Complementary therapies are commonly sought for treatment of pediatric headache by primary care physicians, specialists, and parents alike. Herein, we describe the use of nutraceuticals, manual therapies, and acupuncture for headache treatment. We specifically address safety and efficacy evidence when available for children and teens.
Nutraceuticals
What patients and families need to know
What are nutraceuticals?
Nutraceutical is a word used for supplements that may help a medical symptom or condition. Dietary supplements contain an ingredient already found in the body. Supplements that may help headaches in children include: Riboflavin (B2), Co-enzyme Q10, Magnesium, Omega-3 Polyunsaturated Fatty Acids, Vitamin D, Melatonin, and Folic Acid. These supplements are used as medicine when prescribed to correct a deficiency or as a high-dose treatment. Many of them can also be found in certain foods. Herbal supplements derived from plants that might help headaches include: Feverfew, Butterbur, Capsaicin, Peppermint, and Lavender. You might read about other nutraceuticals being studied to help headaches in children in the future.
Do nutraceuticals work to stop or prevent headache?
The cause of your child’s headache should be diagnosed by a clinician before a supplement is used. Most of the studies looking at supplements for headache are small and in adults with migraine. However, children and teens with different headache types have reported feeling better after trying select supplements. When choosing which treatment, brand, and dose is best for your child, it is important to talk to your child’s clinician. She/he may ask about other symptoms, dietary habits, or sleep patterns. Laboratory testing may be done before suggesting a supplement for your child. When reading about supplements on the internet, search trusted sources (e.g., NIH, FDA, USDA) and avoid those selling products.
Are nutraceuticals safe?
Before buying a supplement, ask your child’s healthcare provider about safe products. You may see supplements advertised as “natural” remedies with no side effects. Just like medicines, supplements can cause side effects and interactions with other medicines. Just like with medicines, supplements cause both known and unknown chemical reactions in the body to occur. Companies do not have to prove a product works or that it is safe in humans before selling it. There have been reports of variable strengths, unidentified ingredients, and contaminants in supplements on the market. There are even concerns with some of the supplements used for headache treatment, so please continue reading for more information.
What a PCP and headache specialist needs to know
Why prescribe nutraceuticals for pediatric headache?
Poor regulation
Why not just provide patients with a list of supplements and let them decide what to purchase? Nutraceuticals are regulated under The Federal Drug Administration’s (FDA’s) Dietary Supplement Health and Education Act (DSHEA) of 1994, which restricts the FDA from evaluating supplements for safety or efficacy prior to being sold. This allows the release of supplements in any combination at any concentration without the efficacy or safety studies in humans required of pharmaceuticals. The FDA is authorized to take supplements off market, if they are misrepresented or unsafe but this must be proven. As a result, there may be many unsafe products on the market today which are falsely advertised or not yet proven harmful.
Shared-decision making
Many of our patients are already using nutraceuticals or other forms of Complementary and Alternative Medicine (CAM) and do not tell us. By prescribing nutraceuticals, providers can direct patients to certified brands with known adherence to good manufacturing practices, accurate ingredients, and in doses shown to provide benefit without inflicting harm. Patients and families may then be more comfortable discussing their use of other CAM treatments allowing for informed discussions and shared decision making.
Limitations of pharmaceuticals
For headache prevention, the available first line pharmaceutical options in children carry the risk of adverse effects and most do not outcompete placebo. For acute treatment of headache in children, there are effective agents such as triptans, acetaminophen, and ibuprofen, but their use is limited due to concerns for developing Medication Overuse Headache (MOH). This leaves several days without treatment options when nutraceuticals may be useful alternatives.
Efficacy, tolerability, mechanisms of action
While nutraceuticals have not been proven efficacious for headache prevention in children, several hold promise in adults, are well-tolerated, and may leverage an already robust placebo response (up to 66.6%) seen in this population. There are several nutraceuticals of interest in pediatric headache. These can be categorized by endogenous dietary supplements and herbal supplements.
Endogenous dietary supplements
The most studied include: Riboflavin (B2), Co-enzyme Q10, and Magnesium.
Riboflavin (B2)
Riboflavin has been assigned Level B (probably effective) rating by the AAN and AHS for headache prevention in adults with five positive studies, including one Class I trial.
There have been four studies examining riboflavin for prevention of pediatric headache. Of the four studies, two were rated Class I trials by AAN/AHS but produced conflicting results. Despite the inability to outcompete placebo in all trials, riboflavin was extremely well tolerated and improvements in headache were observed in all groups. The most common side effect with riboflavin is urine discoloration.
