A Study of Micronutrient Levels in Premature Canities in Children : Indian Journal of Paediatric Dermatology

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Original Article

A Study of Micronutrient Levels in Premature Canities in Children

Yadav, Deepika; Chander, Ram; Mendiratta, Vibhu; Debnath, Ekta1; Bisherwal, Kavita; Das, Suparna

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Indian Journal of Paediatric Dermatology 23(4):p 297-301, Oct–Dec 2022. | DOI: 10.4103/ijpd.ijpd_153_21
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Abstract

Introduction

Hair is said to be prematurely gray if it occurs before 20 years in whites, before 25 years in Asians, and before 30 years in Africans.[1] Bhat et al. found the prevalence of canities to be 1.2%.[2] Rapidly dividing and proliferating cells of hair follicle require synthesis of DNA, which in turn requires sufficient supply of Vitamin B12 and folic acid.[3] Premature graying is also linked to low bone mineral density which may be due to Vitamin D deficiency. Calcium is also involved in the process of melanogenesis.[4] Various minerals such as copper, zinc, and iron are also known to be involved in the process of melanogenesis.[56] Tyrosinase enzyme which is involved in melanogenesis requires binding of copper ions and may be affected in patients of premature canities with low serum copper levels. Magnesium acts as a cofactor for over 300 enzyme systems and plays an important role in nucleotide synthesis, a frequent process in the rapidly dividing hair follicle.[7] Therefore, magnesium deficiency can play a role in the pathogenesis of premature canities.

There is paucity of studies evaluating the micronutrients levels in premature canities in pediatric patients. Therefore, we undertook this study to assess the serum levels of micronutrients in these patients.

Materials and Methods

This was a hospital-based observational study conducted over a period of 17 months from November 2018 to March 2020 in dermatology outpatient department of a tertiary care hospital in North India. Fifty-six cases with premature canities with >5 gray hair fibers and 50 age- and sex-matched healthy controls aged between 12 and 18 years were included in the study. The exclusion criteria were a history of use of supplementary drugs (Vitamin B12 and mineral supplement in the past 3 months), patients with vitiligo, thyroid disorder, alopecia areata, chronic protein loss, premature ageing syndromes, HIV, lymphoma, history of drug use such as chloroquine, mephenesin, and phenylthiourea, in the past 3 months. A detailed history including age of onset, history of hair care procedure, medical history (anemia, thyroid, and chronic kidney disease), and family history was taken. Distribution of canities was examined as approximately 50–60 hairs that were grasped between two fingers from the central regions of five areas of scalp including frontal, bi-temporal, parietal, vertex, and occipital. The number of gray hair fibers in each area was counted and was then added to give “total number of gray hairs.” These total number of gray hairs were then tabulated and accordingly severity was calculated as mild <50 hairs, moderate (50–100 hairs) and severe (>100 hairs).[2]

Venous blood was collected from antecubital vein from all patients and controls after overnight 8 h of fasting. Plasma was separated by centrifugation at 3500 rpm for 15 min and was collected in aliquots and kept at -20° centigrade. Copper, zinc, iron, and magnesium were analyzed using the colorimetric method by respective kits on fully automated analyzed. Deficiency of serum copper was considered as levels <11.0 mmol/l in males and <12.6 mmol/l in females. Deficiency of serum zinc and magnesium was considered as levels <11.5 mmol/l and <1.9 mg/dl, respectively. Deficiency of serum iron was considered as <70 mg/dl in males and <80 mg/dl in females. Vitamin B12, folic acid, and Vitamin D were analyzed by the chemiluminescence method on fully automated immunoassay analyzer. Deficiency of serum Vitamin B12, folic acid, and Vitamin D was considered as <180 pg/ml, <6.5 nmol/l, and <12.5 ng/ml, respectively.

