Herbal Approaches to Pediatric Functional Abdominal Pain: History
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Contributor:
Rebecca N. Cherry
,
Samra S. Blanchard
,
Ashish Chogle
,
Neha R. Santucci
,
Khyati Mehta
,
Alexandra C. Russell

Chronic abdominal pain is one of the most common problems seen by both pediatricians and pediatric gastroenterologists. Abdominal-pain-related functional gastrointestinal disorders (AP-FGIDs) are diagnosed in children with chronic and recurrent abdominal pain meeting clinical criteria set forth in the Rome IV criteria. AP-FGIDs affect approximately 20% of children worldwide and include functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain (FAP), and abdominal migraine. IBS accounts for 45% of pediatric AP-FGIDs. The pathophysiology of functional abdominal pain involves an interplay of factors including early life events, genetics, psychosocial influences, and physiologic factors of visceral sensitivity, motility disturbance, altered mucosal immune function, and altered central nervous system processing. Researchers discuss popular herbal treatments typically used in the field of complementary medicine to treat pediatric AP-FGIDs: peppermint oil, fennel, licorice, and STW5.

  • abdominal pain
  • licorice
  • peppermint
  • fennel
  • STW5
  • Iberogast
  • functional
  • integrative
  • children
  • herbal

1. Peppermint Oil

Peppermint oil (PMO) is extracted from fresh peppermint (Mentha × peperita) leaves by steam distillation and contains menthol as the primary ingredient [1]. PMO has a therapeutic effect in patients with functional gastrointestinal disorders due to its actions at various levels of the microbiome–gut–brain axis. It exerts a spasmolytic effect on smooth muscle cells by decreasing calcium influx via inhibition of L-type Ca2+ channels and reduction of acetylcholine release from enteric nerves via its action on nicotinic receptors in the GI tract [2][3]. The use of PMO for pediatric FGID patients has been examined in several studies. A randomized, double-blind controlled trial by Kline et al. examined the efficacy of pH-dependent, enteric-coated, PMO capsules in the treatment of IBS symptoms in 50 children (8–17 years of age). Children with IBS were given either pH-dependent, enteric-coated PMO capsules (Colpermin®—187 mg of peppermint oil) or placebo (Arachis oil capsule) for 2 weeks. Patients weighing 45 kg or more received two PMO or placebo capsules three times a day. Children with weights between 30 kg to 45 kg were given one capsule three times a day. Of the 42 children that completed the study, 75% who received PMO reported significant improvement in severity of abdominal pain as compared to 19% in the placebo group (p < 0.001) [2]. Similar results were also seen in a randomized controlled study performed by Asgarshirazi et al. that included 120 children (4–13 years of age) with functional abdominal pain, functional abdominal pain syndrome, functional dyspepsia, and IBS [4]. Children were randomized to receive either Lactol® capsules (Bacillus coagulans + fructooligosaccharide), PMO (Colpermin®—187 mg of peppermint oil), or a placebo (folic acid) for one month. The dosing protocol in this study was the same as mentioned in the Kline study above. From the data analysis of 88 children who completed the study, significant improvements in pain duration, severity, and frequency were seen in the PMO group as compared to placebo (p = 0.0001, p = 0.0001, and p = 0.001, respectively). PMO was also found to be superior to Lactol in decreasing pain duration and severity (p = 0.040 and p = 0.013, respectively). No side effects were reported in any of the study groups.
There has been one pediatric study to date assessing the motility effects of PMO in children. This study included 30 children with functional abdominal pain and demonstrated a decrease in whole gut mean peak contraction with PMO but without any significant change in the whole gut transit time [5]. This could explain the effectiveness of PMO in relieving pain in IBS without having a significant impact on the gastrointestinal transit time.
Peppermint oil is generally well tolerated at the commonly recommended dosage. It is contraindicated in patients with hiatal hernia or gastroesophageal reflux disease (GERD) as it can worsen reflux symptoms due to its effects on the lower esophageal sphincter [6][7].

