VITAMIN C: THE NONTOXIC, NONRATE-LIMITED, ANTIOXIDANT FREE RADICAL SCAVENGER0
医学假说.18:61-77, 1985
作者:Robert F. Cathcart, M.D.
来源:www.orthomed.com
翻译:蓝山
摘要：
一个病人口服抗坏血酸（ascorbic acid,AA）但不产生腹泻的量，随疾病的毒性程度而增加，临床上，一种可被抗坏血酸改善的疾病，只有在非常高的剂量，接近如下程度，此时，一种无速度限制的抗氧化自由基清除剂，可预期直接作用于疾病进程，如果所有有害的自由基和高度活跃的氧化物被瞬间克制，疾病的各种症状将被克制。在大多数疾病进程，自由基和高度活跃的氧化物的产生速度，超过有速度限制的抗氧化自由基清除机制能及时克制这些自由基和氧化物的速度。当抗坏血酸作为一种自由基清除剂时，脱氢抗坏血酸（dehydroascorbate，DHA）同时形成。如果AA/DHA的比值保持足够高（氧化还原电位保持还原性质），直至不稳定的脱氢抗坏血酸水解或还原回抗坏血酸，脱氢抗坏血酸将不会产生任何害处。由于即使是很高的剂量，抗坏血酸实际上是无毒的，可能甚至达到足够中和几乎所有不需要的自由基和氧化物的剂量。抗坏血酸能改善的感染性疾病的范围的宽广提示了这些疾病的一些共同的病理过程。
介绍：
依据我过去14年11000例病人的临床经验，病人把抗坏血酸溶于水中口服，不产生腹泻的肠耐受极限量，随疾病的毒性程度而上升。一个平常24小时可耐受10~15克抗坏血酸的人，如得普通感冒，可耐受30~60克， 如得重感冒，可耐受100克，得流行性感冒，可耐受150克，如得单核细胞增多症或病毒性肺炎，可耐受200克或更多，这些疾病以及其他以前描述的疾病的临床症状，只有在接近肠耐受极限量（几乎引起，但不一定引起腹泻的量）才会显著改善（1—6）。
表一：通常的肠耐受极限量
病况： 24小时维生素C量（克） 24小时服用次数
正常 4~15克 4~6
普通感冒 30-60 6~10
严重感冒 60~100 8~15
流行性感冒 100~150 8~20
ECHO, coxsackievirus 100~150 8~20
单核细胞增多症 150~200﹢ 12~25
病毒性肺炎 100~200﹢ 12~25
枯草热、哮喘 10~50 4~8
环境和食物过敏 0.5~50 4~8
烧伤、外伤、手术 25~150 6~20
运动、轻度压力 15~25 4~6
关节强直性脊椎炎 15~100 4~15
癌症 15~100 4~15
Reiter's 综合征 15~40 4~10
急性前葡萄膜炎 30~100 4~15
风湿关节炎 15~100 4~15
细菌感染 30~200﹢ 10~15
感染性肝炎 30~100 6~15
念珠菌感染 15~200 6~25
耐受抗坏血酸极好的病人，明显没有显著的系统困难。这些病人的大多数患某些急性或慢性疾病，可以轻易地服用大量的抗坏血酸。在健康人口服少量抗坏血酸常抱怨的胀气，腹泻，烧心，在患严重疾病的病人很少见。低量或轻量（明显低于肠耐受极限量）通常没有可觉察得到的即时临床效果。但大剂量（耐受者中稍低于导致腹泻的量），在剂量达到肠耐受极限量时，将会有显著克制症状的临床效果。这种突然效应常常是非常惊人的，而且，稍微低于此剂量通常都不会获得这种效果。好像，达到了某一最低基础量，抗坏血酸变得很有效。
在某些场合，使用矿物抗坏血酸混合剂（钙、镁、钾、锌，有时钠），以增加肠耐受极限量，以便产生更好的临床效果。但并不清楚解释，这里正讨论的增加肠耐受极限量现象。
已知的抗坏血酸的维生素功能不会使人预测这些有益效果。服用这些大剂量抗坏血酸的严重困难的缺乏是惊人的。
在实验人群中，抗坏血酸的解毒功能是惊人的
在大剂量时部分突然出现的有益效果是“幸福”的感觉。这种幸福的感觉，尤其在毒性更大的病程中，即使出现胀气及腹泻亦如此。如果其原发疾病导致的痛苦非常巨大（如单核细胞增多症、病毒性肝炎，病毒性肺炎等），抗坏血酸的临床效果是如此明显，以致病人很少会注意轻微的胃肠不适。在肠耐受极限量出现之前过早降低剂量，会导致疾病的反复和疾病的其他急性症状。在最低基础剂量达到的情况下，使用大剂量抗坏血酸经历的临床感觉是身体的“解毒”，通过增加和减少剂量，“毒性”的症状可被有经验的病人随意操纵。
我不能严格强调，就是，在所“选择”的病人（只选能极好耐受抗坏血酸，很好理解测定弹性肠耐受极限量的原则，以及愿意执行具体的细节），这种效果是不变的、惊人的和不会错的。最可能经历这种效果的是：心理素质稳定，不易被说服，现实的，不喜欢病的，并且“消化功能特别好的”人。儿童和青少年，可能相当部分的人会讨厌抗坏血酸溶于水中的口味，但一旦他们体会大剂量抗坏血酸的改善效果，会成为特别好的病人。婴儿接受肌肉注射或静脉注射后，常在几分钟内“解除毒性”，令其父母惊奇和放下心来。
耐受大剂量抗坏血酸的人体现的这种幸福感受是确切的临床证据，表明吸收大剂量抗坏血酸后，无任何酸中毒和毒性代谢效应出现。静脉注射抗坏血酸钠的效果甚至比口服抗坏血酸更显著，同时没有胃肠胀气和腹泻出现。平常相对功能不全的病人，通常可以维持相当的功能，有时甚至参加体育运动，如果经常服用巨大量的抗坏血酸。
必须鼓励病人服用大剂量抗坏血酸。主动服用抗坏血酸的病人，很少服用足够的量以发现这种效果。我不打算给人以这样的印象：这种方法很容易使用。对很多人来说，服用这些剂量的技巧可能会很难掌握。不过，经过适当指引，大多数病人都可取得这些效果。如果一个病人因为肠胃问题而相对不耐受口服抗坏血酸；如果这种病在耐受者中对口服抗坏血酸有良好的效果；如果病情的严重性提示口服的不方便以及病人可负担有关费用，那么，应给予静脉注射治疗。
这种大剂量抗坏血酸的效果不能用已知的维生素C功能解释。对大剂量抗坏血酸有反应的疾病的范围的本身就是一个奇迹。并揭示了一些可能涉及的机制。临床上，只在很高的基础量才经历的“解毒效应”，提示抗坏血酸正参与一个需要极高抗坏血酸浓度的化学反应，或者，某些组织里，抗坏血酸和某些反应物的特定比值必须达到，反应才能正常进行。在很多病理过程(7,8)，自由基和其他高度活跃的氧化物的概念是一个常见的因素。而同时，抗坏血酸是一个抗氧化自由基清除剂，可以解释上述的很多现象。
抗氧化自由基清除剂的限速性——许多病理过程的一个原因
在细胞的正常代谢中，涉及自由基和高度活跃的氧化物的化学反应是必须的。释放能量的耗氧的代谢过程（需氧代谢）是重要的例子。通常，这些反应和合适的酶同时出现，或者在细胞内的适当位置进行。现已发现那些可能有害的反应物从细胞内漏出，并且是有毒的（9）。这些反应物渗漏的速度已足够自身的自由基清除机制去处理。其中一个自然衰老的原因可能就是部分自由基不可避免地逃过被清除。虽然身体有许多自由基清除机制，用以清除体内的自由基。我推测，在病理过程，这些有速度限制的机制被自由基急剧消耗，不足以中和产生的所有自由基。当体内产生的自由基的量达到某一基础量，引发炎症串联反应，能导致免疫抑制和退行性疾病。
