3. Food Supplements and Childhood Illnesses
3.1. Botanical Extracts
3.1.1. Melissa officinalis L.
3.1.2. Foeniculum vulgare Mill.
3.1.3. Matricaria chamomilla L.
3.1.4. Boswellia serrata Roxb. ex Colebr.
3.1.5. Valeriana officinalis L.
3.1.6. Eschscholzia californica Cham.
3.1.7. Grindelia robusta Nutt.
3.1.8. Malva sylvestris L.
3.1.9. Passiflora incarnate L.
3.1.10. Mentha spicata L.
3.1.11. Cuminum cyminum L.
3.1.12. Pimpinella anisum L.
3.2. Bioactive Components
3.2.1. Butyric Acid
3.2.3. Amino Acids
3.2.4. Vitamin D
4. Safety Aspects of Childhood Supplementation
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
- Dwyer, J.; Nahin, R.L.; Rogers, G.T.; Barnes, P.M.; Jacques, P.M.; Sempos, C.T.; Bailey, R. Prevalence and predictors of children’s dietary supplement use: The 2007 National Health Interview Survey. Am. J. Clin. Nutr. 2013, 97, 1331–1337. [Google Scholar] [CrossRef]
- Bailey, R.L.; Gahche, J.J.; Thomas, P.R.; Dwyer, J.T. Why US children use dietary supplements. Pediatr. Res. 2013, 74, 737–741. [Google Scholar] [CrossRef]
- Robinson, M.M.; Zhang, X. Traditional medicines: Global situation, issues and challenges. World Med. Situat. 2011, 3, 1–14. [Google Scholar]
- Wegener, T. Herbal medicinal products in the paediatric population—Status quo and perspectives. Wien. Med. Wochenschr. 2013, 163, 46–51. [Google Scholar] [CrossRef]
- Çiftçi, S.; Samur, F.G. Use of botanical dietary supplements in infants and children and their effects on health. Hacet. Üniv. Sağlık Bilim. Fak Derg. 2017, 4, 30–45. [Google Scholar] [CrossRef]
- Kamboj, V.P. Herbal medicine. Curr. Sci. 2000, 78, 35–39. [Google Scholar]
- Uchida, K.; Inoue, M.; Otake, K.; Koike, Y.; Kusunoki, M. Complementary and alternative medicine use by Japanese children with pediatric surgical diseases. Open J. Pediatr. 2013, 3, 49–53. [Google Scholar] [CrossRef]
- Zhang, Y.; Fein, E.B.; Fein, S.B. Feeding of dietary botanical supplements and teas to infants in the United States. Pediatrics 2011, 127, 1060–1066. [Google Scholar] [CrossRef]
- Pitetti, R.; Singh, S.; Hornyak, D.; Garcia, S.E.; Herr, S. Complementary and alternative medicine use in children. Pediatr. Emerg. Care 2001, 17, 165–169. [Google Scholar] [CrossRef]
- Katz, M.; Adar Levine, A.; Kol-Degani, H.; Kav-Venaki, L. A compound herbal preparation (CHP) in the treatment of children with ADHD: A randomized controlled trial. J. Atten. Disord. 2010, 14, 281–291. [Google Scholar] [CrossRef]
- Tavares-Silva, C.; Holandino, C.; Homsani, F.; Luiz, R.R.; Prodestino, J.; Farah, A.; de Paula Lima, J.; Simas, R.C.; Castilho, C.V.V.; Leitão, S.G. Homeopathic medicine of Melissa officinalis combined or not with Phytolacca decandra in the treatment of possible sleep bruxism in children: A crossover randomized triple-blinded controlled clinical trial. Phytomedicine 2019, 58, 152869. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- Martinelli, M.; Ummarino, D.; Giugliano, F.; Sciorio, E.; Tortora, C.; Bruzzese, D.; De Giovanni, D.; Rutigliano, I.; Valenti, S.; Romano, C. Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA 122) in infantile colic: An open randomized controlled trial. Neurogastroenterol. Motil. 2017, 29, e13145. [Google Scholar] [CrossRef]
- Javid, A.; Haghi, N.M.; Emami, S.A.; Ansari, A.; Zojaji, S.A.; Khoshkhui, M.; Ahanchian, H. Short-course administration of a traditional herbal mixture ameliorates asthma symptoms of the common cold in children. Avicenna J. Phytomed. 2019, 9, 126. [Google Scholar]
- Janssen, G.; Bode, U.; Breu, H.; Dohrn, B.; Engelbrecht, V.; Göbel, U. Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors. Klin. Padiatr. 2000, 212, 189–195. [Google Scholar] [CrossRef]
- Müller, S.; Klement, S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine 2006, 13, 383–387. [Google Scholar] [CrossRef]
- Razlog, R.; Pellow, J.; White, S.J. A pilot study on the efficacy of Valeriana officinalis mother tincture and Valeriana officinalis 3X in the treatment of attention deficit hyperactivity disorder. Health SA Gesondheid 2012, 17, 1–7. [Google Scholar] [CrossRef]
- Canciani, M.; Murgia, V.; Caimmi, D.; Anapurapu, S.; Licari, A.; Marseglia, G.L. Efficacy of Grintuss® pediatric syrup in treating cough in children: A randomized, multicenter, double blind, placebo-controlled clinical trial. Ital. J. Pediatr. 2014, 40, 56. [Google Scholar] [CrossRef]
- Cohen, H.A.; Hoshen, M.; Gur, S.; Bahir, A.; Laks, Y.; Blau, H. Efficacy and tolerability of a polysaccharide-resin-honey based cough syrup as compared to carbocysteine syrup for children with colds: A randomized, single-blinded, multicenter study. World J. Pediatr. 2017, 13, 27–33. [Google Scholar] [CrossRef]
- Carnevali, I.; La Paglia, R.; Pauletto, L.; Raso, F.; Testa, M.; Mannucci, C.; Sorbara, E.E.; Calapai, G. Efficacy and safety of the syrup “KalobaTUSS®” as a treatment for cough in children: A randomized, double blind, placebo-controlled clinical trial. BMC Pediatr. 2021, 21, 29. [Google Scholar] [CrossRef]
- Trompetter, I.; Krick, B.; Weiss, G. Herbal triplet in treatment of nervous agitation in children. Wien. Med. Wochenschr. 2013, 163, 52–57. [Google Scholar] [CrossRef]
- Akhondzadeh, S.; Mohammadi, M.; Momeni, F. Passiflora incarnata in the treatment of attention-deficit hyperactivity disorder in children and adolescents. Clin. Pract. 2005, 2, 609. [Google Scholar] [CrossRef]
- Kiberd, M.B.; Clarke, S.K.; Chorney, J.; d’Eon, B.; Wright, S. Aromatherapy for the treatment of PONV in children: A pilot RCT. BMC Complement. Altern. Med. 2016, 16, 450. [Google Scholar] [CrossRef]
- Adinee, J.; Piri, K.; Karami, O. Essential oil component in flower of lemon balm (Melissa officinalis L.). Am. J. Biochem. Biotechnol. 2008, 4, 277–278. [Google Scholar] [CrossRef]