2. Fennel

Fennel, also known as Foeniculum vulgare, is an herb that grows year long and is one of the oldest plants utilized in traditional medicine [8]. It possesses anti-inflammatory, antioxidant, antispasmodic, and carminative properties [9][10]. Anethole, a component of fennel oil, improves gastric emptying and gastric accommodation in rats, suggesting potential beneficial effects in FD [11]. Given these multiple properties, fennel has been used in different forms over the years for various gastrointestinal symptoms.
Pediatric studies assessing the efficacy of fennel for FGIDs are lacking, although fennel tea has been explored for the treatment of infant colic. In a descriptive study assessing the usage of herbal preparations in Turkey, fennel tea was used by approximately 77% of mothers to treat their children’s gas pain and constipation [12]. A systematic review on herbs demonstrated the efficacy of fennel in different preparations (seed oil, tea, or in combination with other herbs such as Colimil®) to reduce episodes of crying in infants with colic (n = 461, age range 2–12 weeks old) through four randomized controlled trials (RCT) [13]. No side effects were reported in these studies [14][15][16][17].
Studies in adults with IBS have shown some promising findings. In an RCT of 121 adults with IBS, fennel essential oil combined with curcumin improved IBS symptom severity scores and quality of life. A higher response was noted in the treatment compared with the control group (25.9% vs. 6.8%, p = 0.005). The mixture was found to be safe and well-tolerated [10]. Similarly, an open-label study demonstrated the efficacy of Enterofytol®, a product with extracts of turmeric and fennel oil, in improving symptom severity index and quality of life in 211 IBS patients, especially those with diarrhea-predominant IBS [18]. A double-blinded controlled study from Germany evaluated the efficacy of Lomatol® drops (combination of caraway fruit extracts, fruits of fennel, peppermint leaves, and wormwood) in comparison with metoclopramide drops in patients ages 18–85 years with upper abdominal symptoms (n = 60). Lomatol® drops were superior to metoclopramide with greater improvement in abdominal pain (p = 0.02), nausea (p = 0.02), heartburn (p = 0.016), and gastric spasms (p = 0.002). It was also better tolerated with fewer adverse effects than treatment with metoclopramide [19]. While these data are favorable, pediatric studies are necessary to establish safety and efficacy data in children.

3. Licorice

Licorice root (Glycyrrhiza glabra) may have promise for the treatment of pediatric FGIDs. The main constituent of licorice root is the triterpenoid saponin glycyrrhizin (also known as glycyrrhizic acid or glycyrrhizinic acid), which is usually found in concentrations ranging from 6% to 10%. The intestinal flora is believed to hydrolyze glycyrrhizin, yielding the aglycone molecule (glycyrrhetinic acid) and a sugar moiety, which are both absorbed [20][21]. The active components of DGL are flavonoids. Other active constituents of licorice include isoflavonoids (e.g., isoflavonol, kumatakenin, licoricone, glabrol); chalcones; coumarins (e.g., umbelliferone, herniarin); triterpenoids; and sterols, lignins, amino acids, amines, gums, and volatile oils [21].
Deglycyrrhizinated licorice (DGL), a processed licorice extract made by removing the glycyrrhizin molecule to eliminate its mineralocorticoid properties, has been used for several gastrointestinal disorders secondary to its anti-inflammatory, antibacterial, and antiviral pharmacologic actions [21]. DGL is also used in the setting of gastric hyperacidity and functional dyspepsia. However, rather than inhibiting acid release, DGL stimulates the standard defense mechanisms that prevent ulcer formation and promote mucosal healing by increasing blood supply and mucus production [22][23]. In a small, randomized, double-blind, placebo-controlled study of 50 adults with functional dyspepsia as diagnosed by Rome III criteria, subjects were randomized to placebo or a 75 mg extract of Glycyrrhiza glabra (GutGard®, Karnataka, India) for 30 days. Compared to placebo, those receiving the licorice extract showed a significant decrease in total symptom scores and improved quality of life [24].
The dose of licorice for clinical use is based on the content of glycyrrhetinic acid. The standard dosage for DGL in adults is two to four 380 mg chewable tablets 20 min before meals [25]. It is essential to review with patients that DGL is a safer formulation than those containing glycyrrhizin as glycyrrhizin has mineralocorticoid properties that can cause hypertension and hypokalemia-induced secondary disorders [26][27]. There are currently no pediatric studies confirming safety, dosing, or benefit for children with FGIDs.