Statistical analysis

The collected data were entered in Microsoft Excel. Data were analyzed and statistically evaluated using SPSS-PC-19 version (IBM,Version 19.0. Chicago: SPSS Inc). Quantitative data were expressed in mean ± standard deviation or median with inter quartile range. Qualitative data were expressed in percentage. Student’s t-test (unpaired) or Mann–Whitney “U”- test was used to see the difference between two comparable groups. ANOVA or Kruskal–Wallis H-test followed by post hoc test was used for more than two group comparison. Chi-square test or Fisher’s exact test was used to see the statistical differences between the proportions. Spearman correlation coefficient was used to see the correlation between gray hair count with micronutrients levels. “P” < 0.05 was considered statistically significant.

Observations and Results

Demographic data

The mean age of cases was 14.93 ± 2.03 years and that of controls was 14.88 ± 2.35 years (P = 0.82). Out of 56 cases, 29 (51.8%) were male and 27 (48.2%) were female. In control group, 29 (58.0%) were male and 21 (42.0%) were female (P = 0.52).

Clinical data

Duration of disease

Mean duration of disease was 20.45 ± 20.56 months with range varying from 1 to 120 months.

Origin and progression of graying

Premature graying originated from different sites in different patients is shown in Table 1. Progression of graying was present in 54 (96.4%) cases. Majority, i.e., 46 (82.1%) patients progressed to develop diffuse pattern of graying. Four patients (7.1%) progressed to have involvement of vertex, frontal and parietal region, 3 (5.4%) had eventual involvement of vertex and frontal region, frontal and occipital progression was seen in 1 (1.8%) patient. Two (3.6%) patients did not progress beyond occipital region.

T1
Table 1:
Site of origin of graying in premature canities

Severity of canities and number of gray hairs

Maximum number of the patients, 36 (64.3%) had mild grade of severity of premature greying, 16 (28.6%) patients had moderate grade and 4 (7.1%) cases had severe grade. Number of gray hair ranged between 10 and 150 gray hair with the mean number of gray hair fibers being 41.84 ± 29.32.

Family history

In cases, family history of premature graying was present in 29 (51%) patients while in controls, family history was present in 8 (16%) (P < 0.01). Maternal history and paternal history were present in 16 (28.6%) and 8 (14.3%), respectively. Siblings were involved in 5 (8.9%) cases.

History of atopy, procedures, topical application

Atopy was present in 4 (7.1%) cases, while in controls, atopy was present in 3 (6%) patients (P = 0.99). History of hair ironing was present in 2 (3.6%) cases as compared to 5 (10%) in controls (P = 0.25). History of hair coloring was present in two (3.6%) cases, whereas in controls, it was present in 3 (6.0%) patients (P = 0.99).

Biochemical parameters

With respect to micronutrients evaluated, mean copper levels in cases were low as compared to controls (P = 0.07). Among cases, 14 (25.0%) had deficiency of copper against 4 (8.0%) in control group (P = 0.02) [Table 2 and Figure 1]. No significant association between severity of canities and copper levels was found (P = 0.57).

T2
Table 2:
Mean serum levels of micronutrients in cases and controls
F1
Figure 1:
Bar graph showing deficiency of micronutrients in cases and controls

Means serum zinc levels in cases were significantly low as compared to controls (P < 0.0001). Eleven (19.6%) cases had deficiency of zinc against 2 (4.0%) in control group (P = 0.01) [Table 2 and Figure 1]. No significant association between severity of canities and zinc levels were found.

Mean serum iron levels were low in cases as compared to controls (P = 0.44).29 (51.8%) cases had deficiency of iron against 16 (32.0%) in control group, difference was statistically significant (P = 0.03) [Table 2 and Figure 1]. Serum iron levels were low in severe canities compared to mild and moderate grade, however that was not significant.

Mean serum magnesium levels in cases were significantly low as compared to controls. 21 (37.5%) cases had deficiency of magnesium while 3 (6.0%) controls had deficiency of magnesium (P < 0.001) [Table 2 and Figure 1]. No association between serum magnesium and severity of canities was found.

Mean serum Vitamin B12 levels were significantly low in cases compared to controls (P < 0.01). In cases, 22 (39.3%) were deficient in serum Vitamin B12 while in controls, 4 (8.0%) were deficient (P < 0.001) [Table 2 and Figure 1]. Serum levels were low in severe canities compared to mild and moderate severity (P = 0.06).

