簡易檢索 / 詳目顯示

研究生: 張維倫
Wei-Lun Jhang
論文名稱: 連續增補硫辛酸對極限耐力跑過程血液抗氧化系統的動力學探究
Human antioxidative system kinetics of continuousα-lipoic acid supplementationof during extreme endurance running
指導教授: 謝伸裕
Hsieh, Shen-Yu
學位類別: 碩士
Master
系所名稱: 體育學系
Department of Physical Education
論文出版年: 2007
畢業學年度: 95
語文別: 中文
論文頁數: 69
中文關鍵詞: 硫辛酸極限耐力跑氧化傷害
英文關鍵詞: α-lipoic acid, extreme endurance running, oxidative damage
論文種類: 學術論文
相關次數: 點閱:170下載:4
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 目的:探討連續服用強效抗氧化劑硫辛酸 (ALA) 對100公里跑步過程中之人體紅血球抗氧化系統與脂質氧化的影響。方法:將13位受試者隨機分為兩組:安慰劑 (CON) 與硫辛酸 (ALA) 組。兩組皆於賽前與每12 km處進行增補與採血,共計增補9次 (1600 mg)、採血10次。比賽全程佩帶心率錶,賽後分析運動成績與運動強度。血漿樣本分析檢測脂質過氧化物(TBARS) 、肌酸激酶 ( CK ) 活性、血糖與乳酸濃度;紅血球樣本分析檢測超氧離子歧化酶 (SOD) 活性、麩胱苷肽過氧化酶 (GPx) 活性與過氧化氫酶(CAT) 活性。所得數據以獨立樣本 t 考驗、混合設計雙因子 (組別 × 距離) 變異數分析 (ANOVA) 檢定。結果:增補硫辛酸對極限耐力跑過程之乳酸、CK與成績表現在組別上沒有達顯著差異。ALA組之血漿TBARS濃度 (3.7 ± 2.0 uM) 顯著低於CON組 (4.9 ± 2.8 uM)( p < .05)。ALA組之血糖濃度 (141.0 ± 14.9 mg‧dL-1) 顯著高於CON組 (130.7 ± 16.1 mg‧dL-1)(p < .05)。ALA組之紅血球SOD活性 (4461.99 ± 677.22 U‧gHb-1) 顯著低於CON組 (5143.49 ± 554.10 U‧gHb-1)( p < .05)。ALA組之紅血球GPx活性 (125.72 ± 22.43 kU‧gHb-1) 顯著高於CON組 (59.32 ±28.20 kU‧gHb-1)(p < .001)。ALA組之紅血球CAT活性 (24.27 ± 11.32 kU‧gHb-1) 顯著低於CON組 (42.56± 10.10 kU‧gHb-1)(p < .001)。結論:於極限耐力跑過程中連續增補硫辛酸能夠降低脂質過氧化傷害,提高紅血球GPx活性。
    關鍵詞:硫辛酸、極限耐力跑、氧化傷害

    Purpose: To investigate the effects of continuous oral supplementation of alpha-lipoic acid on human antioxidative enzyme activities and lipid peroxidation during extreme endurance running. Methods: A randomized double-blind study was carried out on 13 recreational long-distance runners who were continuously and orally supplemented with placebo (CON, n = 6) or alpha-lipoic acid (LA, n = 7) up to 1600 mg (200 mg for the first 1-7th supplementation and 100 mg for the 8, 9th supplementation) in a 100-km supermarathon race. Heart rates were monitored during running and the plasma concentrations of malondialdehyde (TBARS), glucose, lactate, creatine kinase, as well as antioxidant enzyme activities in red blood cells including superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured 20 min before and at various distances (at 12, 24, 36, 48, 60, 72, 84, 96 and 100 km). Independent t test, mixed design of two-way (group × distance) ANOVA were used for data analysis. Results:. After continuous supplementation of α-lipoic acid in extreme endurance running, plasma lactate, creatine kinase and exercise performance showed no significant differences between groups. TBARS in ALA group (3.65 ± 2.03 uM) was significantly lower than CON group (4.88 ± 2.84 uM)(p < .05). Plasma glucose in ALA group ( 140.95 ± 14.89 mg‧dL-1) was significantly higer than CON group (130.70 ± 16.11 mg‧dL-1)(p < .05). Erythrocyte SOD activity in ALA group (4461.99 ± 677.22 U‧gHb-1) was significantly lower than CON group (5143.49 ± 554.10 U‧gHb-1)(p < .05). Erythrocyte GPx activity in ALA group (125.72 ± 22.43 kU‧gHb-1) was significantly higher than CON group (59.32 ± 28.20 kU‧gHb-1)(p < .001). Erythrocyte CAT activity in ALA group (24.27 ± 11.32 kU‧gHb-1) was significantly lower than CON group (42.56 ± 10.10 kU‧gHb-1)(p < .001). Conclusion:. Runners of 100-km road race benefited from LA supplement with lowered lipid peroxidation and increased GPx activity during exercise.
    Key words:α-lipoic acid, extreme endurance running, oxidative damage