限速的抗氧化自由基清除路径的例子
自由基清除的发生涉及受速度限制的许多复杂的代谢步骤，组成这个系统的各种酶和辅酶的营养素、维生素和矿物质的缺乏，可减慢或停止这个路径。
为了描述其复杂性的印象和它为什么是有限速的，描述其中一种限速的自由基清除机制是适当的。选择的例子涉及谷胱甘肽，因它可能是最重要的代谢路径之一。
当，比如，一个超级过氧化自由基，必须要被清除，超氧化物岐化酶能催化它转化为：O2和H2O2（11）。抗坏血酸、非酶类，亦能转化超级过氧化物为H2O2，但在此过程中其自身变为抗坏血酸自由基和脱氢抗坏血酸。抗坏血酸自由基和脱氢抗坏血酸通过以下路径还原为抗坏血酸：或者被NADH（由半脱氢抗坏血酸还原酶催化和形成NAD）或者被还原型谷胱甘肽（GSH）（由脱氢抗坏血酸还原酶催化和形成氧化型谷胱甘肽（GSSH））（12））。某些过氧化物通过催化可被转化为氧和水，但绝大多数将会被一种需要谷胱甘肽的酶系统破坏。GSH（由谷胱甘肽过氧化酶催化）还原过氧化物为水，但在此过程中，本身被氧化为GSSH。产生的GSSH被NAD（P）H还原（由谷胱甘肽还原酶催化）。产生的NAD通过KREBS循环，被还原为NADH，或者，产生的NADP由HMP（己糖-磷酸路径）还原为NADPH。现在认为，在限速反应的最后的一系列的步骤，由谷胱甘肽过氧化物酶和其辅酶催化，但，其他可以有抑制作用的物质是：维生素E、维生素C、维生素B12、维生素B3、胱氨酸等。注意，这个例子的抗坏血酸是作为维生素C定义的。少量可得到的维生素C被氧化为脱氢抗坏血酸，然后必须被还原为抗坏血酸（通过上述的路径），被作为抗坏血酸再利用。任何人都可以轻易明白这种以及类似的机制可被释放自由基的病原体克制，或被任何原因引起的炎症串联反应克制。
大多数感染性疾病常见的自由基对免疫系统的抑制，被抗坏血酸中和
我进一步假设，大多数急性感染性疾病的病原体，依靠自由基毒性作自我保护，以免受免疫系统的即时消灭。如果一个病原体产生自由基的速度超过宿主产生自由基清除剂来保护免疫系统，病原体将会随意入侵机体和繁殖。毒性更大的病原体产生更多的自由基毒素，多于足够抑制免疫系统，在受感染组织，自由基的漏出达到一个最低基础量，一个炎症串联反应因此形成。
中性粒细胞在试图消灭病原体的过程中，同时在细胞内和细胞外释放自由基和高度活跃的氧化物，这个过程叫“吞噬”（13~18）。吞噬消耗在此过程必须要连续恢复的NADPH。NADPH供应的恢复通过HMP路径，通过各种限速性酶机制完成。
我提出：如果限速酶过程、或白细胞，超氧化物岐化酶 （18）、催化酶（20）、谷胱甘肽过氧化物氧化酶（21~23）的抗氧化自由基清除机制的限制性获得，远不能局限或引导自由基和高度活跃的氧化物对抗病原体，这种失调导致自由基在后院“起火”，损害宿主本身，同时引发炎症串联反应。
如果一个关键组织的自由基清除剂浓度可以保护免疫系统免受病原体产生的自由基侵害，同时，帮助白细胞调节它们自己的自由基产生，免疫系统预期将会通过吞噬作用迅速战胜和消灭病原体。如果一种自由基清除剂被发现在很多疾病有效，它可能提示：在所有这些疾病的发生和发展中存在着一种自由基克制免疫系统的共同机制。直至认为存在这样一种自由基清除剂，可以忽视这样一种对所有疾病都有效的共同机制。我假设，抗坏血酸，事实上，当以此刻讨论的剂量使用时，是这样一种自由基清除剂。它对范围广泛的感染性疾病的有效是存在这样一种共同机制的证据，这种共同的机制就是，许多病原体有克制免疫系统的功能。
通过中和实际上不需要的自由基和毒性氧化物，大剂量的抗坏血酸可以用于保护免疫系统到这样一种程度，在许多急性病毒性疾病的早期，免疫系统可在数小时内消灭病原体，当在一种急性病毒性疾病的后期使用，此时病原体已在组织细胞内建立了牢固的基础，大剂量的抗坏血酸可以保护免疫系统，克制大多数症状，防止继发性并发症，直至免疫系统通过后续手段如各种抗体，消灭病原体。
我已发现，当用于急性细菌性疾病的治疗时，大剂量的抗坏血酸和合适的抗菌素起协同作用，同时，明显增大了其抗菌谱。我未能清楚地探索单独使用抗坏血酸治疗细菌性疾病的有效程度。但已有某些猎奇性的临床证据，即使无使用抗菌素，某些细菌在大剂量抗坏血酸存在的情况下，其活动性受到明显的抑制。
涉及生长缓慢的细菌感染的病变如：气管炎，鼻炎，中耳炎，扁桃体炎，骨髓炎，非特异性尿道炎，等，通常可以用大剂量抗坏血酸治愈。我推测：可能地：诱发性的局部性坏血病在慢性感染组织和病原体之间建立的病理等式中起决定性作用，这种诱发性坏血病，被驱使进入的抗坏血酸，在组织水平达到某一最低基础量时，被消除了。免疫系统常常迅速消除感染，受到感染的组织愈合。
在过敏结合感染起主要作用的疾病中，大剂量的抗坏血酸是有帮助的，但需要持续性的维持量。在这种情形下，连续阻断过敏诱发的炎症串联反应必须维持。
对反复发作的疱疹病毒感染，很高的维持量看来预防某些发作，同时，肠耐受极限会缩短和减轻发作的严重程度。一种局部应用的抗坏血酸糊剂（抗坏血酸或抗坏血酸钠和水）（24）看来对单纯疱疹特别有效。在慢性肝炎，抗坏血酸可能不会治愈它，然而，大剂量抗坏血酸通常会改善病情。同时，我有证据表明，病毒的复制会停止。我未能证实如果大量抗坏血酸中断，病人是否会出现病毒复制。在病毒已牢牢在细胞内扎根的情况下，抗坏血酸帮助免疫系统的能力有某些限制。
抗坏血酸在AIDS的治疗
近来，我已发现抗坏血酸在治疗AIDS中有效。辅助性T细胞已受到严重抑制的AIDS病人，其临床处理类似需要氧气床维持的新生儿。如果，加上我上述的其他措施（24，25），病人每小时口服肠耐受极限量的抗坏血酸（危急情况下静脉注射），尽管其辅助性T细胞持续受到抑制，其临床状况可维持满意的状态。所有这些必须在病人被多种感染摧残以前。已有一些无对照的临床案例表明，在前驱期，辅助性T细胞破坏之前，通过这个方案可避免AIDS的发展。这种可能性的证实等待实验室的长期观察。有证据表明，猫的逆病毒感染，猫白血病毒，在前驱期，可用口服大剂量抗坏血酸配合其他营养素而治愈（26）。
抗坏血酸，一种无限速的，抗氧化物自由基清除剂
我推测：使抗坏血酸真正独特的是很大量的抗坏血酸作为一种无限速的自由基清除剂。