No significant difference was found between mean serum levels of Vitamin D and folic acid in cases and controls. No association with severity was found [Table 2 and Figure 1].

Discussion

Premature canities refers to loss of hair pigment, at an earlier age than normal.[1] Vitamins and minerals are involved in the various steps of melanogenesis. There is paucity in the current literature on possible correlation between the serum levels of micronutrients and premature graying of hair. In demographic data, mean age of cases and controls was 14.93 ± 2.03 years and 14.88 ± 2.35 years, respectively, which was similar to a study conducted by Daulatabad et al.[8] Bhat et al. and Fatemi et al. found mean age as 16.8 years and 17.8 ± 2.0, respectively, which was slightly higher as compared to our study.[29]

In our study, 51.8% were males and 48.2% were female (P = 0.52). In most of the studies, no sex predilection has been reported.[281011] Similar results were seen in our study. However, in a recent study conducted by Saad et al., female predilection was reported.[12]

The mean age of onset of graying in our study was 13.20 ± 1.91 months with range varying from 9 to 17 years. Mean age of onset in our study was similar to the study conducted by Nidhi et al.[13] Mean age of onset was slightly lower in a study conducted by Daulatabad et al. and Sonthalia et al.(11.6 ± 3.6 years and 10.2 ± 3.6 years, respectively).[810]

Mean duration of disease in our study was 20.45 ± 20.56 months with range varying between 1 and 120 months. In the study conducted by Sharma and Dogra, mean duration of disease was 21.74 ± 13.86 months which was similar to our study.[13] Mean duration of disease was higher in study conducted by Daulatabad et al.[8] and Sonthalia et al.[10] probably because of difference in age of patients in both the studies. They had taken patients with <20 years and <25 years, respectively, while in our study, age group comprised of 12–18 years.

The first site of involvement was frontal in most of our cases. This could be because this site is easily amenable to examination. In a study by Daulatabad et al., frontal region was first affected area in maximum no of patients.[8] In a study by Mediratta et al., graying started from occiput in (36.4%) and frontal (34%) in male patients, whereas in females, frontal area (44.6%) was the first involved site.[11]

Daulatabad et al. reported diffuse pattern of graying as the most common pattern of involvement. In their study, frontal and vertex regions were the most affected.[8] In our study also, we reported diffuse pattern of graying as the most common pattern. Frontal region was the most affected region followed by vertex, parietal, and occipital regions. In study by Mediratta et al., frontal area (40%) was involved in the maximum number of patients.[11]

Atopy was present in 4 (7.1%) cases and 3 (6%) controls (P = 0.99). Daulatabad et al. reported significant difference in atopy in cases (36.5%) as compared to controls (9.6%) in their study.[8] In a study by Sharma and Dogra, history of atopic diathesis was present 40.83% patients as compared to 10.83% in controls (P < 0.0001).[13] Mendiratta et al.[11] reported atopy in 31% cases and in study by Acer et al. atopy was present in 17% of patients.[14] However, controls were not included in both the studies. Lower percentage of atopy in our study could be due to unreliable history.

In our study, family history was present in 29 (51%) cases and 8 (16%) in controls (P < 0.01). Siblings were involved in 5 (8.9%) cases, maternal history in 16 (28.6%) cases, and paternal history in 8 (14.3%) cases. In a study by Daulatabad et al., Sonthalia et al., and Sharma and Dogra, family history found was higher than our study as 65.83%, 75%, and 90%, respectively.[81013] Acer et al. reported maternal involvement in 20% patients, paternal involvement in 23% patients. Both were involved in 11% patients.[14] In most of other studies, no sex predilection regarding maternal and paternal involvement was seen.[1415]

Majority of the patients 36 (64.3%) had mild graying while 16 (28.6%) had moderate graying and 4 (7.1%) had severe graying. We have used the criteria for classifying severity similar to Bhat et al.[2] In their study, 11.5% had mild, 65.7% had moderate, and 23% had severe graying of hair.[2] Singal et al. used an objective criteria for classifying the severity and found that graying was mild in 17%, moderate in 61.54%, and severe in 5.7% in their study.[16]