- Caleja, C.; Barros, L.; Barreira, J.C.; Ciric, A.; Sokovic, M.; Calhelha, R.C.; Beatriz, M.; Oliveira, P.; Ferreira, I.C. Suitability of lemon balm (Melissa officinalis L.) extract rich in rosmarinic acid as a potential enhancer of functional properties in cupcakes. Food Chem. 2018, 250, 67–74. [Google Scholar] [CrossRef]
- Haybar, H.; Javid, A.Z.; Haghighizadeh, M.H.; Valizadeh, E.; Mohaghegh, S.M.; Mohammadzadeh, A. The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina. Clin. Nutr. ESPEN 2018, 26, 47–52. [Google Scholar] [CrossRef]
- Moacă, E.-A.; Farcaş, C.; Ghiţu, A.; Coricovac, D.; Popovici, R.; Cărăba-Meiţă, N.-L.; Ardelean, F.; Antal, D.S.; Dehelean, C.; Avram, Ş. A comparative study of Melissa officinalis leaves and stems ethanolic extracts in terms of antioxidant, cytotoxic, and antiproliferative potential. Evid. Based Complement. Alternat. Med. 2018, 2018, 7860456. [Google Scholar] [CrossRef]
- Vasileva, I.; Denkova, R.; Chochkov, R.; Teneva, D.; Denkova, Z.; Dessev, T.; Denev, P.; Slavov, A. Effect of lavender (Lavandula angustifolia) and melissa (Melissa officinalis) waste on quality and shelf life of bread. Food Chem. 2018, 253, 13–21. [Google Scholar] [CrossRef]
- Bordbar, M.; Negahdar, N.; Nasrollahzadeh, M. Melissa officinalis L. leaf extract assisted green synthesis of CuO/ZnO nanocomposite for the reduction of 4-nitrophenol and Rhodamine B. Sep. Purif. Technol. 2018, 191, 295–300. [Google Scholar] [CrossRef]
- Anheyer, D.; Lauche, R.; Schumann, D.; Dobos, G.; Cramer, H. Herbal medicines in children with attention deficit hyperactivity disorder (ADHD): A systematic review. Complement. Ther. Med. 2017, 30, 14–23. [Google Scholar] [CrossRef]
- Gürol, A.; Taplak, A.Ş.; Polat, S. Herbal supplement products used by mothers to cope with the common health problems in childhood. Complement. Ther. Med. 2019, 47, 102214. [Google Scholar] [CrossRef]
- Keskin, I.; Gunal, Y.; Ayla, S.; Kolbasi, B.; Sakul, A.; Kilic, U.; Gok, O.; Koroglu, K.; Ozbek, H. Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on experimental wound healing. Biotech. Histochem. 2017, 92, 274–282. [Google Scholar] [CrossRef]
- Sharopov, F.; Valiev, A.; Satyal, P.; Gulmurodov, I.; Yusufi, S.; Setzer, W.N.; Wink, M. Cytotoxicity of the essential oil of fennel (Foeniculum vulgare) from Tajikistan. Foods 2017, 6, 73. [Google Scholar] [CrossRef]
- EFSA. ESCO report: Advice on the EFSA guidance document for the safety assessment of botanicals and botanical preparations intended for use as food supplements, based on real case studies. EFSA J. 2009, 6, 280. [Google Scholar]
- Mao, J.J.; Xie, S.X.; Keefe, J.R.; Soeller, I.; Li, Q.S.; Amsterdam, J.D. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine 2016, 23, 1735–1742. [Google Scholar] [CrossRef]
- Chauhan, E.S.; Jaya, A. Chamomile an ancient aromatic plant-A review. J. Ayurveda Med. Sci. 2017, 2, 251–255. [Google Scholar] [CrossRef]
- McKay, D.L.; Blumberg, J.B. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother. Res. 2006, 20, 519–530. [Google Scholar] [CrossRef]
- Repčák, M.; Šmajda, B.; Kováčik, J.; Eliašová, A. Circadian rhythm of (Z)-and (E)-2-β-d-glucopyranosyloxy-4-methoxy cinnamic acids and herniarin in leaves of Matricaria chamomilla. Plant Cell Rep. 2009, 28, 1137–1143. [Google Scholar] [CrossRef]
- Jakubcova, Z.; Zeman, L.; Horky, P.; Mrkvicova, E.; Mares, P.; Mrazkova, E.; Stastnik, O. The Influence of the Addition of Chamomile Extract to the Diet of Chickens. In Proceedings of the Conference MendelNet, Brno, Czech Republic, 19–20 November 2014; MendelNet: Brno, Czech Republic, 2014; pp. 147–150. [Google Scholar]
- Sultana, A.; Padmaja, A. Boswellia serrata Roxb. a traditional herb with versatile pharmacological activity: A review. Int. J. Pharm. Sci. Res. 2013, 4, 2106–2117. [Google Scholar]
- Catanzaro, D.; Rancan, S.; Orso, G.; Dall’Acqua, S.; Brun, P.; Giron, M.C.; Carrara, M.; Castagliuolo, I.; Ragazzi, E.; Caparrotta, L. Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage. PLoS ONE 2015, 10, e0125375. [Google Scholar] [CrossRef]
- Majeed, M.; Majeed, S.; Narayanan, N.K.; Nagabhushanam, K. A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee. Phytother. Res. 2019, 33, 1457–1468. [Google Scholar] [CrossRef]
- Holtmeier, W.; Zeuzem, S.; Preiβ, J.; Kruis, W.; Böhm, S.; Maaser, C.; Raedler, A.; Schmidt, C.; Schnitker, J.; Schwarz, J. Randomized, placebo-controlled, double-blind trial of Boswellia serrata in maintaining remission of Crohn’s disease: Good safety profile but lack of efficacy. Inflamm. Bowel Dis. 2011, 17, 573–582. [Google Scholar] [CrossRef]
- Haroyan, A.; Mukuchyan, V.; Mkrtchyan, N.; Minasyan, N.; Gasparyan, S.; Sargsyan, A.; Narimanyan, M.; Hovhannisyan, A. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: A comparative, randomized, double-blind, placebo-controlled study. BMC Complement. Altern. Med. 2018, 18, 7. [Google Scholar] [CrossRef]
- Gupta, I.; Gupta, V.; Parihar, A.; Gupta, S.; Lüdtke, R.; Safayhi, H.; Ammon, H. Effects of Boswellia serrata gum resin in patients with bronchial asthma: Results of a double-blind, placebo-controlled, 6-week clinical study. Eur. J. Med. Res. 1998, 3, 511. [Google Scholar]
- Nandhini, S.; Narayanan, K.; Ilango, K. Valeriana officinalis: A review of its traditional uses, phytochemistry and pharmacology. Asian J. Pharm. Clin. Res. 2018, 11, 36–41. [Google Scholar] [CrossRef]
- Murti, K.; Kaushik, M.; Sangwan, Y.; Kaushik, A. Pharmacological properties of Valeriana officinalis—A review. Pharmacologyonline 2011, 3, 641–646. [Google Scholar]
- Kennedy, D.O.; Little, W.; Haskell, C.F.; Scholey, A.B. Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress. Phytother. Res. 2006, 20, 96–102. [Google Scholar] [CrossRef]