4. STW5

STW5 or Iberogast® is a combination of multiple herbs including an extract from bitter candytuft (Iberis amara), angelica root (Angelica radix), milk thistle (Silybi mariani fructus), celandine herb (Chelidonium majus), caraway fruit (carvi fructus), licorice root (Liquiritiae radix), peppermint (Menthae piperitae folium), lemon balm leaves (Melissa folium), and chamomile flower (Matricariae flos). Bitter candytuft (I. amara) selectively inhibits binding to muscarinic M3 receptors, while extracts of celandine and chamomile inhibit binding to 5-HT4 receptors and licorice root to 5-HT3 receptors [28][29]. (“Peppermint Oil,” and licorice is discussed in Section 2, “Licorice.”) However, the relative importance of each component’s mechanism of action to the overall effects of STW5 use is uncertain.
STW5 has been demonstrated to have multiple effects on the gastrointestinal tract that are conducive to improvement in FGID symptoms. These include modulating visceral hypersensitivity, gastric motility, and gastric accommodation [30]. In rats, oral administration of STW5 showed reduced jejunal afferent sensitivity to mechanical distension, serotonin, and bradykinin [31]. The improvement seen in IBS and functional dyspepsia patients may be attributable to the influence of STW5 on visceral hypersensitivity. STW5 also has organ-specific effects on the gastric fundus and antrum. STW5 has a significant, dose-dependent muscle relaxant effect in the fundus, which can help accommodation in functional dyspepsia, while STW5 stimulates phasic contractility in the antrum [32][33][34].
STW5 has some pediatric clinical data to support its use. A study of 980 children who received STW5, 10–20 drops three times a day for 7 days found improvement in upper and lower gastrointestinal symptoms. Thirty-nine percent of children reported complete relief of their symptoms. STW5 was well tolerated in 94.8% of cases with only four mild adverse events [35].
STW5 has been extensively evaluated for tolerability and side effects since it was introduced to the market in the 1960s. In three large studies, few patients developed abdominal pain, pruritus, alopecia, hypersensitivity, hypertension, vomiting, and headaches as adverse effects but this was not statistically significant compared to placebo [35][36][37]. The first case of acute liver failure was reported in 2018 in Germany and has subsequently been described in Denmark and Switzerland [38][39][40]. The WHO database (VigiBase) contains 70 cases of hepatobiliary disorders associated with STW5 [41]. Among nine herbs in STW5, only Chelidonium majus (Greater celandine) has been associated with liver toxicity. No liver toxicity was reported with other extracts [42]. To develop hepatic side effects, the doses are usually 100–200 times higher than the amount in STW5 [43]. The pathophysiology responsible for the reported herb-induced liver injury (HILI) is mostly compatible with idiosyncratic reaction.
Iberogast® comes as liquid drops. The listed dose for children from 3 to 5 years is ten drops three times a day, for children 6 to 12 years 15 drops three times a day, and for adolescents and adults 20 drops three times a day. It is taken with a small amount of liquid before or during meals.

