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Introduction
Diffuse hair loss is not an infrequent complaint encountered by dermatologists globally, which can be disquieting to patients. Hair loss or alopecia has a diversity of causes which can be due to genetics, hormone imbalances, diet, drugs, stress, infections, or other systemic conditions.
Micronutrients are crucial elements in the hair follicle cycle, playing a pivotal role in cellular turnover, with-in the matrix cells in the follicle bulb1.
Vitamin D, a fat-soluble vitamin, is synthesized mainly by epidermal keratinocytes and dermal papillary cells through UVB-mediated conversion of 7-dehydrocholesterol to cholecalciferol in the skin, followed by further hydroxylation in the liver and kidney to 1, 25-dihydroxy vitamin D(1,25[OH]2D), the active form2,3.
Vitamin D exerts its action through the vitamin D receptor (VDR), whose expression is required for hair follicle differentiation but not for proliferation, and its deficiency can inhibit keratinocyte differentiation and disturb the normal hair follicle cycle4. VDR is also required for anagen initiation5.
Vitamin B12 has two active forms, methylcobalamin and 5 deoxyadenosyl cobalamin. It is a requisite for DNA synthesis, the formation of red blood cells, and neurological function6.
Data suggest that vitamin B12 supports the transition of the hair follicle into anagen by increasing transcription of β-catenin through Wnt signaling and reducing transcription of glycogen synthase kinase-3, which is an inhibitor of Wnt signalling7. Hence, it plays a role in hair follicle proliferation.
Iron deficiency is considered the leading nutritional deficiency affecting all age groups, especially women. An abnormal balance between cellular ferritin and free iron has been suspected as a mechanism for abnormal hair growth8, as dividing cells require higher ferritin. Serum ferritin level can be used as an early marker of iron deficiency as it is a main iron-binding protein in non-erythroid cells reflecting total body iron stores9.
Nutrition and diet can be harnessed to treat hair loss, which represents a vital area of exploration. Studies regarding the association of deficiency of micronutrients and hair loss are still a matter of ongoing research. Providing insights into the role of micronutrients in hair loss opens better therapeutic options.
Our study aims to study the type of hair loss in different age groups and to identify the prevalent micronutrient deficiency linked to hair loss to validate their supplementation in patients with hair loss. To seek to shed light on their connection, we compared serum ferritin, vitamin D, and vitamin B12 levels in individuals with hair loss among and control cases.
Methods
This is a cross-sectional study which included 50 cases of hair loss and 50 healthy age and sex-matched controls who presented to the Dermatology Outpatient Clinic of Katuri Medical College. Cases and controls between the age group of 18-50 years who were inclined to participate were included in the study after obtaining due informed consent. Pregnancy, breastfeeding, patients with chronic medical illness, and patients not willing to participate in the study were excluded from the study. All patients were subjected to detailed clinical history, and the diagnosis was made based on a detailed physical examination by a dermatologist in the department.
Under sterile conditions with minimum atmosphere, venous blood samples were collected from an accessible vein and sent for analysis. The levels of vitamin D, vitamin B12, and serum ferritin were measured by MAGLUMI 2000 Plus Fully Automated Hormone Analyzer using the Flash Chemiluminescent Immunoassay Nanotechnology method. The normal reference intervals were 30-100 ng/mL for vitamin D, 200-1100 pg/mL for vitamin B12, and, for serum ferritin 25-350 ng/ml in males and 13-232 ng/ml in females.
Data obtained were tabulated and assessed by IBM SPSS V20 software. Continuous variables are outlined using frequency, mean, and standard deviation, while categorical variables are summarized using frequency and percentage. Means among groups were compared using an independent t-test, and proportions were compared using the Chi-square test. P < 0.05 was considered statistically significant.
Results
Our study included 50 cases (25 females/25 males) and 50 age and sex-matched controls between the 18 and 50 years age group. The mean age of distribution among cases was 29.68 ± 7.32, and the majority of cases (56%) affected by hair loss were found to be in the 21-30 years age group (Table 1).
