Hair Loss in Females after Sleeve Gastrectomy ...

Hair Loss in Females after Sleeve Gastrectomy: Predictive Value of Serum Zinc and Iron Levels JAIME RUIZ-TOVAR, M.D., PH.D.,* INMACULADA OLLER, M.D., PH.D.,* CAROLINA LLAVERO, R.N.,+ LOREA ZUBIAGA, M.D.,* MARÍA DIEZ, M.D.,* ANTONIO ARROYO, M.D., PH.D.,* ALICIA CALERO, M.D.,* RAFAEL CALPENA, M.D., PH.D.*

Prom the ^Department of Surgery, Bariatric Surgery Unit, General University Hospital Elche, Alicante, Spain; and the fDepartment of Surgical Nursery, Hospital del Sureste, Madrid, Spain A common complication after bariatric surgery is hair loss, which is related to rapid weight reduction, but zinc, iron, and other micronutrient deficiencies can also be involved. Little is studied after laparoscopic sleeve gastrectomy (LSG). A prospective observational study was performed of 42 morbidly obese females undergoing LSG. Incidence of hair loss was monitored. Micronutrients were investigated preoperatively and three, six, and 12 months after surgery. Sixteen patients (41%) reported hair loss in the postoperative course. A significant association was observed between hair loss and zinc levels (P = 0.021) but mean zinc levels were within the normal range in patients reporting hair loss. Only three patients (7.7%) presented low zinc levels, all of them reporting hair loss. There was also a significant association between iron levels and alopecia (P = 0.017), but mean values of the patients with hair loss were within normal range. Only four patients (10.2%) presented low iron levels, all of them presenting hair loss. A variable consisting of the addition of zinc -I- iron showed a significant association with hair loss (P = 0.013). A cutoff point was established in 115 (odds ratio, 4; P == 0.006). All the patients but two reporting hair loss presented addition levels under 115. This variable showed sensibility 88 per cent, specificity 84 per cent, positive predictive value 79 per cent, and negative predictive value 91 per cent to predict hair loss. Hair loss is a frequent condition after sleeve gastrectomy. In most cases, iron and zinc levels are within the normal range. The variable addition (zinc -I- iron) is a good predictor of hair loss. Patients with addition levels below 115 are fourfold more susceptible to present hair loss. In these cases, zinc supplements achieve the stop of hair loss in most cases.

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weight reduction, although it is associated with a higher risk of presendng some nutritional deficiencies. Deficiencies in micronutrients after bariatric procedures are a known threat if not corrected appropriately.'"'' However, some morbidly obese patients present important micronutrient deficits already before the bariatric procedure. The most frequent deficits involve magnesium (19% of the cases), vitamin A (15%), vitamin C (16%), iron (9%), ß-carotene (3%), and vitamin B12 (3%).^ Laparoscopic sleeve gastrectomy (LSG) has become recently popular as a single-stage procedure for the treatment of morbid obesity. Reports on anemia and micronutrient deficiencies in patients undergoing LSG are much lower than in malabsorptive procedures.

Address correspondence and reprint treuqests to Jaime RuizTovar, M.D., Ph.D., Av. Fotógrafo Francisco cano, 113, Bw 41 03540, Alicante, Spain. E-mail: jniiztovar@gmaiLcom.

because the gastrointestinal transit is not altered and there is no malabsorpdon.^ A common complication, but little studied, is hair loss, which is mainly the result of rapid weight loss, but also related to zinc, iron, and other micronutrient deficiencies. The aim of this study was to determine the incidence of hair loss after LSG and correlate it with micronutrient deficiencies. Patients and Methods A prospective observational study was performed. Between May 2008 and May 2012, 42 morbidly obese women underwent a LSG at our institution. Surgical Technique

A longitudinal resection from the angle of His to approximately 3 to 4 cm orally to the pylorus was performed using a 40-French bougie inserted along the lesser curve.

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HAIR LOSS IN FEMALES AFTER SLEEVE GASTRECTOMY

Postoperative Medication

Postoperatively, daily proton pump inhibitor and multivitamin supplements (Multicentrum®; Pfizer) were uniformly prescribed. Composition of the multivitamin supplement is described in Table 1. Compliance with multivitamin supplement intake was investigated. Variables

Changes in body weight and comorbidities were monitored. Baseline hemoglobin, albumin, ferritin, iron, zinc, vitamin B12, and folie acid were obtained before operation and postoperative determinations three, six, and 12 months after surgery. Hair loss was investigated; it was defined as the subjective perception of the women of losing a significantly higher amount of hair when compared with normal situation. Statistical Analysis

Statistical analysis was performed using SPSS Version 19.0 (SPSS Inc., Chicago, IL). Results are expressed as mean ± standard deviation or number and percentages. Paired Student's t tests were used to compare data before and after surgery. Independent Student's t test was used to compare means between groups. X" test was used to compare qualitative variables; when statistical signification is achieved, odds TABLE 1.

