The Journal of Pediatrics
Volume 146, Issue 3 , Pages 311-317, March 2005

Is there clinical evidence supporting the use of botanical dietary supplements in children?

From the Institut fuer Pharmakognosie, Karl-Franzens-Universitaet Graz, Universitaetsplatz 4 A-8010 Graz, Austria; and the Department of Pharmacy Practice and the UIC/NIH Center for Botanical Dietary Supplements Research in Women's Health, College of Pharmacy, University of Illinois at Chicago

Received 12 April 2004; received in revised form 17 August 2004; accepted 4 October 2004.

Article Outline

CAM, Complementary and alternative medicine, DGLA, Dihomo-γ-linoleic acid, EFA, Essential fatty acids, EPO, Evening primrose seed oil, ID, Intellectual deficits, GLA, γ-linoleic acid, PG, Prostaglandin, URI, Upper respiratory tract infection, UTI, Urinary tract infections

 

Consumers in the United States are increasingly using botanical dietary supplements (herbal medicinal products) to treat or prevent a wide array of ailments including the common cold, depression, and other non–life-threatening medical conditions. In a recent survey of women between 40 and 60 years of age it was found that 79% were using botanical dietary supplements, with more than 20% using three or more different botanical supplements.1 Because women make up the largest percentage of botanical users, it is not unexpected that many women also administer herbal remedies to their children. Results from a recent survey of complementary and alternative medicine (CAM) practices have suggested that the use of CAM by parents/caretakers was the single best predictor of CAM use in children.2 In fact, a number of national and international surveys indicate that herbal use in children is on the rise, and it is estimated that 28% to 40% of children may be exposed to herbal preparations for the management of asthma, anxiety, attention deficit hyperactivity disorders, insomnia, and respiratory infections.2, 3 Unfortunately, the administration of herbal products to children often is not discussed with attending pediatricians. This trend presents both interesting opportunities as well as dilemmas for healthcare professionals and parents, as many of these treatments have not been clinically tested for safety and efficacy in pediatric populations.

This purpose of this review is to provide an overview of the medical and scientific information for the most commonly used herbal products (botanical dietary supplements), based on marketing surveys. Retrospective literature searches (1960-2003) were performed for the most commonly used botanicals. The databases searched included PubMed, Napralert, Sci Finder, and Toxline. The review focuses on botanicals for which published clinical studies on safety and efficacy were available, and it includes Andrographis paniculata, cranberry, echinacea, evening primrose oil, garlic, ivy leaf, and valerian. Botanicals such as chamomile, feverfew, ginger, and ginkgo were not included because of the lack of clinical studies in children. In addition, clinical trials evaluating the safety and efficacy of combination products were not included because of the difficulty in determining the efficacy of the individual botanical ingredients.

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Andrographis paniculata 

Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is an annual herbaceous plant, widely found in tropical and subtropical Asia, Southeast Asia, and India.4 The plant is one of the most important medicinal plants used in traditional Chinese and Ayurvedic medicine for the treatment of the common cold, influenza, and other infectious diseases.4 A standardized 60% ethanol extract of the aerial parts of Andrographis has been used extensively in Scandinavia for the past 20 years for the treatment and prevention of the common cold. Numerous human studies have been performed with this extract, including two clinical trials in schoolchildren.4, 5 A randomized, placebo-controlled, double-blind study evaluated a standardized A paniculata extract (4% andrographolides) in the prophylaxis of common colds in 107 schoolchildren (both sexes, mean age 18.4 years) during the winter season.5 The children received 200 mg of the extract or a placebo daily for 3 months and were evaluated weekly by a clinician who diagnosed the presence or absence of common colds. No report on compliance was included in the study. Analysis of the occurrence of colds revealed that there was no difference in the two groups during the first or second months of treatment. However, after the third month of treatment, there was a significant decrease in the occurrence of common colds in the treated group, 30% as compared with 62% in the placebo group (P < .05).5 These data suggest that extracts of A paniculata may have potential for the prevention and treatment of upper respiratory tract infections (URIs) in pediatric populations.5