临床上，抗坏血酸实际上是无毒的（27，28，4）。但，当抗坏血酸作为一个抗氧化物自由基清除剂，它被氧化为脱氢抗坏血酸。已有动物实验表明，脱氢抗坏血酸是有毒的（29~31）。然而，脱氢抗坏血酸，不像其在动物实验，不是直接给予人类的。不管什么脱氢抗坏血酸出现在人体内，都通过抗坏血酸的氧化而成。由于抗坏血酸被用于还原自由基或其他高度氧化的物质。脱氢抗坏血酸产生的损害应比被抗坏血酸还原的有害物小（氧化还原电位已减少）。因此，除非存在某些对脱氢抗坏血酸的异常特异性敏感性，任何一个病人都不应该因脱氢抗坏血酸而变得比其原发病的毒性重（看下面的G-6-PD 缺乏症的讨论）。
当使用我建议的剂量，这里有一个防止脱氢抗坏血酸毒性的更重要的机制。我利用两种事实结合的优势：即使在巨大的剂量，抗坏血酸在临床上是无毒的，同时，脱氢抗坏血酸只在AA/DHA的比值很低时才有毒。
在高组织浓度的最低基础量的有效的还原型氧化还原电位
多名研究员（32~36）已假设和评估了大剂量抗坏血酸的生化有利因素。其中特别有趣的是Lewin的估算假说：就是组织高浓度的AA/DHA比值可以直接还原各种物质（如双硫键）。我推测病理情况下，比肠耐受极限量低得多的剂量所达到的组织浓度，足够显著地取得这些还原。然而，临床上，在达到肠耐受极限量时，某些非常惹人注目的效果会出现。我假设，当一个最低基础量的比值AA/DHA达到时，某些如氧化型谷胱甘肽和肾上腺色素的直接还原就会发生。当一个病人患病或经受很大的压力时，这些可被还原的物质，大大增多。如果没有抗坏血酸去还原这些物质。那些逃过还原或无毒衍生物，会损害病人和引起症状。在这种情况下，如果可得到，大量的抗坏血酸就会用于直接还原目的。这些抗坏血酸还原是无速度限制的。因此，几乎可以瞬间克制有害的氧化物和自由基。
当机体对抗坏血酸的最大需求得到满足，血中的抗坏血酸水平上升，阻止了抗坏血酸从肠道的进一步吸收，很快，足够量的抗坏血酸就会到达直肠，产生腹泻。
依据临床证据，我假设：在极恶劣的情况下，抗坏血酸能够维持这种还原性的氧化还原电位，但，以任何其它的标准来衡量，取得这样的效果所需的抗坏血酸的量是巨大的。大剂量的抗坏血酸的这种抗氧化自由基清除效应看来不依赖于其他营养素。然而，低量维生素C的维生素功能常和其他维生素发生协同作用，本身的作用并被它们加强。如维生素A、锌、硒、生物黄酮和在各种防御机制中发挥作用的其他营养素。
Chayen讨论了氧化还原配对的重要性，以及强调：反应能否从左向右进行，或相反，取决于一对氧化还原配对当中，氧化型成分和还原型成分的比值。他提出议：设计一种氧化还原药物，作为治疗最重要的细胞内系统的氧化还原电位的不平衡的一种万能的方法（37）。
抗坏血酸符合一种无限制的抗氧化自由基清除剂的益处的范围
我期待，如果可以消除大多数游离自由基和高度反应物质，受伤或外科手术后常见的炎症串联反应将不会出现。疼痛，并发症和康复时间将会减少。在下列情况下结合产生的病况：机能障碍、营养缺乏、免疫失调、产生铁和铜的自由基的释放引起的出血、以及继发炎症串联反应（退行性椎间盘疾病，退行性关节炎，风湿性关节炎，关节强直性脊椎炎，脊椎钝挫伤，等）。其治疗效果应与抗坏血酸阻断自由基和炎症串联反应成正相关关系。虽然可以提高某些治疗措施的效果，但不能预期功能性和非自由基造成的损伤逆转。
其作用机理涉及自由基产生的毒性物质，如：蛇和蜘蛛咬伤的毒素，某些药物如：苯巴比妥、化疗介质、麻醉药、强力氧化污染化学物，都可以被中和。由过敏反应引发以及炎症串联反应为基础的病况，应期待可被部分缓解。由肾上腺素和去甲肾上腺素（38）氧化物产生的精神症状，应可部分改善。
通过自由基的毒性攻击机体或避开免疫系统的肿瘤可预期会对抗坏血酸发生程度各异的反应。由于认识到由感染性生物体导致的人类癌症数目的增多，如CMV（39）引起Kaposi氏病变，某些HTLV（40）引起的某些成人的T-细胞淋巴瘤，Papilloma 病毒引起的某些宫颈和阴道癌（41，42），如果认为这类癌症对抗坏血酸有不同程度的反应，是不应该惊奇的。由于在1984年，一个医生以营养素治疗病人是不可思议的违法行为，早期这样认识是可行的，就是，一种由病毒引起的癌症不应再被考虑为癌症（如，Kaposi氏病变）。
如果，对这些疾病，我们增加一些可因饮食中缺乏维生素C或急性诱发维生素C缺乏症引发或加剧的受益于抗坏血酸的病况，就有一个非常符合实际的，使用这些剂量的临床疾病适用范围。所有这些疾病，均受益于抗坏血酸。粗略估算，这些疾病都可改善到一个预期的程度，如果可以消除自由基和高度活跃的氧化物的理想机制可真正实现的话。
6-磷酸葡萄糖脱氢酶缺乏症（G-6-PD）
有担心，给予6-磷酸葡萄糖脱氢酶（G-6-PD）缺乏病人大剂量的抗坏血酸会引起溶血（45，46）。有一病例，一位G-6-PD缺乏的黑人，因一只手烧伤，接受每天80克抗坏血酸静脉注射治疗，连续二天，结果病人出现溶血，肾衰竭，中风，昏迷，最后死亡（46）。目前，供静脉注射用的，有抗坏血酸溶液，而不是抗坏血酸钠。抗坏血酸， 我的观点是，从不直接给予大剂量静脉注射。用前应要进行缓冲以减少酸性。现有标有含防腐剂的维生素C，这种维生素C不应给予使用。从该篇报道，未能得知用什么方法制备此治疗制剂。某些药物引起有G-6-PD缺乏的人产生溶血的细节尚不清楚。看来， G-6-PD缺乏的人的细胞缺乏一种再生氧化型谷胱甘肽（GSSH）为还原谷胱甘肽（GSH）的机制。同时，这个缺乏可能产生几种生物化学结果，最终结果就是红细胞的溶血。谷胱甘肽于还原状态可能是HMP路径的最主要功能。可能，由某些药物引起的溶血是由药物形成的自由基或过氧化氢所激发。当过氧化物还原为水，GSH被氧化为GSSH，一种由谷胱甘肽过氧化物酶催化的反应。正常情况下，GSSH，通过NADPH，还原为GSH，一种由谷胱甘肽还原酶催化的还原。结果产生的氧化型 NADP被还原回NADPH（在人类HMP路径的第一步，当6磷酸葡萄糖被氧化为6-磷酸葡萄糖内酯，这个关键反应被G-6-PD催化。G-6-PD缺乏的细胞会积累氧化其他红细胞成分的过氧化物。（47）
正如我以前讨论的，如果AA/DHA氧化还原配对电位被高浓度的抗坏血酸保持足够的还原态，它将直接还原GSSH为GSH。我假设这种机制应会代偿G-6-PD的缺乏。但我会提出忠告，我没有处理这种病况的经验。很明显，然而，在那个医案里，在整个治疗过程中，氧化还原电位没有保持连续的还原态，以及，有可能有某些变数，在它们很重要时，没有加以重视。
由于日益增多的数以百万计的人服用大剂量维生素C，不可避免，某些有G-6-PD缺乏的人服用这些剂量。猎奇式的数据应该收集。我将欢迎任何完整记录的医案。