Composition of the Multivitamin Supplement Dose

Vitamin A Vitamin D Vitamin E Vitamin K Vitamin C Vitamin B1 Vitamin B2 Vitamin B6 Vitamin B12 Folie acid Biotin Niacin Pantothenic acid Calcium Phosphorus Magnesium Iron Iodine Copper Manganese Chrome Molybdenum Selenium Zinc

800 |xg 5 p.g 15 mg 30 (xg 100 mg 1.4 mg 1.75 mg 2mg 2.5 |xg 200 jxg 62.5 |jLg

20 mg 7.5 mg 162 mg 125 mg 100 mg 5 mg 100 |xg 500jjLg

2mg 50|jLg 30|jLg 5 mg

Percent Recommended Daily Allowance 100

100 125 40 125 127 125 143 100 100 125 125 125 20 18 27 36 67 50 100 100 100 55 50

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ratio was determined as risk measurement. A P value < 0.05 was considered statistically significant. Results Forty-two patients underwent a LSG, all of them females, with a mean age 44.2 ± 10.4 years, ranging from 20 to 62 years. Mean body mass index (BMI) was 51.2 ± 7.8 kg/m^. Comorbidities included diabetes mellitus in 16 (38%) of the patients, dyslipidemia in 21 (50%), hypertension in 26 (62%), osteoarthritis in eight (19%), and obstructive sleep apnea-hypopnea syndrome in seven (17%). Mean excessive BMI loss was 77 per cent after one year and 80.1 per cent after two years. Prevalence of Preoperative Deficiencies

Before surgery, one patient (2.4%) presented hypoalbuminemia, one (2.4%) folie acid deficiency, three (7.2%) iron deficiency, and two (4.8%) zinc deficiency. Hemoglobin, ferritin, and vitamin B12 were always within normal range. Global mean preoperative iron values were 58.4 ± 8.2 |xg/dL and zinc values 84.6 ± 6 jxg/dL. All the patients with iron or zinc deficiencies reported preoperative hair loss. Zinc deficiencies were preoperatively treated with zinc sulphate (12.5 mg daily) and the patients noticed a stop of hair loss. Iron deficiencies were not treated with iron supplements, because the patients did not present anemia. In these cases, hair loss percepdon continued. Prevalence of Postoperative Deficiencies

Three months after surgery, one patient (2.4%) presented hypoalbuminemia, four patients (9.6%) iron deficiency, one pafient (2.4%) ferritin deficiency, and three pafients (7.2%) zinc deficiency. The patient with hypoalbuminemia was the same who presented preoperative hypoalbuminemia. Hemoglobin, folie acid, and vitamin B12 were within the normal range. Global mean iron values were 57.3 ± 29.2 |JLg/dL and zinc values 73.2 ± 10.7 |jLg/dL. Six months after surgery, one patient (2.4%) presented iron deficiency. The rest of parameters were within the normal range. Global mean iron values were 67.6 ± 9.8 |xg/dL and zinc levels 85 ± 7.4 ¡xg/dL. One year after surgery, all the parameters were under normal range. The second year after surgery, the results remain similar. Referring to iron and zinc, there were no significant differences between mean preoperative and 3-, 6-, and 12-month postoperative values. Pre- and postoperative values of the main analytical determinations are described in Table 2.

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TABLE 2.

