老年性耳聋与体内叶酸水平低有关-------英文

ORIGINAL RESEARCH–OTOLOGY AND NEUROTOLOGY A ita th A S, Fa , an Ib No thi AB OB thr fol hea ST SE SU we ph fre and RE sub 41 (H fre no wi cob fre wi Ho sub am ma � � hea serum folate (correlation coefficient � �0.01, P � 0.01) was significant, while vitamin B12 (correlation coefficient � �0.01, P � CO eld sub © Su A oto ha fec infl au ev fol hig Cu Sim co wi im ing the In nu the au wh tip the de su he fol M Study Design Otolaryngology–Head and Neck Surgery (2010) 143, 826-830 019 doi 0.74) was not. NCLUSION: Serum folate was significantly lower among erly with ARHL. Trials on nutritional supplementation may stantiate the role of serum folate in ARHL. 2010 American Academy of Otolaryngology–Head and Neck rgery Foundation. All rights reserved. This is a cross-sectional study of the immunobiology of HL in apparently healthy elderly subjects. The participants were drawn from the community tagged to an outreach program organized for the detection and prevention of illnesses among the elderly. Included in the study were all elderly men and women above 60 years of age who had no known medical condition, Received June 21, 2010; revised August 24, 2010; accepted August 25, 2010. 4-5998/$36.00 © 2010 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved. ge-related hearing loss, v e elderly keem Olawale Lasisi, MBChB, FWAC tai A. Fehintola, MBBS, MSc, FMCP adan, Nigeria sponsorships or competing interests have been disclosed for s article. STRACT JECTIVE: Determine the correlation between the hearing eshold and the serum levels of vitamin B12 (cobalamin) and ic acid among elderly subjects (� 60 years) with age-related ring loss (ARHL). UDY DESIGN: Cross-sectional. TTING: Community. BJECTS AND METHODS: Subjects included elderly who re found apparently healthy following repeated examination by ysicians. The pure tone average (PTA) for the speech and high quencies, and the serum folate and cobalamin were determined the correlation found. SULTS: The mean � SD values of serum folate among the jects with normal PTA in the speech frequencies (0-30 dB) was 2.3 nmol/L� 17.6 nmol/L, while among those with hearing loss L), it was 279.1 nmol/L � 17.2 nmol/L (P � 0.01). In the high quencies, the mean � SD values among the subjects with rmal PTA was 426.3 nmol/L� 17.6 nmol/L, while among those th HL, it was 279.14 nmol/L � 171.2 nmol/L. The serum alamin among the subjects with normal PTA within the speech quencies was 49.7 pmol/L � 9.4 pmol/L, while among those th speech-frequency HL, it was 42.6 pmol/L � 10.2 pmol/L. wever, for high frequencies, the mean � SD values among the jects with normal PTA was 47.4 pmol/L � 7.3 pmol/L, while ong those with HL, it was 41.3 pmol/L � 9.2 pmol/L. Spear- n’s correlation revealed that low folate (correlation coefficient �0.27, P � 0.01) and cyanocobalamin (correlation coefficient �0.35, P � 0.02) were significantly associated with increasing ring threshold in the high frequencies. After adjusting for age, :10.1016/j.otohns.2010.08.031 min B12, and folate in FMCORL, d Oyindamola Bidemi Yusuf, PhD, ge-related hearing loss (ARHL) has been associated with environmental factors such as noise, malnutrition, toxicity, infections, and genetics.1-6 Hearing loss (HL) s been documented as one of the neuropathological ef- ts of some vitamin deficiencies;7 however, the potential uence of the deficiencies of the B group of vitamins on ditory function has received little attention,3 and direct idence linking ARHL with vitamin B12 (cobalamin) or ate deficiency is scarce in the literature. Roman5 found h-frequency sensorineural HL among elderly patients in ba and ascribed it to cobalamin and folate deficiency. ilarly, in a recent study of elderly female subjects, poor balamin and folic acid status were found to be associated th age-related auditory dysfunction.8 In addition, some provements were found in some of these patients follow- replacement