© Springer International Publishing Switzerland 2017
Kenneth L. Koch and William L. Hasler (eds.)Nausea and Vomiting10.1007/978-3-319-34076-0_1212. Complementary and Alternative Medicine for Nausea and Vomiting
(1)
Department of Gastroenterology, Stanford University School of Medicine, Stanford, CA, USA
(2)
Department of Gastroenterology, Johns Hopkins University School of Medicine, Lutherville, MD, USA
Keywords
Complementary medicineHerbal blendsGingerAcupunctureAcupressureAccustimulationNausea and vomitingDyspepsiaIntroduction
Complementary and alternative medicines (CAM) are commonly used in the general population. The allopathic view of nausea and vomiting is that it is a reflex that results from a complex interaction of peripheral and central mechanisms, involving neurotransmitters and receptors. Pharmacologic antiemetic therapies have been developed that antagonize serotonin and NK1 receptors involved in these pathways. Antiemetics, approved for the use of chemotherapy-induced nausea and vomiting, may not be as effective when used off-label for the treatment of nausea and/or vomiting from other causes. This may be in part due to the fact that nausea is subjective, may be anticipatory, and in some clinical scenarios, tends to cluster with other symptoms, such as fatigue, drowsiness, and anorexia, which may independently predict responses to therapy [1].
Other whole health systems, such as Traditional Chinese Medicine, incorporate personal factors, like the patient’s feelings, the appearance and odor of the emesis, and the sound the patient makes when vomiting, which help to establish highly individualized treatment plans that may incorporate diet, herbal therapies, and/or acupuncture [2]. Some plant-based therapies used for thousands of years have recently been found to possess activity against the same serotonin and NK1 receptors targeted by antiemetic therapies. More clinical studies are needed in most cases to establish their safety and usefulness in an integrative approach. This review will describe commonly used herbal remedies and acupuncture for the relief of nausea and vomiting.
Herbal Remedies for Nausea and Vomiting
Ginger, Zingiber officinale Roscoe
Ginger is prescribed in many cultures as a remedy for abdominal discomfort, nausea, and flatulence and has been studied as a potential treatment for motion sickness, postoperative nausea and vomiting, pregnancy-induced nausea and vomiting, and chemotherapy-induced nausea and vomiting (CINV) [3]. It has the advantage of the fresh root being widely available, and not being associated with significant side effects. However, some caution is necessary when using commercially prepared ginger root powder, because among manufacturers there is wide variation in the concentration of bioactive compounds and suggested serving sizes [4]. Several bioactive compounds found in ginger include gingerol, shogaol, and zingerone [5], and these appear to act through serotonin and NK1 receptors in the gut and central nervous system. In a mink model of chemotherapy-induced nausea, gingerol reduced the frequency of cisplatin-induced retching and vomiting in a dose-dependent manner [6]. Gingerol did this in this model by inhibiting the expression of substance P and NK(1) receptors induced by cisplatin in the ileum and area postrema in the medulla. Like the 5HT3 antagonist, ondansetron, ginger extract and its individual compounds antagonized serotonin-evoked current responses in visceral vagal afferent neurons, with a relative inhibitor potency of [6]-shogaol > [6]-gingerol > zingerone [7].
The effect of ginger compounds on gastrointestinal motility has been studied. In the intestine, it has a spasmolytic effect. Ginger extract inhibits 5HT3 receptor activation to reduce isotonic contractions of isolated guinea pig ileum [8]. It exerts antispasmodic effects in isolated rabbit jejunum and rodent ileum by inhibiting 5-HT and K+ induced contractions, but at the same time, appears to stimulate gastric motility [9]. A gastric prokinetic effect has been observed in healthy volunteers, in which ginger extract increased interdigestive antral motility during phase III of the migrating motor complex [10]. Gastric emptying half-time was less after ginger, with increased frequency of antral contractions [11]. In human models of nausea and vomiting, ginger exerts slow wave antiarrhythmic effects to reduce tachygastria triggered by circular vection [12]. It also decreases slow wave dysrhythmias induced by hyperglycemia [13]. These studies suggest that its effects on gastric motility may be related to inhibition of vasopressin release [12] or blunting of endogenous prostaglandin production [13].