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Cranberry 

Cranberry, known scientifically as Vaccinium macrocarpon, is a perennial low-lying shrub native to North America. The small, edible red-black berries were used by Native Americans as a food and medicinally as a wound dressing.6 Standardized extracts and other commercial products of cranberry are prepared from the fresh or dried berries. Currently in the United States, more than 52 million households consume cranberry products, in the form of beverages, foods, teas, and in capsule form. Cranberry juice and extracts are currently used for the prevention and symptomatic treatment of urinary tract infections (UTIs).6 More than 25 clinical trials have assessed the effects of cranberry juice in humans, however only two controlled trials have been performed in children with neurogenic bladder.7, 8

A randomized single-blind crossover study assessed the efficacy of 15 mL/kg/day of cranberry cocktail juice (30% concentrate) as prophylaxis for bacterial UTIs in 40 children (1.4-18 years of age) with neurogenic bladder, managed by intermittent catherterization.7 The subjects were treated for 6 months with either cranberry juice or water as control. Outcomes measured were a positive or negative urine culture with symptomatic UTI. UTI was defined as bacteriuria with fever, abdominal pain, change in continence pattern or change in the color or odor of urine. Twenty-one patients completed the study, and 12 dropped out for reasons related to the cranberry (taste, caloric load, and cost), whereas 7 patients dropped out for other reasons. Statistical analysis of the data revealed no difference between intervention periods with respect to infection. The results showed that cranberry was no better than water in preventing UTI. The results of the study were questionable because of the high drop-out rate, as well as the diagnostic criteria for the UTI being much lower than any other trial (103 colony-forming unit [CFU]/L of a pathogenic organism vs 104 CFU/mL). However, the study did not support the use of cranberry juice as prophylaxis for UTI in children with neurogenic bladder.7

The results of the first trial were confirmed in a double-blind, placebo-controlled, crossover study involving 15 children (2-11 years of age) with neurogenic bladder receiving clean intermittent catheterization.8 Two ounces of cranberry concentrate (equal to 300 mL of cranberry juice cocktail) or placebo were administered daily for 3 months, followed by a 3-month crossover (no washout period was described). Weekly home visits were made, during which a sample of bladder urine was obtained by intermittent catheterization. Signs and symptoms of UTI and all medications were recorded, and compliance was assessed. The results showed that during consumption of the cranberry concentrate, the frequency of bacteriuria (defined as ≥104 CFU/mL) remained high. Cultures of 75% (114 of 151) samples obtained during consumption of placebo were positive for a pathogen (≥104 CFU/mL) compared with 75% (120 of 160) samples obtained during consumption of cranberry concentrate. Escherichia coli remained the most common pathogen during placebo and cranberry periods. Three symptomatic infections each occurred during the placebo and cranberry periods. No significant difference in compliance was reported for the treatment versus placebo groups. No significant difference was observed in the acidification of urine in the placebo group versus the cranberry group (median, 5.5 and 6.0, respectively). Thus, cranberry ingestion did not reduce bacteriuria or symptomatic UTI in this population. On the basis of these data, cranberry juice or supplements do not appear to be effective for the prevention and treatment of UTI in children with neurogenic bladder.8

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Echinacea 

“Echinacea” is one of the most commonly used botanical dietary supplements in the United States. The term refers to several plants in the genus Echinacea, derived from the aboveground parts and roots of Echinacea purpurea (L) Moench, E angustifolia DC, and E pallida (Nutt.) Nutt. [Fam. Asteraceae].9 Based on reviews of the recent literature, pharmacological effects have been found in vitro and in vivo for alcoholic tinctures and the expressed juice of the aboveground parts of E purpurea and for alcoholic extracts of the roots of E pallida, E angustifolia, and E purpurea.9, 10 Several clinical studies have examined the usefulness of echinacea products for the prevention and treatment of common colds and acute upper respiratory tract infections (URIs).11, 12, 13 Clinical studies utilizing preparations made from the pressed juice of the flowering aerial parts of E purpurea have been reviewed and indicate that these preparations can diminish the severity and the length of common colds significantly, and suggest that they also can be safely used in children.14