The first double-blinded RCT revealed greater reductions in headache frequency in the placebo group compared to the riboflavin 200 mg group over twelve weeks. To determine if 400 mg of riboflavin would be more efficacious, a comparison trial (200 mg vs 400 mg) was conducted. Both riboflavin groups reported better responses to abortive medication and 2/3 experienced at least a 50% reduction in headache frequency at 4–6-month follow-up with no significant difference between 200 or 400 mg/day dosing, age, or migraine type. The third trial, a randomized double-blind cross over, then examined the efficacy of riboflavin for pediatric headache prevention at a lower dose, 50 mg, resulting in no significant difference from placebo. The most recent study was a double-blinded RCT using 400 mg of riboflavin or placebo in 98 adolescents with headaches for three months. Headache frequency, duration, and disability were all decreased in the second and third months compared to placebo.
The improvements seen with riboflavin supplementation at higher doses could be attributed to correcting underlying deficiency, its ability to provide mitochondrial support, and potential to lower total homocysteine levels. It may also act as a prebiotic promoting the growth of beneficial gut microbes shown to produce antiinflammatory peptides and improve gut barrier function.
Co-enzyme Q10
Co-enzyme Q10 was designated as Level C (possibly effective) for migraine prevention in adults by the AAN and AHS in a 2012 guideline update with one positive Class II study. A 2019 meta-analysis including five studies with 346 patients (226 adult and 120 pediatric) concluded CoQ10 was effective in both decreasing migraine days per month and migraine duration; however, migraine severity and attacks per month was not significantly improved compared to placebo.
There are two studies in children/adolescents with migraine. The first included children with low CoQ10 levels (> 30% of 1550 seen in a pediatric headache center) who were then supplemented 1–3 mg/kg/day of liquid gel for more than two months. Subsequent rises in CoQ10 serum levels were documented and significant improvements in headache frequency and disability were seen with CoQ10 supplementation. A second crossover RCT ( n = 76) supplementing with 100 mg CoQ10 daily reported a placebo response with an early trend towards improvement in the CoQ10 group. All groups improved over time without significant differences at day 224.
Proposed mechanisms of action for Co-enzyme Q10 include correcting deficiency, providing mitochondrial support, stabilizing endothelial function by protecting lipoproteins, and modulating inflammatory pathways. Co-enzyme Q10 may increase energy, so can also cause insomnia as well as stomach upset.
Magnesium
The AAN and AHS found Magnesium to be Level B, probably effective for migraine prevention based on two positive Class II studies while considering one negative Class III study. Since these recommendations, a meta-analysis of RCTs in adults was conducted. Eleven studies (789 participants) examined the effects of oral magnesium for headache prevention and thirteen studies (948 participants) examined IV magnesium for acute treatment of migraine. Oral magnesium was found to significantly reduce migraine intensity and severity when used alone or in combination with other treatments (e.g., flunarizine hydrochloride, venlafaxine, l -carnitine, riboflavin plus feverfew) over 4–12 weeks. The use of IV magnesium for acute treatment was found to significantly improve migraines within 15–45 min, at 120 min, and 24 h when used alone or in combination with metoclopramide, Ozagrel, lidocaine, or potassium aspartate.
There have been three studies in pediatric patients. The first study was a double-blinded RCT in 86 pediatric patients with migraine receiving magnesium oxide at 9 mg elemental mg/kg (divided in three doses with food) based on positive adult trials using 600 mg elemental Mg daily. Over 16 weeks, there was a trend towards headache reduction, fewer headache days, and headache severity with magnesium. The second was a replication series (with subsequent 1-year follow-up) examining the effect of magnesium pidolate (2.25 g) dosed twice daily for two months in nine pediatric patients with tension-type headaches (5 = episodic, 4 = chronic). The authors do not report the dose of elemental magnesium. Eight of the nine patients reported a 50% or more reduction in headache with marked decreases in the use of acute medications sustained at 1-year. The third showed the 400 mg of magnesium salt daily increased efficacy of acute medications ibuprofen and acetaminophen in pediatric patients without concerns for adverse effects over 18-months of treatment.
Proposed mechanisms for magnesium in the treatment of headache were reviewed by Taylor to include: (1) correcting and preventing magnesium depletion, (2) maintaining magnesium and calcium homeostasis, (3) calcium channel blocking effect on vascular smooth muscle, (4) antidepressant and anxiolytic effects. Magnesium can cause diarrhea or abdominal discomfort.
Other dietary supplements being investigated in the treatment of migraine include Omega-3 Polyunsaturated Fatty Acids, Vitamin D3, Melatonin, Other B vitamins (Folic Acid, B12), Other antioxidants (Vitamin E, Vitamin C), and probiotics.
