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Migraine and Cluster Headaches Treatment Recommendations

This Migraine and Cluster Headaches Treatment Recommendations is provided as information for patients of HealthMasters Naturopath Kevin Tresize ND as part of a treatment plan to assist patients with understanding of their treatment plan and should not be substituted for medical advice, diagnosis or treatment. It is important to note that this is a summary only and is intended to assist discussion between practitioner and patient as part of consultations. This Migraine and Cluster Headaches Treatment Recommendations may be changed to suit the individual requirements of the patient and should not be substituted for medical advice, diagnosis or treatment.

HealthMasters Naturopath Kevin Tresize ND



Treatment Recommendations

1.0 Core Recommendations – Acute management

 

1.1 High Potency Anti-Inflammatory Herbs

Dosage: Take 1 tablet every 2 hours (up to 6 tablets daily).

A combination of BCM-95 Turmeric, BosPure Boswellia, ginger and quercetin to reduce acute increases in inflammatory cytokines and oxidative stress markers associated with migraine and CH symptoms.

Mechanism of Action/Clinical Research:

  • Curcumin has broad anti-inflammatory effects, decreasing many inflammatory mediators including phospholipase, lipoxygenase (LOX), cyclooxygenase–2 (COX-2), leukotrienes (LTs), thromboxane, prostaglandins (PGs), nitric oxide (NO), collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, interferon-inducible protein, tumor necrosis factor- alpha (TNF-α), and interleukin-12 (IL-12).[78],[79]
    • Research in humans has shown 900 mg/d of curcuminoid supplements to significantly reduce levels of CGRP and substance P over eight weeks.[80]
    • Boswellia exerts anti-inflammatory activity further up the inflammatory cascade, inhibiting the activation of pro-inflammatory signalling pathway, nuclear factor kappa B (NFĸB).[81]
    • Ginger constituents, gingerol and gingerdione, have been shown to down-regulate arachidonic acid metabolism via partial inhibition of 5-LOX.[82] Ginger also inhibits NFĸB activation via suppressing the phosphorylation of protein, inhibitor of ĸB (IĸB), thereby keeping NFĸB sequestered and reducing inflammation.[83]
      • Gingerol has further been shown to inhibit the release of substance P levels in animal models.[84]
      • In vitro research has demonstrated quercetin to inhibit mast cell activation and subsequent release of inflammatory mediators including histamine, tryptase, IL-6 and IL-8.[85]

 

1.2 Highly Bioavailable Palmitoylethanolamide (PEA) With Endocannabinoid Action

Dosage: Take 1 capsule twice daily.

Highly bioavailable PEA, providing endocannabinoid-like actions to support pain relief in patients with chronic headache and migraine symptoms.

Mechanism of Action/Clinical Research:

  • In 20 migraine patients, 1,200 mg/day of ultramicronised PEA in combination with non-steroidal anti-inflammatory drugs (NSAID) resulted in statistically significant pain relief after 60 days compared to 20 patients receiving standalone NSAID treatment.[86]
    • PEA reduced the number of attacks per month and the intensity of pain. Patients taking PEA were also able to reduce their intake of NSAIDs.[87]
  • PEA down-regulates mast cell hyperactivity and the release of inflammatory cytokines that can activate the trigeminal nerve, contributing to the neuroinflammatory cascade and migraines.[88]

 

1.3 Highly Bioavailable PEA and Magnesium for Neuromuscular Support and Pain

Dosage: Add 1 level scoop (5 g) to 200 mL of water twice daily, with food.

A combination of PEA and Meta Mag® Magnesium bisglycinate with anti-inflammatory, glutamate-blocking and endocannabinoid-like actions to reduce pain signaling associated with chronic headaches and migraines.

Mechanism of Action/Clinical Research:

  • Low magnesium levels increase pain signalling[89] and are associated with raised substance P and CGRP activity.[90],[91]
  • Replete magnesium levels reduce pain signaling via inhibition of the NMDA receptor and limit excitatory neurotransmission.[92]
  • 600 mg/d of magnesium reduces the frequency and severity of migraine attacks in adults over 12 weeks.
    • Shown to reduce migraine frequency by 33% compared to 16% in the placebo group (p<0.005), and reduce intensity by 47% compared to 0% in the placebo group (p<0.001).[93]
    • After nine weeks, magnesium treatment led to a 41.6% reduction in migraine frequency compared to a 15.8% reduction in the placebo group (p<0.05). The magnesium group also reported significantly fewer days with migraines and reduced use of pharmaceutical relief (p<0.025).[94]
  • PEA reduces mast cell activation and the release of inflammatory cytokines that can activate the trigeminal nerve, contributing to the neuroinflammatory cascade and migraines.[95],[96]
    • 1,200 mg/day of PEA in combination with NSAIDs resulted in statistically significant pain relief after 60 days compared to NSAIDs alone, and significantly reduced number of migraine attacks per month (p<0.0002).[97]

 

1.4 Gamma-Aminobutyric Acid (GABA) 

Dosage: Take 250 mg – 500 mg twice daily.

GABA functions as a primary inhibitory neurotransmitter in the CNS, reducing neuronal hyperexcitation that contributes to increased pain sensitivity.