Although echinacea is often administered to children, few randomized controlled clinical trials have assessed the safety and efficacy of this plant in pediatric populations, and many studies were performed 20 to 40 years ago. Götte and Roschke15 investigated the clinical effectiveness of E purpurea pressed juice in an observational study in which 1322 children were enrolled who were suffering from recurring URIs. The effect was measured using a modified Jackson-Score. In the Jackson-Score rating system, cold symptoms are graded from 0 to 3, absent, mild, moderate, or severe, based on eight symptoms: nasal discharge, nasal congestion, sneezing, cough, malaise, throat discomfort, fever/chills, and headache (cumulative score maximum 24). In addition, the physicians and parents of the patients judged the duration of the disease in comparison with previous URIs. At the first sign of a cold, children 2 to 5 years of age were treated with a dose of 2.5 mL three times daily, children 5 to 12 years of age 5 mL two times daily, and children >12 years of age, 5 mL three times daily for a total of 10 days. The results of the study showed the total modified Jackson-Score reduced after 10 days of treatment from 10.7 to 1.8 with 83.6% of the physicians and 84.8% of the parents having judged the effectiveness of echinacea as being “very good” or “good,” respectively. The duration of the disease was judged to be shorter by 62.2% of the physicians, however, there was no placebo comparison. No difficulties with compliance were reported. The tolerability was determined to be very good or good by almost 90% of the physicians. Only 1.4% of the patients reported adverse drug reactions, including itching, rash, and headache.15

A randomized, double-blind, placebo-controlled trial involving 524 healthy children, 2 to 11 years old, assessed the safety and efficacy of an E purpurea product in reducing the duration and/or severity of URI symptoms.16 Study subjects were randomized to receive either a syrup containing Echinacea extract or placebo for up to three URIs over a 4-month period. Children 2 to 5 years of age received 7.5 mL/day during URI, whereas those children 6 to 11 years of age received 10 mL per day during URI. The study medication was begun at the onset of symptoms and continued throughout the URI, for a maximum of 10 days. The primary outcome measures were the duration and severity of symptoms and adverse events recorded by parents. Secondary outcomes included peak severity of symptoms, number of days of peak severity, number of days of fever, and a global assessment of severity of symptoms by parents of study children. Data were analyzed on 707 URIs that occurred in 407 children, including 337 URIs treated with echinacea and 370 with placebo. There were 79 children who completed their study period without having a URI. The median duration of URIs was 9 days (95% confidence interval, 8-10 days). There was no statistically significant difference in duration between URIs treated with echinacea or placebo (P=.89). There also was no difference in the overall estimate of severity of URI symptoms between the two treatment groups (median, 33 in both groups; P=.69). In addition, there were no statistically significant differences between the two groups for peak severity of symptoms (P=.68), number of days of peak symptoms (1.60 in the echinacea group and 1.64 in the placebo group; P=.97), number of days of fever (0.81 in the echinacea group vs 0.64 in the placebo group; P=.09), or parental global assessment of severity of the URI (P=.67). Overall reported compliance with administering the study medication was 80%. Overall, there was no difference in the rate of adverse events reported in the two treatment groups; however, rash occurred during 7.1% of the URIs treated with echinacea and 2.7% of those treated with placebo (P=.008). The study concluded that the E purpurea product, as dosed in this study, was not effective in treating URI symptoms in patients 2 to 11 years of age, and its use was associated with an increased risk of rash.16

Thus, although clinical reports indicate that echinacea is safe for pediatric use, with the exception of increased frequency of rash, there are no placebo-controlled studies supporting its therapeutic efficacy in children. It has been suggested that echinacea should be avoided in patients with autoimmune disease because of the purported immune stimulating effects. However, to date there are no data supporting this recommendation. In addition, the German Commission E recommends a listing of contraindications that include progressive systemic diseases such as tuberculosis, leucosis, collagenosis, multiple sclerosis, AIDS, HIV infection, and other autoimmune diseases. Again, there are no published data to support these contraindications. Rare allergic reactions to echinacea have been reported. These products should not be administered to patients with allergies to members of the Asteraceae (Daisy) family.17