therapy, suggesting a relationship between deficiencies of these vitamins and auditory dysfunction.8 contrast, many works have found no association between tritional biology and auditory function.1-4,9 This suggests need for continued research into the role of vitamins in ditory function, particularly in developing countries ere malnutrition is still rife. Our hypothesis is that mul- le vitamin deficiencies may be a significant contributor to severity of ARHL. The objective of this study was to termine, in a population of apparently healthy elderly bjects with ARHL, the association, if any, between the aring threshold and the serum levels of cobalamin and ic acid. ethod wh dia no or Pa Pa rep pre wa rec illn fre rec an cal ica tus los ask me qu in, we da us am wa lis elb ma ton the all Th Re Bl Ap the we fol Pu Th dio As the su pre me Hz 10 (P Hz PT Qu A int ac an ch an for fer fol rap Qu Int N mi Na pH tub 20 an we rel wa by co St Th an de wi 30 wh Co wa co the fol sig Re Th fem SD au tio (B 827Lasisi et al Age-related hearing loss, vitamin B12, and... ile the exclusion criteria involved those with history of betes, stroke, hypertension, ear diseases, exposure to ise and ototoxic drugs such as aminoglycoside antibiotics diuretics, ear infections, ear trauma, or ear surgery. rticipants Recruitment rticipants included elderly subjects who have been examined eatedly by physicians in the outreach program; the blood ssure and random blood sugar were tested, and urinalysis s done. The subjects were repeatedly examined in order to ruit them among those elderly with no known medical ess. Consecutive eligible participants who were found to be e of any medical conditions were counseled for consent and ruitment into the study. Each participant was taken through already prepared questionnaire for that purpose. Specifi- ly, questions aimed at eliciting otological and general med- l conditions were asked and these included: otorrhea, tinni- , vertigo, otalgia, polyuria, polydipsia, significant weight s, chronic cough, and palpitation. Participants were also ed about history suggestive of allergy and use of such dications as: aminoglycosides, diuretics, and 4-amino- inolines antimalarial drugs. History of living near noise, as for example, a blacksmith shop, radio room/disco room, or lding shop for at least two hours per day for at least five ys a week was also obtained. This was followed by ENT examination and hearing test ing pure tone audiometry. Specifically, subjects were ex- ined for evidence of arteriosclerosis by palpating the lls of the radial artery or presence of locomotor brachia- —observing the pulsation of the brachial artery at the ow. After the examination, collection of blood for esti- tion of serum levels of folate and vitamin B12, and pure e audiometry were done. The criteria for the diagnosis of medical condition were based on simple definitions, and the subjects with medical conditions were excluded.10,11 e study was approved by the Oyo State Research Ethical view Committee. ood Sample Collection and Storage proximately 5 mL of whole blood was collected using antecubital vein under aseptic conditions. The samples re stored at �80°C in batches for quantitative assay of ate and vitamin B12. re Tone Audiometry e pure tone audiometry was done using a computer au- meter BA 20 Kamplex (Interacoustic A/S, DK 5610, sens, Denmark) with the subjects in a sitting position in soundproof (acoustic) booth in the ENT clinic. The bjects were instructed to raise their hand if the tone sented to the ears was heard. The hearing acuity was asured in decibels (dB) at the frequencies 250 to 8000 . The average for the four frequencies, 250 Hz, 500 Hz, 00 Hz, and 2000 Hz was recorded as pure tone average TA) for speech frequency, while the average for the 3000 for fre , 4000 Hz, 6000 Hz, and 8000 Hz was recorded as the A for the high frequencies. antitative Assay of Folate sample was