毒理性
◉ 母乳喂养期间使用概述：甘草（Glycyrrhiza glabRA）根含有甘草酸（也称为甘草苷酸或甘草酸）以及甘草酸钾和钙盐的混合物。甘草酸在肠道中被代谢为活性甘草素。去甘草酸甘草（DGL）已去除甘草酸。甘草被认为是一种催乳剂，包含在某些亚洲专利混合物中，用以增加乳汁供应；然而，没有科学有效的临床试验支持这种用途。实际上，甘草通常会降低血清催乳素水平，这可能会在哺乳早期阶段减少乳汁产量。服用甘草的妇女会出现血压升高的情况。催乳剂不应替代对影响乳汁产量的可修改因素的评估和咨询。在土耳其，据报道有些母亲使用甘草来改善她们的乳汁口感和质量。
甘草酸可以在一些服用甘草的妇女的母乳中被检测到，但是尚未进行测量甘草素的试验。甘草与其他草药配伍，作为婴儿的茶水，在短期内治疗疝痛方面已被安全有效地使用。然而，两名母亲过量饮用含有甘草的草药茶水后，婴儿出现了莳萝醇中毒的迹象。因为这两篇论文报告的都是草药混合物，所以无法确定甘草单独的效果。美国食品药品监督管理局将甘草和甘草提取物认定为“普遍认为安全”（GRAS）的食物。长期过量使用甘草可能会导致高血压、低钾血症和肾上腺激素紊乱，因此在哺乳期间应尽量避免。
膳食补充剂不需要从美国食品药品监督管理局获得广泛的市场前批准。制造商负责确保产品的安全，但在市场销售前不需要证明膳食补充剂的安全性和有效性。膳食补充剂可能含有多种成分，并且经常发现标签上的成分或其含量与实际成分或含量存在差异。制造商可以与独立组织签订合同，以验证产品或其成分的质量，但这并不证明产品的安全或有效性。由于上述问题，一个产品的临床试验结果可能不适用于其他产品。关于膳食补充剂的更详细信息可以在LactMed网站的其它地方找到。
◉ 对母乳喂养婴儿的影响：两名分别年龄为15天和20天的母乳喂养婴儿因过去7至10天内体重增长不足而入院，原因是“喂养困难”。父母报告过去一天内有不安和呕吐的情况。其中一名母亲还报告感到困倦和虚弱。检查时，婴儿体温正常，但出现肌张力减退、嗜睡、呕吐、哭声微弱、吸吮力弱和对疼痛刺激反应弱。婴儿的实验室值、心电图和血压正常，脓毒症排查阴性。两位母亲都曾每天饮用超过2升据报道含有甘草、茴香、八角和山羊豆的草药茶水，以刺激泌乳。母亲停止哺乳和草药茶后，婴儿在24至36小时内有所改善。停止草药茶后，受影响的母亲的症状也迅速缓解。两天后，重新开始哺乳，婴儿没有再出现症状。六个月大时，两名婴儿情况良好。作者将母婴的症状归因于莳萝醇，莳萝醇存在于八角和茴香中；然而，母乳中的莳萝醇水平未经过测量，也未对茶水进行含量检测。
◉ 对泌乳和母乳的影响：一名有大量摄入甘草历史的妇女出现闭经、严重头痛、高血压、低钾血症。她的血清催乳素水平升高，在停用甘草后一个月内仍然异常，六个月后恢复正常。
在一项对25名男性和25名女性的研究中，测量了基线和促甲状腺激素刺激下的血清催乳素水平，以确定正常的血清催乳素值。定期摄入甘草的受试者其基础和刺激后的血清催乳素浓度都较低。
一种传统的、非标准化的芍药和甘草根的煎剂，在中国称为芍药甘草汤，在日本称为芍薬甘草湯，在长期（>6个月）摄入利培酮导致血清催乳素升高的妇女中进行了研究。患者接受溴隐亭5毫克/日，连续服用4周，随后服用4周的芍药甘草煎剂，每日22.5克（相当于25毫克的甘草素），或者相反顺序的相同药物。评估血清催乳素发现，两种治疗在4周和8周时均使血清催乳素从基线下降了21至28%。
四十名在分娩后5天抱怨乳汁供应不足的妇女被给予一种组合草药补充剂，每天3次，每次2粒Lactare（Pharma Private Ltd.，马德拉斯，印度；目前可从TTK Pharma，金奈，印度获得）胶囊。每粒胶囊含有野芦笋200毫克、印度人参（Withania somnifeRA）100毫克、葫芦巴50毫克、甘草50毫克和大蒜20毫克。治疗4天后，没有婴儿需要补充喂养。在治疗第五天，婴儿在每次喂养前后称重，以确定摄入的乳汁量。在测试称重的当天，婴儿的牛奶摄入量平均为388毫升，液体和卡路里的摄入量被认为是充足的
◉ Summary of Use during Lactation:Licorice (Glycyrrhiza glabra) root contains glycyrrhizin (also called glycyrrhizic acid or glycyrrhizinic acid) and a mixture of the potassium and calcium salts of glycyrrhizic acid. Glycyrrhizin is metabolized to the active glycyrrhetinic acid in the intestine. Deglycyrrhizinated licorice (DGL) has had glycyrrhizin removed. Licorice is a purported galactogogue, and is included in some Asian proprietary mixtures to increase milk supply; however, no scientifically valid clinical trials support this use. In fact, licorice usually reduces serum prolactin, which might decrease milk production in the early stages of lactation. Women taking licorice have experienced elevated blood pressure. Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production. Some mothers in Turkey reportedly use licorice to improve the taste and quality of their milk.