Omega-3 polyunsaturated fatty acids
Omega-3 supplementation was rated a Level U by the AAN and AHS, inadequate or conflicting data to support or refute medication use, based on one Class I study in adults. Adults with migraine were given 3 g of omega-3 twice daily for 4 weeks. The omega-3 group experienced a 55% decrease in headaches, the placebo group 45%, suggesting a robust placebo response. A meta-analysis (including four additional small RCTs) reported omega-3 supplementation may reduce headache duration but concluded that there were no significant reductions in frequency or severity given available data.
Of these RCTs, one was a crossover design conducted in adolescents with recurrent migraines. The treatment group ( n = 14) were given 2 g of fish oil daily for 2 months while the control received olive oil capsules. More than 75% reported benefit, with nearly all participants (91%) stating they would recommend fish oil or olive oil to a relative or friend with headache.
Omega-3 Polyunsaturated Fatty Acids possess antivasopressor effects, ability to decrease the production of leukotrienes and prostaglandins, and are antiinflammatory.
Vitamin D3
There have been two large reviews both concluding vitamin D supplementation may be helpful for reducing headache frequency, especially in patients with migraine and a documented deficiency.
One retrospective pediatric migraine trial compared the effects of vitamin D 2000 iu/day (2 months) then 600–1000 iu/day (6 months) in patients with low baseline 25-OH levels ( n = 42) versus those with normal levels ( n = 50). Patients with a baseline deficiency in vitamin D experienced significant reductions in migraine frequency, duration, and disability.
Vitamin D holds neuroprotective and antioxidant properties while possessing ability to modulate neuronal calcium and mechanism for detoxification. A meta-analysis confirmed serum 25(OH)D is consistently lower in people with migraine than healthy controls suggesting correction of insufficiency or deficiency as a potential mechanism of action.
Melatonin
A review and meta-analysis found that melatonin was effective and safe for migraine prevention in adults based on 3 positives and 1 negative RCT but data in children was limited (1 RCT). Also reviewed were adult comparison trials revealing melatonin was more effective than pizotifen but did not outcompete amitriptyline, sodium valproate, or propranolol.
The RCT in pediatric patients (80 participants) found improvements in 62% of those treated with melatonin (0.3 mg/kg or max 6 mg) and in 82.5% treated with amitriptyline (1 mg/kg/day or max 50 mg) over three months. Both were determined to be effective and safe. While amitriptyline demonstrated superior efficacy, melatonin was better tolerated. An earlier open-label trial of 22 children with tension-type headache reported improvements in headache frequency and duration in 14/21 participants after 3 months of melatonin 3 mg.
Melatonin has been shown to have an analgesic effect of gamma-aminobutyric acid, protect against glutamate toxicity, modulate dopamine and serotonin, possess antiinflammatory properties, anxiolytic effects, and decreases pain peptides. Supplementation may correct an endogenous dysregulation. Melatonin is also used for delayed sleep phase syndrome and insomnia which may worsen headaches in some pediatric patients.
Other B vitamins (folic acid, B6, B12)
There have been a few studies (3) in adults and one in children evaluating supplementation of folic acid, B6, and/or B12 on migraine. The study in children was a small, uncontrolled trial of sixteen patients with documented hyperhomocysteinemia, and a methylenetetrofolate reductase (MTHFR) gene mutation with at least a one-year history of recurrent migraine. After 6 months of supplementation with 5 mg folic acid daily, all sixteen patients had normal plasma homocysteine levels and reported at least a 50% reduction in headache frequency.
The interest in folic acid, vitamin B6, and B12 likely stems from their ability to lower total homocysteine levels. Homocysteine levels have been found to be elevated in people with migraine with aura, particularly those with MTHFR gene mutation. These mutations may disrupt the enzymatic activity of MTHFR which interferes with the remethylation of homocysteine resulting in increased plasma levels. Lower folate levels, elevated homocysteine levels, and MTHFR mutations have also been observed as more common amongst pediatric migraineurs.
Other antioxidants (vitamin E, vitamin C, NAC)
There are four studies in adults examining the efficacy of other antioxidants on migraine prevention in adults. The first was an uncontrolled preliminary study in 12 patients with refractory migraines demonstrating significant reductions in headache frequency, severity, and disability with a combination of pine bark extract (flavonoid) 120 mg, vitamin C 60 mg, and vitamin E 30 IU dosed daily over three months. Sustained benefit and ongoing improvement were later observed at 12-months. Vitamin E may be beneficial for menstrual migraine (1 RCT) while combination N -acetylcysteine 300 mg, vitamin E 125 IU, and vitamin C 250 mg (dosed two capsules twice daily) demonstrated promise in episodic migraine (1 randomized sham-controlled pilot).
