Cyclic Changes of Vitamin D and PTH are Primarily Regulated by Solar Radiation: 5-Year Analysis of a German (50° N) Population

Abstract

Cutaneous vitamin D precursor production depends on UV-exposure and is ineffective in most regions above latitudes of 50° in winter. We hypothesized whether the cyclic course of vitamin D levels can be modelled with sunshine duration and would affect parathyroid hormone concentrations, but not calcium in a large patient population. We investigated 13330 blood samples from 6099 in- and out patients for 25(OH)D₃, 1,25(OH)₂D₃, PTH, and total Ca in Frankfurt, Germany over 6.5 years. Vitamin D deficiency [25(OH)D₃ <10 ng/ml] was found in 12.23% and vitamin D insufficiency [25(OH)D₃ <20 ng/ml] in 40.62% of all the blood samples and more frequently during winter. We observed a significant difference between men and women, children and adults, migrants and local residents. Cycling of the curve was significantly related to Julian day for 25(OH)D₃ and parathyroid hormone (PTH), but not for 1,25(OH)₂D₃ and Ca. The peak concentration of 25(OH)D₃ was found at Aug 16th and correlated well with the length of day whereas PTH is inversely related with 25(OH)D₃. Seasonal cycling of 25(OH)D₃-levels correlated significantly with Julian Day and inversely with PTH. This tight feed back ensures stable Ca concentrations within narrow limits. We conclude that changes in vitamin D levels are mainly regulated by solar radiation and to a lesser degree by other factors such as nutrition.

Key words

UV radiation - seasonal variations - colecalciferol - calcium - parathyroid hormone

