The use of nutraceutics in children‘s and adolescent’s headache

DOI: https://doi.org/10.1007/s10072-017-2896-7

Abstract-Summary Nutraceutics are the most used non-pharmacological remedies for migraine’s pro- phylaxis in children and adolescents.

There is a lack of official guidelines about use of nutraceuticals in migraine’s prevention in children and adolescent and there are few studies with limited efficacy evidences.

The most used nutraceuticals for adolescent’s and children’s headache prophy- laxis are: magnesium, coenzyme Q10, riboflavin, butterbur, feverfew and melatonin.

Introduction In USA 12% of children and adolescents use CAM and in particular nutraceuticals in most of cases [628].

An Italian study shows CAM use, in prevalence nutraceuticals use, in 76% of

children and adolescents with headache, in large part with self prescription [629].

Pediatricians who have interest on CAM use for an integrative approach on chil- dren diseases and/or who are ready to ask for advice with families choices, should have appropriate information on treatments’ efficacy and safety.

Since in children’s and adolescent’s migraine we expect a placebo efficacy among 10–50% of cases, a suitable comparison’s evaluation between nutraceuticals vs placebo needs RCT studies with a wide number of patient [530].

Magnesium Magnesium’s indication for migraine’s therapy rests on the hypothesis of its role on migraine’s pathogenesis and on evidence indicating its deficiency in a part of adult’s and children’s migraineurs [630].

Attack frequency was reduced by 41.6% in the magnesium group, compared to

only by 15.8% in the placebo group in a RCT vs placebo study [630].

A RCT trial Mg oxide (9 mg/kg tid) vs placebo in 118 migraineurs children and adolescents (3–17 years) showed a limited evidence of efficacy after 4 months treatment.

After 6 weeks therapy there was a statistically significant downward trend in migraine frequency (p = 0.037) and in its severity (p = 0029) in magnesium group but not in the placebo group (p = 086).

The available trial did not tested pre-treatment magnesium level thus avoiding an evaluation of efficacy difference in magnesium- deficient patients vs non defi- cient ones.

Coenzyme Q10 Hershey et al. suggested that Cq10 supplementation might be particularly beneficial in migraine’s treatment, finding a Cq10 deficiency in 32% of adolescents (13.3 ± 3.5 years) with frequent migraine [631, 632].

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A first open label trial after 3 months of Cq10 supplementation (1–3 mg Kg/die) in patients with coenzyme deficiency show Cq10 levels increase with a decrease of migraine frequency (p < 001) and of pediatric migraine disability index (PedMIDAS) (p < 001)(3)(5).

The same group later published a double bind RCT trial evaluating the efficacy of Cq10 (100 mg/daily for 4 months regardless of coenzyme plasmatic level) in 120 children and adolescents (6–17 years) with chronic and episodic migraine [632].

The same authors conclude that children’s and adolescent’s migraine could improve with a standardized multidisciplinary treatment indifferently by the use of Cq10 or placebo.

Riboflavin (B2 vit) The RCT studies did not show differences between riboflavin and placebo in terms of frequency, severity and duration of migraine attacks while the observational one showed a statistically significant decrease on frequency and severity of migraine [632].

An RCT compared riboflavin 200 mg/daily to placebo in 48 children (5–15

years) with migraine.

A second double blind cross-over RCT study compared placebo with 42 patients (6–13 years) with migraine and tension-type headache treated with 16 weeks ribo- flavin (50 mg/daily).

An open label trial evaluate the response to 200–400 mg/daily riboflavin given for 6 months to an heterogeneous group of children and adolescents (7–18 years) affected by headache (migraine with and without aura, frequent tension-type head- ache, basilar migraine and paroxysmal benign vertigo) not responding to pharmaco- logical prophylaxis.

After 3 and 4 months treatment riboflavin efficacy was statistically significant in terms of decrease of frequency and intensity (p < 0.01); otherwise after 6 months there was no difference between group and placebo.