理解下述是很重要的，G-6-PD缺乏者的临床严重程度的表现有极大的差异性。严重缺乏者是罕见的，只在地中海和亚洲地区发现。黑人患病程度较轻，但患病率更高。随着年龄的增长，这种病的活动性减低。出现下列情况的人有不同程度和不同形式的G-6-PD缺乏的可能性：1）：维生素C 无任何引起伤害的作用。 2）：维生素C 对某人有特别的作用，任何显著增加的量将会产生溶血。3）：维生素C在低量和温和量会产生溶血，而大剂量维生素C，维持一个持续的还原型氧化还原电位将不会引起溶血，并会防止其他原因引起的溶血。这个最后的可能性将不能确定，除非服用维生素C的人异常进取，以及不减少用量，直至服用维生素C 的首要原因已经完全消除。
因为我正讨论的这个剂量的抗坏血酸的巨大价值，在正常人已经变得完全清楚。预防有G-6-PD缺乏并且受到可产生红细胞大量溶血的病理氧化压力的人的溶血的理论上的可能性可能被认识。同时，我忠告，大剂量抗坏血酸不给予G-6-PD缺乏的病人。我建议，如果把抗坏血酸用于G-6-PD缺乏的人，只是为促进资料的收集和建议对这方面作研究。
Calabrese 曾建议，大剂量抗坏血酸对患有镰状细胞特征和镰状细胞贫血的病人可能会引发溶血的危险，因为他们的红细胞有比正常人的红细胞多的铜。抗坏血酸显著增加铜诱发的溶血（48）。我再次建议：如果在镰状细胞危机的时候，给予足够大量的抗坏血酸，他可以维持多种有问题的系统的氧化还原电位于还原态。维生素E可能更进一步促进这些有益的效果（49）。
其他可能的困难
任何人都可能因为我的“肠耐受”病人的条件而持不必要的谨慎。任何真正的问题一直很罕见。我不能想起任何病人曾经因大剂量抗坏血酸而受伤害（除了对牙釉质的局部腐蚀作用）。某些之前存在的消化道困难，比如消化性溃疡或结肠炎，或许有可能因抗坏血酸的局部作用而加剧。但对这些问题的忠告是很难给予，因为同样的问题可能会受益。所有这些困难都会通过静脉注射抗坏血酸而避免。
有食物或化学物过敏的人多数可能会对维生素C产生厌恶感。然而，应尽力让这些病人服用抗坏血酸，因为很显著的效果通常会取得。特别是用钙、镁和钾盐合成的抗坏血酸。这些病人当中的许多会适应。通常，在给予硒制剂之后，有化学物过敏的病人，会更好耐受抗坏血酸。Levine曾提议：化学物过敏病人常受益于硒，因硒会增强谷胱甘肽过氧化物酶的活性（18）。我已有一些临床证据，一些有化学物过敏的病人在克服少剂量抗坏血酸的厌恶感问题后，可以从连续服用大剂量抗坏血酸中获得益处。其机理可能是化学物过敏病人较常人易积聚脱氢抗坏血酸，因为其缺乏谷胱甘肽过氧化物酶。我有一个化学物过敏的病人，对静脉注射抗坏血酸反应很好，直至静脉注射结束一个小时。之后，她出现了严重的头痛，持续了几个小时。回顾此案例，看来，静脉注射抗坏血酸可以维持一种还原态氧化还原电位，在静脉注射中断后，氧化还原电位回到氧化态的一边。
由抗坏血酸引起的真正过敏反应看来都可追踪到制造抗坏血酸的原料，或在制造过程中使用的化学物，而和抗坏血酸本身无关。
草酸盐结石
草酸盐肾结石曾被认为是一个理论上的问题。因为草酸盐是抗坏血酸的降解产物之一（50）。在我的临床经验中，抗坏血酸，不但不会引起肾结石，而且，看来可以预防原来有肾结石的病人出现肾结石。尿液酸性的轻度的增加，以及轻度的利尿作用帮助溶解钙盐。我认为高浓度的抗坏血酸，通过在尿液产生抑制细菌作用，应该可以防止常常形成草酸盐结石的许多感染的小病灶生成。增加的抗坏血酸浓缩物和钙离子结合，减少钙和草酸盐结合形成草酸钙的钙离子的数量（34）。这里再次出现令人矛盾的情形，当少量口服抗坏血酸时，这种营养素的大多数，可能，被氧化为脱氢抗坏血酸，然后，某些会形成草酸，理论上有可能，增加结石形成的倾向。然而，我发现这个很难令人信服，如果这是事实，数以百万计的人正在服用少量维生素C，这个倾向不可能没有被注意到。我假设，通过肠耐受极限量的方法测定需要服用的量，不管脱氢抗坏血酸形成多少，以及由此产生多少草酸，尿中抗坏血酸的排泄将会保持甚高水平，应该可以阻止草酸结石的形成。
抗坏血酸缺乏症和急性诱发性坏血病
我提议：机体为清除自由基而对抗坏血酸的巨大需求，可能会耗竭现存的已知的作为一种维生素维护功能的维生素C。我称这种状态为急性诱发性坏血病。这种缺乏开始于疾病直接涉及的组织，然后，血液中的维生素C水平下降（抗坏血酸缺乏症），然后，是远离原发病灶的组织亦被波及。各种可通过全面满足机体对抗坏血酸需求而避免的并发症出现（4）。
抗坏血酸可以帮助免疫系统对抗病原体的一个很重要的原因是，血清和白细胞的抗坏血酸水平升高到足以驱使抗坏血酸进入感染组织的内部。身体需要抗坏血酸，以满足其在病变组织内部作为自由基清除剂而被大量利用的量，得到供应。受感染组织依赖于维生素C的维持功能的关闭，以及依赖于维生素C的免疫功能的关闭得以避免。
突发婴儿死亡综合征
我认为，在有证据表明婴儿正患某种感染性疾病之前，许多突发婴儿死亡综合征是急性诱发性坏血病引起。Kalokerinos (28)已经展示了维生素C在预防突发婴儿死亡综合征的价值。我看过许多成年人在外部病征出现之前，其抗坏血酸的肠耐受极限量显著的增加。不难想象，当婴儿的某些最重要的中心，当抗坏血酸用作急性自由基清除目的而失去维生素C 的供应时，其功能会衰竭。从多方面来说，不幸的是，这个抗氧化自由基清除剂的抗坏血酸同时是作为维生素C的同一样物质。除了相当的维持量，当患病时，即使婴儿亦应给予大剂量的维生素C。应给予足够的量以减轻发烧，烦躁不安和其他毒性的外在症状。
小结
在不否定服用大剂量的抗坏血酸可能会有十分罕见的严重并发症的同时，担心这个可能性不应该阻止大剂量抗坏血酸在代谢正常的人的使用。在我的经验，大剂量抗坏血酸产生显著并发症的安全范围，大于阿斯匹林、抗组胺药、抗生素、所有止痛药、肌松药、镇静药、催眠药、利尿药等。抗坏血酸不但有益的安全范围大，而且，和其他药一同使用时，会起协同作用，比单一药物使用有更大的安全范围。在抗坏血酸可以阻断某些催眠药和麻醉药的作用的同时，大剂量抗坏血酸通常可以缓和机体对这些药物的需求。
临床上，这里描述的在大剂量水平的抗坏血酸，是十分有效和安全的，作为范围宽广的疾病的治疗的一部分，尤其是感染性疾病。我的假设是：当一个关键的最低基础量达到时，如达到肠耐受极限量时出现的腹泻，其临床有效性的出现是因为，一是大剂量的抗坏血酸可作为一种非限速的抗氧化自由基清除剂，另一方面，急性诱发性坏血病得以避免。当在病变涉及组织达到足够的抗坏血酸水平时，系统的AA/DHA的氧化还原电位在这些组织被维持还原态，如氧化态的谷胱甘肽等物质被直接还原，而游离自由基被快速克制。
抗坏血酸的这种效果只会被服用抗坏血酸的人的勇气的缺乏以及服用者肠耐受极限的限制。我希望通过指出：临床观察其毒性的缺乏，以及理论上毒性缺乏的依据，而增加这种勇气。
当这种作用被理解时，开拓了一个宽广的机会去理解某些病变的进程。在感染性疾病，这个尤其重要，因为各种病原体拥有的自由基毒性可能是其克制免疫系统的共同机制。增加的肠耐受极限量可作为一种公正准确的量度某些疾病进程的“毒性”和活动性的尺度。