Table 1 Sociodemographic profile among cases and controls
| Sociodemographic profile | Cases | Controls |
|---|---|---|
| Gender | ||
| Male | 25 (50%) | 28 (56%) |
| Female | 25 (50%) | 22 (44%) |
| Age | ||
| < 20 | 4 (8%) | 3 (6%) |
| 21-30 | 28 (56%) | 29 (58%) |
| 31-40 | 13 (26%) | 16 (32%) |
| 40-50 | 5 (10%) | 2 (4%) |
| Age (mean ± SD) | 29.68 ± 7.32 | 28.9 ± 5.02 |
| Vitamin D | 24.23 ± 12.45 | 34.78 ± 9.64 |
| Vitamin B12 | 194.61 ± 72.75 | 248.38 ± 103.10 |
| Serum ferritin | 26.07 ± 13.92 | 32.01 ± 14.20 |
Out of different causes of hair loss, telogen effluvium was diagnosed in 30 patients (60%), followed by androgenetic alopecia, 18 cases in male patients (36%), and 2 in female (4%). The distribution of diagnosis was similar.
In all age groups, females had a greater predominance of telogen effluvium, while males had a greater predominance of androgenetic alopecia.
Vitamin D, vitamin B12, and serum ferritin were significantly low among cases compared to controls, as shown in figure 1. Females had considerably low levels of serum ferritin compared to males cases (p = 0.0001), while no such difference was seen with vitamin D (p = 0.185), and vitamin B12 (p = 0.802), as depicted in table 2.
Figure 1 Comparison of percentage of vitamin D, vitamin B12, and serum ferritin deficit among cases and controls.
Table 2 Mean values of vitamin D, vitamin B12, and serum ferritin among males and females
| Cases | Gender | t-value | p-value | |
|---|---|---|---|---|
| Male (mean ± SD) | Female (mean ± SD) | |||
| Vitamin D | 26.58 ± 13.43 | 21.88 ± 11.17 | 1.346 | 0.185 |
| Vitamin B12 | 192 ± 72.38 | 197.23 ± 74.51 | 0.252 | 0.802 |
| Serum ferritin | 35.65 ± 11.31 | 16.50 ± 8.77 | 6.69 | 0.0001 |
SD: standard deviation.
We observed low serum vitamin D levels in 62% (31 patients) of cases compared to 22% (11 patients) in controls with vitamin D level remarkably lower in cases than in controls (p = 0.0001), as shown in table 3.
Table 3 Vitamin D, vitamin B12, and serum ferritin percentages among cases and controls
| Vitamin D | Chi-square value | p-value | ||||
|---|---|---|---|---|---|---|
| Normal | Percentage | Deficit | Percentage | |||
| Cases | 19 | 38 | 31 | 62 | 16.42 | 0.0001 |
| Controls | 39 | 78 | 11 | 22 | ||
| Vitamin B12 | Chi-square value | p-value | ||||
| Normal | Percentage | Deficit | Percentage | |||
| Cases | 27 | 54 | 23 | 46 | 4.34 | 0.01 |
| Controls | 37 | 74 | 13 | 26 | ||
| Serum ferritin | Chi-square value | p-value | ||||
| Normal | Percentage | Deficit | Percentage | |||
| Cases | 35 | 70 | 15 | 30 | 6.25 | 0.006 |
| Controls | 45 | 90 | 5 | 10 | ||
Serum vitamin B12 was found to be deficient in 46% (23 patients) of cases compared to 26% (13 patients) in controls, with statistically significant lower levels in cases compared to controls (p = 0.01), as depicted in table 3.
Serum ferritin levels were low in 30% (15 patients) of cases compared to 10% (five patients) in controls, and the difference between case and control values was statistically significant (p = 0.006) (Table 3).