Exploring potential benefits from CoQ10 and other antioxidants for migraine treatment is appealing given the established role of oxidative stress, generation of free radicals, and neurogenic inflammation on migraine pathophysiology.
Probiotics
Preliminary evidence (1 positive DBRCT, 1 negative RCT, 2 positive open-label trials) exists for daily supplementation with a diverse probiotic in both episodic and chronic adult migraineurs.
Migraine may lead to a disruption in microflora composition in the gut affecting the gut-brain axis. In turn, alterations in microflora have been shown to alter tryptophan metabolism, immune, and enteroendocrine cells resulting in an increase in peptides (CGRP) and inflammatory cytokines while decreasing serotonin which may trigger migraine. Connections between dysbiosis and migraine could explain the higher prevalence of GI disorder amongst patients with migraine(IBS, IBD, CD, gastroparesis, and HP infections).
Although unclear, proposed mechanisms for the efficacy of probiotic use in migraine include: increase in gastric emptying rate, improving intestinal integrity, and decreasing inflammatory cytokines via suppression of nuclear factor kappa-B pathway.
Herbal supplements
The most studied include: Feverfew and Butterbur.
Feverfew ( Tanacetum parthenium )
The AAN and AHS determined MIG-99 (a CO 2 stabilized extract of feverfew) was probably effective (Level B) for migraine prevention in adults based on one positive Class I, one positive Class II, and one negative Class II trial. This recommendation was continued from the earlier recommendation supported by 2 positive Class II and one negative Class III study. The CHS recommends against the use of feverfew based on poor quality evidence (rated by AAN/AHS as Class I).
The initial Cochrane Review concluded feverfew was ineffective for adult migraine prevention based on five trials with conflicting outcomes and heterogeneous interventions, participants and designs. The review was updated to include the larger positive RCT using MIG-99 (a CO 2 stabilized extract of feverfew) finding there is now low quality evidence to support its use without safety concerns. It is theorized that earlier studies were conflicting due to the instability of feverfew extracts, varying as much as 400% in parthenolide content.
While most studies have examined the use of feverfew for prevention, one RCT found a combination of feverfew and ginger given sublingually may also be effective for acute migraine relief.
In children, an observational study of 91 pediatric patients with migraine or tension-type headaches evaluated the effect of a combination supplement containing Magnesium 169 mg, CoQ10 20 mg, Vitamin B2 48 mg, and Feverfew 150 mg (1,2 mg Parthenolides), and Andrographis paniculata 100 mg. Improvements in headache frequency were observed without safety concerns reported.
While there were no adverse effects linked to feverfew in adult migraine trials, there was a possible “post-feverfew” syndrome observed following withdrawal. Symptoms included: anxiety, nervousness, sleep problems, and musculoskeletal aches/pains.
Proposed mechanisms reviewed by Taylor for feverfew in the treatment of headache include the inhibitions of prostaglandin biosynthesis, Phospholipase A, Nuclear factor kappa B (NF-0B), NO synthesis, and platelet aggregation. It may also increase serotonin release from WBCs and platelets.
Butterbur ( Petasites hybridus )
Petasites was granted a Level A classification and determined to be effective for migraine prevention in adults by the AAN and AHS based on two Class I trials.9 These recommendations were later withdrawn in 2017 given concerns for hepatoxicity with petasites/butterbur products in the United Kingdom. While commercially prepared forms, such as Petadolex, are reportedly free of the hepatotoxic pyrrolizidine alkaloids found in petasites prior to purification, there have still been case reports of transaminitis, so petasites are not currently recommended.
There are two small trials examining the effect of Petasites preparations for headache prevention in children. The first was an open-label trial in 108 children with migraine given the brand supplement Petadolex 25–50 mg 2–3 times daily for 4 months. More than 75% of participants experienced at least a 50% reduction in headaches, while nearly all (91%) reported feeling improvements. The second was a 3-armed RCT comparing music therapy to Petadolex (25–50 mg 2–3 times daily). All groups reported a decrease in headaches. At 12-weeks, music therapy outcompeted placebo then at 6-month follow-up both music therapy and Petadolex surpassed placebo.
The benefits from butterbur in migraine prevention is thought to be attributed to its antiinflammatory properties, ability to regulate calcium channels, and inhibit leukotriene biosynthesis.
Other botanicals of interest include: Capsaicin, Peppermint, Lavender, Boswellia serrata , Andrographis paniculate, and Marijuana.