- Wilts, B.D.; Rudall, P.J.; Moyroud, E.; Gregory, T.; Ogawa, Y.; Vignolini, S.; Steiner, U.; Glover, B.J. Ultrastructure and optics of the prism-like petal epidermal cells of Eschscholzia californica (California poppy). New Phytol. 2018, 219, 1124–1133. [Google Scholar] [CrossRef]
- Ikezawa, N.; Iwasa, K.; Sato, F. CYP719A subfamily of cytochrome P450 oxygenases and isoquinoline alkaloid biosynthesis in Eschscholzia californica. Plant Cell Rep. 2009, 28, 123–133. [Google Scholar] [CrossRef]
- Balažová, A.; Urdová, J.; Bilka, F.; Holková, I.; Horváth, B.; Forman, V.; Mučaji, P. Evaluation of manganese chloride’s effect on biosynthetic properties of in vitro cultures of Eschscholzia californica Cham. Molecules 2018, 23, 971. [Google Scholar] [CrossRef]
- Lim, T.K. Eschscholzia californica. In Edible Medicinal and Non-Medicinal Plants; Springer: Amsterdam, The Netherlands, 2012; Volume 8, pp. 622–632. [Google Scholar]
- Demystified, V.; Orders, M. The 5 Best Natural Sleep Remedies for Kids. Children 2017, 5, 12. [Google Scholar]
- Rolland, A.; Fleurentin, J.; Lanhers, M.-C.; Younos, C.; Misslin, R.; Mortier, F.; Pelt, J.M. Behavioural effects of the American traditional plant Eschscholzia californica: Sedative and anxiolytic properties. Planta Med. 1991, 57, 212–216. [Google Scholar] [CrossRef]
- Hanus, M.; Lafon, J.; Mathieu, M. Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr. Med. Res. Opin. 2004, 20, 63–71. [Google Scholar] [CrossRef]
- Parslow, R.; Morgan, A.J.; Allen, N.B.; Jorm, A.F.; O’Donnell, C.P.; Purcell, R. Effectiveness of complementary and self-help treatments for anxiety in children and adolescents. Med. J. Aust. 2008, 188, 355–359. [Google Scholar] [CrossRef]
- Fayol, C.M.; Maruška, A.S.; Ragažinskienė, O. Phytochemical Analysis of Grindelia Robusta Nutt. Depending on Phenologic Stades, the Vital Nature Sign [Elektroninis išteklius]: 9th International Scientific Conference: Abstract Book; Vytautas Magnus University: Kaunas, Lithuania, 2015. [Google Scholar]
- Ferreres, F.; Grosso, C.; Gil-Izquierdo, A.; Valentão, P.; Azevedo, C.; Andrade, P.B. HPLC-DAD-ESI/MSn analysis of phenolic compounds for quality control of Grindelia robusta Nutt. and bioactivities. J. Pharm. Biomed. Anal. 2014, 94, 163–172. [Google Scholar] [CrossRef]
- Jaradat, N.A.; Abualhasan, M.; Ali, I. Comparison of anti-oxidant activities and exhaustive extraction yields between wild and cultivated Cyclamen persicum, Malva sylvestris and Urtica pilulifera leaves. J. Appl. Pharm. Sci. 2015, 5, 101–106. [Google Scholar] [CrossRef]
- Zahedi, S.M.; Ansari, N.A. Allelopathic potential of common mallow (Malva sylvestris) on the germination and the initial growth of tomato, cucumber and cress. Asian J. Agric. Sci. 2011, 3, 235–241. [Google Scholar]
- Yarijani, Z.M.; Godini, A.; Madani, S.H.; Najafi, H. Reduction of cisplatin-induced renal and hepatic side effects in rat through antioxidative and anti-inflammatory properties of Malva sylvestris L. extract. Biomed. Pharmacother. 2018, 106, 1767–1774. [Google Scholar] [CrossRef]
- Güleç, M.; Tan, N.; Canverdi, Ö.; Tan, E. The usage of the most frequently preferred herbal products in Turkey in nursing mothers, newborns, infants and children. Istanbul J. Pharm. 2017, 47, 84–96. [Google Scholar]
- Benso, B.; Rosalen, P.L.; Alencar, S.M.; Murata, R.M. Malva sylvestris inhibits inflammatory response in oral human cells. An in vitro infection model. PLoS ONE 2015, 10, e0140331. [Google Scholar] [CrossRef]
- Aman, U.; Subhan, F.; Shahid, M.; Akbar, S.; Ahmad, N.; Ali, G.; Fawad, K.; Sewell, R.D. Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms. BMC Complement. Altern. Med. 2016, 16, 77. [Google Scholar] [CrossRef]
- Gadioli, I.L.; da Cunha, M.d.S.B.; de Carvalho, M.V.O.; Costa, A.M.; Pineli, L.D.L.D.O. A systematic review on phenolic compounds in Passiflora plants: Exploring biodiversity for food, nutrition, and popular medicine. Crit. Rev. Food Sci. Nutr. 2018, 58, 785–807. [Google Scholar] [CrossRef]
- Patel, S.; Verma, N.; Gauthaman, K. Passiflora incarnata Linn: A review on morphology, phytochemistry and pharmacological aspects. Pharmacogn. Rev. 2009, 3, 186. [Google Scholar]
- Akhondzadeh, S.; Naghavi, H.; Vazirian, M.; Shayeganpour, A.; Rashidi, H.; Khani, M. Passionflower in the treatment of generalized anxiety: A pilot double-blind randomized controlled trial with oxazepam. J. Clin. Pharm. Ther. 2001, 26, 363–367. [Google Scholar] [CrossRef]
- Kiani, S.; Minaei, S.; Ghasemi-Varnamkhasti, M. Real-time aroma monitoring of mint (Mentha spicata L.) leaves during the drying process using electronic nose system. Measurement 2018, 124, 447–452. [Google Scholar] [CrossRef]
- Ben Saad, A.; Rjeibi, I.; Alimi, H.; Ncib, S.; Bouhamda, T.; Zouari, N. Protective effects of Mentha spicata against nicotine-induced toxicity in liver and erythrocytes of Wistar rats. Appl. Physiol. Nutr. Metab. 2018, 43, 77–83. [Google Scholar] [CrossRef]
- Bardaweel, S.K.; Bakchiche, B.; ALSalamat, H.A.; Rezzoug, M.; Gherib, A.; Flamini, G. Chemical composition, antioxidant, antimicrobial and antiproliferative activities of essential oil of Mentha spicata L. (Lamiaceae) from Algerian Saharan atlas. BMC Complement. Altern. Med. 2018, 18, 201. [Google Scholar] [CrossRef]
- Shaheen, S.; Abbas, S.; Hussain, J.; Mabood, F.; Umair, M.; Ali, M.; Ahmad, M.; Zafar, M.; Farooq, U.; Khan, A. Knowledge of medicinal plants for children diseases in the environs of district Bannu, Khyber Pakhtoonkhwa (KPK). Front. Pharmacol. 2017, 8, 430. [Google Scholar] [CrossRef]
- Ulbricht, C.; Costa, D.; Grimes Serrano, J.M.; Guilford, J.; Isaac, R.; Seamon, E.; Varghese, M. An evidence-based systematic review of spearmint by the natural standard research collaboration. J. Diet. Suppl. 2010, 7, 179–215. [Google Scholar] [CrossRef]