Glycyrrhizin is detectable in the breastmilk of some women taking licorice, but studies measuring glycyrrhetinic acid have not been performed. Licorice has been used safely and effectively in combination with other herbs given to infants as a tea for the short-term treatment of colic. However, two infants whose mothers had an excessive intake of an herbal tea that contained licorice had signs of anethole toxicity. Because both of these papers reported on herbal mixtures, the effect(s) of licorice alone cannot be determined. Licorice and licorice extract are "generally recognized as safe" (GRAS) as foods by the U.S. Food and Drug Administration. Long-term, excessive use of licorice can cause hypertension, hypokalemia, and disturbances of adrenal hormones, and therefore should probably be avoided during nursing.
Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site.
◉ Effects in Breastfed Infants:Two breastfed infants, aged 15 and 20 days, were admitted to the hospital for a reported lack of weight gain in the previous 7 to 10 days, caused by "difficult feeding". The parents reported restlessness and vomiting during the past day. One of the mothers also reported feeling drowsy and weak. On examination, the infants were afebrile but had hypotonia, lethargy, emesis, weak cry, poor sucking and weak responses to painful stimuli. Infant laboratory values, electrocardiograms and blood pressures were normal, and septic work-ups were negative. Both mothers had both been drinking more than 2 liters daily of an herbal tea mixture reportedly containing licorice, fennel, anise, and goat's rue to stimulate lactation. After the mothers discontinued breastfeeding and the herbal tea, the infants improved within 24 to 36 hours. Symptoms of the affected mother also resolved rapidly after discontinuing the herbal tea. After 2 days, breastfeeding was reinstituted with no further symptoms in the infants. Both infants were doing well at 6 months of age. The authors attributed the maternal and infant symptoms to anethole, which is found in both anise and fennel; however, the anethole levels were not measured in breastmilk, nor were the teas tested for their content.
◉ Effects on Lactation and Breastmilk:A woman with a history of excessive licorice intake had amenorrhea, severe headaches, hypertension, hypokalemia. She had elevated serum prolactin levels that remained abnormal for one month after licorice discontinuation and normalized by 6 months after discontinuation.
In a study of 25 men and 25 women, the baseline and thyrotropin-stimulated serum prolactin levels were measured to determine normal serum prolactin values. Subjects who regularly ingested licorice had lower basal and lower stimulated serum prolactin concentrations.
A traditional, nonstandardized decoction of peony and licorice roots called Shaoyao-Gancao-Tang in Chinese and Shakuyaku-Kanzo-To in Japanese was studied in women with elevated serum prolactin caused by long-term (>6 months) ingestion of risperidone. Patients received either bromocriptine 5 mg daily for 4 weeks followed by 4 weeks of 22.5 grams daily of the peony-licorice decoction (equivalent to 25 mg of glycyrrhetinic acid), or the same drugs in the reverse order. Evaluation of serum prolactin found that both treatments reduced serum prolactin by 21 to 28% from baseline at 4 and 8 weeks.