    目次 碩士論文通過簽名書..........................................i 碩士論文授權書.............................................ii 中文摘要..................................................iii 英文摘要..................................................iv 謝誌......................................................v 目次......................................................vi 表次......................................................ix 圖次......................................................x 第壹章 緒論..............................................1 一、 問題背景.............................................1 二、 研究目的............................................4 三、 研究範圍與限制.......................................4 四、 名詞操作性定義.......................................5 第貳章 文獻探討...........................................6 一、 自由基與氧化壓力......................................6 二、 運動與氧化壓力.......................................9 三、 硫辛酸與抗氧化壓力...................................11 第參章 研究方法與步驟.....................................20 一、 研究對象............................................20 二、 實驗設計與實驗變項...................................20 三、 比賽名稱與地點......................................21 四、 實驗方法與步驟......................................21 五、 血液樣本分析分析....................................24 六、 統計分析...........................................25 第肆章 結果.............................................26 一、 受試者基本資料......................................26 二、 兩組賽前、後之體重與體脂率比較........................26 三、 極限耐力跑之成績表現.................................27 四、 極限耐力跑之運動強度.................................27 五、 脂質過氧化物 (TBARS)................................29 六、 血糖 (glucose).....................................31 七、 抗氧化酶活性........................................33 八、 乳酸 (lactate).....................................39 九、 肌酸激酶 (CK).......................................41 第伍章 討論與結論...........................................43 一、 增補硫辛酸對極限耐力運動表現的影響.....................43 二、 極限耐力運動對於血漿CK活性的影響......................44 三、 增補硫辛酸對極限耐力運動之血漿TBARS的影響..............45 四、 增補硫辛酸對極限耐力運動之紅血球抗氧化酶活性的影響.......47 五、 增補硫辛酸對極限耐力運動之血漿血糖與乳酸濃度的影響.......49 六、 結論...............................................51 引用文獻...................................................52 附錄一 受試者須知及同意書....................................60 附錄二 受試者健康情況調查表..................................63 附錄三 本研究之血液生化檢體分析..............................64 附錄四 本研究使用之硫辛酸....................................68 個人小傳...................................................69

    李淑玲 ( 2001 )。補充含抗氧化劑之碳水化合物飲料對耐力運動期及恢復
    期生理與生化值之影響。未出版碩士論文,國立體育學院,台北縣。

    林天送(1996)。你的生命活力─從自由基談起。吳氏圖書,台北市。

    劉欣怡(2003)。探討甲型硫辛酸對B16-F1黑色素瘤細胞中pheomelanin
    生合成之影響。未出版碩士論文,私立中山醫學大學營養科學研究所。台
    中市。

    施曉婷(2004)。透過抗發炎、抗氧化及抗腫瘤促進作用評估硫辛酸在化學預
    防上可能扮演的角色。未出版碩士論文,國立成功大學環境醫學研究所。
    台南市。

    詹惠貴、許美智(1999)。國內優秀運動選手常用補充劑之探討。大專體育學
    刊,1(1),39-48。

    姚承義、沈淑貞(2003)。硫辛酸增補對單次激烈運動與魚油引致氧化壓力的
    影響。Proceeding of the Society of Chinese Scholars on
    Exercise Physiology and Fitness Conference (SCSEPF) ,
    p. 87

    姚承義、梁衍明、馮柏菁、沈淑貞(2004)。硫辛酸與肌酸增補介入游泳訓練
    對血漿生化指標的影響。中華民國九十三年大專體育學術研討會體育學術
    研討會專刊,338-352。

