Vitamin D is a fat-soluble secosteroid, that is, a steroid molecule with an open ring. It can be produced by the human body endogenously: for example, by exposure of the skin to sunlight.  

Vitamin D refers to five compounds (vitamins: D₁, D₂, D₃, D₄ and D₅), of which the most important are:

• vitamin D₂ ergocalciferol 
• vitamin D₃ cholecalciferol 

Vitamin D₂ derives from irradiation of the plant sterol, ergosterol, and is provided by the diet. Vitamin D₃ originates from a cutaneous compound by endogenous synthesis. Vitamin D was initially described at the time of the industrial revolution, when England faced rickets; since then, the relation between vitamin D and calcium-phosphorus metabolism has never been discussed. However, over the last four decades, other activities of vitamin D have been highlighted. Actually, vitamin D is considered as a neurohormone that regulates cell growth and proliferation and immunomodulation (1).

Description of raw materials used in production. 

• Vitamin D₃ can be derived from various sources, including lanolin (a fatty substance derived from sheep's wool) and cod liver oil.

Step-by-step summary of industrial production process.

• Extraction of raw material. For instance, lanolin is extracted from washed sheep’s wool.
• UV Irradiation. Lanolin or 7-dehydrocholesterol is irradiated with UV light to convert it into cholecalciferol.
• Purification. Cholecalciferol is purified through various filtration and separation processes.
• Packaging. The final product, vitamin D₃, is then packaged in various forms, such as capsules or drops, for distribution.

Commercial applications. 

Vitamin D₃ is used in dietary supplements, fortified foods, and medications to help maintain bone health and support the immune system.

Dietary Supplementation. Vitamin D₃ is widely used in dietary supplements to support bone health, promoting calcium absorption and bone mineralization.

Food Industry. It's also used as a food additive to fortify various products, like milk, juices, and cereals, to enhance vitamin D content.

Pharmaceuticals. In the pharmaceutical industry, Vitamin D₃ is utilized in various formulations for treating deficiencies and supporting skeletal health.

Cosmetics. In some skincare products, Vitamin D₃ is utilized for its antioxidant properties and support of skin health.

Medical Research. Vitamin D₃ is the subject of numerous studies exploring its effects on various bodily functions and health conditions beyond bone health, such as the immune system and preventing certain chronic diseases.

Vitamin D₃ that we find in pharmacies comes in transparent liquid form, gel. tablets, chewing gum. Industrially it is a fine white powder. Vitamin D₃ can present in various commercial forms, including capsules, tablets, drops, and powders. Generally, in its pure forms, it may appear as a crystalline powder that is white or slightly yellow in color.

Vitamin D₃ , Dry Eye Disease and Ocular inflammation

To investigate the efficacy of topical carbomer-based lipid-containing artificial tears (CLAT) and hyaluronate (HU) in patients with dry eye disease (DED) based on serum 25-hydroxyvitamin D (25HD) levels and cholecalciferol (vitamin D) supplementation. The effect of topical CLAT and HU was dependent on serum 25HD levels. Cholecalciferol supplementation enhanced the efficacy of topical treatment and may be a useful adjuvant therapy for patients with DED refractory to topical lubricants (2).

Poor corneal permeability, nasolacrimal drainage and requirement of chronic administration are major drawbacks of existing therapies for ocular inflammation. Hence, we designed topical micelles of PEG2000 conjugated with cholecalciferol (PEGCCF). Integrin targeted tacrolimus loaded PEGCCF micelles (TTM)  is an innovative delivery system for improving ocular inflammation due to a) integrin targeting b) PEGCCF in the form of carrier and c) anti-inflammatory and synergistic effect (due to Pgp inhibition) with TAC (3).

Vitamin D₃ and weight loss

Obesity, a chronic condition associated with several life-threatening diseases, affects a significant proportion of the global population and has long been associated with vitamin D deficiency. Based on  results, a combined Ca and vitamin D₃ supplement appears to enhance weight loss and improve some of the blood metabolic profiles in obese women subjected to a weight loss diet, thus supporting our study hypothesis (4).

Vitamin D₃ as prophylaxis in patients with benign prostatic hyperplasia

To explore the role of cholecalciferol for the prophylaxis against recurrent urinary tract infection (UTI) in patients with benign prostatic hyperplasia (BPH). Adjuvant cholecalciferol supplementation may be protective against recurrent UTI among patients with BPH receiving tamsulosin therapy without extra adverse effects (5).