- Fitzgerald, M.; Culbert, T.; Finkelstein, M.; Green, M.; Johnson, A.; Chen, S. The effect of gender and ethnicity on children’s attitudes and preferences for essential oils: A pilot study. Explore 2007, 3, 378–385. [Google Scholar] [CrossRef]
- Messaoudi, M.; Begaa, S. Dietary intake and content of some micronutrients and toxic elements in two Algerian spices (Coriandrum sativum L. and Cuminum cyminum L.). Biol. Trace Elem. Res. 2019, 188, 508–513. [Google Scholar] [CrossRef]
- Al-Snafi, A.E. The pharmacological activities of Cuminum cyminum—A review. IOSR J. Pharm. 2016, 6, 46–65. [Google Scholar]
- Rai, N.; Yadav, S.; Verma, A.; Tiwari, L.; Sharma, R.K. A monographic profile on quality specifications for a herbal drug and spice of commerce-Cuminum cyminum L. Int. J. Adv. Herbal Sci. Technol. 2012, 1, 1–12. [Google Scholar]
- Farzaneh, V.; Gominho, J.; Pereira, H.; Carvalho, I.S. Screening of the antioxidant and enzyme inhibition potentials of Portuguese Pimpinella anisum L. seeds by GC-MS. Food Anal. Methods 2018, 11, 2645–2656. [Google Scholar] [CrossRef]
- Iannarelli, R.; Marinelli, O.; Morelli, M.B.; Santoni, G.; Amantini, C.; Nabissi, M.; Maggi, F. Aniseed (Pimpinella anisum L.) essential oil reduces pro-inflammatory cytokines and stimulates mucus secretion in primary airway bronchial and tracheal epithelial cell lines. Ind. Crops Prod. 2018, 114, 81–86. [Google Scholar] [CrossRef]
- Bettaieb Rebey, I.; Bourgou, S.; Aidi Wannes, W.; Hamrouni Selami, I.; Saidani Tounsi, M.; Marzouk, B.; Fauconnier, M.-L.; Ksouri, R. Comparative assessment of phytochemical profiles and antioxidant properties of Tunisian and Egyptian anise (Pimpinella anisum L.) seeds. Plant Biosyst. 2018, 152, 971–978. [Google Scholar] [CrossRef]
- Burgess, I.F.; Brunton, E.R.; Burgess, N.A. Clinical trial showing superiority of a coconut and anise spray over permethrin 0.43% lotion for head louse infestation, ISRCTN96469780. Eur. J. Pediatr. 2010, 169, 55. [Google Scholar] [CrossRef]
- Canani, R.B.; Terrin, G.; Cirillo, P.; Castaldo, G.; Salvatore, F.; Cardillo, G.; Coruzzo, A.; Troncone, R. Butyrate as an effective treatment of congenital chloride diarrhea. Gastroenterology 2004, 127, 630–634. [Google Scholar] [CrossRef]
- Kumpu, M.; Kekkonen, R.; Kautiainen, H.; Järvenpää, S.; Kristo, A.; Huovinen, P.; Pitkäranta, A.; Korpela, R.; Hatakka, K. Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: A randomized, double-blind, placebo-controlled trial. Eur. J. Clin. Nutr. 2012, 66, 1020–1023. [Google Scholar] [CrossRef]
- Grandy, G.; Medina, M.; Soria, R.; Terán, C.G.; Araya, M. Probiotics in the treatment of acute rotavirus diarrhoea. A randomized, double-blind, controlled trial using two different probiotic preparations in Bolivian children. BMC Infect. Dis. 2010, 10, 253. [Google Scholar] [CrossRef]
- Shaaban, S.Y.; El Gendy, Y.G.; Mehanna, N.S.; El-Senousy, W.M.; El-Feki, H.S.; Saad, K.; El-Asheer, O.M. The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutr. Neurosci. 2018, 21, 676–681. [Google Scholar] [CrossRef]
- Jordan, I.; Balaguer, M.; Esteban, M.E.; Cambra, F.J.; Felipe, A.; Hernández, L.; Alsina, L.; Molero, M.; Villaronga, M.; Esteban, E. Glutamine effects on heat shock protein 70 and interleukines 6 and 10: Randomized trial of glutamine supplementation versus standard parenteral nutrition in critically ill children. Clin. Nutr. 2016, 35, 34–40. [Google Scholar] [CrossRef]
- Badaloo, A.; Reid, M.; Forrester, T.; Heird, W.C.; Jahoor, F. Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition. Am. J. Clin. Nutr. 2002, 76, 646–652. [Google Scholar] [CrossRef]
- Camargo, C.A.; Ganmaa, D.; Frazier, A.L.; Kirchberg, F.F.; Stuart, J.J.; Kleinman, K.; Sumberzul, N.; Rich-Edwards, J.W. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. Pediatrics 2012, 130, e561–e567. [Google Scholar] [CrossRef]
- Manaseki-Holland, S.; Qader, G.; Isaq Masher, M.; Bruce, J.; Zulf Mughal, M.; Chandramohan, D.; Walraven, G. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: A randomised controlled trial. Trop. Med. Int. Health. 2010, 15, 1148–1155. [Google Scholar] [CrossRef]
- Rosendahl, J.; Valkama, S.; Holmlund-Suila, E.; Enlund-Cerullo, M.; Hauta-alus, H.; Helve, O.; Hytinantti, T.; Levälahti, E.; Kajantie, E.; Viljakainen, H. Effect of higher vs. standard dosage of vitamin D3 supplementation on bone strength and infection in healthy infants: A randomized clinical trial. JAMA Pediatr. 2018, 172, 646–654. [Google Scholar] [CrossRef]
- Lind, T.; Lönnerdal, B.; Stenlund, H.; Gamayanti, I.L.; Ismail, D.; Seswandhana, R.; Persson, L.-Å. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: Effects on growth and development. Am. J. Clin. Nutr. 2004, 80, 729–736. [Google Scholar] [CrossRef]
- Roy, S.; Hossain, M.J.; Khatun, W.; Chakraborty, B.; Chowdhury, S.; Begum, A.; Mah-e-Muneer, S.; Shafique, S.; Khanam, M.; Chowdhury, R. Zinc supplementation in children with cholera in Bangladesh: Randomised controlled trial. BMJ 2008, 336, 266–268. [Google Scholar] [CrossRef]
- Acevedo-Murillo, J.A.; Garcia-Leon, M.L.; Firo-Reyes, V.; Santiago Cordova, J.L.; Gonzalez-Rodriguez, A.P.; Wong-Chew, R.M. Zinc supplementation promotes a Th1 response and improves clinical symptoms in less hours in children with pneumonia younger than 5 years old. A randomized controlled clinical trial. Front. Pediatr. 2019, 7, 431. [Google Scholar] [CrossRef]
- Schall, J.I.; Mascarenhas, M.R.; Maqbool, A.; Dougherty, K.A.; Elci, O.; Wang, D.-J.; Altes, T.A.; Hommel, K.A.; Shaw, W.; Moore, J. Choline supplementation with a structured lipid in children with cystic fibrosis: A randomized placebo-controlled trial. J. Pediatr. Gastroenterol. Nutr. 2016, 62, 618. [Google Scholar] [CrossRef]