    姚承義、謝伸裕、沈淑貞(2005)。魚油增補對運動引發氧化壓力的探討。運
    動生理暨體能學報2,67-78。

    徐台閤(1997)。半程馬拉松對自由基及自然殺手細胞之影響。大專運動科學
    86年度研究獎助專刊,135-148。

    黃奕仁 (2004)。24小時超級馬拉松跑者肝膽功能之影響。大專體育學刊6
    (1),275-283。

    李建明 (2002)。不同年齡層參與馬拉松賽的血液生化值之比較。大專體育
    學刊,4(2),157-164。

    黃森芳 (2004)。42.2公里跑步對大學男生周邊血液中淋巴細胞增殖功能與自
    然殺手細胞毒殺活性之影響。大專體育學刊,6(1),285-298。

    邱亦涵 (2003)。42公里馬拉松賽跑對初級細胞性免疫的抑制與恢復狀況之
    探討。北體學報,11,17-27。

    Alessio, H. M. (1993). Exercise-induced oxidative stress.
    Medicine and Science in Sports and Exercise, 25(2), 218
    -224.

    Alessio, H. M., Hanninen, O., Packer, L., & Sen, C.K.
    (2000). Handbook of Oxidants and Antioxidants in
    Exercise. Elsevier of Amsterdam,115-128.

    Armstrong, L. E. & Maresh, C. M. (1996). Vitamin and
    mineral supplements as nutritional aids to exercise
    performance and health. Nutrition Review, 54, 149-158.

    Aruoma, O. I. (1994). Nutrition and health aspects of free
    radicals and antioxidants. Food & Chemical Toxicology,
    32(7), 671-83.

    Baynes, J.W., & Thorpe, S.R. (1999). Role of oxidative
    stress in diabetic complications: a new perspective on
    an old paradigm. Diabetes, 48, 1-9.

    Biewenga, G.P., Haenen, G.R., & Bast, A. (1997). The role
    of lipoic acid in the treatment of diabetic
    polyneuropathy. Drug Metabolism Rviews, 29, 1025-1054.

    Biewenga, G. P., Haenen, G. R., & Bast, A. (1997). The
    pharmacology of the antioxidant lipoic acid. General
    Pharmacology, 29, 315-31.

    Binzi, G. (1993). Aerobic performance and oxygen free
    radicals. Journal of Sports Medicine and Physical
    Fitness, 33, 205-222.

    Blumenthal, S. A. (1984). Inhibition of gluconeogenesis in
    rat liver by lipoic acid. Evidence for more than one
    site of action. The Biochemical Journal, 219, 773-780.

    Child, R. B.,Wilkinson, D. M., Fallowfied J. L., & Donelly.
    A. E. (1998). Elevated serum antioxidantcapacity and
    plasma malondiadehyde concentration in response to a
    simulatedhalf-marathon run. Medicine and Science in
    Sports and Exercise, 30, 1603-1607.

    Christen, Y. (2000). Oxidative stress and Alzheimer
    disease. The American Journal of Clinical Nutrition,
    71, 621S-629S.

    Clarkson, P. M., & Thompson, H. S. (2000).
    Antioxidants :What role do they play in physical
    activity and health? American Journal of Clinical
    Nutrition,72(Suppl.), 637S-646S.

    Diaz, M.N., Frei, B., Vita, J.A., & Keaney, J.F. (1997).
    Antioxidants and atherosclerotic heart disease. The New
    England Journal of Medicine, 337, 408-416.

    Del Rio, D., Stewart, A.J., & Pellegrini, N. (2005). A
    review of recent studies on malondialdehyde as toxic
    molecule and biological marker of oxidative stress.
    Nutrition, Metabolism, and Cardiovascular Dideases, 1
    5(4), 316-328.

    Dufaux, B., Heine, O., Kothe, A., Prinz, U., & Rost, R.
    (1997). Blood glutathione status following distance
    running. International Journal of Sports Medicine, 18
    (2), 89-93.

    Ernster, L. (1986). Oxygen as an environmental poison.
    Chemical Scripta, 26, 525-534.

    Evans, J.L., & Goldfine, I.D. (2000). α-Lipoic acid: A
    multi-functional antioxidant that improves insulin
    sensitivity in patients with type 2 diabetes. Diabetes
    Technol Therap, 2, 401-413.

