Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(4):e2024232 1 Filling the Gaps: Vitamin D Status in Diffuse Hair Fall Among Pakistanis Palwasha Jalil1, Sadia Masood2, Muhammad Sadique3, Maimoona Abdul Jalil4, Malghalura Jalil5, Laila Khan6 1 Consultant Dermatologist at (Aria Institute of Medical Sciences Quetta) 2 Associate professor of Dermatology at Aga khan University Hospital Karachi 3 Consultant Nephrologist at Balochistan Institute of Nephrology and Urology Quetta 4 Lecturer of physiotherapy at Indus Hospital Karachi 5 Consultant Gynecology and Obstetrics, Aria Institute of Medical Sciences Quetta 6 Consultant Ophthalmologist at Helper Eye institute Quetta Key Message: Our study underscores a significant link between low vitamin D levels and diffuse hair fall in Pakistani patients. A substantial number of individuals with hair loss were found to have inadequate vitamin D levels, highlighting the importance of considering vitamin D status in managing hair health. Key words: alopecia areata, diffuse hair fall, pattern hair loss, vitamin D3 Citation: Jalil P, Masood S, Sadique M, Abdul Jalil M, Jalil M, Khan L Filling the Gaps: Vitamin D Status in Diffuse Hair Fall Among Pakistanis. Dermatol Pract Concept. 2024;14(4):e2024232. DOI: https://doi.org/10.5826/dpc.1404a232 Accepted: May 8, 2024; Published: October 2024 Copyright: ©2024 Jalil et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Palwasha Jalil, Aria Institute of Medical Sciences Quetta; Phone: 03151820220; E-mail: drhilmand@gmail.com Introduction: Hair loss can happen for various reasons, including emotional stress, physical strain, certain medical issues, and nutritional gaps. When it comes to nutrition, a lack of vitamin D3 could be linked to diffuse hair loss. Objectives: The aim was to look for the frequency of vitamin D3 deficiency with diffuse hair fall, especially in the Pakistani population. Methods: A total of 120 patients of both sexes and all ages presenting to the Dermatology Clinic with complaints of non-scarring alopecia and loss of over 100 strands of hair within a 24-hour period (counted by patient) of any duration and positive hair pull test were advised to take serum vitamin D3. Tests and results were then analyzed by SPSS statistical software package (version 19.0 for Windows). Results: The mean age of participants enrolled in the study was 28.56 ± 11.62 years. The majority of the patients, i.e., 77 (63.64%), were ≤30 years of age. Among the 120 patients, 17 were males and 103 were females. Mean serum vitamin D3 levels were 17.33 ± 5.43 ng/ml. 95 (79.17%) patients ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(4):e2024232 Introduction Hair loss is frequently reported as a common concern among patients seeking care at dermatology clinics. It is often a dis- tressing problem with a great effect on the social and psycho- logical well-being of a person. Hair is not only an accessory and important aesthetically, but it also reflects many dis- eases, both systemic and localized to scalp. Around 100,000 hair follicles exist on the scalp of a healthy human, each going through various stages of the hair cycle simultaneously. A problem in any of the three stages of the hair cycle, i.e., anagen (active growth stage), catagen (stage of regression), or telogen (resting stage), can cause loss of hairs [1]. Hair fall, generally called alopecia, is defined as the loss of more than 100–150 hairs in the telogen phase [2]. Hair fall can broadly be classified into two classes ac- cording to the area of involvement: diffuse and focal hair fall [3]. Hair loss can happen for various reasons, including emotional stress, physical strain, certain medical issues, and nutritional gaps. When it comes to nutrition, a lack of vita- min D3 could be linked to diffuse hair loss [4, 5]. Vitamin D has an indispensable role in human health maintenance, growth, and development. It is a steroid with hormone-like activity. Vitamin D is acquired through diet, and its synthesis also happens under UV-B light (290-315 nm) effect in epidermal keratinocytes [6]. Observations from studies conducted on animals suggest that vitamin D3 plays a significant part in various stages of the hair follicle cycle [7]. This fact has been strengthened by some more studies carried out in patients having hereditary