Butterbur The presence in Petasites Hybridus (Phy) of pyrrolizidine alkaloids (PA), which have known hepatotoxic properties, limits the use in children over all [630, 632].

Phy products are available with the recommendation to use only the PA-free

treatments (Petadolex) monitoring liver function during the therapy [630, 632].

A RCT compared placebo and music therapy to Petadolex (50–150 mg) bid given to 63 migraineurs children (8–12 years).All patients received educational advice to deal with migraine.

The authors postulated that both music therapy and Butterbur root extract have

promising properties in children’s migraine prophylaxis [632].

Ginkgolide B There are only open label trial evaluating GB efficacy associated with other ele- ments with anti-migraine proprieties in children and adolescents [630, 632].

An open label trial assessed the efficacy of a 6 months treatment combination of GB (80 mg/d), coenzyme Q10 (20 mg/d), B1 vitamin (6 mg/d) and magnesium (300 mg/d) in 24 children (8–18 years) with migraine.

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Another open label trial compared the same preparation with GB (preparation A) with a complex of Griffonia simplicifolia (5-hydroxytriptophan), l-tryptophan, vita- min PP and vitamin B6 (preparation B) in 374 children with migraine without aura (10.7 ± 1.8 years) [633].

Because of the presence in these products of other anti-migraine components and the lack of study RCT-placebo, we cannot say that GB is effective in isolation in children’s and adolescent’s migraine prophylaxis.

Feverfew The extract from the leaves of Tenacetum Partheniunim (Feverfew) tree contain parthenolides, substances with probably anti-migraine activity [630].

The ANN Guidelines consider feverfew to be possibly effective in adult’s

migraine prevention with level B evidence [630].

Adult’s trial with variable dose of Feverfew showed contradictory evidence of

efficacy [630].

A recent RCT trial in adults treated for migraine with 6.23 mg/tid with Feverfew showed a significant (p = 0.053) decrease of attacks (≥50%) after 3 months therapy when compared with placebo.

Melatonin A recent open label trial tested the efficacy of 3 months Melatonin treatment (0.3 mg/kg/d) in children (10.31 ± 2.39 years) with migraine with and without aura.

Melatonin is commonly used in sleep’s disturbance of children and the lack of night restore is considered a trigger for migraine A RCT study in adults compared melatonin (3 mg), amitriptyline (25 mg) and placebo.

Melatonin and amitriptyline had the same efficacy, with a statistical significance

(p = 0.009) when compared to placebo.

Polyunsatured fatty acid Polyunsatured fatty acid (PUFAs) have anti-vasopressor effects and anti-inflamma- tory properties which should have anti-migraine functions.

A RCT study in adolescents with chronic migraine did not showed significant difference in frequency and severity of migraine when comparing PUFAs and pla- cebo (olive oil) [631].

Conclusions Only 1/3 of migraineurs children and adolescents receive a prophylactic therapy and often the proposed treatment has low demonstration of efficacy [634].

The non pharmacological option of treatments includes behavioral and physical

therapies and nutraceuticals including vitamins, minerals and herbal preparations.

Considering the increase in nutraceuticals use for children’s migraine treatment,

is important to have high- quality evidence supporting their use.

The evaluation of nutraceutical’s efficacy (and of pharmacological treatment in general) is difficult in children and adolescents with migraine because of the high response to placebo in this population.

Migraine’s treatment in children and adolescent should be a “tailor-made” inter- vention with nutraceuticals, other CAM (music therapy, ago puncture…) and/or

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pharmacy resting on a global evaluation and living educational advises to face up migraine and daily stress to maximize the resource change behavior and habits hav- ing a role on migraine genesis.

Acknowledgement A machine generated summary based on the work of Sangermani, R.; Boncimino, A. 2017 in Neurological Sciences.

Comparison of a pediatric practice-based therapy and an interdisciplinary ambulatory treatment in social pediatric centers for migraine in children: a nation-wide randomized- controlled trial in Germany: “moma – modules on migraine activity”