Capsaicin
Small studies have shown that capsaicin may be helpful in both the prevention and acute treatment of headache disorders in adults. A series of trials demonstrated potential benefit for cluster headache patients with the nasal administration of capsaicin followed by one very small RCT reporting possible benefits with repeated intranasal capsaicin for chronic migraineurs. More recently, a topical formulation capsaicin jelly was shown to reduce scalp tenderness in adult migraineurs.
There are no pediatric studies to date, although one case report exists for migraine relief in an adolescent after ingesting capsaicin containing “chili sauce.” She had previously suffered from 6 months of intense headaches before finding relief with “chili sauce.”
As an agonist of the transient receptor potential vanilloid type 1, Capsaicin induces the release and subsequent inactivation of CGRP and other pain peptides. Desensitization of sensory neurons may lead to a decrease in headache severity.
Peppermint (Mentha × piperita)
There have been small trials supporting the use of topical peppermint preparations for the acute relief of headache. Interest in peppermint for headache relief may have been partly inspired by an early RCT finding a topical peppermint oil preparation (peppermint 10 g plus ethanol 90%) decreased pain sensitivity, improved mood, and promoted relaxation of the temporalis muscle on EMG when applied to the foreheads and temples of thirty-two healthy adult subjects following acute head pain induction. Subsequent trials demonstrated benefit from topical peppermint preparations for the acute treatment of tension-type headache, migraine pain, nausea, photophobia, and phonobia. Intranasal administration of peppermint oil may also be efficacious in migraine rescue.
Oral peppermint may be safe and effective in alleviating symptoms of IBS in children, however there are no trials to date evaluating peppermint for headache relief in children.
Peppermint likely improves tension and migraine headaches given its spasmolytic and analgesic properties achieved via stimulation of cation channels.
Lavender
One trial in adults found that inhalation of lavender essential oil for 15 min at the onset of migraine may be an effective rescue treatment, while another supports consideration of oral lavender essential oil for migraine prevention. Topical administration of lavender oil was found to reduce pain prior to dialysis needle insertion in adults suggesting potential benefit with procedural pain associated with injection headache treatments.
There are no studies in children examining the use of lavender for headache prevention or rescue treatment, although, one study found inhaled lavender decreased the use of analgesics in pediatric patients post-tonsillectomy.
Like peppermint, lavender possesses analgesic and spasmolytic properties which may lead to headache relief. Lavender is also an anxiolytic with sedative effects which may be of additional benefit to those identifying sleep problems or anxiety as potential headache triggers.
Marijuana
While a large body of evidence supports consideration of marijuana for chronic pain, evidence in headaches is limited to mostly retrospective case studies, case series, surveys, and reports. There was one controlled trial examining the use of a synthetic formulation, Nabilone. This was a double-blind RCT with crossover design in 26 patients with MOH refractory to treatment. Nabilone 0.5 mg daily compared to 400 mg ibuprofen daily for 8 weeks with one week washout in between significantly decreased headache pain, medication use, and disability.
The most recent survey collected data from a vast number of adult participants (1019 with migraine and 1876 with other headaches) using Stainprint a free medical cannabis app collecting strains and dosing in addition to headache response. Users reported nearly a 50% reduction in both migraine and other headaches with cannabis. The concentrate was reportedly more effective for headache, while there were no differences pertaining to strain or dose in migraine patients. Tolerance was observed but patients appeared to self-titrate with no concerns for MOH detected in either group. Another survey based study of 445 headache patients identified the top 15 preferred strains using data from ID Migraine questionnaire. All preferred strains were hybrid, most being high THC: low CBD.
While young adults using cannabis have reported self-medicating for pain, anxiety, or depression, there is only one pediatric case study reporting the effects of dronabinol on two adolescents with refractory depression and neuropathic pain. Only one of the participants endorsed a decrease in pain severity, but both noted improvements in pain perception, mood, sleep, academic performance, relationship, and activities of daily life with dronabinol.
Marijuana contains a variety of active compounds. While the cannabinoids CBD and THC have been the most studied to date, the plant contains hundreds of phytochemicals including cannabinoids, terpenes, terpenoids, flavonoids, and many other compounds. Mechanisms proposed for headache relief are believed to be complex and dependent on the constitution of the strain since these phytochemicals vary in ratios from strain to strain producing a wide variety of effects. Cannabinoids alone modulate inflammation and pain pathways extensively by binding to cannabinoid receptors located along the pain pathway and in immune cells influencing releases of cytokines, chemokines, glutamate, 5-hydroxytryptamine (5-HT) (serotonin), acetylcholine, gamma-aminobutyric acid (GABA), noradrenaline, dopamine, d -aspartate, and cholecystokinin receptors while also acting at serotonin, opioid, and NMDA receptors (see review by Baron 2018).