prepared by pipetting 1.5 mL of the sample o a set of centrifuge tubes, and then 20.0 mL of ascorbic id and 10.0 mL of sodium hydroxide (NaOH) were added d mixed properly. To this was added 5.0 mL of hydrogen loride (HCl), and the mixture was shaken for 30 minutes d then centrifuged at 1500 revolutions per minute (rpm) 30 minutes. The supernatant was collected and trans- red onto a set of clean vials, and determination of the ate was done with high-performance liquid chromatog- hy (HPLC).12 antitative Assay of Vitamin B12 o a clean beaker, 1.0 mL of the sample and 25 mL of 0.2 HCl was added and warmed in a water bath for 30 nutes, then cooled and the pH adjusted to 6.0 using OH. This was followed by adding 1N HCL to lower the to 4.5, then transferred into a set of 50.0-mL centrifuge es, shaken for 30 minutes, and centrifuged for a period of .0 minutes at 2000 rpm. The supernatant was collected, d vitamin B12 determined by HPLC.12 As a quality control measure, control and standard sera re included in the analysis at every sera assay to ensure iability and quality of the procedure. An initial pilot study s conducted to test all instruments, and this was followed a preliminary statistical analysis to detect outliers and rrect factors. atistics e main outcome variables were the serum levels of folate d vitamin B12 in elderly subjects with audiometric evi- nce of HL in the speech and high frequencies and those th normal PTA. In this study, HL was defined as PTA � dB, and the control subjects were selected among elderly o have normal PTA (0-30 dB). Data were initially explored using Stata software (Stata- rp LP, College Station, TX), and Spearman’s correlation s utilized to determine the correlation between ranked and ntinuous variables. In order to adjust for the effect of age on hearing threshold and the plasma levels of vitamin B12 and ate, a linear regression model was used. Level of statistical nificance was at P � 0.05 for all the analyses. sults e subjects included 126 elderly subjects (males and ales) and the ages ranged from 60 to 98 years (mean � � 66.9 � 0.77). Among the 126 subjects who had diometry, the mean � SD of the PTA for the air conduc- n was 29.4 dB � 1.6 dB, while for the bone conduction C) it was 36.5 dB � 1.8 dB. The mean � SD of the PTA the early frequency was 30.1 dB� 1.5 dB, while the late quency was 50.8 dB � 2.0 dB. inc cia hig Sp ad cre wa ser ing Ta the 41 ab 38 cy thr wi tw the sp nm 27 me eld nm 27 eld sp am pm me eld pm 41 lat ica sub ad lat he no T S M P T S M P 828 Otolaryngology–Head and Neck Surgery, Vol 143, No 6, December 2010 The prevalence of speech-frequency HL increased with reasing age; Spearman’s correlation revealed that the asso- tion was significant (P� 0.03). Similarly, the prevalence of h-frequency HL increased with increasing age, although earman’s correlation was not significant (P � 0.09). In dition, increasing age was significantly associated with de- asing levels of serum cyanocobalamin (P � 0.04), while it s not significant for serum folate (P � 0.2). Tables 1 and 2 show the frequency distribution of the um levels of folate and cobalamin, respectively, accord- to the range of the PTA among the elderly subjects. ble 1 shows that the mean serum levels of folate among subjects with normal hearing threshold (0-30 dB) was 2.3 nmol/L, while among those with hearing threshold ove 30 dB, the mean was between 195.1 nmol/L and 0.0 nmol/L. Table 2 shows that the mean serum levels of anocobalamin among the subjects with a normal hearing eshold (0-30 dB) was 49.7 pmol/L, while among those th a hearing threshold above 30 dB, the mean was be- een 39.9 pmol/L and 46.4 pmol/L. The mean � SD values of serum levels of folate among elderly subjects with normal hearing threshold in the eech frequencies (0-30 dB) was 412.3 nmol/L � 17.6 ol/L, while among the elderly subjects with HL, it was able 1 erum folate in nmol/L and pure tone average, in decibe ean hearing threshold (PTA), in decibels Number of subjects M 0-30 38 31-40 20 41-50 15 51-60 24 61-70 14 71-80 15 TA, pure tone average. able 2 erum levels of cyanocobalamin in pmol/L and pure ton ean hearing threshold (PTA), in decibels Seru Number of subjects M 0-30 38 31-40 20 41-50 15 51-60 24 61-70 14 71-80 15 TA, pure tone average. 