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Evening primrose oil 

The evening primrose (Oenothera biennis) is a native American wildflower, with large, delicate yellow blooms that usually last for only one evening. The seeds of the flower are rich in essential fatty acids (EFAs) including γ-linoleic acid (GLA), an intermediate in the synthesis of prostaglandins (PGs) in humans. Modern uses for evening primrose seed oil (EPO) include the treatment of atopic eczema, cyclic and noncyclical mastalgia, premenstrual syndrome, psoriasis, rheumatoid arthritis, chronic fatigue syndrome, and diabetic neuropathy.6

Seven clinical trials have assessed the safety and efficacy of EPO in pediatric populations.18, 19, 20, 21, 22, 23, 24 Three of these investigations focused primarily on atopic dermatitis, of which two were controlled trials. A double blind, placebo-controlled parallel group trial, involving 58 children assessed the efficacy of EPO for the treatment of atopic dermatitis. The children were treated orally with either placebo or EPO (2-3 g per day) for 16 weeks.24 During the trial, plasma concentrations of EFAs increased significantly in the seed oil–treated group demonstrating compliance. Symptomatic improvements were reported in both groups; however, no significant difference was found between the two treatments.24 In this study, the “placebo” contained sunflower oil, which has a similar spectrum of EFAs as EPO. This may be a limitation of the design of the study.

The second study, a double-blind placebo-controlled clinical trial involving 51 children (mean age 4.2 years) with atopic dermatitis, assessed the effects of two different doses of EPO.22 The children were treated with placebo or 0.5 g/kg/day of seed oil or a combination of 50% placebo and 50% seed oil (0.5g/kg/day) for 16 weeks. Clinical assessment of the severity of the disease was based on 10 clinical features: erythema, scaling, crusting, edema, vesciculation, infection, lichenification, pigmentation, papules, and excoriation. A significant improvement in the overall severity of clinical symptoms was observed in children treated with the seed oil (0.5g/kg/day). The treatment also increased the concentration of n-6 fatty acids in erythrocyte cell membranes, thereby demonstrating compliance to the study medication.22 Thus, based on these trials, EPO may have some benefit for the treatment of atopic dermatitis in children and a dose of 0.5g/kg/day appears to be needed for a clinical response.

Previous research has suggested that altered ratios of EFAs, particularly the omega-6 and omega-3 polyunsaturated fatty acids, may be associated with hyperactivity in some children. The ratio between omega-3 and omega-6 polyunsaturated fatty acids influences various aspects of serotoninergic and catecholaminergic neurotransmission in the brain, as well as a reduction in the production of inflammatory PGs by omega-3 supplements. In addition, a deficiency of GLA has been suggested.20 Thus, EFA supplementation may be a potential treatment for hyperactive children.18

Two clinical studies were conducted to evaluate the efficacy of EPO in children with attention-deficit hyperactivity.18, 20 The first study was a double-blind, placebo-controlled crossover trial involving 31 children with marked attention-deficit and hyperactivity disorder.18 The children were treated with three capsules of an EPO product (each capsule contained 360 mg of linoleic acid and 45 mg of GLA) or matching placebo (liquid paraffin containing no fatty acids) twice daily over a period of 4 weeks. The subjects were tested for cognitive function and motor behavior before treatment, as well as 2 and 4 weeks after treatment. Moreover, blood samples were taken to analyze the changes of EFA levels and to monitor compliance. The EPO supplementation resulted in significantly lower levels of palmitoleic acid and significantly higher concentrations of dihomo-γ-linoleic acid (DGLA) (an EFA found to be deficient in some hyperactive children) indicating compliance with the study medication. Supplementation also was associated with significant (P <.05) changes on two performance tasks and with significant (P <.05) improvement to parent ratings on the subscales designated as Attention Problem and Motor Excess of the Revised Behavior Problem Checklist. However, a variety of eight other psychomotor performance tests and two standardized teacher rating scales failed to indicate other treatment effects. Thus, supplementation with the seed oil produced only minimal or no behavioral improvements in hyperactive children.18