While there is the potential for benefit from marijuana, or specifically CBD and THC, there are also potential risks. Marijuana has been associated with prolonged vomiting, psychosis, and cognitive changes amongst other problems. The long-term side effects of marijuana use in children and teens are not known.
Boswellia serrata , Andrographis paniculate , basil essential oil, Homeopathy
Small adult trials exist for Boswellia serrata , Andrographis paniculate, Basil essential oil, and homeopathy in the prevention of headaches. Since nearly 200 medicinal plants have been documented for use in headaches dating back to the 6th century, it is likely that nutraceuticals will continue to be investigated for headache management in years to come.
When and how to prescribe nutraceuticals for pediatric headache?
Primary headaches
The use of nutraceuticals in pediatric headache assumes that diagnostic work-up is complete and that secondary causes of headache have been excluded ( Table 1 ).
| Nutraceutical | Laboratory Data | Sources | Adverse effects reported in pediatric headache trials | Other possible adverse effects |
|---|---|---|---|---|
| Magnesium | Magnesium, RBC Ionized magnesium Magnesium, plasma Tolerance test, urine | Almonds, spinach Cashews | Diarrhea or soft stools (58) Unpleasant taste None reported | Nausea, abdominal cramping Toxicity (> 5000 mg/d) Avoid in pregnancy (fetal skeletal abnormalities) Avoid in renal failure (inability to remove Mg) Medication Interactions: fluoroquinolones, tetracyclines, bisphosphonates, diuretics, proton pump inhibitors |
| CoQ10 (Ubiquinol, Ubiquinone) | CoQ10, plasma CoQ10/cholesterol ratio b, | Meat, poultry, fish Nuts | None reported | Insomnia, digestive upset May make warfarin less effective May interact with insulin and cancer treatments |
| Vitamin D | Serum 25(OH)D levels (ng/mL) Calcium, phosphorus alkaline phosphatase, parathormone | Fatty fish (cod liver, trout, salmon), sun exposed mushrooms Sun exposure | None reported | Hypercalcemia (rare) Long term toxicity may be possible > 10,000 IU daily or 25(OH)D > 50–60 ng/mL Medication interactions: orlistat, statins, steroids, thiazide diuretics |
| Melatonin | Prolactin | Darkness | Daytime sleepiness (3) (1) | Nocturia, headache, dizziness, agitation, nausea Avoid long term use in children Monitor for changes in menstrual cycles or delays in puberty May worsen or improve seizures May increase effects of warfarin |
| Riboflavin | Erythrocyte glutathione reductase activity coefficient (EGRAC) | Beef liver, oats Cereals, yogurt Milk, clams, beef | Diarrhea (12), Polyuria (18) Vomiting (1),Appetite increase (1) None reported Bright yellow/orange urine | No known medication interactions No known adverse effects from 400 mg/day for 3 months |
| B6 | Pyridoxal 5′ phosphate (PLP) B6, RBC B6, plasma | Chickpeas, beef liver, tuna, salmon, chicken | N/A | Toxicity (1-6 g for 1–3 years) may cause neuropathy, skin lesions, photosensitivity, nausea, and heartburn Neuropathy reported in doses < 500 mg/d Medication Interactions: antiepileptics, theophylline, cycloserine |
| B12 | B12, plasma Methylmalonic acid | Clams, beef liver, trout, salmon, tuna, nutritional yeast, haddock, beef, milk, yogurt, cheese | N/A | No known adverse effects B-vitamins are Possibly carcinogenic especially with long-term use Medication interactions: Chloramphenicol, Proton pump inhibitors, H2 receptor antagonists, and metformin may all interfere with B12 absorption |
| Folic acid | Folate, RBC Folate, plasma | Beef liver, spinach, black-eyed peas | None reported | May mask B12 deficiency by correcting anemia High doses may accelerate preneoplastic lesions High doses (> 1000 μg/d) may impair cognitive development when taken periconception Medication interactions: methotrexate, antiepileptic, sulfasalazine |
| Omega 3 | Omega-3 Index (% in RBC) a Omega Check a Omega-3 and -6, plasma a | Salmon, fatty fish | None reported | Unpleasant taste, bad breath, heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, odoriferous sweat May decrease immune response at high doses Antiplatelet effects are possible with high doses Medication interactions: Anticoagulants |
| Probiotics | None a | Yogurt, kimchi, kombucha, sauerkraut, miso, pickles, apple cider vinegar, and other fermented foods | N/A | Flatulence Some strains (unlikely lactobacillus or bifidobacterium) may increase opportunistic infection (review strain/indication especially immunocompromised individuals) |