This entry is adapted from the peer-reviewed paper 10.3390/children9081266

References

  1. Grigoleit, H.G.; Grigoleit, P. Pharmacology and preclinical pharmacokinetics of peppermint oil. Phytomedicine 2005, 12, 612–616.
  2. Amato, A.; Liotta, R.; Mule, F. Effects of menthol on circular smooth muscle of human colon: Analysis of the mechanism of action. Eur. J. Pharmacol. 2014, 740, 295–301.
  3. Grigoleit, H.G.; Grigoleit, P. Gastrointestinal clinical pharmacology of peppermint oil. Phytomedicine 2005, 12, 607–611.
  4. Asgarshirazi, M.; Shariat, M.; Dalili, H. Comparison of the Effects of pH-Dependent Peppermint Oil and Synbiotic Lactol (Bacillus coagulans + Fructooligosaccharides) on Childhood Functional Abdominal Pain: A Randomized Placebo-Controlled Study. Iran. Red Crescent Med. J. 2015, 17, e23844.
  5. Shulman, R.J.; Chumpitazi, B.P.; Abdel-Rahman, S.M.; Garg, U.; Musaad, S.; Kearns, G.L. Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain. Br. J. Clin. Pharmacol. 2021, 88, 1321–1333.
  6. Pimentel, M.; Bonorris, G.G.; Chow, E.J.; Lin, H.C. Peppermint Oil Improves the Manometric Findings in Diffuse Esophageal Spasm. J. Clin. Gastroenterol. 2001, 33, 27–31.
  7. Sigmund, C.J.; McNally, E.F. The action of a carminative on the lower esophageal sphincter. Gastroenterology 1969, 56, 13–18.
  8. Rauf, A.; Akram, M.; Semwal, P.; Mujawah, A.A.H.; Muhammad, N.; Riaz, Z.; Munir, N.; Piotrovsky, D.; Vdovina, I.; Bouyahya, A.; et al. Antispasmodic Potential of Medicinal Plants: A Comprehensive Review. Oxidative Med. Cell. Longev. 2021, 2021, 4889719.
  9. Scalbert, A.; Manach, C.; Morand, C.; Rémésy, C.; Jiménez, L. Dietary Polyphenols and the Prevention of Diseases. Crit. Rev. Food Sci. Nutr. 2005, 45, 287–306.
  10. Portincasa, P.; Bonfrate, L.; Scribano, M.L.L.; Kohn, A.; Caporaso, N.; Festi, D.; Campanale, M.C.; Di Rienzo, T.; Guarino, M.; Taddia, M.; et al. Curcumin and Fennel Essential Oil Improve Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome. J. Gastrointest. Liver Dis. 2016, 25, 151–157.
  11. Asano, T.; Aida, S.; Suemasu, S.; Mizushima, T. Anethole restores delayed gastric emptying and impaired gastric accommodation in rodents. Biochem. Biophys. Res. Commun. 2016, 472, 125–130.
  12. Gürol, A.; Taplak, A.; Polat, S. Herbal supplement products used by mothers to cope with the common health problems in childhood. Complement. Ther. Med. 2019, 47, 102214.
  13. Anheyer, D.; Frawley, J.; Koch, A.K.; Lauche, R.; Langhorst, J.; Dobos, G.; Cramer, H. Herbal Medicines for Gastrointestinal Disorders in Children and Adolescents: A Systematic Review. Pediatrics 2017, 139, e20170062.
  14. Duygu, A.; Handan, A.; Gözüm, S.; Orbak, Z.; Çifçi, E.K. Effectiveness of massage, sucrose solution, herbal tea or hydrolysed formula in the treatment of infantile colic. J. Clin. Nurs. 2008, 17, 1754–1761.
  15. Alexandrovich, I.; Rakovitskaya, O.; Kolmo, E.; Sidorova, T.; Shushunov, S. The effect of fennel (Foeniculum Vulgare) seed oil emulsion in infantile colic: A randomized, placebo-controlled study. Altern. Ther. Health Med. 2003, 9, 58–61.
  16. Savino, F.; Cresi, F.; Castagno, E.; Silvestro, L.; Oggero, R. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breastfed colicky infants. Phytother. Res. 2005, 19, 335–340.
  17. Weizman, Z.; Alkrinawi, S.; Goldfarb, D.; Bitran, C. Efficacy of herbal tea preparation in infantile colic. J. Pediatr. 1993, 122, 650–652.
  18. Di Ciaula, A.; Portincasa, P.; Maes, N.; Albert, A. Efficacy of bio-optimized extracts of turmeric and essential fennel oil on the quality of life in patients with irritable bowel syndrome. Ann. Gastroenterol. 2018, 31, 685–691.
  19. Westphal, J.; Horning, M.; Leonhardt, K. Phytotherapy in functional upper abdominal complaints: Results of a clinical study with a preparation of several plants. Phytomedicine 1996, 2, 285–291.
  20. Hattori, M.; Sakamoto, T.; Kobashi, K. Metabolism of glycyrrhizin by human intestinal flora. Planta Med. 1983, 48, 38–42.
  21. Chandler, R.F. Licorice, more than just a flavour. Can. Pharm. J. 1985, 118, 421–424.
  22. Van Marle, J.; Aarsen, P.N.; Lind, A. Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium. Eur. J. Pharmacol. 1981, 72, 219–225.