vitamin D recep- tor (VDR) deficiency, which showed a correlation between vitamin D3 levels and alopecia in these individuals [8]. On the other hand, more than one billion people are affected by vitamin D deficiency (25-hydroxyvitamin D) worldwide [9]. It is emerging as an epidemic involving every segment of the population irrespective of sex and age. Studies done in Pakistan showed 53.5% of the population to be vitamin-D3 deficient, 31.2% with low vitamin D3, and a mere 15.3% having sufficient vitamin D [10]. A previous study reported that 81.8% of patients presenting with diffuse hair fall in the clinics have vitamin D deficiency [2]. Objectives Our study sought to explore the frequency of vitamin D3 de- ficiency with diffuse hair fall. Numerous studies conducted in different parts of the world have indicated a significant connection between lower levels of vitamin D3 and hair loss [2, 4, 5, 8, 11]. More than 50% of the Pakistani population is suffering from vitamin D3 deficiency [10], but local data for the deficiency of vitamin D3 in patients having diffuse hair fall are not available. Methods Following the approval of the ethics review committee at a tertiary care hospital, we conducted this descriptive cross-sectional study in the department of dermatology over a 6-month period. A total of 120 patients of both sexes and all ages presenting in the dermatology clinic for complaints of non-scarring alopecia with a loss of over 100 strands of hair within a 24-hour period (counted by patient) of any du- ration and positive hair pull test (about 10% of hairs are easily pulled away from the scalp) were included. Patients who had been taking vitamin D supplements within one year or had anemia, thyroid abnormalities, bone diseases, or re- nal failure were excluded. Informed consent was taken from each patient. The hair pull test was performed, and a serum vitamin D3 test was recommended. The principal investiga- tor then entered the data into the proforma. Statistical Analysis We analyzed the results using the SPSS statistical software package (version 19.0 for Windows). The continuous vari- ables, such as duration, vitamin D3 levels, and age, are described using mean ± SD. Frequencies (%) were com- puted for categorical variables (male, female, vitamin D3 deficient yes and no, female pattern hair loss, male pattern hair loss, diffuse alopecia areata, telogen effluvium) for the characteristics of participating subjects. Vitamin D3 levels were categorized as either less than 20 ng/ml or more than 20 ng/ml. were found to be vitamin D3 deficient, with 37 patients having female pattern hair loss, seven patients with male pattern hair loss, seven patients with diffuse alopecia areata, and 44 patients with telogen effluvium. Conclusions: This study concluded that there is considerable frequency of vitamin D3 deficiency in individuals with diffuse hair fall. Therefore, we recommend that there should be early recognition and treatment of this condition in these particular patients in order to reduce hair fall. Original Article | Dermatol Pract Concept. 2024;14(4):e2024232 3 To manage effect modifiers like age, sex, and duration, we implemented stratification. Subsequently, a chi-square test with post-stratification was performed, using a signifi- cance level of P ≤ 0.05. Results The mean age of the patients enrolled in the study was 28.56 ± 11.62 years. Most of the patients, i.e., 77 (63.64%), were ≤30 years of age. Mean duration of disease was 3.76 ± 2.38 years (Table 1). Of the 120 patients, 17 (14.17%) were males and 103 (85.83%) were females, with a male-to-female ratio of 1:5.7. The distribution of patients according to diagnosis and stratification for vitamin D3 deficiency with respect to age group, sex, duration, and diagnosis of disease is shown in Table 1. Mean serum vitamin D3 levels were 17.33 ± 5.43 ng/ml. Frequency of vitamin D3 deficiency in patients with diffuse hair fall was seen in 95 (79.17%) patients (figure I), with 37 patients having female pattern hair fall, seven patients with male pattern hair fall, seven patients with diffuse alopecia areata, and 44 patients with telogen effluvium. Discussion It is a well-known fact that 1,25-(OH)2 D exerts its effects when it attaches to vitamin D receptor (VDR). VDR is dis- tributed throughout