- Wozniak, J.R.; Fuglestad, A.J.; Eckerle, J.K.; Fink, B.A.; Hoecker, H.L.; Boys, C.J.; Radke, J.P.; Kroupina, M.G.; Miller, N.C.; Brearley, A.M. Choline supplementation in children with fetal alcohol spectrum disorders: A randomized, double-blind, placebo-controlled trial. Am. J. Clin. Nutr. 2015, 102, 1113–1125. [Google Scholar] [CrossRef]
- San Miguela, A.; Salgado, M.T.; Rodrígueza, M.S.M.; Pachónb, J.; Sánchez, M.A.; Martína, P.C.L.; Pastorc, M.R. Role of butyric acid in food and intestinal health. Immunol. Infect. 2018, 1, 1–5. [Google Scholar]
- Manrique, D.V.; González, M.S. Short chain fatty acids (butyric acid) and intestinal diseases. Nutr. Hosp. 2017, 34, 58–61. [Google Scholar]
- Leonel, A.J.; Alvarez-Leite, J.I. Butyrate: Implications for intestinal function. Curr. Opin. Clin. Nutr. Metab. Care 2012, 15, 474–479. [Google Scholar] [CrossRef]
- Pituch, A.; Walkowiak, J.; Banaszkiewicz, A. Butyric acid in functional constipation. Prz. Gastroenterol. 2013, 8, 295. [Google Scholar] [CrossRef]
- Załęski, A.; Banaszkiewicz, A.; Walkowiak, J. Butyric acid in irritable bowel syndrome. Prz. Gastroenterol. 2013, 8, 350. [Google Scholar] [CrossRef]
- Schnekenburger, M.; Diederich, M. Nutritional epigenetic regulators in the field of cancer: New avenues for chemopreventive approaches. In Epigenetic Cancer Therapy; Gray, S., Ed.; Elsevier: Hoboken, NJ, USA, 2015; pp. 393–425. [Google Scholar]
- Sossai, P. Butyric acid: What is the future for this old substance? Swiss Med. Wkly. 2012, 142, w13596. [Google Scholar] [CrossRef]
- Edelman, M.J.; Bauer, K.; Khanwani, S.; Tait, N.; Trepel, J.; Karp, J.; Nemieboka, N.; Chung, E.-J.; Van Echo, D. Clinical and pharmacologic study of tributyrin: An oral butyrate prodrug. Cancer Chemother. Pharmacol. 2003, 51, 439–444. [Google Scholar] [CrossRef]
- Wang, W.; Chen, L.; Zhou, R.; Wang, X.; Song, L.; Huang, S.; Wang, G.; Xia, B. Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. J. Clin. Microbiol. 2014, 52, 398–406. [Google Scholar] [CrossRef]
- Raqib, R.; Sarker, P.; Mily, A.; Alam, N.H.; Arifuzzaman, A.S.M.; Rekha, R.S.; Andersson, J.; Gudmundsson, G.H.; Cravioto, A.; Agerberth, B. Efficacy of sodium butyrate adjunct therapy in shigellosis: A randomized, double-blind, placebo-controlled clinical trial. BMC Infect. Dis. 2012, 12, 111. [Google Scholar] [CrossRef]
- Odièvre, M.H.; Brun, M.; Krishnamoorthy, R.; Lapouméroulie, C.; Elion, J. Sodium phenyl butyrate downregulates endothelin-1 expression in cultured human endothelial cells: Relevance to sickle-cell disease. Am. J. Hematol. 2007, 82, 357–362. [Google Scholar] [CrossRef] [PubMed]
- Mishra, S.S.; Behera, P.K.; Kar, B.; Ray, R.C. Advances in probiotics, prebiotics and nutraceuticals. In Innovations in Technologies for Fermented Food and Beverage Industries; Springer: Berlin/Heidelberg, Germany, 2018; pp. 121–141. [Google Scholar]
- Suvarna, V.; Boby, V. Probiotics in human health: A current assessment. Curr. Sci. 2005, 88, 1744–1748. [Google Scholar]
- Delgado, S.; Sánchez, B.; Margolles, A.; Ruas-Madiedo, P.; Ruiz, L. Molecules produced by probiotics and intestinal microorganisms with immunomodulatory activity. Nutrients 2020, 12, 391. [Google Scholar] [CrossRef] [PubMed]
- Chugh, B.; Kamal-Eldin, A. Bioactive compounds produced by probiotics in food products. Curr. Opin. Food Sci. 2020, 32, 76–82. [Google Scholar] [CrossRef]
- De Filippis, A.; Ullah, H.; Baldi, A.; Dacrema, M.; Esposito, C.; Garzarella, E.U.; Santarcangelo, C.; Tantipongpiradet, A.; Daglia, M. Gastrointestinal disorders and metabolic syndrome: Dysbiosis as a key link and common bioactive dietary components useful for their treatment. Int. J. Mol. Sci. 2020, 21, 4929. [Google Scholar] [CrossRef]
- Agostoni, C.; Axelsson, I.; Braegger, C.; Goulet, O.; Koletzko, B.; Michaelsen, K.F.; Rigo, J.; Shamir, R.; Szajewska, H.; Turck, D. Probiotic bacteria in dietetic products for infants: A commentary by the ESPGHAN Committee on Nutrition. J. Pediatr. Gastroenterol. Nutr. 2004, 38, 365–374. [Google Scholar] [CrossRef]
- Elazab, N.; Mendy, A.; Gasana, J.; Vieira, E.R.; Quizon, A.; Forno, E. Probiotic administration in early life, atopy, and asthma: A meta-analysis of clinical trials. Pediatrics 2013, 132, e666–e676. [Google Scholar] [CrossRef]
- Martin, C.R.; Ling, P.-R.; Blackburn, G.L. Review of infant feeding: Key features of breast milk and infant formula. Nutrients 2016, 8, 279. [Google Scholar] [CrossRef] [PubMed]
- Semba, R.D.; Shardell, M.; Ashour, F.A.S.; Moaddel, R.; Trehan, I.; Maleta, K.M.; Ordiz, M.I.; Kraemer, K.; Khadeer, M.A.; Ferrucci, L. Child stunting is associated with low circulating essential amino acids. EBioMedicine 2016, 6, 246–252. [Google Scholar] [CrossRef]
- Bala, K.; Dogan, M.; Mutluer, T.; Kaba, S.; Aslan, O.; Balahoroglu, R.; Cokluk, E.; Ustyol, L.; Kocaman, S. Plasma amino acid profile in autism spectrum disorder (ASD). Eur. Rev. Med. Pharmacol. Sci. 2016, 20, 923–929. [Google Scholar]
- De Vivo, D.C.; Bohan, T.P.; Coulter, D.L.; Dreifuss, F.E.; Greenwood, R.S.; Nordli, D.R., Jr.; Shields, W.D.; Stafstrom, C.E.; Tein, I. L-carnitine supplementation in childhood epilepsy: Current perspectives. Epilepsia 1998, 39, 1216–1225. [Google Scholar] [CrossRef]
- Misra, M.; Pacaud, D.; Petryk, A.; Collett-Solberg, P.F.; Kappy, M. Vitamin D deficiency in children and its management: Review of current knowledge and recommendations. Pediatrics 2008, 122, 398–417. [Google Scholar] [CrossRef] [PubMed]
- Bailey, R.L.; Fulgoni, V.L., III; Keast, D.R.; Lentino, C.V.; Dwyer, J.T. Do dietary supplements improve micronutrient sufficiency in children and adolescents? J. Pediatr. 2012, 161, 837–842. [Google Scholar] [CrossRef]
- Lee, J.Y.; So, T.-Y.; Thackray, J. A review on vitamin d deficiency treatment in pediatric patients. J. Pediatr. Pharmacol. Ther. 2013, 18, 277–291. [Google Scholar] [CrossRef]