In our study, mean serum level of copper in cases (14.67 ± 3.43 mmol/l) was low as compared to controls (15.82 ± 2.72 mmol/l) (P = 0.07). 14 (25.0%) cases and 4 (8.0%) controls had deficiency of copper (P = 0.02). There are very few studies evaluating serum copper levels and premature hair graying in the literature. In study by Fatemi et al., mean serum copper levels in cases (90.7 ± 37.4) mg/dl were significantly low as compared to controls (105.3 ± 50.2).[9] No significant differences were found in a study conducted by Chakrabarty et al. and El-Sheikh et al.[1718]

We found mild negative correlation with severity of canities, however that was non significant. Similar results were also found in other study. We found significantly decreased serum zinc levels in cases as compared to controls (12.72 ± 3.01 vs. 16.76 ± 5.27 mmol/l) (P < 0.0001). No of cases having deficiency were also high in cases compared to controls, difference being statistically significant. However, no significant difference in serum zinc levels was found between cases and controls in other studies.[918] We found no association with severity of canities and there are no other studies comparing severity with zinc levels.

We found decreased serum iron levels in cases compared to controls (P = 0.44). Number of cases having deficiency was higher in cases compared to controls that were significant (51.8% vs. 32%). In studies by El-Sheikh et al. and Bhat et al., mean serum levels were low in cases and difference was statistically significant.[1719] We found no significant association with severity of canities. Bhat et al. also found no association with severity of canities.[19] However, significant negative correlation with severity was found in another study.[17]

In our study, mean serum level of magnesium in cases (1.97 ± 0.34 mg/dl) was significantly low as compared to controls (2.23 ± 0.34 mg/dl) (P < 0.001). Twenty-one (37.5%) cases had deficiency of magnesium, whereas 3 (6.0%) controls had deficiency of magnesium (P < 0.001). This was first study evaluating serum magnesium in premature canities. We could not find any other study evaluating the serum levels of magnesium in premature graying of hair in the literature.

Mean serum level of Vitamin B12 in cases was significantly low as compared to controls (P < 0.01) in our study. 22 (60.7%) cases and 4 (8.0%) controls had deficiency of Vitamin B12 (P < 0.001). In the study by Daulatabad et al., mean serum Vitamin B12 levels were significantly low in cases.[20] Sharma and Dogra reported Vitamin B12 deficiency in 64.17% cases and 15% controls.[13] We found mild negative correlation of Vitamin B12 with gray hair count (r = − 0.068) but that was not significant.

We found no significant difference in mean serum Vitamin D levels between cases and controls. Results similar to our study were found in other studies.[1318] However, Bhat et al. found high number of deficient and insufficient among cases compared to controls.[2] No significant difference in serum folic acid levels was found between cases and controls. Thompson et al. found results similar to our study.[21] However, Daulatabad et al. found significant difference between cases and controls.[20] Oral zinc, iron, Vitamin D, B12, and folic acid were started in deficient patients. Oral magnesium was supplemented in severely deficient patients. Progression of graying was stopped in the maximum number of patients after around 3 months of supplementation. Few patients reported reversing of gray hairs after supplementation.

To the best of our knowledge, ours is the first study evaluating serum magnesium levels in premature canities patients. Fewer studies are available evaluating serum copper and zinc levels in premature canities in young population. Our study showed significant deficiency of copper and zinc in cases compared to controls. Further studies should be done evaluating their levels in premature graying of hair. Our study showed deficiency of Vitamin B12 levels in cases which were in concordance to previous studies. However, we did not find any significant difference in serum Vitamin D and folic acid levels between cases and controls.

Limitations

Our study included a small sample size. Confounding factors such as dietary habits were not taken into account. Objective method for graying severity score was not used.