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Main Analytical

Hemoglobin (g/dL) Albumin (g/dL) Ferritin (ng/dL) Iron (|JLg/dL) Zinc (|JLg/dL) Vitamin B12 (pg/mL) Folie acid (ng/mL)

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Determinations Preoperative

3 Months after Surgery

13.2 3.7 55.3 58.4 84.6 391.3 6.1

12.6 3.6 51.2 57.3 73.2 398.2 6.6

All the patients affirm that they have not discontinued the multivitamin supplements intake during the first year after surgery. Incidence of Hair Loss and Correlation with Micronutrient Levels:

Seventeen patients (40.5%) referred hair loss in the postoperative course, beginning in all of them between three and six months after surgery. A significant association was observed between hair loss and zinc levels. Mean zinc levels were 72.1 ± 5.7 |xg/dL in the hair loss group versus 88.7 ± 8 |JLg/dL in the group of patients not reporting hair loss (P = 0.021). However, normal range of serum zinc levels is between 70 and 114 |jLg/dL. Only three patients of our series (7.2%) presented zinc levels below 70 |xg/dL, all of them referring hair loss. Iron levels are similar to zinc levels. There was a significant difference in the iron levels between the patients reporting hair loss and those who did not (42.2 ± 5.7 |jLg/dL vs 91.8 ± 16.6 |jLg/dL; P = 0.017). As happens with the zinc levels, mean values of the patients reporting hair loss were inside the normal range (37 to 170 (xg/dL). Only four pafients (9.6%) presented iron levels below 37 |xg/dL, but all of them presented hair loss. Analyzing ferritin as a related factor with iron levels, the mean values of the patients reporting hair loss tend to be lower (62.3 ±51.9 ng/mL vs 83.1 ± 83.4 ng/mL; P = 0.081), but both inside the normal range. Only one patient (2.4%) presented ferritin deficiency, corresponding to one with iron deficiency and therefore reporting hair loss. Analyzing hemoglobin levels, there were no significant differences between groups (12.5 vs 12.8; P = 0.343). No patient presented anemia. Only one patient (2.4%) presented a combined deficiency of iron and zinc. Globally, only seven patients (17%) presented zinc and/or iron deficiency, far away from the 40.5 per cent of patients with hair loss. A cutoff point within the normal range above which obtained significant differences between groups was not found for iron and zinc serum levels.



13 3.6

13.3

54.7 67.6 404.5

55.6 68.4 86.9 400.8

7.5

7.2

160 120 100 80 60 40 20

0 -J

12-15.5 3.5-5 6.2-137 37-170 70-114 239-931 3-20

3.8

85

Normal Range

MM

1 1Ironm , p»0.017

• zinc p=0.021

• —•

D Hair loss • Not hair loss

•w m

ZInc+lron p-0.013

FIG. 1. Different levels of iron, zinc, and addition variable (zinc + iron) between the patients reporting hair loss and those who did not. The bar indicates the lower limit of normal range for the three variables, indicating that only in the addition (zinc + iron) variable, the hair loss group presented mean levels below the lower limit of normal range.

We established the hypothesis that probably the combination of both micronutrients should reach a minimum level, although separately zinc and iron levels were under the normal range. Therefore, we created a variable consisting of the addition of zinc + iron and named it addition. A significant difference was observed in the addition levels between the patients reporting hair loss and those who did not (104.1 ± 8.4 vs 155.9 ± 37.7; P = 0.013). With this addition variable, we established a maximal difference in the cutoff point 115 (odds ratio, 4; 95% confidence interval, 2.7 to 21.8; P = 0.006). All the patients but two reporting hair loss presented addition levels under 115. The accuracy of this addition cutoff point to predict hair loss was sensibility 88 per cent, specificity 84 per cent, positive predictive value 79 per cent, and negative predictive value 91 per cent. Different levels of zinc, iron, and addition between groups are shown in Figure 1. Correlation of Hair Loss with Weight Loss

A correlation between hair loss with weight loss, BMI loss, and excess weight loss could not be established. Management of the Patients with Hair Loss

All the patients with iron deficiencies (four patients) were treated with ferrous sulfate at 105 mg/day, which

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were taken one hour before lunch. Treatment was maintained during two months, except in the patient who continued with iron deficiency, in which iron supplement was maintained during four months up to the analytical confirmation of iron levels was within the normal range. However, in this patient, even without reaching iron levels within the normal range, hair loss stopped after the second month of treatment. Notwithstanding, addition level was 117.8 in this ease. The rest of the patients with zinc deficieneies or with addition levels under 115 (11 patients) were treated with zinc sulfate at 12.5 mg/day that were taken two hours after lunch. Treatment was also maintained during two months. All the patients receiving treatment did not refer hair loss after finishing it. After treatment, laboratory data of the patients previously referring hair loss were: zinc 85.6 ± 6.2 |xg/dL, iron 60.4 ± 7.8 |xg/dL, ferritin 65.7 ± 32.9 ng/mL, and addition 128.6 ± 10.2. From this moment on, mean zinc, iron, and addition values remained at similar levels to that obtained after finishing the treatment. The two patients with normal iron and zinc levels and addition levels over 115 did not receive any treatment and continued referring hair loss from the third up to the ninth postoperative day. There were no significant analytical differences in the iron, zinc, ferritin, hemoglobin, folie acid, vitamin B12, or albumin levels during the hair loss period and after its disappearance.