- Fares, M.M.; Alkhaled, L.H.; Mroueh, S.M.; Akl, E.A. Vitamin D supplementation in children with asthma: A systematic review and meta-analysis. BMC Res. Notes 2015, 8, 23. [Google Scholar] [CrossRef] [PubMed]
- Gupta, A.; Sjoukes, A.; Richards, D.; Banya, W.; Hawrylowicz, C.; Bush, A.; Saglani, S. Relationship between serum vitamin D, disease severity, and airway remodeling in children with asthma. Am. J. Respir. Crit. Care Med. 2011, 184, 1342–1349. [Google Scholar] [CrossRef] [PubMed]
- Litonjua, A.A.; Carey, V.J.; Laranjo, N.; Harshfield, B.J.; McElrath, T.F.; O’Connor, G.T.; Sandel, M.; Iverson, R.E.; Lee-Paritz, A.; Strunk, R.C. Effect of prenatal supplementation with vitamin D on asthma or recurrent wheezing in offspring by age 3 years: The VDAART randomized clinical trial. JAMA 2016, 315, 362–370. [Google Scholar] [CrossRef] [PubMed]
- Mohammadifard, N.; Humphries, K.H.; Gotay, C.; Mena-Sánchez, G.; Salas-Salvadó, J.; Esmaillzadeh, A.; Ignaszewski, A.; Sarrafzadegan, N. Trace minerals intake: Risks and benefits for cardiovascular health. Crit. Rev. Food Sci. Nutr. 2019, 59, 1334–1346. [Google Scholar] [CrossRef]
- Wu, D.; Lewis, E.D.; Pae, M.; Meydani, S.N. Nutritional modulation of immune function: Analysis of evidence, mechanisms, and clinical relevance. Front. Immunol. 2019, 9, 3160. [Google Scholar] [CrossRef] [PubMed]
- Vaughn, A.R.; Foolad, N.; Maarouf, M.; Tran, K.A.; Shi, V.Y. Micronutrients in atopic dermatitis: A systematic review. J. Altern. Complement. Med. 2019, 25, 567–577. [Google Scholar] [CrossRef]
- Rivera, J.A.; Hotz, C.; González-Cossío, T.; Neufeld, L.; García-Guerra, A. The effect of micronutrient deficiencies on child growth: A review of results from community-based supplementation trials. Nutr. J. 2003, 133, 4010S–4020S. [Google Scholar] [CrossRef]
- Bhutta, Z.; Black, R.E.; Brown, K.; Gardner, J.M.; Gore, S.; Hidayat, A.; Khatun, F.; Martorell, R.; Ninh, N.; Penny, M. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials. J. Pediatr. 1999, 135, 689–697. [Google Scholar] [CrossRef]
- Tielsch, J.M.; Khatry, S.K.; Stoltzfus, R.J.; Katz, J.; LeClerq, S.C.; Adhikari, R.; Mullany, L.C.; Black, R.; Shresta, S. Effect of daily zinc supplementation on child mortality in southern Nepal: A community-based, cluster randomised, placebo-controlled trial. Lancet 2007, 370, 1230–1239. [Google Scholar] [CrossRef]
- Snider, S.A.; Margison, K.D.; Ghorbani, P.; LeBlond, N.D.; O’Dwyer, C.; Nunes, J.R.; Nguyen, T.; Xu, H.; Bennett, S.A.; Fullerton, M.D. Choline transport links macrophage phospholipid metabolism and inflammation. J. Biol. Chem. 2018, 293, 11600–11611. [Google Scholar] [CrossRef] [PubMed]
- USDA Nutrient Data Laboratory. National Agricultural Library, U.S.D. o. A. USDA Food Composition Databases. Available online: https://www.nal.usda.gov/fnic/nutrient-lists-standard-reference-legacy-2018 (accessed on 13 December 2020).
- Blusztajn, J.K.; Slack, B.E.; Mellott, T.J. Neuroprotective actions of dietary choline. Nutrients 2017, 9, 815. [Google Scholar] [CrossRef] [PubMed]
- Zeisel, S.H.; Da Costa, K.-A. Choline: An essential nutrient for public health. Nutr. Rev. 2009, 67, 615–623. [Google Scholar] [CrossRef]
- Wiedeman, A.M.; Barr, S.I.; Green, T.J.; Xu, Z.; Innis, S.M.; Kitts, D.D. Dietary choline intake: Current state of knowledge across the life cycle. Nutrients 2018, 10, 1513. [Google Scholar] [CrossRef] [PubMed]
- Gardiner, P. Dietary supplement use in children: Concerns of efficacy and safety. Am. Fam. Physician 2005, 71, 1068. [Google Scholar]
- Misra, S.M. Integrative therapies and pediatric inflammatory bowel disease: The current evidence. Children 2014, 1, 149–165. [Google Scholar] [CrossRef]
- Woolf, A.D. Herbal remedies and children: Do they work? Are they harmful? Pediatrics 2003, 112, 240–246. [Google Scholar]
- Saper, R.B.; Kales, S.N.; Paquin, J.; Burns, M.J.; Eisenberg, D.M.; Davis, R.B.; Phillips, R.S. Heavy metal content of ayurvedic herbal medicine products. JAMA 2004, 292, 2868–2873. [Google Scholar] [CrossRef]
- Bianco, M.I.; Lúquez, C.; de Jong, L.I.; Fernández, R.A. Presence of Clostridium botulinum spores in Matricaria chamomilla (chamomile) and its relationship with infant botulism. Int. J. Food Microbiol. 2008, 121, 357–360. [Google Scholar] [CrossRef] [PubMed]
- Bagheri, H.; Broué, P.; Lacroix, I.; Larrey, D.; Olives, J. Fulminant hepatic failure after herbal medicine ingestion in children. Thérapie 1998, 53, 82–83. [Google Scholar]
- Ladas, E.; Bhatia, M.; Chen, L.; Sandler, E.; Petrovic, A.; Berman, D.; Hamblin, F.; Gates, M.; Hawks, R.; Sung, L. The safety and feasibility of probiotics in children and adolescents undergoing hematopoietic cell transplantation. Bone Marrow Transplant. 2016, 51, 262–266. [Google Scholar] [CrossRef]
- Weizman, Z.; Alsheikh, A. Safety and tolerance of a probiotic formula in early infancy comparing two probiotic agents: A pilot study. J. Am. Coll. Nutr. 2006, 25, 415–419. [Google Scholar] [CrossRef]
- Snydman, D.R. The safety of probiotics. Clin. Infect. Dis. 2008, 46, S104–S111. [Google Scholar] [CrossRef]
- Döneray, H.; Özkan, B.; Özkan, A.; Koşan, C.; Orbak, Z.; Karakelleoğlu, C. The clinical and laboratory characteristics of vitamin D intoxication in children. Turk. J. Med. Sci. 2009, 39, 1–4. [Google Scholar]
- Cesur, Y.; Caksen, H.; Gündem, A.; Kirimi, Ε.; Odabaş, D. Comparison of low and high dose of vitamin D treatment in nutritional vitamin D deficiency rickets. J. Pediatr. Endocrinol. Metab. 2003, 16, 1105–1110. [Google Scholar] [CrossRef] [PubMed]
|Botanical Extract||Study Design||Intervention||Main Results||Reference|
|Compound herbal preparation |
A. platensis, and
|Randomized controlled trial, |
120 children with ADHD (mean age: 9.82 years for treatment group and 9.36 years for control group) were recruited.