    Freisleben, H. J. (2000). Lipoic acid reduces ischemia-
    reperfusion injury in animal models. Toxicology, 148,
    159-171.

    Gissel, H. & Clausen, T. (2000). Excitation-induced Ca2+
    influx in rat soleus and EDL muscle: Mechanisms and
    effects on cellular integrity. American Journal of
    Physiology, Regulatory, Integrative and Comparative
    Physiology,279(3), R917-924.

    Giugliano D, Ceriello A, & Paolisso G. (1995). Diabetes
    mellitus, hypertension, and cardiovascular disease:
    which role for oxidative stress? Metabolism, 44, 363-
    368.

    Greenberg, E.R., & Sporn, M.B. (1996). Antioxidant
    vitamins, cancer, and cardiovascular disease. The New
    England Journal of Medicine, 334, 1189-1190.

    Guillausseau, P. J. (1994). Preventive treatment of
    diabetic microangiopathy: blocking the pathogenic
    mechanisms. Diabète & Métabolisme, 20(2), 219-28.

    Hagen, T. H., Ingersoll, R. T., Lykkesfeldt, J., Wehr, C.
    M., Vinarsky, V., Bartholomew, J.C., & Ames, A. B.
    (1999). (R)-Alpha-lipoic acid-supplemented okd rats
    have improved mitochondrial function, decreased
    oxidative damage, and increaede metabolic rate. The
    FASEB Journal, 13(2), 411-418.

    Halliwell, B., & Gutteridge, J. M. (2000). Free Radicals in
    Biology and Medicine. Oxford,Oxford University.

    Haffner, S.M. (2000). Clinical relevance of the oxidative
    stress concept. Metabolism, 49, 30-34.

    Han, D., Tritschler, H. J., & Packer, L. (1995). Alpha-
    lipoic acid increases intracellular glutathione in a
    human T-lymphocyte Jurkat cell line. Biochemical and
    Biophysical Research Communications, 207(1), 258-264.

    Harrison, E. H. & McCormick, D. B. (1974). The metabolism
    of dl-[1,6-14C] lipoic acid in the rat. Archives of
    Biochemistry and Biophysics, 160, 514-522.

    Hartnett, M.E., Stratton, R.D., Browne, R.W., Rosner, B.A.,
    Lanham, R.J., & Armstrong, D. (2000). Serum markers
    for oxidative stress and severity of diabetic
    retinopathy. Diabetes Care, 23, 234-240.

    Henriksen, E. J. (2006). Exercise training and the
    antioxidant alpha-lipoic acid in the treatment of
    insulin resistance and type 2 diabetes. Free Radical
    Biology & Medicine, 40(1), 3-12.

    Honing, M.L., Morrison, P.J., Banga, J.D., Stroes, E.S., &
    Rabelink, T.J. (1998). Nitric oxide availability in
    diabetes mellitus. Diabetes Metabolism Reviews, 14, 241-
    249.

    Ji, L. L. (1993). Antioxidant enzyme responses to exercise
    and ageing. Medicine and Science in Sports and
    Exercise, 25, 225-231.

    Ji, L. L., & Fu, R. (1992). Responses of glutathione system
    and antioxidant enzymes to exhaustive exercise and
    hydroperoxide. Journal of Applied Physiology, 72, 549-
    554.

    Jones, A.F., Winkles, J.W., Jennings, P.E., Florkowski,
    C.M., Lunec, J., & Barnett, A. H. (1998). Serum
    antioxidant activity in diabetes mellitus. Diabetes
    Research (Edinburgh, Lothian), 7, 89-92.

    Kagan, W., Kuklinski, B., Ruhlmann, C. & Plotzs, C. (1992).
    Recycling of vitamin E in human low density
    lipoproteins. Journal of Lipid Research, 33, 385-397.

    Khanna, Savita., Atalay, M. Lodge, J. K., Laaksonen D.,
    Mustafa, G., Sashwati, R., & Sen, C. K. (1999). α-
    lipoic acid supplementation: tissue glutathione
    homeostasis at rest and after exercise. Journal of
    Applied Physiology, 86(4), 1191-1196.

    Lenaz, G. (1998). Role of mitochondria in oxidative stress
    and ageing. Biochimica Biophysica Acta, 1366, 53-67.