在毒性的病变中，机体为清除这些自由基而对抗坏血酸的利用，导致局部和全身维生素C的缺乏，因此，没有剩余足够的这种营养素以满足依赖于维生素C的维护功能。我称这种状况为急性诱发性坏血病。这种状况可由任何压力诱发，并且是许多疾病的大多数的继发性并发症的重要原因。这种清除功能对抗坏血酸的需求的幅度是巨大的。正如增加的肠耐受极限量和疾病的毒性程度呈正相关的关系所揭示的。只有这里讨论的剂量能完全满足这种需求。
我认为大多数突发婴儿死亡综合征是由急性诱发性坏血病引起。
我在这里假设：在G-6-PD缺乏病人中，大剂量抗坏血酸可能有令人矛盾的益处。但我忠告，在获得更多的资料之前，应持谨慎态度。抗坏血酸，当使用得当，对化学物过敏病人，可产生极大的益处。
擦掉牙齿上的抗坏血酸和碳酸盐抗坏血酸，因为延长对抗坏血酸的接触会引起牙釉质的损坏。
感谢
部分由BURTON GOLDBURG 基金会的支持。作者赞赏STEPHEN A.LEVIN 和PARRIS M.KIDD所作的评述。
http://www.orthomed.com/nonrate.htm
(C) Robert F. Cathcart, III Allergy, Environmental, and Orthomolecular Medicine 127 Second Street, Los Altos, California 94022, USA Telephone 650-949-2822
The amount of oral ascorbic acid that a patient can tolerate without diarrhea, increases somewhat proportionately to the "toxicity" of his disease. Clinically, in a disease ameliorated by ascorbate, there is a suppression of symptoms only with very high doses and approximately to that extent which a nonrate-limited,_antioxidant_free_radical_scavenger, might be expected to affect that disease process if all harmful free radicals and highly reactive oxidizing substances were quenched. In most pathologic processes, the rate at which free radicals and highly reactive oxidants are produced, exceeds the rate at which the ordinary rate-limited antioxidant free radical scavenging mechanisms can quench those free radicals and oxidants. When ascorbate acts as a scavenger, dehydroascorbate is formed; but if the ascorbate/dehydroascorbate (AA/DHA) ratio is kept high (the redox potential kept reducing) until the unstable dehydro- ascorbate undergoes hydrolysis or can be reduced back to ascorbate, the dehydroascorbate will do no harm. Since even at very high doses, ascorbate is virtually nontoxic, it may be given in the enormous doses necessary to quench almost all unwanted free radicals and oxidants. The wide spectrum of infectious diseases ameliorated by massive doses of ascorbate indicates some common pathologic processes in these diseases.
Based on my experience with over 11,000 patients during the past 14 years, it has been my consistent observation that the amount of ascorbic acid dissolved in water which a patient, tolerant to ascorbic acid, can ingest orally without producing diarrhea, increases considerably somewhat proportionately with the "toxicity" of his illness. A person who can tolerate orally 10 to 15 grams of ascorbic acid per 24 hours when well, might be able to tolerate 30 to 60 grams per 24 hours if he has a mild cold, 100 grams with a severe cold, 150 grams with influenza, and 200 grams per 24 hours with mononucleosis or viral pneumonia. The clinical symptoms of these diseases and other conditions previously described, are markedly ameliorated only as bowel_tolerance dose levels (the amount that almost, but not quite, causes diarrhea) are approached (1-6).