|Three mL of compound herbal preparation 3 times a day in 50–60 mL water.||Significant improvement of TOVA scores, attention, cognition, and impulse control in intervention group.|||
|M. officinalis and |
|Crossover randomized triple-blinded controlled trial, |
52 children with sleep bruxism with mean age of 6.62 years were selected.
|The study included 4 phases of 30-day treatment (placebo, M. officinalis 12 c, P. decandra 12c and M. officinalis 12c + P. decandra 12c) with a washout period of 15 days between treatments.||Significant decrease in VAS in M. officinalis treated phase. |
No improvement of results was seen in combination of M. officinalis with P. decandra.
|F. vulgare||Double blind, placebo-controlled study, |
125 infants with 2–12 weeks of age, diagnosed with infantile colic were selected for the trial.
|A mixture of 0.1% of F. vulgare oil emulsion and 0.4% polysorbate in water. |
Five to twenty milliliters of mixture administered 4 times a day before meal at a maximum dose of 12 mL/kg/day.
|Significant recovery of the colic symptoms in F. vulgare treated group.|||
|M. chamomilla and |
|Multicenter, randomized controlled trial, |
Children with infantile colic were recruited.
|Patients were treated with mixture of M. chamomilla, M. officinalis and tyndallized Lactobacillus acidophilus HA122 or Lactobacillus reuteri DSM 17,938 for 28 days.||One hundred and seventy-six children completed the study. |
The symptoms of infantile colic relieved with a significant decrease in mean daily crying in both groups.
|Herbal mixture of |
Z. jujube, and
|Double-blind randomized clinical trial, |
46 children aged 7–12 years old diagnosed with intermittent asthma were selected.
|Children were treated with herbal mixture (5 mL three times a day) or placebo for 5 days.||Significant reduction in the severity of cough and nighttime awakenings in the treatment group. |
No improvement of wheezing, respiratory distress, tachypnea, peak expiratory flow rate, asthma exacerbations, outpatient visits, oral administration of prednisone or β-agonists and hospitalization.
|Boswellic acid |
|Nineteen children and adolescents (mean age of 8.4 years) with progressive or relapsed brain tumors were selected for trial.||Patients received boswellic acid at a maximum dose of 126 mg/kg/day for duration of 1–26 months (median 9 months).||Improvement of general status of patients and neurological symptoms (parses and ataxia), increased muscular strength, regression of peritumoral edema and regression of the volume of a tumor cyst.|||
|V. officinalis and |
|Multicenter observational study, |
918 children with restlessness and dyssomnia were recruited for the study.
|Each patient received a maximum of 2 × 2 tablets per day for 4 weeks, where each tablet contains valerian root dry extract (160 mg) and lemon balm extract (80 mg).||Improvement of symptoms associated with restlessness and dyssomnia in intervention group.|||
|V. officinalis||Randomized double-blind placebo-controlled trial, |
30 children with ADHD (age: 5–11 years) were selected.
|Patients were treated with V. officinalis mother tincture (MT) or V. officinalis 3X three times a day for 2 weeks.||A significant improvement in ADHD symptoms in patients treated with V. officinalis MT or 3X in reference to sustained attention, impulsivity, hyperactivity and anxiety.|||
|Pediatric syrup Grintuss ® |
P. lanceolata, and honey)
|Double-blind, randomized, placebo-controlled trial, |
102 children aged 3–6 years, with persistent cough for at least 7 days up to 3 weeks and not treated with any antitussive agent were recruited.
|Patients were treated with placebo (n = 51) or Grintuss ® syrup (n = 51) 4 doses/day, 5 mL each dose for 8 days.||Significant improvement in daytime and night-time cough scores.|||
|Polysaccharide-resin-honey (PRH)-based cough syrup |
(G. robusta, H. italicum and P. lanceolata)
|Randomized, single-blind multicenter study, |
150 children aged 2–5 years with upper respiratory tract infection, nocturnal and daytime cough and illness duration of ≤ 7 days were participated.
|Patients were treated with PRH cough syrup (20 mL/day) or carbocysteine based syrup (control, 25 mg/kg/day) in three divided doses for 3 consecutive days.||PRH cough syrup showed more rapid and greater improvement in all clinical cough symptoms measured compared to carbocysteine based syrup.|||
|KalobaTUSS ® pediatric cough syrup |
I. helenium, M. sylvestris, H. stoechas, and P. major)
|Randomized double-blind, placebo-controlled trial, |
106 children with persistent cough are recruited in the study.
|Patients were treated with cough syrup or placebo 4 doses daily, 5 mL each for 8 days.||Cough syrup significantly reduces the severity and duration of cough as compared to placebo.|||
|Herbal triplet |
H. perforatum and
|Multicenter, prospective, observational study, |
115 children aged 6–12 years with history of nervousness and agitation (including agitated depression) due to affective disorders were selected for the study.
|Dry extract of herbal triplet administered in tablet form via oral route, containing V. officinalis (28 mg/tablet), H. perforatum (60 mg/tablet) and P. incarnate (32 mg/tablet). |
Patients were accessed at baseline, after 2 weeks of treatment and then after 4 weeks of treatment.
|Herbal triplet showed a distinct improvement in children with attention problems, social withdrawal, and mood troubles (anxiety and depression).|||
|P. incarnata||Double-blind randomized clinical trial, |
34 children with ADHD were recruited in an 8-week clinical trial.
|Children were treated with P. incarnata (0.04 mg/kg/day) or methylphenidate (control, 1 mg/kg/day) tablets, two times a day. |
The patients were examined at baseline and14, 28, 42, and 56 days after the start of treatment.
|Both groups were clinically effective in the improvement of ADHD. |
However, P. incarnata was inferior to methylphenidate in decreasing anxiety and nervousness.
|Aromatherapy essential oils (M. spicata, |
M. piperita, Z. officinale, and L. angustifolia)
|Pilot randomized controlled trial, |
39 patients with age range of 4–16 years with postoperative nausea and vomiting were selected for the trial.