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gastrectomy; thus, there is no malabsorption associated with this procedure. However, absorption is also related to zinc concentration in food and red meat is the richest common source of readily available zinc, providing approximately 50 per cent of dietary intake." Some studies that evaluated food records found that zinc intake was not enough in almost all patients in the first months after bariatric surgery based on a limited quantity of red meat intake. In our patients, solid food intake begins one month after surgery, but chicken is the main meat included in this first solid diet. Red meat is progressively introduced, but most patients reported difl'icult digestion with this red meat and they decided to reduce their ingestion. It is at approximately the third postoperative month when they can ingest red meat without problems. This could be one of the reasons that might explain the lowering of early postoperative zinc levels despite in most cases that these values are within the normal range.'^' '-^ It has been described that zinc deficiency is an indicator of protein malnutrition early after surgery, suggesting a correlation of plasma zinc concentrations and indirect markers of protein nutritional status such as prealbumin.''* If we assume that the main source of zinc is red meat, it is also the main source of proteins in the diet. In our country, red meat is the main source of proteins; however, in our series, we did not observe any correlation between zinc and total proteins, albumin, prealbumin, or transferrin (another marker of nutritional status) pre- or postoperatively. However, the sample size of our study is small and larger studies Discussion must be conducted to confirm this affirmation. The phenomenon of unexplained hair loss is multiThe fact that after zinc supplement intake, hair loss factorial. In 95 per cent of the males, hair loss is the stopped in most patients, even in those with zinc levels results of the patient's androgenetic situation. There- within normal range, reveals that there is a mild defore, we have omitted them and analyzed the re- ficiency after sleeve gastrectomy, which probably lationship between micronutrient deficits and hair loss alone is not enough to produce hair loss but associated only in women. Zinc is the most frequently suspected with iron mild deficiency (also with levels within deficiency with rapid clinical responses reported from normal range), it can appear. There are currently no therapy.^ Zinc is the second most prevalent trace found guidelines for zinc supplementation and optimal dose in the human body after iron. It is essential for normal and rules of prescription after sleeve gastrectomy are cell function and metabolism, playing a central role in still to be determined. In our series, just a small dose of over 300 enzymatic reactions, and protects cells from 12.5 mg/day (125% Recommended Daily Allowance) free radical damage.^' ^ The central role of zinc in cell during two months was enough to slightly increase the growth and differentiation explains the dramatic effect serum zinc levels and to stop hair loss. As a proof zinc deficiency in tissues with a rapid cell turnover phylactic measure against hair loss, it could be hysuch as hair growth.^ pothesized to use a routine supplementation with low After bariatric surgery, many factors contribute to an doses of zinc after sleeve gastrectomy. However, durimpairment of zinc levels, including malabsorption ing zinc supplementation, it is necessary to monitor caused by bypassing of the duodenum and proximal periodically the serum concentrations to avoid the apjejunum, the main site for zinc absorption, and a re- pearanee of adverse effects associated with overload. duced stomach production of hydrochloric acid reThe second micronutrient mostly associated with quired for zinc bioavailability and absorption.^' '° The hair loss is iron. Currently, there is sufficient evidence reduction of gastric acid segregation is probably the to recommend universal screening for iron deficiency main explanation for zinc deficiencies after sleeve in patients with hair loss. The iron deficiency after