the body in appendageal structures like hair follicles, in immune and other system cells involved in bone and calcium metabolism [12]. The expression of VDR in the mesenchymal dermal papilla cells and epidermal ke- ratinocytes varies based upon the phase of the hair cycle [13]. Considering this perspective, several studies have been conducted, such as the one by Dorach et al., exploring the connections between serum vitamin D levels, disease sever- ity, and the expression of the vitamin D receptor (VDR) in hair follicles of patients with alopecia areata (AA). The au- thors compared 30 AA patients with 30 healthy controls and found that 96.7% of AA patients had vitamin D deficiency, while only 73.3% of healthy controls were deficient. The duration of the disease and severity negatively correlated with serum vitamin D levels, but there was no correlation between the VDR expression on the hair follicles and the pattern of AA. In tissue samples obtained from the patients, VDR expression was diminished in all of them and remained within the standard range in the control group. Additionally, it was found that VDR expression was significantly reduced in areas of increased inflammation [14]. Many other studies have explored the involvement of vi- tamin D in telogen effluvium (TE), with conflicting results. Rasheed et al. [15] and Nayak et al. [2] documented that female patients with TE were found to have significantly reduced serum vitamin D levels compared to their healthy controls, with the most diminished levels observed among individuals with the most pronounced hair loss. This implies a potential role of vitamin D in TE. However, Karadag et al. discovered notably elevated serum vitamin D levels in TE patients compared to the control group. Interestingly, a higher concentration of serum 25(OH) D in the upper quad- rant was linked with an increased likelihood of having TE. The authors proposed that the noted rise in serum vitamin D levels in patients with TE could be a compensatory response to hair loss rather than the cause [16]. Similarly, Yilmaz et al. documented no notable connection between 1,25 (OH)2 D levels and the severity of hair fall, the duration of the disease, the count of patches, or nail involvement in 42 patients with AA [17]. However, further studies reported a correlation be- tween these factors. The differences in results could be due to variations in enrollment criteria, including AA severity and Table 1. Stratification of vitamin D3 deficiency with respect to demographic variables and disease diagnosis. No of Patients Vitamin D3 Deficiency P-ValueYes No Age (years) ≤16 12 10 02 0.708 >16 108 85 23 Duration (years) ≤5 years 89 72 17 0.429 >5 years 31 23 08 Sex Male 17 14 03 0.727 Female 103 81 22 Diagnosis Male pattern hair loss 08 07 01 0.137 Female pattern hair loss 53 37 16 Diffuse alopecia areata 09 07 02 Telogen effluvium 50 44 06 4 Original Article | Dermatol Pract Concept. 2024;14(4):e2024232 2. Nayak K, Garg A, Mithra P, Manjrekar P. Serum vitamin D3 levels and diffuse hair fall among the student population in South India: a case–control study. Int J Trichology.2016;8(4):160. DOI: 10.4103/ijt.ijt_57_16. 3. Mubki T, Rudnicka L, Olszewska M, Shapiro J. Evaluation and diagnosis of the hair loss patient: part I. History and clinical examination. J Am Acad Dermatol. 2014;71(3):415. e1-. e15. DOI: 10.1016/j.jaad.2014.04.070. 4. Guo EL, Katta R. Diet and hair loss: effects of nutrient deficiency and supplement use. DOI: 10.5826/dpc.0701a01 Dermatol Pract Concept. 2017;7(1):1. DOI: 10.5826/dpc.0701a01. 5. Gerkowicz A, Chyl-Surdacka K, Krasowska D, Chodorowska G. The role of vitamin D in non-scarring alopecia. Int J Mol Sci. 2017;18(12):2653. DOI: 10.3390/ijms18122653. 6. Wierzbicka JM, Żmijewski MA, Piotrowska A, Nedoszytko B, Lange M, Tuckey RC, et al. Bioactive forms of vitamin D selectively stimulate the skin analog of the hypothalamuspituitary-adrenal axis in human epidermal keratinocytes. Mol Cell Endocrinol. 2016;437:312-22. DOI: 10.1016/j.mce.2016.08.006. 7. Lisse TS, Saini V, Zhao H, Luderer HF, Gori F, Demay MB. The vitamin D receptor is required for activation of cWnt and hedgehog signaling in keratinocytes. Mol Endocrinol. 2014; 28(10):1698-706. DOI: 10.1210/me.2014-1043. 