References

• 1 Reichrath J, Lehmann B, Carlberg C, Varani J, Zouboulis CC. Vitamins as hormones.  Horm Metab Res. 2007;  39 71-84
• 2 Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ. Prevalence of vitamin D insufficiency in an adult normal population.  Osteoporos Int. 1997;  7 439-443
• 3 Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young adults.  Am J Med. 2002;  112 659-662
• 4 Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents.  Arch Pediatr Adolesc Med. 2004;  158 531-537
• 5 Vecino-Vecino C, Gratton M, Kremer R, Rodriguez-Mañas L, Duque G. Seasonal variance in serum levels of vitamin D determines a compensatory response by parathyroid hormone: study in an ambulatory elderly population in Quebec.  Gerontology. 2006;  52 33-39
• 6 Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients.  N Engl J Med. 1998;  338 777-783
• 7 Levis S, Gomez A, Jimenez C, Veras L, Ma F, Lai S, Hollis B, Roos BA. Vitamin D deficiency and seasonal variation in an adult South Florida population.  J Clin Endocrinol Metab. 2005;  90 1557-1562
• 8 Mei IAF van der, Ponsonby A, Engelsen O, Pasco JA, MacGrath JJ, Eyles DW, Blizzard L, Dwyer T, Lucas R, Jones G. The high prevalence of vitamin D insufficiency across Australian populations is only partly explained by season and latitude.  Environ Health Perspect. 2007;  115 1132-1139
• 9 Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review.  Altern Med Rev. 2005;  10 94-111
• 10 Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clinic proceedings.  Mayo Clinic. 2006;  81 353-373
• 11 Lips P. Relative value of 25(OH)D and 1,25(OH)₂D measurements.  J Bone Miner Res. 2007;  22 1668-1671
• 12 Holick MF. Vitamin D deficiency.  N Engl J Med. 2007;  357 266-281
• 13 Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes.  Am J Clin Nutr. 2006;  84 18-28
• 14 Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency.  Lancet. 1998;  351 805-806
• 15 Holick MF. The vitamin D epidemic and its health consequences.  J Nutr. 2005;  135 2739S-2748S
• 16 Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency.  Am J Clin Nutr. 2004;  80 1706S-1709S
• 17 Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.  JAMA. 2005;  293 2257-2264
• 18 Rejnmark L, Vestergaard P, Brot C, Mosekilde L. Parathyroid response to vitamin D insufficiency: relations to bone, body composition, and to life style characteristics.  Clin Endocrinol (Oxf). 2008;  69 29-35
• 19 Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.  Am J Clin Nutr. 2007;  85 1586-1591
• 20 Porojnicu A, Robsahm TE, Berg JP, Moan J. Season of diagnosis is a predictor of cancer survival. Sun-induced vitamin D may be involved: a possible role of sun-induced Vitamin D.  J Steroid Biochem Mol Biol. 2007;  103 675-678
• 21 Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC. Vitamin D and prevention of breast cancer: pooled analysis.  J Steroid Biochem Mol Biol. 2007;  103 708-711
• 22 Bouillon R, Eelen G, Verlinden L, Mathieu C, Carmeliet G, Verstuyf A. Vitamin D and cancer.  J Steroid Biochem Mol Biol. 2006;  102 156-162
• 23 Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new etiological and therapeutical considerations.  Ann Rheum Dis. 2007;  66 1137-1142
• 24 Hewison M, Zehnder D, Chakraverty R, Adams JS. Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase.  Mol Cell Endocrinol. 2004;  215 31-38
• 25 Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.  Science. 2006;  311 1770-1773
• 26 Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease.  Am J Clin Nutr. 2004;  80 1678S-1688S
• 27 Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.  JAMA. 2006;  296 2832-2838
• 28 Pedersen LB, Nashold FE, Spach KM, Hayes CE. 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking.  J Neurosci Res. 2007;  85 2480-2490
• 29 Ponsonby A, Lucas RM, Mei IAF van der. UVR, vitamin D and three autoimmune diseases--multiple sclerosis, type 1 diabetes, rheumatoid arthritis.  Photochem Photobiol. 2005;  81 1267-1275
• 30 Soilu-Hänninen M, Airas L, Mononen I, Heikkilä A, Viljanen M, Hänninen A. 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis.  Mult Scler. 2005;  11 266-271
• 31 Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system.  Arch Biochem Biophys. 2000;  374 334-338
• 32 Guillemant J, Cabrol S, Allemandou A, Peres G, Guillemant. Vitamin D-dependent seasonal variation of PTH in growing male adolescents.  Bone. 1995;  17 513-516
• 33 Engelsen O, Brustad M, Aksnes L, Lund E. Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness.  Photochem Photobiol. 2005;  81 1287-1290
• 34 Batschelet E. Circular statistics in biology. New York: Academic Press 1981
• 35 Mirsaeid Ghazi AA, Rais Zadeh F, Pezeshk P, Azizi F. Seasonal variation of serum 25 hydroxy D3 in residents of Tehran.  J Endocrinol Invest. 2004;  27 676-679
• 36 Melin A, Wilske J, Ringertz H, Sääf M. Seasonal variations in serum levels of 25-hydroxyvitamin D and parathyroid hormone but no detectable change in femoral neck bone density in an older population with regular outdoor exposure.  J Am Geriatr Soc. 2001;  49 1190-1196
• 37 Bouillon RA, Auwerx JH, Lissens WD, Pelemans WK. Vitamin D status in the elderly: seasonal substrate deficiency causes 1,25-dihydroxycholecalciferol deficiency.  Am J Clin Nutr. 1987;  45 755-763
• 38 Chatfield SM, Brand C, Ebeling PR, Russell DM. Vitamin D deficiency in general medical inpatients in summer and winter.  Intern Med J. 2007;  37 377-382
• 39 Dattani JT, Exton-Smith AN, Stephen JM. Vitamin D status of the elderly in relation to age and exposure to sunlight.  Hum Nutr Clin Nutr. 1984;  38 131-137