9.1 nmol/L � 17.2 nmol/L. In the high frequencies, the an � SD values of serum levels of folate among the erly subjects with normal hearing threshold was 426.3 ol/L � 17.6 nmol/L, while among those with HL, it was 9.14 nmol/L � 171.2 nmol/L. For the serum cobalamin, the serum levels among the erly subjects with normal hearing threshold within the eech frequencies was 49.7 pmol/L � 9.4 pmol/L, while ong those elderly with speech-frequency HL, it was 42.6 ol/L � 10.2 pmol/L. However, for high frequencies, the an � SD values of serum levels of cobalamin among the erly subjects with normal hearing threshold was 47.4 ol/L � 7.3 pmol/L, while among those with HL, it was .3 pmol/L � 9.2 pmol/L. Spearman’s correlation revealed that decreasing serum fo- e (P � 0.01) and cyanocobalamin (P � 0.02) were signif- ntly associated with increasing hearing threshold among jects with high-frequency HL (Table 3). However, after justing for age, linear regression revealed significant corre- ion between the levels of serum folate (P � 0.01) and aring threshold in the high frequencies (Table 4). On the other hand, the serum levels of folate and cya- cobalamin did not show any significant correlation with m levels of folate in nmol/L m Maximum Mean SD 589.0 412.3 17.6 587.3 287.9 16.7 499.3 195.2 9.7 581.5 284.5 16.5 581.5 273.5 16.2 581.5 380.0 12.4 rage, in decibels els of cyanocobalamin in pmol/L m Maximum Mean SD 62.1 49.7 9.2 66.7 42.9 11.8 66.7 39.9 10.9 58.1 42.0 9.4 70.2 42.9 13.5 65.0 46.4 10.6 e ave m lev inimu 29.0 27.2 26.0 29.0 26.2 28.1 ls Seru inimu 135.0 134.3 100.1 126.0 134.0 121.1 he HL Di Th fol qu fou ser be vit for nu for Th sen Cu thy int ac fou the tha eff he fol HL co ex ov wi wi lev Be lev lev nm we co be tw rep fol B1 cit me low do be po to ass sig cie it inc fre the thi fol of vit mi T S p t h F C T L alam h S F C * F C 829Lasisi et al Age-related hearing loss, vitamin B12, and... aring threshold among subjects with speech-frequency (Table 5). scussion e main finding in this study is that low serum levels of ic acid are significantly associated with HL in high fre- encies among apparently healthy elderly people. Also, we nd correlation between high-frequency HL and low- um vitamin B12, although serum vitamin B12 seemed to affected by increasing age, hence the correlation with amin B12 was not found to be significant after adjusting age. These findings suggest that the low levels of these tritional markers, particularly folate, may be significant the development of HL among these elderly subjects. is is similar to the findings of Roman,5 who reported sorineural hearing impairment in the high frequencies in ba. In that study on an epidemic of peripheral neuropa- , he found association between sensorineural HL and low akes of vitamin B12, folate, thiamine, and sulfur amino ids. It is also supported by an animal experiment, which nd impairment in the cellular mechanism involving both nervous and vascular systems, hence, it was concluded t B12 deficiency is responsible for the neuropathological ect.6 The fact that our selected subjects were apparently althy elderly people suggests to us that the low-serum ate and cobalamin might be the factor responsible for the . This could be due to the eighth-nerve neuropathy or chleopathy, or both. A controlled study by Houston et al8 amined 55 healthy elderly women and found that PTAs er the 500- to 4000-Hz range were inversely correlated th serum vitamin B12 and red cell folate, and that women th impaired hearing had a 38 percent lower B12 vitamin able 3 pearman’s coefficient comparing the