Conclusion

We conclude that patients of premature graying can have micronutrient deficiencies including copper, zinc, iron, magnesium, and Vitamin B12. Hence, these micronutrients should be analyzed in patients of premature canities if facilities are available and if patients are found deficient they should be supplemented for the same. However, further studies on a larger population and effect of supplementation of these micronutrients on premature graying are required.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Tobin DJ, Paus R Graying:Gerontobiology of the hair follicle pigmentary unit Exp Gerontol 2001 36 29 54
2. Bhat RM, Sharma R, Pinto AC, Dandekeri S, Martis J Epidemiological and investigative study of premature graying of hair in higher secondary and pre-university school children Int J Trichology 2013 5 17 21
3. Volkov I, Press Y, Rudoy I Vitamin B12 could be a “master key” in the regulation of multiple pathological processes J Nippon Med Sch 2006 73 65 9
4. Orr-Walker BJ, Evans MC, Ames RW, Clearwater JM, Reid IR Premature hair graying and bone mineral density J Clin Endocrinol Metab 1997 82 3580 3
5. Park HY, Kosmadaki M, Yaar M, Gilchrest BA Cellular mechanisms regulating human melanogenesis Cell Mol Life Sci 2009 66 1493 506
6. Di Donato P, Napolitano A, Prota G Metal ions as potential regulatory factors in the biosynthesis of red hair pigments:A new benzothiazole intermediate in the iron or copper assisted oxidation of 5-S-cysteinyldopa Biochim Biophys Acta 2002 1571 157 66
7. Thompson JM, Mirza MA, Park MK, Qureshi AA, Cho E The Role of Micronutrients in Alopecia Areata:A Review Am J Clin Dermatol 2017 18 663 79
8. Daulatabad D, Singal A, Grover C, Chhillar N Profile of Indian patients with premature canities Indian J Dermatol Venereol Leprol 2016 82 169 72
9. Fatemi Naieni F, Ebrahimi B, Vakilian HR, Shahmoradi Z Serum iron, zinc, and copper concentration in premature graying of hair Biol Trace Elem Res 2012 146 30 4
10. Sonthalia S, Priya A, Tobin DJ Demographic characteristics and association of serum Vitamin B12, ferritin and thyroid function with premature canities in Indian patients from an Urban skin clinic of North India:A retrospective analysis of 71 cases Indian J Dermatol 2017 62 304 8
11. Mediratta V, Rana S, Rao A, Chander R An observational, epidemiological study on pattern of clinical presentation and associated laboratory findings in patients of premature hair graying Int J Trichology 2018 10 93 5
12. Saad M, Babar NF, Majeed R, Rehman AU, Khan OA, Chatha DE, et al. Impact of premature greying of hair on socio-cultural adjustment and self-esteem among medical undergraduates in Foundation University, Islamabad Cureus 2019 11 e5083
13. Sharma N, Dogra D Association of epidemiological and biochemical factors with premature graying of hair:A case-control study Int J Trichology 2018 10 211 7
14. Acer E, Kaya Erdoğan H, İğrek A, Parlak H, Saraçoğlu ZN, Bilgin M Relationship between diet, atopy, family history, and premature hair graying J Cosmet Dermatol 2019 18 665 70
15. Shin H, Ryu HH, Yoon J, Jo S, Jang S, Choi M, et al. Association of premature hair graying with family history, smoking, and obesity:A cross-sectional study J Am Acad Dermatol 2015 72 321 7
16. Singal A, Daulatabad D, Grover C Graying severity score:A useful tool for evaluation of premature canities Indian Dermatol Online J 2016 7 164 7
17. El-Sheikh AM, Elfar NN, Mourad HA, Hewedy ES Relationship between trace elements and premature hair graying Int J Trichol 2018 10 278 83
18. Chakrabarty S, Krishnapp PG, Gowda DG, Hiremath J Factors associated with premature hair graying in a young Indian population Int J Trichol 2016 8 11 4
19. Bhat YJ, Hassan I, Sajad P, Malik R, Majid S, Mubashir S Serum iron, ferritin and calcium levels in premature canities Hair Ther Transplant 2016 6 2167 951
20. Daulatabad D, Singal A, Grover C, Chhillar N Prospective analytical controlled study evaluating serum biotin, Vitamin B12, and folic acid in patients with premature canities Int J Trichol 2017 9 19 24
21. Thompson KG, Marchitto MC, Ly BC, Chien AL Evaluation of physiological, psychological, and lifestyle factors associated with premature hair graying Int J Trichol 2019 11 153 8
Keywords:

Canities; copper; magnesium; micronutrients; premature; zinc

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