In contrast to preclinical studies, clinical trials of ginger for the treatment of nausea and/or vomiting have produced conflicting results. In patients with functional dyspepsia, ginger stimulated gastric emptying and antral contractions, but there was no significant improvement in symptoms [14]. Powdered or fresh ginger root did not improve motion sickness in one study [15], but in another study, volunteers with a history of motion sickness who were pretreated with 1000 mg of a commercial preparation of a ginger supplement experienced a delay in the onset of nausea and it was less severe [12]. In the case of CINV, a recent review of randomized controlled or crossover trial identified seven studies with variable methodological quality and produced variable results [16]. In most studies, patients were administered 1–2 g of ginger divided into four to eight capsules and consumed over a period of up to 10 days. The first dose was typically given within 1 h of the first chemotherapy session. Five of the studies used standard antiemetic medication in conjunction with ginger. Three studies demonstrated a positive effect when compared to placebo with a reduction in measures of CINV by 16–47 %; two gave positive results when compared to metoclopramide but had no placebo arm; and the remaining two yielded negative results [16].
Studies on the effect of ginger on postoperative nausea and vomiting have been mostly conducted in patients undergoing gynecologic surgery and have also yielded inconsistent findings. Typically, ginger is administered 1 h prior to surgery. The studies have been small in numbers of subjects [17–23].
Ginger is one of the most commonly used supplements by pregnant women in a multinational study to manage nausea symptoms of colds and flu, and to promote health and treat other GI disorders [24]. A meta-analysis based on six randomized placebo controlled trials with extractable data found that 1 g of ginger daily for at least 4 days is associated with fivefold likelihood of improvement in symptoms [25]. Another meta-analysis, published that same year, identified 12 randomized controlled trials and found that although ginger significantly improved the symptoms of nausea when compared to placebo, it did not reduce the number of vomiting episodes [26]. Importantly, the authors did not find that ginger had significant side effects or risk for spontaneous abortion [26].
Ginseng
Ginseng is used in traditional Chinese medicine for the alleviation of nausea and vomiting. Its antiemetic effects have been attributed to saponins. Indeed, saponin has been demonstrated to inhibit current flow in a concentration-dependent manner through the 5HT(3A) receptor using the voltage-clamp technique [27]. Preclinical studies using Korean red ginseng extract in ferrets attenuated nausea and vomiting [28]. Saponin and the non-saponin fraction of ginseng were associated with less cisplatin-induced pica in a rat model [29, 30]. No human studies on nausea and vomiting have been done.
Cannabis Sativa L
Cannabis has a long history of use for the treatment of nausea and other GI ailments, but psychotropic side effects and regional legal issues have limited its use. More than 60 teperno-phenols have been isolated from this plant, but the most studied has been the major psychoactive substance, delta-9-tetrahydrocannabinol (THC). Synthetic analogues of THC, which suppress vomiting by binding to CB1 brainstem receptors, are approved for the treatment of chemotherapy-induced nausea and vomiting and are discussed elsewhere in this volume. New combination formulations of THC and cannabidiol, a non-psychoactive marijuana constituent that suppresses vomiting through 5-HT1A receptors, as an oromucosal spray are under investigation [31]. Endogenous cannabinoids like anandamide and 2-arachidonyl glycerol suppress nausea and are stimulating development of pharmacologic agents that target enzymes that interfere with the degradation of endogenous cannabinoids [32, 33].
Despite the availability of THC analogues, many patients still prefer using medical marijuana, which may be inhaled by smoking or vaporization, eaten or drunk as a tea, or topically applied [34]. The pharmacokinetics are likely to differ depending on each mode of administration, and the potential pulmonary and other health effects of smoking it require further investigation [35, 36]. However, in contrast to the number of trials using cannabinoid derivatives, there are very few clinical studies that examine the antiemetic effect of medicinal or crude marijuana [37] despite the interest expressed by patients. An observational study of inhalation marijuana showed improvement in 78 % of 56 cancer patients with intractable nausea and vomiting [38]. Another study of 13 healthy volunteers in which emesis was induced by Ipecac, found that marijuana smoked 2 h before administration of Ipecac, reduced “queasiness” modestly and only slightly reduced vomiting compared to a placebo cigarette. Ondansetron [39], on the other hand, entirely blocked the emetic effects of Ipecac.
Rikkunshito
A traditional Japanese phytomedicine that contains eight herbal constituents: Aurantii pericarpium (bitter orange), Ginseng radix (Ginseng root), Zingiberis rhizoma, Jujubae (zizyphi) fructus (Jujubae fruit), Pinellia tuber (Crow-dipper), Atractylodis rhizoma, Glycyrrhiza radix (licorice root), Porio cocos. Its antiemetic effect had been attributed to ginger, but a recent study demonstrated glycyrrhiza as the most potent inhibitor of current flow in 5HT3A-expressing Xenopus oocytes using the two-electrode voltage clamp technique; the flavanoid (−)-liquiritigenin is the putative component responsible for this effect [40]. Ginseng, Atractylodis, and Aurantii extracts also inhibited 5HT3A in this model. Another Rikkunshito component, hesperidin derived from Aurantii, had previously been shown to inhibit 5HT3 receptor activation with an effect as great as ondansetron in rats [41]. These represent candidates for future investigation.