Out of 30 telogen effluvium cases, 20 (66%) had low vitamin D levels, 16 (53%) had low vitamin B12, and 14 (46%) had low serum ferritin levels.
Among the 18 cases of male androgenetic alopecia, 9 (50%) had low vitamin D, 7 (38%) had low vitamin B12, and 1 (5.5%) had low serum ferritin levels. On the other hand, the 2 (100%) cases of female androgenetic alopecia had low vitamin D levels, normal vitamin B12, and serum ferritin.
Discussion
Vitamin D, vitamin B12, and iron may be related to hair loss through several ascribed mechanisms. VDR activation plays a key role in the hair follicle cycle5 and its role in hair loss needs to be emphasized. To date, iron deficiency runs the most reported nutritional cause of hair loss. Evaluation of low iron stores is done through serum ferritin levels. Vitamin B12 association with hair loss stays an ongoing debate for years.
After exploring all contrasting reports regarding micronutrients and hair loss, we chalked out a strategy to evaluate serum vitamin D, vitamin B12, and serum ferritin levels in all patients with hair loss.
The age of disease distribution was between 18 and 45 years, most frequently 21-30 years, with a mean age of 29.68 ± 7.32 years. The common cause of hair loss according to our study, was telogen effluvium (60%), similar to the study by Rasheed et al.10 which included 80 female patients with a similar mean age (29.8 ± 9.3), of which 50% were telogen effluvium cases.
In this study, serum vitamin D, vitamin B12, and serum ferritin levels were significantly lower in cases with hair loss in accordance with Farah et al.8.
There is a significant difference between cases and controls (62% vs. 22%, p = 0.0001) considering serum vitamin D, which is in accordance with a study by Rasheed et al.10 who compared serum 25(OH)D levels in female patients with chronic telogen effluvium, female androgenetic alopecia, and healthy controls and also reported significantly lower serum 25(OH)D levels compared to the control group.
Similarly, Moneib et al.11 reported significantly lower serum 25(OH) D levels in patients with female androgenetic alopecia than in controls, and Samar et al.12 reported significantly lower vitamin D levels in male androgenetic alopecia cases.
Contrary to these studies, Karadag et al.13 found significantly higher serum 25(OH)D levels in patients with telogen effluvium than in controls.
Our study showed significantly low levels of vitamin B12 among cases than controls (46% vs. 26%, p = 0.01), consistent with results reported by Ebru et al.14, whereas Özden et al.15 found low vitamin B12 levels in only 2% of 100 individuals with diffuse hair loss.
The present study displays a significant correlation between hair loss and serum ferritin levels when compared with controls (30% vs. 10%, p = 0.006). These low serum ferritin levels were noted specially among females when compared to males (35.65 ± 11.31 vs. 16.50 ± 8.77, p = 0.0001).
Rasheed et al.10 also reported significantly low serum ferritin levels in both telogen effluvium and female androgenetic alopecia patients compared to controls and Tamer et al.16 also found that hair loss is associated with low serum ferritin levels in 54 patients with hair loss compared to controls. However, on the contrary, Bregy and Trueb17 found no association between serum ferritin level and hair loss.
Our study has certain limitations, such as a relatively small sample size (none of the pediatric age range, post-menopausal women, or elderly males are included), the absence of other types of hair loss (alopecia areata, frontal fibrosing alopecia, etc.), and the diagnosis being based only on the board-certified dermatologists' clinical experience. The study would have been more valuable if these components had been included from the study.
Conclusion
This study suggests that low levels of serum vitamin B12 and serum ferritin and particularly serum vitamin D may play a role in hair loss, especially in telogen effluvium among females. The identification of exact etiology of hair loss remains a primary concern as it is multifactorial, which paves the path to appropriate and effective treatment, evaluation of serum levels of these nutrients could aid the clinician in opting for a more precise complementary therapeutic modality, patient-wise.