    Machefer G., Groussard C., Rannou-Bekono F., Zouhal H.,
    Faure H., Vincent S., Cillard J., & Gratas-Delamarche
    A. (2004). Extreme running competition decreases blood
    antioxidant defense capacity. Journal of the American
    College of Nutrition, 23(4), 358-64.

    Maria, L. U., & Priscilla M. C. (2003). Oxidative stress,
    exercise, and antioxidant supplementation. Toxicology,
    189, 41-54.

    Marangon, K., Devaraj, S., Tirosh, O., Packer, L., &
    Jialal, I. (1999). Comparison of the effect of alpha-
    lipoic acid and alpha-tocopherol supplementation on
    measures of oxidative stress. Free Radical Biology &
    Medicine, 27(9-10), 1114-21.

    Marsh, S. A., P. B. Laursen, & J. S. Coombes. (2006).
    Effects of antioxidant supplementation and exercise
    training on erythrocyte antioxidant enzymes.
    International Journal for Vitamin and Nutrition
    Research, 76, 324-331.

    Maxwell, S. R. J., Thomason, H., Sandler, D., Leguen, C.,
    Baxter, M.A., Thorpe, G. H. G., Jones, A. F., &
    Barnett, A. H. (1997). Antioxidant status in patients
    with uncomplicated insulin-dependent and non-insulin-
    dependent diabetes mellitus. European Journal of
    Clinical Investigation, 27, 484-490.

    Maxwell, S. R., Jaleman, P. Thomason, H., Leguen, C. &
    Thorpe, G. H. (1998). Changes in plasma antioxidant
    status during eccentric exercise and the effect of
    vitamin supplementation. Free Radical Research, 84, 407-
    412.

    Moini, H., Packer, L., & Saris, N.E. (2002). Antioxidant
    and prooxidant activities of alpha-lipoic acid and
    dihydrolipoic acid. Toxicology & Applied Pharmacology,
    182(1), 84-90.

    Nourooz-Zadeh, J., Rahimi, A., Tajaddini-Sarmadi, J.,
    Tritschler, H., Rosen, P., Halliwell, B., & Betteridge,
    D.J. (1997). Relationships between plasma measures of
    oxidative stress and metabolic control in NIDDM.
    Diabetologia 40, 647-653.

    Nourooz-Zadeh, J., Tajaddini-Sarmadi, J., Mccarthy, S.,
    Betteridge, D.J., & Wolff, S.P. (1995). Elevated levels
    of authentic plasma hydroperoxides in NIDDM. Diabetes,
    44, 1054-1058.

    Opara, E.C., Abdel-Rahman, E., Soliman, S., Kamel, W.A.,
    Souka, S., & Lowe, J.E. (1999). Abdel-Aleem S:
    Depletion of total antioxidant capacity in type 2
    diabetes. Metabolism, 48, 1414-1417.

    Packer, L., Witt, E. H., & Tritschler, H. J. (1995). Alpha-
    lipoic acid as a biological antioxidant. Free Radical
    Biology & Medicine, 19(2), 227-250.

    Packer, L., Roy, S., & Sen, C. K. (1997). Alpha-lipoic
    acid: a metabolic antioxidant and potential redox
    modulator of transcription. Advances in Pharmacology,
    38, 79-101.

    Paolisso, G., Esposito, R., D'Alessio, M. A., & Barbieri,
    M. (1999). Primary and secondary prevention of
    atherosclerosis: is there a role for antioxidants?
    Diabetes & Metabolism, 25, 298-306.

    Paolisso, G., D'Amore, A., Volpe, C., Balbi, V.,
    Saccomanno, F., Galzerano, D., Giugliano, D.,
    Varricchio, M., & D'Onofrio, F. (1994). Evidence for a
    relationship between oxidative stress and insulin
    action in non-insulin-dependent (type II) diabetic
    patients. Metabolism: Clinical and Experimental, 43,
    1426-1429.

    Pedersen, B. K., Bruunsgaard, H., Ostrowski, K., Krabbe,
    K., Hansen, H., & Krzywkowski, K. et al. (2000).
    Cytokines in aging and exercise. International Journal
    of Sports Medicine, 21 (Suppl 1), S4-9.