| Vitamin C | Vitamin C, plasma | Citrus fruits, broccoli, strawberries, Brussel sprouts, tomato, melon, cabbage, cauliflower | N/A | GI upset (diarrhea, nausea, abdominal cramps) Conflicting evidence for increasing risk for kidney stones, cardiovascular mortality, cancer under certain conditions, B12/copper deficiency, erosion of enamel, or allergic responses Medication interactions: Chemotherapy, statins |
| Vitamin E | Vitamin E (alpha-tocopherol), plasma | Wheat germ oil, sunflower seeds, almonds, sunflower oil, safflower oil, hazelnuts | N/A | Antiplatelet at high doses, hemorrhagic effects Increased risk of prostate cancer unclear Increased morality risk unclear with > 150 iu in combination with other supplements Medication Interactions: anticoagulants, antiplatelets, chemotherapy, statins |
| Feverfew Tenacetum Partheniunim | None | N/A | N/A | Nausea, bloating, digestive problems Withdrawal (pain, anxiety, insomnia) Avoid in pregnancy (uterine contractions) Avoid if tree allergies |
| Butterbur Petasites (Petadolex) | Liver function tests | N/A | GI upset, bitter taste, dermal/allergic, dizziness, fatigue, pain, asthma flares (similar to placebo) Burping (4), nausea (1), abdominal pain (1) | Transaminitis Belching, headache, itchy eyes, diarrhea, breathing difficulties, fatigue, upset stomach, and drowsiness. Avoid in pregnancy Avoid if plant allergies (ragweed, chrysanthemums, marigolds, and daisies) |
| Capsaicin | None | Chili peppers (powders, sauces, etc.) | N/A | Burning and rhinorrhea with nasal formulation Heat, ache, itching, dislike of odor |
| Lavender | None | Herb source (used in drinks or cooking), lavender tea or water | N/A | Gynecomastia (dose-dependent) Contact dermatitis |
| Peppermint | None | Herb source (used in drinks or cooking), peppermint tea or water | N/A | Allergic reactions Heartburn (avoid in patients with reflux) Expected burning sensation (use in small amounts) |
| Marijuana (THC, CBD, terpenes, flavonoids, other compounds) | Liver function tests | THC, CBD – Hempseeds, hempseed oil Terpenes—wide variety of herbs (cooking and medicinal), spices, fruits, vegetables, hops Flavenoids—many fruits and vegetables | N/A | Avoid in pregnancy (low birth weight) Increased risk for motor vehicle accidents and other injuries Craving, withdrawal, lack of control, negative impact on work/family responsibilities Orthostatic hypotension, worsening psychiatric symptoms Lung injuries when smoked CBD only—diarrhea, fatigue, transaminitis |
a May only be available through specialty labs.
b Obtaining Serum Coq10/cholesterol ratio may be preferred because coq10 levels may be artificially increased due to cholesterol (19,20).
Disability
While pediatric data for pharmaceutical preventive treatments is conflicting, the AAN and AHS 2019 practice guideline update assigned level B recommendations to discuss pharmaceutical options with patients and families when PedMIDAS score is > 30 and/or headaches are frequent and to engage in shared decision making.
Nutraceuticals may be more appropriately presented as complementary treatment when disability is moderate to severe and a monotherapy option if disability is low, pharmaceutical agents were not tolerated or ineffective.
Offer an individualized approach
Coexisting symptoms, medications, diet, and lifestyle should be assessed and considered. Like pharmaceutical agents, there are secondary benefits with select nutraceuticals. Certain medications, dietary habits, lifestyle, or genetic mutations may predispose one to a deficiency. While laboratory data exists for many of these endogenous therapies, they should be ordered and interpreted with caution given the variabilities (biologic and analytic), potential for recent dietary influences and costs associated with serial testing. Patients should be directed to avoid taking supplements or making changes in diet for one week prior to lab testing. If labs are inconsistent or unavailable, it is reasonable to rely on clinical responsiveness.
Quality
If prescription grade supplements are unavailable, nutraceuticals labels should be assessed for disclosure statements in addition to seals or notations representing degrees of voluntary paid regulation by third parties (e.g., National Nutritional Foods Association (NNFA)) GMP confirms the facility complies with manufacturing procedures. NNFA TruLabel certifies product quantity and freedom from contaminants. NSF International and U.S. Pharmacopeia (USP) seals verify good manufacturing practices in addition to accuracy of contents, quantity, and freedom of contaminants. Consumer Labs (CL) further assesses products for bioavailability. Labdoor adds a quality score considering safety and efficacy data. Some companies attest to internal product testing.