• 40 Davies M, Mawer EB, Hann JT, Taylor JL. Seasonal changes in the biochemical indices of vitamin D deficiency in the elderly: a comparison of people in residential homes, long-stay wards and attending a day hospital.  Age Ageing. 1986;  15 77-83
• 41 Devgun MS, Paterson CR, Johnson BE, Cohen C. Vitamin D nutrition in relation to season and occupation.  Am J Clin Nutr. 1981;  34 1501-1504
• 42 Harris SS, Dawson-Hughes B. Seasonal changes in plasma 25-hydroxyvitamin D concentrations of young American black and white women.  Am J Clin Nutr. 1998;  67 1232-1236
• 43 Krall EA, Sahyoun N, Tannenbaum S, Dallal GE, Dawson-Hughes B. Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women.  N Engl J Med. 1989;  321 1777-1783
• 44 Lamberg-Allardt C. Vitamin D intake, sunlight exposure and 25-hydroxyvitamin D levels in the elderly during one year.  Ann Nutr Metab. 1984;  28 144-150
• 45 Lawson DE, Paul AA, Black AE, Cole TJ, Mandal AR, Davie M. Relative contributions of diet and sunlight to vitamin D state in the elderly.  Br Med J. 1979;  2 303-305
• 46 Lester E, Skinner RK, Wills MR. Seasonal variation in serum-25-hydroxyvitamin-D in the elderly in Britain.  Lancet. 1977;  1 979-980
• 47 Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications.  Endocrine reviews. 2001;  22 477-501
• 48 Maxwell JD. Seasonal variation in vitamin D.  Proc Nutr Soc. 1994;  53 533-543
• 49 Nakamura K, Nashimoto M, Yamamoto M. Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women.  Int J Biometeorol. 2000;  44 186-189
• 50 Omdahl JL, Garry PJ, Hunsaker LA, Hunt WC, Goodwin JS. Nutritional status in a healthy elderly population: vitamin D.  Am J Clin Nutr. 1982;  36 1225-1233
• 51 Ono Y, Suzuki A, Kotake M, Zhang X, Nishiwaki-Yasuda K, Ishiwata Y, Imamura S, Nagata M, Takamoto S, Itoh M. Seasonal changes of serum 25-hydroxyvitamin D and intact parathyroid hormone levels in a normal Japanese population.  J Bone Miner Metab. 2005;  23 147-151
• 52 Pasco JA, Henry MJ, Kotowicz MA, Sanders KM, Seeman E, Pasco JR, Schneider HG, Nicholson GC. Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures: the Geelong Osteoporosis Study.  J Bone Miner Res. 2004;  19 752-758
• 53 Perry HM, Horowitz M, Morley JE, Patrick P, Vellas B, Baumgartner R, Garry PJ. Longitudinal changes in serum 25-hydroxyvitamin D in older people.  Metabolism. 1999;  48 1028-1032
• 54 Poskitt EM, Cole TJ, Lawson DE. Diet, sunlight, and 25-hydroxy vitamin D in healthy children and adults.  Br Med J. 1979;  1 221-223
• 55 Sherman SS, Hollis BW, Tobin JD. Vitamin D status and related parameters in a healthy population: the effects of age, sex, and season.  J Clin Endocrinol Metab. 1990;  71 405-413
• 56 Stamp TC, Round JM. Seasonal changes in human plasma levels of 25-hydroxyvitamin D.  Nature. 1974;  247 563-565
• 57 Storm D, Eslin R, Porter ES, Musgrave K, Vereault D, Patton C, Kessenich C, Mohan S, Chen T, Holick MF, Rosen CJ. Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial.  J Clin Endocrinol Metab. 1998;  83 3817-3825
• 58 Stryd RP, Gilbertson TJ, Brunden MN. A seasonal variation study of 25-hydroxyvitamin D3 serum levels in normal humans.  J Clin Endocrinol Metab. 1979;  48 771-775
• 59 Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls – a cross-sectional study.  Br J Nutr. 2006;  96 124-130
• 60 Webb AR, Pilbeam C, Hanafin N, Holick MF. An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston.  Am J Clin Nutr. 1990;  51 1075-1081
• 61 Woitge HW, Scheidt-Nave C, Kissling C, Leidig-Bruckner G, Meyer K, Grauer A, Scharla SH, Ziegler R, Seibel MJ. Seasonal variation of biochemical indexes of bone turnover: results of a population-based study.  J Clin Endocrinol Metab. 1998;  83 68-75
• 62 Woitge HW, Knothe A, Witte K, Schmidt-Gayk H, Ziegler R, Lemmer B, Seibel MJ. Circaannual rhythms and interactions of vitamin D metabolites, parathyroid hormone, and biochemical markers of skeletal homeostasis: a prospective study.  J Bone Miner Res. 2000;  15 2443-2450
• 63 Adams JS, Chen H, Chun R, Ren S, Wu S, Gacad M, Nguyen L, Ride J, Liu P, Modlin R, Hewison M. Substrate and enzyme trafficking as a means of regulating 1,25-dihydroxyvitamin D synthesis and action: the human innate immune response.  J Bone Miner Res. 2007;  22 ((Suppl 2)) V20-V24
• 64 Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status.  Osteoporos Int. 2005;  16 713-716
• 65 MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3.  J Clin Invest. 1985;  76 1536-1538
• 66 Hintzpeter B, Scheidt-Nave C, Müller MJ, Schenk L, Mensink GBM. Higher prevalence of vitamin D deficiency is associated with immigrant background among children and adolescents in Germany.  J Nutr. 2008;  138 1482-1490
• 67 Rejnmark L, Gloth FM, Tobin JD. Vitamin D deficiency in older people.  J Am Geriatr Soc. 1995;  43 822-828
• 68 Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D.  Am J Clin Nutr. 2007;  85 6-18
• 69 Zittermann A, Scheld K, Stehle P. Seasonal variations in vitamin D status and calcium absorption do not influence bone turnover in young women.  Eur J Clin Nutr. 1998;  52 501-506
• 70 Hintzpeter B, Mensink GBM, Thierfelder W, Müller MJ, Scheidt-Nave C. Vitamin D status and health correlates among German adults.  Eur J Clin Nutr. 2008;  62 1079-1089
• 71 Reichel H, Schmidt-Gayk H. The role of 25-hydroxyvitamin D in normal and disturbed calcium metabolism.  Eur J Clin Invest. 2003;  33 281-282
• 72 MacKenna MJ. Differences in vitamin D status between countries in young adults and the elderly.  Am J Med. 1992;  93 69-77

Correspondence