8. Casey G, McPherson T, Kini U, Ryan F, Taibjee SM, Moss C, et al. Hereditary vitamin d–resistant rickets presenting as alope- cia. Pediatr Dermatol. 2014;31(4):519-20. DOI: 10.1111/pde .12327. 9. Sahota O. Understanding vitamin D deficiency. Age Ageing. 2014;43(5):589. DOI: 10.1093/ageing/afu104. 10. Riaz H, Finlayson A, Bashir S, Hussain S, Mahmood S, Malik F, et al. Prevalence of Vitamin D deficiency in Pakistan and impli- cations for the future. Expert Rev Clin Pharmacol. 2016;9(2): 329-38. DOI: 10.1586/17512433.2016.1122519. 11. Aksu Cerman A, Sarikaya Solak S, Kivanc Altunay I. Vitamin D deficiency in alopecia areata. Br J Dermatol. 2014;170(6): 1299-304. DOI: 10.1111/bjd.12980. 12. Demay MB. The hair cycle and Vitamin D receptor. Arch Biochem Biophys. 2012;523:19–21. DOI: 10.1016/j.abb.2011.10.002. patient numbers, or seasonal variations in serum 25(OH) D levels. Aksu Cerman et al. [18] carried out their study in winter, while Yilmaz et al. conducted theirs in the summer. Additionally, there are inconsistent findings regarding the se- rum vitamin D levels of female and male AA patients. Some studies report lower levels in males, while others report the opposite or no association with sex. This variation could be influenced by cultural and religious factors affecting vitamin D formation [18-21]. Conclusion Keeping in mind the sparsity of similar data in the Pakistani population, in this study, the aim was to ascertain the frequency of vitamin D3 deficiency in patients with diffuse hair fall. The results showed that out of the 120 patients with diffuse hair fall, including female pattern hair fall (n=37), male pattern hair fall (n=7), diffuse alopecia areata (n=7), and telogen effluvium (n=44), 95 (79.17%) had vitamin D3 deficiency which is sig- nificantly low enough to conclude the necessity of inquiring about any vitamin D deficiency-related symptoms, advising the relevant investigations, and then replenishing the deficiency in the patient presenting with hair fall as the early recognition and treatment of this condition may help reduce hair fall. However, it is important to acknowledge that our study’s small sample size (n=120) is a limitation, and future studies with larger sam- ples are needed to confirm and generalize our findings. References 1. Oh JW, Kloepper J, Langan EA, Kim Y, Yeo J, Kim MJ, et al. A guide to studying human hair follicle cycling in vivo. J Invest Dermatol. 2016;136(1):34-44. DOI: 10.1038/JID.2015.354. Figure 1. Frequency of vitamin D3 deficiency in patients presenting with diffuse hair fall (n=120). Original Article | Dermatol Pract Concept. 2024;14(4):e2024232 5 17. Yilmaz, Nigar & Serarslan, Gamze & Gokce, Cumaali. (2012). Vitamin D Concentrations are Decreased in Patients with Alopecia Areata. Vitamin Trace Elem. 01. 10.4172/2167-0390 .1000105. DOI:10.4172/2167-0390.1000105. 18. Aksu Cerman A, Sarikaya Solak S, Kivanc Altunay I. Vitamin D defi ciency in alopecia areata. Br J Dermatol. 2014;170: 1299–304. DOI: 10.1111/bjd.12980. 19. D’ Ovidio R, Vessio M, d’ Ovidio FD. Reduced level of 25- hydroxyvitamin D in chronic/relapsing Alopecia Areata. Dermatoendocrinol. 2013;5:271–3. DOI: 10.4161/derm.24411. 20. Ghafoor R, Anwar MI. Vitamin D Deficiency in Alopecia Areata. Br. J. Dermatol. 2017;27:200–202. PMID: 28492146. 21. Darwish NMM, Marzok HF, Gaballah MAM, Adbellatif HE. Serum level of vitamin D in patients with alopecia areata. Egypt. J. Basic Appl. Sci. 2017;4:9–14. https://doi.org/10.1016/j.ejbas .2016.12.001. 13. Demay MB, MacDonald PN, Skorija K, Dowd DR, Cianferotti L, Cox M. Role of the vitamin D receptor in hair follicle biology. J Steroid Biochem Mol Biol. 2007;103:344–6. DOI: 10.1016 /j.jsbmb.2006.12.036. 14. Daroach M, Narang T, Saikia UN, Sachdeva N, Sendhil Kumaran M. Correlation of vitamin D and vitamin D receptor expression in patients with alopecia areata: a clinical paradigm. Int J Dermatol. 2018;57(2):217–22. DOI: 10.1111/ijd.13851. 15. Rasheed H, Mahgoub D, Hegazy R, El-Komy M, Abdel Hay R, Hamid MA, et al. Serum ferritin and vitamin d in female hair loss: do they play a role? Skin Pharmacol Physiol. 2013;26: 101–7. DOI: 10.1159/000346698. 16. Karadag AS, Ertugrul DT, Tutal E, Akin KO. The role of anemia and Vitamin D levels in acute and chronic telogen effluvium. Turk. J. Med. Sci. 2011;41:827–833. https://doi.org/10.3906 /sag-1005-853.