GRAMS PER NUMBER OF DOSES
CONDITION 24 HOURS PER 24 HOURS
normal 4 - 15 4 - 6
mild cold 30 - 60 6 - 10
severe cold 60 - 100+ 8 - 15
influenza 100 - 150 8 - 20
ECHO, coxsackievirus 100 - 150 8 - 20
mononucleosis 150 - 200+ 12 - 25
viral pneumonia 100 - 200+ 12 - 25
hay fever, asthma 15 - 50 4 - 8
environmental and
food allergy 0.5 - 50 4 - 8
burn, injury, surgery 25 - 150+ 6 - 20
anxiety, exercise and
other mild stresses 15 - 25 4 - 6
cancer 15 - 100 4 - 15
ankylosing spondylitis 15 - 100 4 - 15
Reiter's syndrome 15 - 60 4 - 10
acute anterior uveitis 30 - 100 4 - 15
rheumatoid arthritis 15 - 100 4 - 15
bacterial infections 30 - 200+ 10 - 25
infectious hepatitis 30 - 100 6 - 15
candidiasis 15 - 200+ 6 - 25
There was a remarkable lack of systemic difficulties in these patients that could be directly related to the massive doses of ascorbate. The majority of these patients, ill with some acute or chronic disease, were able to take massive doses of ascorbic acid orally without difficulties. Minor complaints about ascorbic acid such as it causing gas, diarrhea, or acid stomach, while common in well persons even at low doses, were rare in very sick patients. Low or moderate doses (doses substantially below bowel tolerance) usually had no noticeable immediate beneficial effects, but high doses (doses just below the amount that would produce diarrhea in a patient tolerant to ascorbate) would have the effect of markedly suppressing symptoms as the high dose levels were reached. This sudden effect is often quite dramatic clinically and is not usually obtained even partially at lower doses. It is as if a threshold were reached at which point the ascorbate becomes very effective.
Mixtures of mineral ascorbates (calcium, magnesium, potassium, zinc, and sometimes sodium) are used in certain circumstances to increase bowel tolerance for even more clinical effectiveness but do not clearly demonstrate the increasing bowel tolerance phenomenon being discussed here.
Knowledge of the known vitamin functions of ascorbate would not have allowed one to predict these beneficial results. The lack of serious difficulties with these massive doses is surprising.
Part of the unexpected benefit at the high dose levels is frequently a feeling of well-being. This feeling of well-being, especially with the more toxic conditions, is despite the gas and diarrhea sometimes produced. If the malaise from the basic disease is great (e.g. mononucleosis, acute hepatitis, viral pneumonia, etc.), the obvious benefit from ascorbic acid is usually so great that the patient usually cares little about the minor gastrointestinal disturbances. Lowering dose levels too soon before bowel tolerance decreases, results in the return of the malaise and other acute symptoms of the disease. The_clinical_sensation_experienced_with_the_massive doses_of_ascorbate_is_one_of_"detox- ification"_as_a_threshold_is_reached. By raising and lowering the doses, the symptoms of "toxicity" can be readily turned off and on rapidly by some skilled patients.
I cannot emphasize enough that in "selected" patients (selected only by excellent tolerance to ascorbic acid, good understanding of the principles of determining the flexible bowel tolerance doses, and the willingness to follow directions in fine detail), this effect is invariable, dramatic, and unmistakable. The patient most likely to experience this effect is the psychologically stable, not suggestible, practical, not liking to be sick patient, with a "cast iron stomach." Children and teenagers, much as they may hate the taste of ascorbic acid in water, make particularly good patients once they experience the ameliorating effects of these massive doses. Infants, upon receiving very large intramuscular or intravenous injections, frequently "detoxify" in minutes to the astonishment and marked relief of their parents.
These feelings of well-being experienced by tolerant patients from the ingestion of massive doses of ascorbic acid are definite clinical indications that no acidosis or other acute toxic metabolic effect is resulting. Massive intravenous doses of sodium ascorbate are even more impressive than oral ascorbic acid, because the beneficial effects are even more dramatic and gastrointestinal gas and diarrhea are not produced. Patients who ordinarily would be relatively incapacitated, can usually remain functional and sometimes even participate in athletics if frequent and massive ascorbate doses are maintained.
Patients must be encouraged to take these massive doses. Patients taking vitamin C on their own, seldom take doses high enough to discover this effect. I do not want to give the impression that this method is easy to use; the mechanics of taking these doses can be very difficult for many patients. Nevertheless, when properly instructed, the majority of patients are able to achieve these effects. If a patient is relatively intolerant to oral ascorbate only because of gastrointestinal complaints, and if his disease is one that usually responds to oral ascorbate in tolerant patients, and if the severity of the condition warrants the inconvenience and expense, then intravenous ascorbate is indicated.
Such effects of these large doses of ascorbate cannot be readily explained from its known vitamin functions. The spectrum of diseases affected by massive doses of ascorbate is a wonder in itself, but also gives some hint at the probable mechanisms involved. The sudden detoxifying effect experienced clinically only at the very high threshold doses, suggests that ascorbate is participating in chemical reactions where a critical concentration of ascorbate is necessary, or where a certain ratio between ascorbate and certain other reactants must be achieved. The concept that free radicals and other highly reactive oxidants are a frequent factor in pathologic processes (7,8) and that ascorbate is an antioxidant free radical scavenger, could explain much of this.
Chemical reactions involving free radicals and highly reactive oxidants are necessary in the normal metabolism of cells. Metabolic processes utilizing oxygen (aerobic metabolism) which release energy are important examples. Ordinarily, these reactions occur in conjunction with appropriate enzymes or in the proper places within the cells. While it has been documented that potentially harmful reactants leak from their normal cellular confines and are potentially toxic (9), these rates of leakage are usually low enough for the natural antioxidant, free radical scavenging mechanisms to handle. One of the causes of natural aging may be that some (albeit small) portion of stray free radicals inevitably escape quenching (10). While the human body does contain many free radical scavenging mechanisms for the purpose of mopping up free radicals, I hypothesize that in_pathologic processes_these_rate-limited,_mechanisms_are_acutely_inadequate_t o_neutralize the_volume_of_free_radicals_produced. A threshold is reached where these additional free radicals produced, initiate an inflammatory cascade, can cause immune suppression, and can result in degenerative diseases.
In general free radical scavenging occurs through complex metabolic pathways involving many steps which are rate-limited. Deficiencies of nutrients, vitamins and minerals, which make up the enzymes and coenzymes of these systems can slow down or halt certain pathways.
It is apposite to describe one of these rate-limited, free radical scavenging mechanisms, to give the impression of its complexity and why it is rate-limited. The example chosen involves the glutathione pathway which is possibly one of the most important pathways.
When, for example, a superoxide radical must be destroyed, superoxide dismutase can catalyze its conversion to O2 and H2O2 (11). Ascorbate, nonenzamatically, also converts superoxide to H202 but is oxidized in the process to the ascorbate free radical and dehydroascorbate. The ascorbate free radical and the dehydroascorbate are reduced back to ascorbate either by NADH (catalyzed by semidehydroascorbate reductase and forming NAD) or reduced glutathione (GSH) (catalyzed by dehydroascorbate reductase and forming oxidized glutathione (GSSG)) (12). Some of the peroxide can be converted to oxygen and water by catalase but most will be destroyed by a glutathione-requiring enzyme system. GSH (catalyzed by glutathione peroxidase) reduces the peroxide to water but in the process is oxidized to GSSG. The resulting GSSG is reduced by NAD(P)H (catalyzed by glutathione reductase). The resulting NAD is reduced back to NADH by way of the Krebs cycle or resulting NADP is reduced back to NADPH by the hexose monophosphate (HMP) pathway. It is thought that commonly the rate-limiting step in the last series of reactions is that catalyzed by glutathione peroxidase and its cofactor selenium, but other substances which could limit all this are the vitamin E, vitamin C, vitamin B2, vitamin B3, cysteine, etc. Note: the ascorbate used in this example is as in the vitamin C sense; the small amount available is oxidized to dehydroascorbate and then must be reduced back to ascorbate by the pathway described, to be reused as ascorbate. One can easily see how this mechanism and similar mechanisms could be overwhelmed by a toxic pathogen liberating free radicals or by an inflammatory cascade regardless of its cause.
