Beneficial Effects of Plant Extracts and Bioactive Food Components in Childhood Supplementation
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
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|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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Ullah, H.; De Filippis, A.; Baldi, A.; Dacrema, M.; Esposito, C.; Garzarella, E.U.; Santarcangelo, C.; Tantipongpiradet, A.; Daglia, M. Beneficial Effects of Plant Extracts and Bioactive Food Components in Childhood Supplementation. Nutrients 2021, 13, 3157. https://doi.org/10.3390/nu13093157
Ullah H, De Filippis A, Baldi A, Dacrema M, Esposito C, Garzarella EU, Santarcangelo C, Tantipongpiradet A, Daglia M. Beneficial Effects of Plant Extracts and Bioactive Food Components in Childhood Supplementation. Nutrients. 2021; 13(9):3157. https://doi.org/10.3390/nu13093157Chicago/Turabian Style
Ullah, Hammad, Anna De Filippis, Alessandra Baldi, Marco Dacrema, Cristina Esposito, Emanuele Ugo Garzarella, Cristina Santarcangelo, Ariyawan Tantipongpiradet, and Maria Daglia. 2021. "Beneficial Effects of Plant Extracts and Bioactive Food Components in Childhood Supplementation" Nutrients 13, no. 9: 3157. https://doi.org/10.3390/nu13093157