Forty women who complained of an insufficient milk supply at 5 days postpartum were given a combination herbal supplement as 2 capsules of Lactare (Pharma Private Ltd., Madras, India; currently available from TTK Pharma, Chennai, India) 3 times daily. Each capsule contained wild asparagus 200 mg, ashwagandha (Withania somnifera) 100 mg, fenugreek 50 mg, licorice 50 mg, and garlic 20 mg. By day 4 of therapy, no infants required supplementary feeding. Infants were weighed before and after each feeding on the fifth day of maternal therapy to determine the amount of milk ingested. On the day of the test weighing, infants' milk intake averaged 388 mL, and the fluid and caloric intake was considered adequate. This study cannot be considered as valid evidence of a galactogogue effect of these herbs because it lacks randomization, blinding, a placebo control, and maternal instruction in breastfeeding technique. Additionally, infants were breastfed only 6 to 8 times daily, which is insufficient to maximize milk supply at this stage of lactation.
Women who were between 14 and 90 days postpartum and reported lactation failure were given instructions on breastfeeding technique and encouraged to exclusively breastfeed. If their infant had gained less than 15 grams in 1 week, they were randomized to receive either two tablespoonfuls of a mixture containing wild asparagus or an identical placebo for 4 weeks. In each 100 grams, the mixture contained Asparagus racemosus 15 grams, Anethum soiva 1 gram, Ipomea digitata 1 gram, Glycyrrhiza glabra 1 gram, Spinacia oleracea 2.5 grams, Cuminum cyminum 0.5 gram, and panchatrinamol 1 gram. Of the 64 women randomized, 11 did not complete the trial. Serum prolactin measurements were made before a morning nursing before treatment and after 4 weeks of treatment. Infant weight gains and the number of supplemental feedings were recorded initially and after 4 weeks of therapy. No differences were found in the changes in serum prolactin, infant weight gain or amount of supplementation between the treatment and placebo groups after 4 weeks of therapy. No side effects or changes in liver function tests occurred during the study.
A study in Japan compared the use of a mixture of 13 herbs, including licorice, to ergonovine for their effects on lactation and serum prolactin in postpartum women. The herbal mixture, called Xiong-gui-tiao-xue-yin, was given in a randomized fashion to 41 women in a dose of 2 grams of a dried aqueous extract 3 times daily. A comparable group of 41 women were randomized to receive methylergonovine 0.375 mg daily. Therapy was started on the day of delivery, but the duration of therapy was not specified. Plasma oxytocin and prolactin were measured on days 1 and 6; milk volumes were measured daily, although the method of measuring milk volume was not specified. Serum prolactin was higher on days 1 and 6 in the women who received the herbals; plasma oxytocin was lower on day 1 in the women who received the herbal, but not different on day 6. Milk volumes were greater on days 4, 5, and 6 in women who received the herbal mixture. This study has serious flaws that make its interpretation impossible. First, milk volume measurement is subject to considerable variability depending on the measurement method used, but the method was not specified. Second, methylergonovine has caused decreases in serum prolactin and milk production in some studies. Because of the lack of a placebo group, the differences found could be a negative effect of methylergonovine rather than a positive effect of the herbal preparation. Because this study used a multi-ingredient combination product in which licorice was only one component, the results might be different from studies in which licorice was used alone.
In an uncontrolled, non-blinded multicenter study in India, 1132 patients who reported inadequate milk supply were give a mixture (Lactancia, Corona Remedies Pvt. Ltd.) To take in a dose of 30 grams twice daily. The product contains Asparagus racemosus (wild asparagus, shatavari), Cuminum cyminum (cumin), Glycyrrhiza glabra (licorice), Spinacia oleracea (spinach) as well as amino acids, vitamins, minerals and DHA. Most of the mothers (1049) had improved lactation and increased infant weight. However, with no placebo control group, results cannot be attributed to the product.
来源:Drugs and Lactation Database (LactMed)