Vitamin D₃ and pregnancy

In summary, the observational and randomized clinical trials present a clear message: that 4,000 IU/d vitamin D3 supplementation is beneficial to both mother and her developing fetus through optimization of vitamin D metabolism that goes beyond classical calcium and bone homeostasis. While further work is needed to determine what the optimal dose of vitamin D supplementation during pregnancy is based on various genotype differences for the vitamin D binding protein and the vitamin D receptor, body mass index, status at the time of conception, and other factors such as sunlight exposure and latitude, based on our work and that of others, we believe that all individuals, including pregnant women, should achieve a target circulating 25(OH)D concentration of 100 nmol/L (40 ng/mL) as early as possible. Because of individual differences in what is required to attain this target concentration of 25(OH)D, we believe all women should consume at least 4,000 IU/d vitamin D₃ prior to conception and throughout pregnancy (6).

Vitamin D₃ and Type1 Diabetes 

Recent prospective studies have found the associations between type 1 diabetes (T1D) and vitamin D deficiency. We investigated the role of vitamin D in the regulation of 25OHD-1α-hydroxylase (CYP27B1) and VDR expression in different tissues of T1D rats. T1D-induced vitamin D deficiency is associated with impairments of renal and extrarenal CYP27B1 and VDR expression. Cholecalciferol can be effective in the amelioration of diabetes-associated abnormalities in the vitamin D-endo/para/autocrine system (7).

The aim of this study was to examine the effects of vitamin D supplementation in patients newly diagnosed with type 1 diabetes (T1D) assessed by insulin needs and changes in glycemic indices, as evidenced by randomized controlled trials (RCTs). Vitamin D supplementation in the form of alphacalcidole and cholecalciferol appears to be beneficial in the treatment of T1D patients by attenuating the natural history of the disease (8).

Typical optimal characteristics of a Vitamin D₃ commercial product 

• Molecular Formula  C₂₇H₄₄O 
  
• Molecular Weight  384.6
  
• CAS    67-97-0
•  UNII 1C6V77QF41
• EC Number    200-673-2    215-797-2
• DSSTox Substance ID: DTXSID1026295
• MDL number  MFCD00078131
• NCI   C48194
• PubChem Substance ID  329823242
• Bellstein   2339331
• InChIKey:    QYSXJUFSXHHAJI-YHJXBONMSA-N
• NACRES  NA.24

References________________________________________________

 (1) Bivona G, Agnello L, Ciaccio M. The immunological implication of the new vitamin D metabolism. Cent Eur J Immunol. 2018;43(3):331-334. doi: 10.5114/ceji.2018.80053. 

 (2) Hwang JS, Lee YP, Shin YJ. Vitamin D Enhances the Efficacy of Topical Artificial Tears in Patients With Dry Eye Disease. Cornea. 2019 Mar;38(3):304-310. doi: 10.1097/ICO.0000000000001822. 

 (3) Kutlehria S, Vhora I, Bagde A, Chowdhury N, Behl G, Patel K, Singh M. Tacrolimus Loaded PEG-Cholecalciferol Based Micelles for Treatment of Ocular Inflammation. Pharm Res. 2018 Apr 16;35(6):117. doi: 10.1007/s11095-018-2376-7. 

 (4) Subih HS, Zueter Z, Obeidat BM, Al-Qudah MA, Janakat S, Hammoh F, Sharkas G, Bawadi HA. A high weekly dose of cholecalciferol and calcium supplement enhances weight loss and improves health biomarkers in obese women. Nutr Res. 2018 Nov;59:53-64. doi: 10.1016/j.nutres.2018.07.011. 

 (5) Safwat AS, Hasanain A, Shahat A, AbdelRazek M, Orabi H, Abdul Hamid SK, Nafee A, Bakkar S, Sayed M. Cholecalciferol for the prophylaxis against recurrent urinary tract infection among patients with benign prostatic hyperplasia: a randomized, comparative study. World J Urol. 2019 Jul;37(7):1347-1352. doi: 10.1007/s00345-018-2536-8.

 (6) Wagner CL, Hollis BW. The Implications of Vitamin D Status During Pregnancy on Mother and her Developing Child. Front Endocrinol (Lausanne). 2018 Aug 31;9:500. doi: 10.3389/fendo.2018.00500.

 (7) Mazanova A, Shymanskyi I, Lisakovska O, Hajiyeva L, Komisarenko Y, Veliky M. Effects of Cholecalciferol on Key Components of Vitamin D-Endo/Para/Autocrine System in Experimental Type 1 Diabetes. Int J Endocrinol. 2018 Feb 6;2018:2494016. doi: 10.1155/2018/2494016.

 (8) Gregoriou E, Mamais I, Tzanetakou I, Lavranos G, Chrysostomou S. The Effects of Vitamin D Supplementation in Newly Diagnosed Type 1 Diabetes Patients: Systematic Review of Randomized Controlled Trials. Rev Diabet Stud. 2017 Summer-Fall;14(2-3):260-268. doi: 10.1900/RDS.2017.14.260.