowell LB, Blackmon JR. Human cardiovascular adjustments to acute hypoxaemia. 1987;349–76.

 10.        Narvaez-Guerra O, Herrera-Enriquez K, Medina-Lezama J, Chirinos JA. Systemic Hypertension at High Altitude. Hypertension .

 11.        Function C. Studyof Cardiopulmonary Function on Exposure to HighAltitude. 1972;106:404–13.

 12.        Vogel, James R., Harris CW. Cardiopulmonary Responses of Resting Man during Early Exposure to high altitude. J Appli Physiol. 1967;(22):1124–8.

 13.        Hegstrand L, Reeves JT, Mcmurty IF, Molinoff PB, Norbert F, John T, et al. Effects of hypoxia on density receptors of. Reactions. 1981.

 14.        Rune Tønnesen,Peter Schwarz,Peter Hovind,and Lars Thorbjørn Jensen. Modulation of the sympathetic nervous system in youngsters by vitaminâ€D supplementation. Physiol Rep, 6 (7), 2018, e13635

 15.        Baksi, S. N., and Hughes M. J. 1984. Alteration of adrenal catecholamine levels in the rat after dietary calcium and vitamin D deficiencies. 1984. J. Auton. Nerv.Syst. 11:393–396.

 16.      Baksi, S. N., and Hughes M. J.. 1986. Deficiency in dietary vitamin D, not   calcium, alters noradrenergic responsiveness in rat atria in vitro. J. Mol. Cell. Cardiol. 18:653–656.

 17.        Baksi, S. N.  Altered pressor response to norepinephrine in calcium†and vitamin Dâ€deficient rats. 1988.Clin Exp*.* Hypertens*. A* 10:811–832.