The Chemistry of Vitamin D: Synthesis, Metabolism, and the Paradox of Deficiency in Sun-Rich Countries

Al-Johani, Adel Zaidan Masoud; Alenzi, Ali Saleh; Aldossari, Arwa Khalid; Alrowaily, Rimah Ali; Alanazi, Maha; Alkhadrawi, Mariam; Alfardan, Abrar; Alsumali, Ayan Mohammed; Alrashidi, Wedad Mohammed; Alanazi, Abdulrahman Rashed; Alanazi, Mohammed  Ayyat; Alyamani, Ibrahim Mohammed; Almontashiri, Mohammad Hamed; Alqurashi, Saud Mohsen; Alsomali, Manal Salem; Alrwis, Abdullah Saad; Hudays, Hussain Abdullah Yahya

doi:10.21608/ejchem.2025.419720.12275

The Chemistry of Vitamin D: Synthesis, Metabolism, and the Paradox of Deficiency in Sun-Rich Countries

Articles in Press

Document Type : Review Articles

Authors

¹ Ministry of National Guard, Saudi Arabia

² King Khalid University Hospital, King Saud University

10.21608/ejchem.2025.419720.12275

Abstract

Vitamin D, a secosteroid hormone, has a core role in calcium homeostasis and bone health, with recent studies suggesting its role in immune function, cardiovascular health, and cancer prevention. Its peculiar mechanism of synthesis, initiated by solar ultraviolet B (UVB) radiation in the skin, renders it an important interface between environmental exposure and biochemical regulation. In this review, we detail the intricate photochemistry of cutaneous vitamin D synthesis from its precursor 7-dehydrocholesterol through pre-vitamin D3 formation and its subsequent thermal isomerization. We then detail the enzymatic hydroxylation cascade in the liver and kidney, controlled by cytochrome P450 enzymes (CYP2R1 and CYP27B1), that produces the biologically active hormone, 1,25-dihydroxyvitamin D [1,25(OH)2D]. The main paradox discussed is the prevalence of vitamin D deficiency and insufficiency that is widespread and often high in populations residing in sun-rich geographical regions. This review synthesizes current evidence to describe the chemical, behavioral, and environmental determinants of this paradox, including the UVB-absorbing properties of melanin, the photolytic degradation of vitamin D and its precursors, clothing and sunscreen use, cultural practices, atmospheric pollution, and adiposity. We deduce that the simplistic equating of abundant sunshine with vitamin D sufficiency is both chemically and biologically naive, and public health policy must evolve to address this complex interplay of influences in order to reduce the health burden of widespread hypovitaminosis D.

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