Artichoke Leaf (Cynara scopymus)
Artichoke has been used since ancient Greece and Rome to aid digestion [42]. Cynaropicrin, a sesquiterpene lactone derived from artichoke, demonstrated antispasmodic activity against guinea pig ileum, with similar potency to papaverine [43]. In a double-blind, randomized controlled trial of 247 patients with functional dyspepsia, patients received 640 mg of artichoke leaf extract (ALE) or placebo. The ALE group demonstrated significantly improved symptoms and improvement in quality of life scores. The intensity of dyspeptic symptoms was also evaluated, and while there were statistically significant differences in fullness and flatulence, there was no significant difference in nausea or vomiting between ALE and placebo groups [44]. In a multicenter, double-blind, randomized placebo-controlled trial over 4 weeks using ALE with ginger [45], patients receiving the supplements reported more symptomatic improvement than the placebo group. Secondary outcomes included intensity of individual symptoms; there was a significant reduction in intensity score for nausea, but not for vomiting.
Padma Digestin®
A blend of 5 herbs manufactured in Switzerland based on Tibetan Traditional formula, Se ‘bru, prescribed for digestive problems and malabsorption. Capsules contain derivatives of pomegranate seed, lesser galangal, long pepper, cardamom fruit, and cassia bark. Its physiologic effects have been described in only one study in which the formulation increased contractility in muscle strips derived from the antrum and pylorus but decreased it in duodenal and jejunal strips. An open-label observational study of 31 patients with functional dyspepsia found significant improvement in nausea and postprandial fullness without significant adverse events related to the formulation [46].
STW 5 (Iberogast®)
A blend manufactured in Germany consisting of nine herbs: Angelica root, milk thistle fruit, caraway fruit, celandine herb, licorice root, chamomile flower, lemon balm leaf, peppermint leaf and bitter candytuft. STW 5 has been studied in the treatment of functional dyspepsia and irritable bowel syndrome. STW 5 exhibits spasmolytic activities in isolated guinea pig ileum stimulated with either acetylcholine or histamine [47]. In human physiology studies, STW 5 increased gastric accommodation and antral contractility, but did not accelerate gastric emptying of solids [48]. In a multicenter, placebo-controlled double-blind study of 103 patients with functional dyspepsia and gastroparesis demonstrated significant symptom improvement when compared to placebo, but no significant change in gastric emptying [49]. In addition to its effects on gastrointestinal motility, STW 5 reduces afferent sensitivity in the rat small intestine [50, 51]. Ethanolic extracts of celandine herb and chamomile flower selectively bound to 5-HT4, and licorice root to 5-HT3 receptors in the intestine [52].
Acupuncture, Acupressure and Acustimulation
Acupuncture and acupressure aim to correct the imbalance in “yin-yang” and “qi” that causes symptoms, by inserting needles (acupuncture) or applying hand pressure (acupressure) on specific points on the body. Acupuncture has been used in Chinese medicine before the first century BC, but did not populate “Western medicine” until the 1970s [53]. In 1997, an NIH Consensus Development Panel reviewed the available literature and concluded that acupuncture yielded “promising results” in the treatment of postoperative and chemotherapy-induced nausea and vomiting in adults [54]. Neiguan or P6 is the most commonly studied acupuncture point for nausea and vomiting. It is located approximately 3 finger breadths proximal to the wrist between the tendons of the flexor carpi radialis muscle and the palmaris longus muscle [55–57].
The mechanism of action of acupuncture is still unknown. The analgesic effects of acupuncture may be related to release of endogenous opioids, activation of the hypothalamus and pituitary gland, and/or alterations in neurotransmitters and immune function [53, 54]. There is also evidence that stimulation of acupuncture sites affects gastric myoelectrical activity. Gastric slow waves originate in the proximal stomach and determine the frequency and direction of gastric contractions. Gastric dysrhythmias have been associated with impaired gastric motility and gastroparesis [58]. Hu et al. demonstrated that acupressure at the P6 point decreased nausea related to visually induced motion sickness and gastric dysrhythmias measured by electrogastrography (EGG) [59]. Similarly, combined acupuncture of P6 (Neiguan), SP4 (Gong sun), and DU20 (Baihui) improved symptoms of nausea and improved gastric dysrhythmias in an uncontrolled group of patients with refractory nausea and/or abdominal pain/bloating [60]. Acupuncture stimulation of P6 in healthy controls resulted in increased vagal modulation, with evidence of decreased heart rate (increased R-R interval) and increased high-frequency power measured by heart rate variability, which is a measure of cardiovagal tone [61]. Stimulation of the ST36 (Zu San Li) point below the knee has been shown to affect gastrointestinal motility, including decrease transient lower esophageal sphincter relaxation, increase gastric accommodation, decrease gastric dysrhythmias, and increase antral and colonic contractions [62].