More recently, I have found ascorbate useful in the management of the acquired immune deficiency syndrome (AIDS). The AIDS patient who has already suffered a marked suppression of helper T-cells, presents a clinical problem of management similar to a bubble baby. If, in addition to the other measures described in my previous reports (24,25), the patient takes bowel tolerance doses of ascorbic acid orally almost every hour (intra- venously in emergencies), he may remain clinically well despite the continuing severe suppression of the helper T-cells. All this must be started before multiple infections riddle the patient's body with excessive sources of free radicals. There have been suggestive anecdotal cases which indicate that in the prodromal period, before the destruction of the helper T-cells, there might be avoidance of the development of the AID syndrome by this program. Confirmation of this possibility awaits long- term laboratory follow-up. There is evidence that a retroviral infection in cats, the feline leukemia virus, can be cured in the prodromal stage with large oral doses of ascorbate used in combination with other nutrients (26).
It is my hypothesis that what makes ascorbate truly unique is that very large amounts can act as a nonrate-limited antioxidant free radical scavenger.
Clinically, ascorbate is virtually nontoxic (27,28,4). But as ascorbate acts as an antioxidant free radical scavenger in the body, it is oxidized to dehydroascorbate. There are animal experiments that indicate that dehydroascorbate is toxic (29-31). However, dehydroascorbate is not administered directly to humans as it was in the animal experiments. Whatever dehydro- ascorbate comes to exist in the human body, comes by way of the oxidation of ascorbate, as the ascorbate is utilized to reduce free radicals or other reactive oxidizing substances. The potential of the dehydroascorbate to do damage should be less than the harmful potential of the substances it reduces to become dehydroascorbate (the oxidizing redox potential has been diminished). Therefore a patient should not be expected to be more toxic from the dehydroascorbate formed than he was from the original disease unless there is some peculiar specific sensitiv- ity to dehydroascorbate (see discussion of G-6-PD deficiencies below).
Used in the doses I suggest, there is an even more important mechanism which prevents toxicity from dehydroascor- bate. I take advantage of a combination of the facts that even in enormous doses, ascorbate is not clinically toxic, and that dehydroascorbate is only toxic when there is a low AA/DHA ratio.
Several (32-36) have hypothesized and reviewed many of the biochemical advantages of large doses of ascorbate. Of particular interest are Lewin's calculations and hypotheses (34) that high tissue concentrations of ascorbate to dehydroascorbate can directly reduce various substances (e.g. the disulfides). I doubt that tissue levels of ascorbate achieved with doses much below bowel tolerance are sufficient to significantly accomplish these reductions under pathological circumstances. Clinically however, something very dramatic happens as bowel tolerance is approached. I hypothesize that as a certain threshold ratio of ascorbate to dehydroascorbate is reached, certain direct reductions of substances such as oxidized glutathione and adreno- chrome by ascorbate begin. When a patient is sick or experiencing much stress, the amounts of these substances which can potentially and beneficially be reduced, increases greatly. If ascorbate is not available to reduce these substances, those that escape reduction to nontoxic derivatives by the rate-limited, antioxidant free radical scavenging mechanisms, damage the patient and cause symptoms. Under these circumstances, when made available, large amounts of ascorbate are utilized for these direct reducing purposes. These ascorbate reductions are not rate-limited, and therefore quench the harmful oxidants and free radicals almost instantly.
When the potential need for ascorbate for these purposes is satisfied, the blood level of ascorbate rises and retards the absorption of ascorbate from the gut. Soon, sufficient amounts of ascorbate reach the rectum to produce diarrhea.
Based on clinical evidence, I hypothesize that ascorbate can maintain this reducing redox potential under very adverse circumstances, but that the doses necessary to do this are enormous by any other standards. This antioxidant free radical scavenging effect of enormous doses of ascorbate seems not particularly contingent upon other nutrients. However, vitamin functions of lower doses of vitamin C are frequently potentiated by and work in conjunction with vitamin A, zinc, selenium, bioflavonoids, and other nutrients which play roles in various defense mechanisms.
Chayen has discussed the significance of redox couples and has emphasized that whether a reaction will proceed left to right, or in reverse, depends upon the ratio of the oxidized to the reduced members of a redox couple. He suggests designing "redox drugs" as a possible way of treating imbalances of oxidation-reduction potentials of critical intracellular systems (37).
I would anticipate that if it were possible to eliminate the vast majority of stray free radicals and highly reactant oxidative substances, the usual inflammatory cascade would not occur following injury or surgery. Pain, complications, and recovery times would be reduced. In conditions resulting from combinations of mechanical derangements, nutritional deficien- cies, immune dysregulations, hemorrhage with release of free radical generating iron and copper atoms, and then secondary inflammatory cascades (e.g. degenerative disc disease, degenera- tive arthritis, rheumatoid arthritis, ankylosing spondylitis, blunt trauma of the spine, etc.), therapeutic effects could be expected proportional to what might result from blocking of the free radicals and the inflammatory cascade. Reversal of the mechanical and nonfree radical injury could not be expected, although certain healing mechanisms might be enhanced.
Toxic substances, whose mechanisms of action involve free radical generation, e.g. toxic poisons such as snake bites and spider bites, certain drugs, such as barbiturates, chemotherapeutic agents, narcotics, and powerful oxidizing pollutant chemicals, might be neutralized. Conditions triggered by allergic reactions and perpetuated by the inflammatory cascade might be expected to be partially alleviated. Psychological symptoms resulting from oxidative products such as adrenochrome and noradrenochrome (38), would be expected to be ameliorated to a degree.
Tumors invading the body or holding off the immune system by way of free radical toxicity might be expected to respond to varying degrees. As an increasing number of human cancers are recognized as probably being caused and possibly maintained by infectious organisms (e.g. Kaposi's lesions by the CMV (39), some adult T-cell lymphomas by the HTLV (40), certain cervical and vaginal cancers by the papilloma virus (41,42)), it should not be surprising if such tumors would respond in various degrees to ascorbate. Since any treatment of cancers by a physician with nutritional substances is incredibly a felony in California in 1984, it may be practical to recognize early that a tumor caused by a virus should no longer be considered a cancer (e.g. Kaposi's lesions).
If, to these diseases, we add conditions benefitted which could be caused or aggravated by actual dietary deficiency of vitamin C, or from an acute induced deficiency of vitamin C, there is a very close approximation to the clinical spectrum of disease conditions which in the experience of those actually using such doses (4,26-28,32,33,43,44), appear to be beneficially affected. In a rough way, these conditions are ameliorated to the degree that one might anticipate if this ideal mechanism of being able to quench all stray free radicals and highly reactant oxidative substances, were actually accomplished.