levels of lasma folate and cyanocobalamin with hearing hreshold among subjects with high-frequency earing loss Variables Spearman’s coefficient Significance olate �0.27 0.01 yanocobalamin �0.35 0.01 able 4 inear regression comparing plasma folate and cyanocob igh-frequency hearing loss Variables Coefficient olate* �0.01 yanocobalamin* �0.01 Adjusted for age. el and a 31 percent lower red cell folate level. In contrast, rner et al13 did not find any association between hearing els and either B12 vitamin, folic acid, or homocysteine els in elderly subjects. In our study, the serum levels of folate were between 100.1 ol/L and 589.0 nmol/L, while the levels of vitamin B12 re between 26.2 pmol/L and 70.2 pmol/L. This was low mpared to the work of Berner et al,13 which reported folate tween 295 nmol/L and 1160 nmol/L and vitamin B12 be- een 90 pmol/L and 737 pmol/L. But it is comparable to the ort of Houston et al8 on elderly women, which reported ate to be between 79 nmol/L and 380 nmol/L and vitamin 2 between 28 pmol/L and 502 pmol/L. These two studies ed are from developed countries of the West; however, in dically underserved populations like ours, these relatively levels of vitamins are expected. Although there is no cumented figure for the country as of now, these figures may a reflection of the low levels of the vitamins in the general pulation. It may be due to poor nutrition and may also be due problems with storage of specimens and other stages in the ay procedure. In addition, our findings revealed that increasing age had nificant effect on hearing threshold in the speech frequen- s and the serum levels of vitamin B12, but not folate. Thus, is suggested that low serum folate could account for the reased hearing threshold observed among those with high- quency HL. Similar to the question raised for reduction in other medical conditions,14,15 one main issue arising from s study is whether elderly people should, in general, receive ate and vitamin B12 supplements in order to reduce the risk hearing impairment. It has been proposed that low levels of amin B12 and folate are associated with destruction of the crovasculature of the stria vascularis, which might result in in with hearing threshold among subjects with ignificance 95% confidence interval 0.01 �0.01–0.01 0.74 �0.01–0.01 able 5 pearman’s coefficient comparing the levels of lasma folate and cyanocobalamin with hearing hreshold among subjects with speech-frequency earing loss Variables Spearman’s coefficient Significance olate 0.04 0.68 yanocobalamin –0.08 0.39 T S p t h decreased endocochlear potential and hence, hearing impair- ment.16-18 Vitamin B12 has been used in conjunction with other agents, such as clarithromycin, prednisolone, and immu- no co sym bo ma rel dis Co Se wi sta Ac We Iba Gu Au Fro Cli of Un Co CO Co Nig E-m Au Ak and imp lish dat app and con Di Co Sp Re 1. 2. Willot JF. Anatomic and physiologic aging: a behavioral neuroscience perspective. J Am Acad Audiol 1996;7:141–51. 3. Shemesh Z, Attias J, Ornan M, et al. Vitamin B12 deficiency in 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 830 Otolaryngology–Head and Neck Surgery, Vol 143, No 6, December 2010 globulin G, to treat auditory dysfunction.19-25 In addition, gnitive indexes 25 and peripheral and central nervous system ptoms26 indicating deficiencies of vitamin B12, folate, or th, have been sometimes reversed following repletion. This y change our present belief about the irreversibility of age- ated hearing impairment, thus improving the outcome of the ease and quality of life of the affected elderly people. nclusion rum folate was significantly lower among elderly people th ARHL. Trials on nutritional supplementation may sub- ntiate the role of serum folate in ARHL. knowledgments thank Prof. B. L. Salako, who was generous with the facilities of the dan-Loyola University Genetics of Hypertension project, and Prof. Oye reje of the Iba