Dose and duration
Dosing should be guided by age, weight, patient history, safety, and efficacy data (see Table 2 ). Weekly titrations may prevent adverse effects. As with pharmaceuticals, benefits from nutraceuticals may not be achieved for three months or longer. The long-term use of nutraceuticals should be avoided due to lack of long-term safety data. Consider switching to dietary sources when available by encouraging a diverse diet in whole foods.
| Nutraceutical | Formulations/sources | Dosing (Children < 12yo) | Adult dosing | Prescribing notes |
|---|---|---|---|---|
| Magnesium (Mg) Salt | Tablets, capsule, or powder Oxide, pidolate, Citrate, Trimagnesium dicitrate, 2-propylvalerate, aspartate, sulfate Others: Malate, Gluconate, Taurate, Glycinate, etc. | 9 mg/kg/day (bid) | 102–800 mg (divided 1–3 times daily) | Titrate as tolerated Oxide used to treat constipation, inexpensive Citrate is better absorbed, inexpensive Glycinate if diarrhea Chelated forms better tolerated Adults may tolerate up to 400 mg tid |
| CoQ10 (Ubiquinol, Ubiquinone) | Liquid gel capsules 100 mg chewable tablets 100 mg liquid melt, liquid | 1–3 mg/kg/day 100 mg/day | 100–400 mg/day | Liquid best absorbed Frequent dosing may be more effective |
| Vitamin D | Ergocalciferol (vitamin D2) or Cholecalciferol (vitamin D3) 50,000 IU capsule (prescription) Tablet, capsule, liquid, or dissolvable (400, 1000, 2000, 5000 and 10,000) | 400–5000 IU/day | 50,000 IU weekly for 12 weeks or 800–5000 IU daily | Consider maintenance dosing once deficiency corrected vitamin D3 may be better absorbed |
| Melatonin | Tablet, capsules, liquid, or dissolvable (0.3, 0.5, 1, 3, 5 mg), immediate or extended release | 0.3 mg/kg, (up to 6 mg) | 3–10 mg HS | Lower doses may be more effective for insomnia Higher doses may be more effective for anxiety Take 1–2 h HS |
| Riboflavin (B2) | Tablet or capsule (25, 50, 100, 200, or 400 mg) | 200–400 mg/day | 400 mg daily | Water soluble, split dose Take with food |
| B6 B12 plus B6 plus folic acid Folic acid | Tablet (sublingual, chewable), capsule, liquid dissolvable Tablet or capsule Tablet or capsule | N/A N/A 5 mg/day | 80 mg daily 400 μg (B12), 25 mg (B6), 2 mg/day (folic acid) 2 mg/day | Water soluble, split dose Take with food Take with food |
| Omega 3 | Capsules, liquid | 1–2 g/day | 1–6 g/day | Confirm Omega 3 contains both eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) |
| Probiotics | Capsules, powders, liquids | N/A | 2 × 10 9 CFU/day | CFU count should be listed as by expiration date vs time of packaging Contains prebiotics (inulin and other fructo-oligosaccharides) |
| Vitamin E | Tablets, capsules | N/A | 400–500 iu/day | Take with food |
| N -acetylcysteine + Vitamin E + Vitamin C | Capsules | N/A | NEC (NAc 600 mg) bid Vitamin E 250 iu bid Vitamin C 500 mg bid | Take with food |
| Feverfew Tenacetum Partheniunim | Capsules, liquid extract | N/A | 6.25 mg tid | CO2 stabilized formula Monitor for allergic reaction |
| Butterbur Petasites | Petadolex 25 mg capsules | 25–75 mg bid | 50–75 mg bid | Needs to be PA free Monitor for allergic reaction |
| Capcaisin | Intranasal, topical | N/A | Intranasal 300 μL/100 μL suspension daily via pipette in one or both nostrils for 5–7 days or as tolerated or 100 μL of a 10 − 2 M solution 3% camphor in 0.025% applied via cotton tip one-half inch up the nostril ipsilateral to headache bid for 7 days Topical 1 g tid (0.05%) or 0.05–0.10 mL 0.1% to each temporal artery for 30 min | N/A |
| Lavender | Liquid, capsules, aromatherapy, topical | N/A | PO 10 drops of extract into water (1 mL from 100 g dried plant in ethanol/water 80/20) nightly Aromatherapy 15 min at onset of headache | If PO, use ingestible grade essential oil Monitor for allergic reaction Oral was standardized linalyl acetate (0.6%) and linalool (0.4%) |
| Peppermint Menthol (33%–60% peppermint) | Liquid, capsules, aromatherapy, topical | N/A | Apply 1 mL of topical solution (peppermint or menthol 10% in ethanol preparation) to forehead/temples for 3 min at onset, 15 min, 30 min | If PO, use ingestible grade essential oil Monitor for allergic reaction |
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