The second study was conducted in a Latin-square double-crossover design with random assignment to sequence.20 Eighteen boys between 6 and 12 years of age, with attention-deficit hyperactivity disorder were treated with EPO or placebo (liquid paraffin) and D-amphetamine or matching placebo daily for 1 month. Every subject took five capsules each morning (one of them was D-amphetamine or matching placebo, the other four were EPO or placebo) and four capsules each afternoon (EPO or placebo). Each EPO capsule contained 500 mg of the oil, which supplied 40 mg of GLA and 350 mg of linoleic acid. Before treatment and every 2 weeks during the study, blind behavioral ratings were conducted. The study continued for 12 weeks with crossover occurring at 4 weeks and 8 weeks. At the end of the study, the teachers' ratings showed a trend of EPO effect between placebo and D-amphetamine. The trend reached significance (P < .05) only for the Conners Hyperactivity Factor. Power analysis of the subject numbers suggested that if the same trend were sustained in an expanded sample size (30 children as opposed to 18) there would be a 50% chance of significance on most of the other outcome measures. Moreover, the authors of the study suggest that there may have been a possible drug interaction between D-amphetamine and seed oil, as there appeared to be an order effect in which administration of D-amphetamine for 1 month before the administration of the EPO appeared to neutralize the oil effect. In 12 subjects who received a dose of the seed oil for 1 month before the course of D-amphetamine, or had these two treatments separated by one month of placebo had better outcomes than those children who received D-amphetamine for the month immediately before EPO, indicating a possible interaction between the two study medications.20 Further clinical trials, using larger sample sizes appear to be warranted. The authors also suggested that a higher dose of EPO (five capsules twice daily) may be necessary as additional data indicated that this higher dose may be optimal.20

EPO supplementation also has been evaluated in diabetic children because diabetes mellitus is known to alter the cellular production of eicosanoids. Elevated levels of prostaglandin (PG)E2 and PGF2 have been implicated in a number of chronic diseases, such as diabetic neuropathy associated with diabetes. One double-blind, placebo-controlled study assessed the effect of EPO on serum EFA and plasma PGE2 and PGF2 concentrations in 11 children with insulin-dependent diabetes mellitus.19 The children received either two capsules of seed oil, each containing 45 mg GLA and 360 mg linolenic acid, or placebo daily for 4 months and then four capsules daily for a further 4-month period. The serum fatty acid, plasma DGLA, PGE2, and PGF2 levels were measured at the beginning, after 4 months, and at the end of the study. The administration of four EPO capsules per day significantly increased the DGLA level and significantly decreased the PGE2 plasma concentrations (P < .01) compared with placebo, but no significant changes in serum linoleic acid could be observed. Neither fatty acid nor PGE2 and PGF2 concentrations were altered after the administration of two capsules daily. Overall, studies in diabetes have shown that the levels and rates of formation of long-chain n-6 polyunsaturated EFAs, such as DGLA, are consistently low in diabetes patients, thus resulting in a reduced formation of PGE1 and higher concentrations of PGE2 and PGF2.19 Higher concentrations of PGE2 and PGF2 may increase the risk of developing the chronic sequelae associated with diabetes. The results of this small study suggest that EPO may cause alterations in EFA and PG metabolism in diabetic children. It remains unknown if EPO supplementation may have a preventive effect on diabetic vascular complications by a mechanism that involves altered EFA and PG metabolism.19

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Garlic 

Garlic, known scientifically as Allium sativum, and also known as “the spice of life,” was one of the earliest documented examples of a food plant also used for the prevention and treatment of disease.6 Although garlic has been used for the treatment of a wide range of medical conditions, it is most commonly linked to the prevention and treatment of hyperlipidemia and coronary heart disease. More than 26 clinical trials and three meta-analyses support the use of garlic and garlic preparations as an adjunctive therapy to dietetic management of hyperlipidemia, and for the prevention of atherosclerotic (age associated) vascular changes in adults.6