One might remain unnecessarily cautious in the use of ascorbate because of my qualification about "tolerant" patients. Any real problems have been rare. I cannot recall any patient who has been damaged by large doses of ascorbate (other than the topical effect of the acid on tooth enamel). Some preexisting gastrointestinal tract difficulties, such as peptic ulcer or colitis, may have been aggravated by topical effects, but advice on these is difficult to give because more frequently the same conditions may be benefitted. All these topical difficulties are circumvented by using intravenous ascorbate.
A high percentage of persons with food and/or chemical sensitivities may have nuisance difficulties with vitamin C. However, attempts to have these sensitive patients take ascorbate should be made because great benefits can often be obtained, particularly from calcium, magnesium, and potassium ascorbate, in many of these patients. Frequently, after the administration of selenium, ascorbate is better tolerated by chemically allergic patients. Levine has suggested that chemically allergic patients frequently benefit from selenium because selenium augments the glutathione peroxidase activity (8). I have had some clinical evidence that certain chemically allergic patients who force through nuisance problems of low doses of ascorbate, can derive benefits from consistently taken large doses. It may be that chemically allergic persons accumulate dehydroascorbate more readily than others because of a deficiency of glutathione per- oxidase. I had one chemically allergic patient who responded well to intravenous ascorbate until an hour after it was discon- tinued. She then developed a severe headache that lasted several hours. In retrospect, it seems possible that the intravenous ascorbate was able to maintain a reducing redox potential, which then returned to the oxidizing side after the intravenous ascorbate was discontinued.
True allergic reactions seem always traceable to substances from which the ascorbate is made, or chemicals used in its manufacture, and not to the ascorbate itself.
Oxalate kidney stones have been suggested as a theoretical problem, in that oxalate is one of the breakdown products of ascorbate (50). In my experience clinically, ascorbate in these doses not only does not cause kidney stones but seems to prevent stones in patients who have had them previously. The slight increase in the acidity of the urine from ascorbate (51,52), and the slight diuresis (53) solubilizes calcium salts. I think that high concentrations of ascorbate, by being bacteriostatic in the urine, should prevent many of the niduses of infection around which oxalate stones frequently form. The increased ascorbate concentration complexes Ca++ and thereby decreases the amount of Ca++ available to complex with oxalate (34). Here again is the paradoxical situation where with small doses of vitamin C, it is possible that where most of the nutrient is oxidized to dehydro- ascorbate and then some to oxalic acid, it is theoretically possible that there could be a slight increase in tendency to form stones. However, I find it difficult to believe that if this were the case, that this tendency would not have been noticed with the millions taking small doses of vitamin C. I hypothesize that by using the bowel tolerance method of determining the dosages of ascorbate to be taken, that no matter how much dehydroascorbate is formed and hence oxalic acid, the spill of ascorbate in the urine will be kept very high and should prevent oxalate stones.
I suggest that the enormous draw on ascorbate for free radical scavenging purposes, can exhaust the vitamin C available for known housekeeping functions of the vitamin. I term this condition acute_induced_scurvy. This deficiency starts in the tissues directly involved in the disease; then blood levels of vitamin C drop (anascorbemia); and then tissues distant from the primary focus of the disease become involved. Secondary complications occur which can be averted by fully satisfying the increased need for ascorbate (4).
A very important part of these very large doses of ascorbate being able to assist the immune system against pathogens is likely that serum levels and leukocyte levels of ascorbate are raised enough to drive ascorbate into the depths of infected tissues. The amount of ascorbate needed to satisfy the enormous potential utilization of ascorbate as an antioxidant free radical scavenger in the depths of the diseased tissues is provided. The shut down of vitamin C dependent housekeeping functions of affected cells and the shut down of vitamin C dependent immune system functions are prevented.
I think that many crib deaths are caused by this acute induced scurvy even before it is evident that the infant is sick with some infectious disease. Kalokerinos (28) has demonstrated the value of vitamin C in preventing crib deaths. I have seen enormous increases in bowel tolerance to ascorbate in adults several hours before there was any outward sign of their getting sick. It is easy to imagine certain vital centers in an infant failing when suddenly deprived of vitamin C by the ascorbate being used up for acute free radical scavenging purposes. For_many_reasons, it is unfortunate that the free radical scavenger ascorbate is the same substance as vitamin C.Infants tolerate ascorbate well. In addition to substantial maintenance doses of vitamin C, even infants should be given large doses of ascorbate when ill. Amounts should be given sufficient to relieve fever, irritability, and other outward signs of toxicity (4).
While it is not denied that there could be very rare serious complications associated with the use of massive doses of ascorbate, fear of this possibility should not retard use of the substance in patients with normal metabolism. In my experience, the margin of safety (therapeutic index or selectivity) for massive doses of ascorbate as related to significant complica- tions is greater than aspirin, antihistamines, antibiotics, all pain medications, muscle relaxants, tranquilizers, sedatives, diuretics, etc. Not only is the margin of safety of ascorbate extremely favorable but when used with most of these drugs, the combination frequently acts synergistically and has a margin of safety greater than with the drug alone. While ascorbate may block the effects of some sedatives and narcotics, massive doses of ascorbate frequently alleviate the need for those substances.
Clinically, ascorbate in the very large doses described is very effective and safe as part of the treatment of a wide variety of conditions, especially infectious diseases. It is my hypothesis that this clinical effectiveness when a critical threshold is reached, as indicated by bowel intolerance to ascorbic acid in the form of diarrhea, occurs both because massive doses of ascorbate can act as a nonrate-limited, antioxidant free radical scavenger and because acute induced scurvy is avoided. When high enough tissue levels are reached in tissues directly affected by the disease processes, the redox potential of the AA/DHA system in those tissues is kept reducing; substances such as oxidized glutathione are directly reduced; and stray free radicals are rapidly quenched.
This effect of ascorbate is rate-limited only by the lack of courage of those administering ascorbate or the tolerance of the patient taking it. I hope to increase that courage by pointing out the observed lack of toxicity clinically and the theoretical reasons for that lack of toxicity.
This effect, when understood, opens up a wide range of opportunities to understand certain pathological processes. It is especially important in the case of infectious diseases because of the probable common mechanism of free radical toxicity that many pathogens have of suppressing the immune system. The increasing bowel tolerance to ascorbic acid can be used as a fairly accurate measure of the "toxicity" and activity of certain disease processes.
In toxic conditions, the use of ascorbate by the body for these scavenging purposes, results in such a localized and systemic deficiency of vitamin C that there is not enough of the nutrient remaining for vitamin C dependent housekeeping functions. I call this condition acute_induced scurvy. This condition can be induced by any stress and is responsible for a high percentage of the secondary complications of many diseases. The magnitude of this scavenging drain on ascorbate is enormous as revealed by the increasing bowel tolerance to ascorbic acid somewhat proportional to the toxicity of the disease process. Only the doses discussed can fully satisfy this need.
I think that most crib deaths are due to acute induced scurvy.
I have hypothesized here that massive doses of ascorbate may paradoxically be of benefit in G-6-PD deficiency, but have urged caution until more data is obtained. Ascorbate, when used with care, can be of great benefit in chemically allergic patients.
Rinse ascorbic acid and carbonated ascorbates off the teeth as prolonged exposure may cause damage to the enamel.
Partly supported by the Burton Goldberg Foundation. The author appreciates the comments of Stephen A. Levine and Parris M. Kidd
参考书目
Dr. Cathcart
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