别拿豆包不当干粮：营养补充疗法也可治疗癌症

　　癌症辅助营养干预（ANICA）研究是19世纪90年代哥本哈根的Lockwood牵头开展的一项对照研究，以高风险的乳腺癌患者为研究对象，在标准治疗之外，辅以鸡尾酒式的营养补充疗法，即多种抗氧化素、维生素、氨基酸等元素协同治疗。

　　辅酶Q10是一种营养素，一般不单独使用，可作为鸡尾酒疗法的一种成分或与其他营养素混合使用。Folkers等发现肿瘤患者血液中辅酶Q10的浓度低于正常组，使用辅酶Q10治疗肿瘤患者，可以获得生存获益且无明显副作用。

　　ANICA研究介绍

　　ANICA研究设计是基于肿瘤可能与多种化学物质功能失调和维生素缺乏有关的理论，初始研究设计的鸡尾酒方案包含维生素C、维生素E、β-胡萝卜素、硒、脂肪酸、γ-亚麻酸、不饱和脂肪酸、辅酶Q10。研究目的为验证各种营养素对肿瘤患者的治疗价值。

　　研究在32例乳腺癌患者中开展，年龄32～81岁，均存在腋下淋巴结转移，此类患者为高风险，一般5年生存率低于50%，该研究预期随访时间超过5年，以既往研究数据为对照。

　　ANICA研究在随访18个月时，1993年秋季的一个会议上，研究人员公布了早期的随访结果：32例患者均存活，无出现远处转移者，患者的生活质量有所提高（无体重下降、疼痛减轻），6例PR，随后研究人员将这6例患者治疗方案中辅酶Q10的剂量增加，1个月后，其中2例达到完全缓解的效果。

　　随访至4.5年时，6例患者死亡，其中2例是非癌症相关性死亡，其他患者有显著生存获益，外周血中辅酶Q10的水平均有上升。

　　营养补充疗法的理论依据

　　ANICA研究取得如此喜人的结果，可能与前列腺素的表达被抑制以及多种营养素协同的抗氧化还原作用有关。不同的营养素成分发挥不同的作用。

　　硒和谷胱甘肽可调节脂肪酶A2、COX-1、COX-2的表达，而COX-2可能参与T细胞免疫调节、MAPK信号通路介导的抗凋亡作用，与肿瘤的侵袭、转移密切相关。

　　辅酶Q10在鸡尾酒成分中作用十分突出，研究初试阶段辅酶Q10的剂量为90mg/d，后来增加至390mg/d。肿瘤细胞内高氧化性导致辅酶Q10丢失迅速，且合成减少，故而细胞内活性氧增多，ATP减少，细胞损伤严重。

　　维生素E的作用尚有争议，因为单独使用维生素E治疗其他疾病并未获得积极的结果，但是在本研究中的鸡尾酒疗法中，维生素E和辅酶Q10联合使用的抗氧化作用大于各自单独使用。

　　硒对正常肝脏细胞的作用与其剂量相关。小剂量使用具有抗氧化作用，而大剂量使用具有细胞毒性作用。本研究中硒的剂量在研究过程中被减少，因为研究发现常规剂量的硒在肿瘤细胞中依然可以发挥细胞毒性作用，以期在肿瘤细胞内发挥抗氧化作用。

　　ANICA研究原本拟定随访5年，而随访至5年时，患者生存获益明显，明显优于当时已发表的生存率，原本打算延长随访时间，而研究者本人去世了。虽然ANICA研究的最终结果曾多次被提起，但是最终的数据始终未发表。从知晓的早期数据来看，研究结果非常喜人，值得进一步的探讨，研究抗氧化性维生素、辅酶Q10、硒以及脂肪酸等以营养素的协同抗肿瘤作用。

Mol Aspects Med. 1994;15 Suppl:s231-40.

Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10.

Lockwood K, Moesgaard S, Hanioka T, Folkers K.

Private Outpatient Clinic, Copenhagen, Denmark.

Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because of tumor spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 micrograms plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). The ANICA protocol is based on the concept of testing the synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical markers, clinical condition, tumor spread, quality of life parameters and survival were followed during the trial. Compliance was excellent. The main observations were: (1) none of the patients died during the study period. (the expected number was four.) (2) none of the patients showed signs of further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers). (4) six patients showed apparent partial remission.

PMID: 7752835

DOI: 10.1016/0098-2997(94)90033-7

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Nutr Cancer. 2015;67(8):1355-8.

The Adjuvant Nutritional Intervention in Cancer (ANICA) Trial.

Bjorklund G.

Council for Nutritional and Environmental Medicine, Mo i Rana, Norway.

Adjuvant Nutritional Intervention in Cancer (ANICA) was a clinical study carried out in Denmark in the 1990s with 32 typical patients with breast cancer, aged 32-81 yr and classified high risk because of tumor spread to the lymph nodes. The patients received standard therapy for their breast cancer, but got from the start additionally an adjuvant therapy in form of a cocktail consisting of vitamin C (2,850 mg/day), vitamin E (2,500 IU/day), beta-carotene (32.5 IU/day), selenium (Se; 387 micrograms/day), various other vitamins and essential trace elements, essential fatty acids (1.2 g gamma-linolenic acid/day and 3.5 g omega-3 PUFAs/day), and coenzyme Q10 (CoQ10, 90 mg/day). The protocol was later changed, with reduction of the Se intake and more coenzyme Q10 than when the study was started. The average survival of high-risk breast patients in the study was 50% after 5 yr, whereas for low-risk breast cancer patients (without metastases in the axilla when treatment was started), the average survival was 90% after ten years. The main investigator died, and the final report from the ANICA study was therefore never written. However, the published preliminary results from the trial were very promising; it seems, therefore, important to follow-up this study.

PMID: 26473998

DOI: 10.1080/01635581.2015.1085582