Since the first description of acupuncture for the prophylaxis of postoperative nausea and vomiting in 1986 [63], there have been a number of controlled trials that have shown benefit of P6 stimulation in PONV and chemotherapy-induced nausea and vomiting (CINV), which have included acupressure, acupuncture, electroacupuncture, and transcutaneous electrical stimulation [56, 57]. A Cochrane Review of P6 acupoint stimulation (acupressure, needle acupuncture, electroacupuncture, transcutaneous electrical stimulation) for prevention of postoperative nausea and vomiting was updated in 2015 (initially published in 2004) [55]. This review included 59 trials involving 7667 patients comparing acupoint stimulation versus sham or antiemetics or P6 stimulation plus antiemetic versus antiemetic alone. Compared to sham, this review found that P6 stimulation decreased nausea (RR = 0.68, 95 % CI = 0.60–0.77), vomiting (RR = 0.60, 95 % CI = 0.51–0.71), and need for rescue antiemetics (RR = 0.64, 95 % CI = 0.55–0.73). There were no differences in symptom reduction when P6 stimuation alone or P6 stimulation plus antiemetic were compared to various antiemetics (metoclopramide, cyclizine, prochlorperazine, droperidol, ondansetron, and dexamethasone). Stimulation of P6 is similar to antiemetic therapy in reducing symptoms of nausea and vomiting. The effect of combined P6 stimulation plus antiemetic therapy versus either therapy alone is unclear. Adverse events related to acupuncture are transient and mild, including forgotten needles, orthostasis/dizziness, needling site pain/hematoma, minor bleeding, and skin irritation [53, 55, 56].
Acupressure
Pressure stimulation to P6 can be applied manually with the fingers or by wearing an elastic wristband with an embedded plastic button or pearl that provides constant pressure (SeaBandTM, Sea-band Ltd., Leicestershire, England). Studies on the use of acupressure for PONV and CINV have had conflicting results with heterogeneity in study design [56]. However, pooled analysis of six trials in PONV involving 292 acupressure and 288 sham controls found that acupressure significantly reduced postoperative nausea (30.8 % vs. 43.4 %, RR = 0.71, 95 %CI 0.57–0.87, p = 0.001) and vomiting frequency (24.2 % vs. 38.8 %, RR = 0.61, 95 %CI 0.49–0.80, p <0.001) [64]. Acupressure reduces acute nausea but not vomiting in CINV [65]. The effectiveness of P6 acupressure for nausea and vomiting in early pregnancy is conflicting; however, there were no significant adverse events associated with this therapy [66].
Acupoint stimulation is also commonly used for GI diseases with nausea and vomiting as part of the constellation of symptoms, including functional dyspepsia and gastroparesis [67, 68]. Studies of functional dyspepsia and gastroparesis most commonly evaluated the stimulation of the ST36 (zusanli) site, which in general increased gastric accommodation [69], increased antral contractions [70], improved gastric dysrhythmias [71], and reduced visceral hyperalgesia [72]. Studies comparing acupuncture to domperidone and/or sham found that acupuncture improved gastroparesis symptoms but not gastric emptying or glycemic control in patients with diabetic gastroparesis [73, 74].
Electrical Acupressure/Transcutaneous Electrical Stimulation
The ReliefBand® (Woodside Biomedical Systems, Carlsbad, CA) is a wristband worn like a watch that provides transcutaneous electrical stimulation of the P6 acupoint. Although difficult to compare given the differences in the control groups (electroacupressure vs. sham or antiemetic plus sham) across various studies, electroacupressure was effective in PONV, variably effective for motion sickness, and ineffective for CINV and nausea and vomiting in pregnancy [56].
Related posts:
Nutritional Management for Patients with Nausea and Vomiting and Gastroparesis or Dumping Syndrome
Future Directions in Understanding Nausea and Vomiting
The Physiology of Vomiting
Gastric Electrical Stimulation, Pyloroplasty, Gastrectomy, and Acustimulation for the Treatment of Nausea and Vomiting in the Setting of Gastroparesis
Physiology of Nausea
The Psychophysiology of Nausea
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