Only one study has been performed in a pediatric population to determine whether garlic extract therapy is efficacious and safe in children with familial hyperlipidemia.25 A randomized, double-blind, placebo-controlled clinical trial involving 30 pediatric patients, 8 to 18 years of age, who had familial hyperlipidemia and a minimum fasting total cholesterol level >4.8 mmol/L (>185 mg/dL) assessed the effect of a commercially available garlic extract.25 The patients were treated with the extract at a dose of 300 mg, three times a day, or an identical placebo, for 8 weeks. The main outcomes measured included absolute and relative changes in fasting lipid profile parameters. The groups were equivalent at baseline and compliance was similar in the two groups (P=.45). The results of this trial showed no significant relative attributable effect of garlic extract on fasting total cholesterol (+0.6% [95% confidence interval, −5.8% to +6.9%]) or low-density lipoprotein cholesterol (−0.5% [95% confidence interval, −8.7% to +7.6%]). In addition, no significant effect was observed on the concentrations of high-density lipoprotein, triglycerides, apolipoprotein B-100, lipoprotein (a), fibrinogen, homocysteine, or blood pressure. There was a small effect on apolipoprotein A-I (+10.0% [95% confidence interval, +1.2% to +16.5%]; P=.03). There were no differences in adverse effects between groups. The study concluded that garlic extract therapy has no significant effect on cardiovascular risk factors in pediatric patients with familial hyperlipidemia.25

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Ivy leaf 

Ivy leaf consists of the dried leaf of Hedera helix L. It is native to Europe and northern and central Asia, and it is naturalized to the United States.17 Extracts obtained from the ivy leaves are used for the symptomatic treatment of acute and chronic URIs and coughs.26 According to the German Commission E, suggested doses of the dried herb for oral administration per day are: 0 to 1 year of age: 0.02 to 0.05 g/day; >1 to 4 years of age: 0.05 to 0.15 g/day; >4 to 10 years of age: 0.1 to 0.2 g/day; 10 to 16 years of age: 0.2 to 0.3 g/day.17, 26 Because of the very low, single doses, the use standardized extracts is strongly recommended by the German Commission E.17

A water-ethanol solution of the extract was tested in a randomized, double-blind, placebo-controlled crossover study in 24 children (4-12 years of age) with bronchial asthma.27 The protocol consisted of treatment periods of 3 days alternating with washout periods of 3 to 5 days. The daily dose of ivy extract administered was 35 mg, equivalent to 210 mg of the crude herb. All medications were taken and all measurements were performed at the same time of day. The main test parameter was airway resistance. Secondary parameters were intrathoracic gas volume, residual volume, and several other spirometric parameters. Children treated with the ivy extract showed statistically significant and clinically relevant improvements, especially in airway resistance and intrathoracic gas volume, compared with the placebo-treated controls. The extract produced no adverse effects when taken over a period of 3 to 4 weeks.27

The safety and efficacy of effervescent cough tablets, containing 65 mg of dried ivy leaf extract (herb-to-extract ratio 5-7.5:1) were investigated in a multi-center, prospective, postmarketing surveillance study focusing on patients with chronic bronchitis.28 The study included 1350 male and female patients ≥4 years of age who were treated in one of 135 participating medical practices and who suffered from chronic bronchitis (with or without airway obstruction). During a scheduled observational period of 4 weeks, the patients had to take one or two tablets per day, depending on their age, corresponding to 97.5 or 130 mg of dried ivy leaf extract (about 585-780 mg of drug). Treatment success was assessed by observing the changes in the direct symptoms of chronic bronchitis between the baseline examination and the end of treatment. Safety was evaluated by analyzing adverse events. In comparison with baseline in this uncontrolled study, the following percentages of patients showed improved symptoms or were cured at treatment end: cough 92.2%, expectoration 94.2%, dyspnoea 83.1%, and respiratory pain 86.9%. In each of the four symptoms at least 38% of the initially affected patients were completely free of complaints. Three patients (0.2%) experienced adverse events in which a causal relationship to the drug under investigation could not be excluded, two cases of eructation and one case of nausea.28