  23. Goso, Y.; Ogata, Y.; Ishihara, K. Effects of traditional herbal medicine on gastric mucin against ethanol-induced gastric injury in rats. Comp. Biochem. Physiol. Part C Pharmacol. Toxicol. Endocrinol. 1996, 113, 17–21.
  24. Raveendra, K.R.; Jayachandra; Srinivasa, V.; Sushma, K.R.; Allan, J.J.; Goudar, K.S.; Shivaprasad, H.N.; Venkateshwarlu, K.; Geetharani, P.; Sushma, G.; et al. An Extract of Glycyrrhiza glabra (GutGard) Alleviates Symptoms of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study. Evid. Based Complement. Altern. Med. 2011, 2012, 216970.
  25. Feldman, H.; Gilat, T. A trial of deglycyrrhizinated liquorice in the treatment of duodenal ulcer. Gut 1971, 12, 499–555.
  26. Nazari, S.; Rameshrad, M.; Hossainzade, H. Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review. Phytother. Res. 2017, 31, 1635–1650.
  27. Penninkilampi, R.; Eslick, E.M.; Eslick, G.D. The association between consistent licorice ingestion, hypertension and hypokalaemia: A systematic review and meta-analysis. J. Hypertens. 2017, 31, 699–707.
  28. Brierly, S.M.; Kelber, O. Use of natural products in gastrointestinal therapies. Curr. Opin. Pharmacol. 2011, 11, 604–611.
  29. Simmen, U.; Kelber, O.; Okpanyi, S.N.; Jaeggi, R.; Bueter, B.; Weiser, D. Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors. Phytomedicine 2006, 13 (Suppl. 5), 51–55.
  30. Wegener, T.; Wagner, H. The active components and the pharmacological multi-target principle of STW 5 (Iberogast). Phytomedicine 2006, 13 (Suppl. 5), 20–35.
  31. Müller, M.; Liu, C.-Y.; Glatzle, J.; Weiser, D.; Kelber, O.; Enck, P.; Grundy, D.; Kreis, M. STW 5 (Iberogast®) reduces afferent sensitivity in the rat small intestine. Phytomedicine 2006, 13, 100–106.
  32. Schemann, M.; Michel, K.; Zeller, F.; Hohenester, B.; Ruhl, A. Region-specific effects of STW 5 (Iberogast®) and its components in gastric fundus, corpus and antrum. Phytomedicine 2006, 13 (Suppl. 5), 90–99.
  33. Pilichiewicz, A.N.; Horowitz, M.; Russo, A.; Maddox, A.F.; Jones, K.L.; Schemann, M.; Holtmann, G.; Feinle-Bisset, C. Effects of Iberogast® on proximal gastric volume, antropyloroduodenal motility and gastric emptying in healthy men. Am. J. Gastroenterol. 2007, 102, 1276–1283.
  34. Braden, B.; Caspary, W.; Börner, N.; Vinson, B.; Schneider, A.R. Clinical effects of STW 5 (Iberogast®) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis. Neurogastroenterol. Motil. 2009, 21, 632–638.e625.
  35. Vinson, B.; Radke, M. The herbal preparation STW 5 for the treatment of functional diseases in children aged 3–14 years: A prospective non-interventional study. Gastroenterology 2011, 140, S102.
  36. Von Arnim, U.; Peitz, U.; Vinson, B.; Gundermann, K.J.; Malfertheiner, P. STW 5, a phytopharmacon for patients with functional dyspepsia: Results of a multicenter, placebo-controlled double-blind study. Am. J. Gastroenterol. 2007, 102, 1268–1275.
  37. Madisch, A.; Holtmann, G.; Plein, K.; Hotz, J. Treatment of irritable bowel syndrome with herbal preparations: Results of a double-blind, randomized, placebo-controlled, multi-centre trial. Aliment. Pharmacol. Ther. 2004, 19, 271–279.
  38. Leroy, A.; Perrin, H.; Porret, R.; Sempoux, C.; Chtioui, H.; Fraga, M.; Bart, P.A. Iberogast-induced Acute Liver Injury—A case report. Gastro Hep Adv. 2022, 1, 601–603.
  39. Sáez-González, E.; Conde, I.; Díaz-Jaime, F.C.; Benlloch, S.; Prieto, M.; Berenguer, M. Iberogast-Induced Severe Hepatotoxicity Leading to Liver Transplantation. Am. J. Gastroenterol. 2016, 111, 1364–1365.
  40. Gerhardt, F.; Benesic, A.; Tillmann, H.L.; Radem-acher, S.; Wittekind, C.; Gerbes, A.L. Iberogast-Induced Acute Liver Failure-Reexposure and In Vitro Assay Support Causality. Am. J. Gastroenterol. 2019, 114, 1358–1359.
  41. WHO Database Vigilyze. 2021. Available online: https://vigilyze.who-umc.org/#/ (accessed on 22 March 2021).
  42. Bunchorntavakul, C.; Reddy, K.R. Review article: Herbal and dietary supplement hepatotoxicity. Aliment. Pharmacol. Ther. 2012, 37, 3–17.
  43. Ottillinger, B.; Storr, M.; Malfertheiner, P.; Allescher, H.-D. STW 5 (Iberogast®)—A safe and effective standard in the treatment of functional gastrointestinal disorders. Wien. Med. Wochenschr. 2012, 163, 65–72.
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