|Children were treated with a single placebo or aromatherapy.||Non-significant improvement of postoperative nausea and vomiting with aromatherapy. |
Though the preparation has been recommended for large-scale randomized clinical trials.
|Bioactive Food Components||Study Design||Intervention||Main Results||Reference|
|Butyric acid||Case study, |
11-year-old boy with CLD, admitted to hospital because of recurrent abdominal sub-occlusions and chronic watery diarrhea.
|The patient was treated with butyric acid in dose of 50 mg/kg/day administered in 2 doses for 1 week, which increased gradually in increments of 25 mg/kg/day every consecutive week to a maximum dose of 100 mg/kg/day for the next 12 months.||The normalization of stool pattern and serum/fecal electrolytes concentration with 100 mg/kg/day was observed with a dose of 100 mg/kg/day. |
Rectal dialysis showed induced pro-absorptive effects induced by butyrate on Na+, Cl−, and K+ intestinal transport.
|Probiotic supplement||Randomized clinical trial, |
523 children aged 2–6 years attending day care centers were recruited in the study to evaluate the effects of probiotic supplementation in respiratory illnesses.
|Children were supplemented with normal milk or milk containing probiotic Lactobacillus rhamnosus GG on 3 daily meals for 28 days.||The probiotic supplementation showed a reduced occurrence of respiratory illness in children attending daycare centers.|||
|Probiotic complex (L. rhamnosus, |
B. longum, and
|Randomized double-blind controlled clinical trial, |
Children aged 1–23 months hospitalized with acute rotavirus diarrhea were selected for the trial.
|Patients were treated with oral rehydration therapy plus placebo, oral rehydration therapy plus S. boulardii or oral rehydration therapy plus probiotic complex.||Sixty-four cases finished the protocols and were analyzed for results, which showed a significant decrease in median duration of diarrhea, vomiting and fever in probiotics treated groups. |
Effect of probiotics on duration of hospitalization was neutral.
|Probiotic formula |
L. acidophilus, and
|Prospective, open label study, |
30 autistic children aged 5–9 years were selected for the study.
|Children were supplemented with probiotic formula containing 100 × 106 CFU/g of three probiotic strains (L. rhamnosus, L. acidophilus, and B. longum).||q-PCR of stool samples showed an increase in the colony units of Lactobacilli and Bifidobacteria levels, with a significant decrease in body weight and improvement in the severity of autism and GI symptoms, as compared to baseline results.|||
|Glutamine supplementation||Randomized clinical trial, |
critically ill children with age range of 1 month to 14 years that were required parenteral nutrition for at least 5 days were recruited in clinical trial to evaluate the effectiveness of glutamine versus standard parenteral nutrition on HSP 70 and interleukins 6 and 10.
|Children were treated with glutamine (n = 49) or standard parenteral nutrition (n = 49).||Glutamine supplementation maintained high HSP 70 levels for longer time. |
The effect of glutamine was not significant on IL-6 while the effect on IL-10 was neutral.
|Cysteine supplementation||Randomized clinical trial, |
16 edematous malnourished children (age: 6–18 months) were selected for study.
Erythrocyte cysteine and GSH concentrations, and fractional and absolute GSH synthesis rates were measured 3 times after hospital admission, at 2 days (period 1), 11 days, when they were malnourished and infected (period 2), 50 days, when they malnourished but cleared from infection (period 3) and when they recovered.
|Children were supplemented with 0.5 mmol/kg/day N-acetylcysteine (NAC group) or alanine (control group)||The concentration and absolute synthesis of GSH increased significantly from period 1 to period 2 in NAC group.|||
|Vitamin D||Double-blind, randomized clinical trial, |
744 school children were selected for the trial to demonstrate the effectiveness of vitamin D in acute respiratory infections in winter (January–March).
|Children consumed unfortified regular milk (control) or milk fortified with vitamin D3 (300 IU).||The vitamin D level in blood considerably increases in children supplemented with fortified milk (from 7 ng/mL to 19 ng/mL). |
A significantly low rate of acute respiratory infections was found in these children.
|Vitamin D||Randomized controlled trial, |
453 children aged 1–36 months, diagnosed with pneumonia were recruited for the trial.
|A single dose of 100,000 IU Vitamin D3 oral drops (n = 224) or placebo (n = 229) was added to routing treatment of patients.||The risk of a repeat episode of pneumonia in children received vitamin D3 was significantly lower. |
However, no significant difference was seen on the mean number of days to recover between both groups.
|Vitamin D||Randomized clinical trial, |
975 healthy infants aged 2 weeks to 24 months were recruited to compare the effects of standard dose (400 IU/day) versus high dose (1200 IU/day) vitamin D on bone strength and infections.
|Children were randomized to receive standard dose of vitamin D3 (n = 489) or high dose of vitamin D3 (n = 486).||A standard dose of vitamin D3 was found adequate to maintain vitamin D sufficiency in children younger than 2 years, with increased bone strength and reduced rate of infections. A higher dose did not show any additional benefits over standard dose.|||
|Zinc and Iron||Randomized clinical trial, |
680 children (6–12 months age) were recruited to investigate the potential role of Zn and Fe on growth and development.
|Children received daily placebo, Fe (10 mg), Zn (10 mg) or Fe + Zn (10 mg each) for 12 months.||Supplementation with Fe alone improved growth and psychomotor development. |
Zn significantly improved growth.
Combined Fe and Zn supplementation possessed no additional benefits.
|Zinc||Double blind, placebo-controlled, randomized clinical trial, |
179 children aged 3–4 years with watery diarrhea and tested positive for V. cholera were selected for the study.
|Patients were randomly assigned to receive daily dose of 30 mg/day elemental Zn (n = 90) or placebo (n = 89) until recovery. |
Each patient also received erythromycin suspension (12.5 mg/kg) every 6 h for three days.
|Eighty-two patients in each group completed the study. |
Zn supplements showed faster recovery and 12% shorter duration of diarrhea than placebo with 11% less stool output.
|Zinc||Randomized controlled clinical trial, |
103 children younger than 5 years, diagnosed with pneumonia were recruited.
|Children received Zn sulfate (10 mg children younger than 1 year and 20 mg for children older than 1 year of age).||Zn supplementation improved patient’s clinical status, respiratory rate, oxygen saturation, and increased blood levels of IFNγ and IL-2.|||
|Choline-rich structured lipid (LYMX-SORB™ or LXS)||Randomized placebo-controlled trial, |
110 children (age: 5 to 17.9 years) with cystic fibrosis and pancreatic insufficiency were included in the trial.
|Children were treated with LXS, mixed with participant selected foods or beverages for 12 months in a dose range equivalent to a choline concentration of 591–887 mg/day. |
LXS powder comprised of lysophosphatidylcholine, monoglycerides and fatty acids in a molar ratio of 1:4:2.
|The muscle and plasma concentration of choline was increased in LXS-treated group. |
LXS supplementation improved the dietary fat absorption and, nutritional and growth status.
|Choline||Randomized double-blind placebo-controlled clinical trial, |
60 children aged 2.5–5 years with fetal alcohol spectrum disorder were recruited in the trial.
|Children were treated with 500 mg choline or placebo daily for 9 months.||Choline supplementation significantly improved the primary and secondary measures of memory.|||
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