    Pedersen, B. K., Ostrowski, K., Rohde, T., & Bruunsgaard,
    H. (1998). The cytokine response to strenuous exercise.
    Canadian Journal of Physiology and Pharmacology, 76
    (5), 505-511.

    Packer, L., Witt, E.H., & Tritschler, H. J. (1995). alpha-
    Lipoic acid as a biological antioxidant. Free Radical
    Biology & Medicine, 19, 227-250.

    Podda, M., Zollner, T. M., Grundmann-Kollmann, M., Thiele,
    J. J., Packer, L., & Kaufmann R. (2001). Activity of
    alpha-lipoic acid in the protection against oxidative
    stress in skin. Current Problems in Dermatology, 29, 43-
    51.

    Rehman, A., Nourooz-Zadeh, J., Moller, W., Tritschler, H.,
    Pereira, P., & Halliwell, B. (1999). Increased
    oxidative damage to all DNA bases in patients with type
    II diabetes mellitus. FEBS Letters, 448, 120-122.

    Rodney, C. R. & Roger, B. M. (2001). Use of antioxidant
    nutrients in the prevention and treatment of type 2
    diabetes. Journal of the American College of Nutrition,
    20(5), 363-369.

    Rosenberg, H. R., & Culik, R. (1959). Effect of α-lipoic
    acid on vitamin C and vitamin E deficiencies. Archives
    of Biochemistry and Biophysics, 80, 86-93.

    Saleem, M., Alam, A., Arifin, S., Shah, M. S., Ahmed, B., &
    Sultana, S. (2001). Lupeol, a triterpene, inhibits
    early responses of tumor promotion induced by benzoyl
    peroxide in murine skin. Pharmacological Research, 43
    (2), 127-34.

    Shigenaga, M., & Hagen, T. (1994). Ames Oxidative damage
    and mitochondrial decay in aging. Proceedings of the
    National Academy of Sciences of the United States of
    America, 91, 10771-10778.

    Salonen, J. T., Nyyssonen, K., Tuomainen, T. P., Maenpaa,
    P. H., Korpela, H., Kaplan, G.A., Lynch, J., Helmrich,
    S.P., & Salonen, R. (1995). Increased risk of non-
    insulin dependent diabetes mellitus at low plasma
    vitamin E concentrations: a four year follow up study
    in men. British Medical Journal, 311, 1124-1127.

    Shigeta, Y., Hiraizumi, G., Wada, M., Oji, K., & Yoshida,
    T. (1961) Study on the serum level of thioctic acid in
    patients with various diseases. The Journal of
    Vitaminology, 7, 48-52.

    Suh, J. H., Shigeno, E. T., Morrow, J. D., Cox, B., Rocha,
    A. E., Frei, B., & Hagen, T.M. (2001). Oxidative stress
    in the aging rat heart is reversed by dietary
    supplementation with (R)-(alpha)-lipoic acid. The FASEB
    Journal, 15(3), 700-706.

    Wollin, S. D., & Jones, P. J. (2003). Alpha-lipoic acid and
    cardiovascular disease. Journal of Nutrition, 133, 3327-
    3330.

    Turgut, G., Demir, S., Genc, O., Karabulut, I., & Alalin,
    N. (2003). The effect of swimming exercise on lipid
    peroxidation in the rat brain, liver and heart. Acta
    Physiological et Pharmacolobical Bulbarica, 27(2-3), 43-
    45.

    Warner, J. G., Ullrich, J. R., Albrink, M. J., & Yeater, R.
    A. (1989). Combined effects of aerobic exercise and
    omega-3 fatty acids in hyperlipidemic persons. Medicine
    and Science in Sports and Exercise, 21(5), 498-505.

    Wolff, S. P., & Jiang, Z.Y. (1991). Protein glycation and
    oxidative stress in diabetes mellitus and ageing. Free
    Radical Biology & Medicine, 10, 339-352.

    Yau, C. Y., Lian, Y. M., & Shen, S. C. (2004). Effects of
    alpha-lipoic acid and creatine supplementation on
    exercise -induced oxidative stress. 2004 Pre-Olympic
    Congress; Thessaloniki, Greece.

    Ziegler, D. G. (1997). Alpha-lipoic acid in the treatment
    of diabetic peripheral and cardiac autonomic
    neuropathy. Diabetes, 46 (Suppl,2), 62-66.

    QR CODE