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Valerian 

Valeriana officinalis L and other Valeriana species commonly known as valerian are the most well known herbal sedatives, and they are listed in at least 20 different pharmacopoeias worldwide.6 Extracts of valerian root, alone and in combination with other plant extracts, are often used in Europe and other parts of the world as a substitute for the benzodiazepines in the treatment of insomnia and anxiety. To date, approximately 11 clinical trials have evaluated the safety and efficacy of commercial valerian products. Ten of these trials have assessed the effects of valerian extracts in healthy adult volunteers, patients with sleep disorders, and pharmacodynamic studies based on quantitative electroencephalogram analysis.6 Only one small, controlled clinical trial has assessed the effects of a valerian extract (V edulis) in children.29

A randomized, double blind, placebo-controlled crossover trial involving five boys (7 to 14 years of age) with varying intellectual deficits (ID) (IQ <70, along with conditions such as epilepsy, hyperactivity, and attention-deficit disorder) and different primary sleep problems, assessed the effects of valerian as a sleep aid.29 On a scale of 1 to 10, all parents rated their childrens' sleep difficulties as a 10 in severity. Subjects received treatment or placebo for 2 weeks, followed by a 7-day washout period, during which sleep was still monitored. After the washout, the children were administered the alternate treatment for 2 weeks, followed by another monitored 7-day washout period. Parents gave a single nightly dose (20 mg/kg of body weight of the valerian extract or placebo) at least 1 hour before bedtime. An 8-week diary was used to record outcomes including sleep latency (time to fall asleep), time spent awake during the night, and sleep quality. Baseline measurements were performed during a 2-week period before treatment. During the next 2 weeks, the children were randomized to either valerian or placebo. Week 5 was a posttreatment period with continued monitoring. Week 6 and 7 consisted of crossover to the alternative treatment. Week 8 was a posttreatment period with continued sleep monitoring. All monitoring was performed via sleep diaries. Compared with baseline, valerian treatment significantly decreased sleep latency (P=.05) and nocturnal time awake (P=.02) and increased total sleep time (P < .01), with no significant changes observed with placebo. Both treatments caused a significant increase in sleep quality (valerian: P < .01, placebo: P=.04). No adverse effects were reported. The results demonstrate that valerian treatment led to significant reductions in sleep latencies and nocturnal time awake, lengthened total sleep time, and improved sleep quality in children with ID that involved hyperactivity.29 These results, although preliminary, suggest that valerian may be useful in the treatment of intransigent sleep difficulties in children with ID and therefore warrants further investigation.

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Conclusions 

As more and more children are exposed to botanical products, it is important that the safety and efficacy of these treatments be well established in controlled clinical trials. Review of the scientific literature shows that for specific botanical dietary supplements data from recent randomized controlled clinical trials exist for pediatric populations. Some studies suffer from methodological flaws such as small sample size, lack of product quality control, improper placebo, and dose issues. For many agents, when a clinical trial has been done, only a single study is available. Because some studies have demonstrated effectiveness, the use of botanicals for the treatment of specific pediatric disorders, such as attention-deficit with hyperactivity, recurrent URIs, otitis media, and sleep disorders may be at least promising. Further well-designed randomized, controlled clinical trials should be performed to evaluate these therapies.

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 This review was funded by NIH grant P50 AT00155 jointly provided to the UIC/NIH Center for Botanical Dietary Supplements Research by the National Center for Complementary and Alternative Medicine, the Office of Dietary Supplements, the National Institute for General Medical Sciences, the Office for Research on Women's Health.The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

PII: S0022-3476(04)00956-4

doi:10.1016/j.jpeds.2004.10.018

The Journal of Pediatrics
Volume 146, Issue 3 , Pages 311-317, March 2005

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