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sleeve gastreetomy ean be partially explained by the pre-existing shortage, but also by the bariatrie proeedure itself. Iron needs to be transformed to an absorbable form by hydroehlorie aeid in the normal stomach. The quantity of hydrochloric acid produced after gastric resection is reduced and nutrients may pass the stomach faster after sleeve gastreetomy, making it more diffieult to absorb iron."*- '^"'^ Hemoglobin concentration can be used to screen for iron deficiency, whereas serum ferritin concentration can be used to confirm it.'^ Some authors defend that a serum ferritin level of 70 ng/mL should be targeted when hair loss is unexplained.'' In our series, significant differences in hemoglobin and ferritin levels between groups could not be observed. Even after treatment, when all the patients but two did not refer hair loss any more, mean ferritin values did not reaeh the eutoff point of 70 ng/mL. Moreover, the two patients continuing with hair loss presented ferritin levels of 85 and 88 ng/mL. It has been reported that serum ferritin levels may be altered with infectious, inflammatory, and neoplastic conditions.'^ After bariatrie surgery, there is a eatabolie status assoeiated with the weight loss. Therefore, ferritin levels eould be altered in this situation and it is possibly not an optimal marker for the sereening of iron status. Up to date, there is insuffieient evidenee to reeommend giving iron supplementation therapy to patients with hair loss and iron defieieney in the absenee of anemia, beeause an exeessive iron supplementation ean cause an overload that may lead up to the development of hemochromatosis.'* In our series, we decided to administrate iron supplementation to the four patients with iron defieieney and hair loss, beeause hemoglobin levels were in the lower limit of the normal range (12 g/dL) and there was a ferritin deficiency (one patient) or ferritin eoneentrations were very elose to the lower limit of the normal range (6.5 to 9 ng/mL). The formulation of the addition variable showed a strong correlation with hair loss and we think it can be used to identify subjects at risk of developing hair loss after sleeve gastreetomy in the future despite the faet that they present zine and iron levels within the normal range. There were two patients in our series reporting hair loss who did not present altered zine, iron, or addition variable levels. They did not reeeive any treatment, beeause a deficiency was not identified, and hair loss persisted up to the ninth postoperative month, when it spontaneously disappeared. Apart from zinc and iron, there are other factors that may be involved in hair loss and we did not analyze them in our study. Among them, selenium and copper are two of the most important mieronutrient defieieneies associated with hair loss.' When hair loss is not associated with zinc or iron deficiencies, these micronutrients must be investigated.

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The multivitamin regimen used in this study has shown to be insufficient for supplementing zinc after sleeve gastreetomy. Therefore, we reeommend to perform a sereening of the addition variable in the postoperative eourse to add zine supplements in those cases with levels below 115. However, the main limitation of this study is the small sample size. More studies with a greater number of patients must be conducted in the future to confirm our results. Conclusion Hair loss is a frequent condition after sleeve gastreetomy in morbidly obese patients. In most eases with hair loss, serum iron and zine levels are within the normal range. The variable addition (zine + iron) is a good predietor of hair loss. Patients with addition levels below 115 are fourfold more suseeptible to present hair loss. In these eases, zine supplements aehieve the stop of hair loss in most patients. REFERENCES 1. Rojas P, Goseh M, Basfi-fer K, et al. Alopeeia en mujeres con obesidad mórbida severa sometidas a cirugía bariátrica. Nutr Hosp 2011;26:856-62. 2. Bloomberg RD, Fleishman A, Nalle JE, et al. Nutritional defieieneies following bariatrie surgery: what have we learned? Obes Surg 2005;15:145-54. 3. Mason ME, Jalagani H, Vinik AI. Metabolic complications of bariatrie surgery: diagnosis and treatment issues. Gastroenterol Clin North Am 2005;34:25-33. 4. Nicoletti CF, Lima TP, Donadelli SP, et al. New look at nutritional care for obese patient candidates for bariatrie surgery. Surg Obes Relat Dis 2013;9:520-5. 5. Aarts EO, Janssen IMC, Berends FJ. The gastric sleeve: losing weight as fast as micronutrients? Obes Surg 2011;21: 207-11. 6. Daniells S, Hardy G. Hair loss in long-term or home parenteral nutrition: are mieronutrient defieieneies to blame? Curr Opin Clin Nutr Metab Care 2010;13:690-7. 7. Chimenti F, Aouffen M, Favier A, et al. Zinc homeostasisregulating proteins: new drug target for triggering cell fate. Curr Drug Targets 2003;4:323-38. 8. McCall KA, Huang C, Fierke CA. Function and mechanism of zinc metalloenzymes. J Nutr 2000; 130:1437^6. 9. Salle A, Demarsy D, Poirier AL, et al. Zinc defieieney: a frequent and underestimated complication after bariatrie surgery. Obes Surg 2010;20:1660-70. 10. Schweitzer DH, Posthuma EF. Prevention of vitamin and mineral deficiencies after bariatrie surgery: evidence and algorithms. Obes Surg 2008; 18:1485-8. 11. Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 2006; 20:3-18. 12. Cooper PL, Brearley LK, Jamieson AC, et al. Nutritional consequences of modified vertieal gastroplasty in obese subjects. Int J Obes Relat Metab Disord 1999;23:382-8.

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