Mechanism of Action/Clinical Research:

  • GABA down-regulates neural excitability to reduce pain perception.[98] GABA neurons and receptors, found in supraspinal sites, regulate sensory information processing in the spinal cord, subsequently altering pain perception in response to painful stimuli.[99]
  • GABA regulates neuronal excitability by binding to GABA receptor subunits, which are classified into three main groups (alpha, beta and gamma).[100]

 

OR

 

1.5 Herbal Support for Hyper HPA and Stress

Dosage: Take 1-2 tablet three times daily.

A combination of ziziphus, passionflower, kudzu and magnolia to support a healthy stress response and enhance GABA activity in the brain, alleviating anxiety and nervous tension associated with stress, as well as reducing pain sensitivity.

Mechanism of Action/Clinical Research:

  • Zizyphus has been shown to modify the GABAα receptor subunits expressional levels,[101] which opposes glutamate-mediated excitability in the brain, contributing to its pain-desensitising effects.[102]
  • Passionflower has been found to modulate the GABA system, demonstrating an affinity for both GABAα and GABAβ receptors, increasing its inhibitory effects.[103]
    • A clinical trial involving 154 participants with prolonged nervous tension were treated with 1,020 mg/d of passionflower for 12 weeks. Passionflower significantly improved stress-associated symptoms including restlessness, sleep disturbances, exhaustion, anxiety, poor concentration, nausea, tremors, and palpitations.[104]
  • Kudzu has demonstrated β-adrenoceptor blocking activity[105],[106] similar to pharmacological beta-blockers, which are used to reduce the physical effects of anxiety and stress such as palpitations, high blood pressure, tremor, and sweating.
  • Magnolia exhibits muscle relaxing effects via GABAergic mechanisms,[107] as well as neuroprotective properties.[108],[109]

 

2.0 Core Recommendations – Preventative support

Continue to attenuate excessive pain sensitisation and reduce the frequency of migraines and CH.

 

2.1 Highly Bioavailable Palmitoylethanolamide (PEA) With Endocannabinoid Action

Dosage: Take 1 capsule twice daily.

 For information see 1.2 above.

 

2.2 Highly Bioavailable PEA and Magnesium for Neuromuscular Support and Pain

Dosage: Add 1 level scoop (5 g) to 200 mL of water twice daily, with food.

 For informations see 1.3 above.

 

PLUS

 

2.3 Enhanced Bioavailability Ubiquinol for Energy and Cardiovascular Health

Dosage: Take 1 capsule daily with food.

Active ubiquinol (CoQ10) to support mitochondrial respiration and ATP production required for cellular energy and maintenance of neuronal energy reserves, which are inversely associated with headache and migraine severity.

Mechanism of Action/Clinical Research:

  • CoQ10 participates in redox reactions within the electron transport chain,[110] which occurs in the mitochondria to produce ATP.[111]
    • In a study of 45 women with headaches and migraines, significant improvement was found in patients taking 400 mg/d of CoQ10 (n=23) versus placebo (n=17), including reduced frequency, duration and severity of migraines, as well as reducing levels of inflammatory mediators, TNF-a and CGRP.[112]
    • In 80 migraine patients taking preventative drugs, 100 mg/d of CoQ10 reduced the number and severity of migraines over three months compared to prophylactic drugs alone. Additionally, symptoms of nausea, photophobia and phonophobia were also reduced in the treatment group.[113]
    • A recent meta-analysis of five studies has found that 100 mg/d to 150 mg/d of CoQ10 was more effective than placebo in reducing migraine days/month and migraine duration.[114]

 

If vitamin D levels are <75 nmol/L:

2.4 Vitamin D3

Dosage: Take 1-4 capsules or 1/4-1ml daily with food.

Vitamin D to attenuate deficiency, which has been associated with migraine and headache frequency and severity.

Mechanism of Action/Clinical Research:

  • Serum vitamin D level between 50 ng/mL and 100 ng/mL has been associated with 80% lower odds of migraine headache, compared to serum levels below 20 ng/mL.[115]
  • Migraine sufferers have been shown to have significantly lower vitamin D levels compared to healthy subjects.[116]
    • One clinical study showed that 60% of a group of 60 migraine sufferers were deficient in vitamin D versus 13% in a control of 30 individuals. While 43% of the control group had adequate serum levels of vitamin D compared to 6.7% of the migraine group.[117]
    • In a retrospective observational study conducted in 157 patients, 94.9% migraineurs had vitamin D insufficiency (less than or equal to 20 ng/L 25(OH)D).[118]

 

2.5 High Purity, Low Reflux, Concentrated Fish Oil Liquid or Capsules

Dosage: 4.2 mL (1 tsp) daily or 2 capsules twice daily.

Omega-3 essential fatty acids (EFAs) to reduce the production of inflammatory cytokines and neuroinflammatory cascades that cause headaches and migraines symptoms.

Mechanism of Action/Clinical Research:

  • Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulate the production of eicosanoids, cytokines and other factors such as peroxisome proliferator-activated receptors (PPARs), which regulate the inflammatory response.[119],[120],[121]
    • In a study of 51 chronic migraine sufferers who were also on prophylactic amitriptyline (tricyclic antidepressant), 1.5 g/d of fish oil containing 800 mg EPA and 700 mg DHA, taken for 60 days, resulted in an 80% reduction in the number of headache days per month.[122]

 

3.0 Additional Considerations

If patients present with low mood or depression:

3.1 BCM-95 Turmeric & Saffron for Depression

Dosage: Take 1 capsule twice daily with food.

BCM-95 Turmeric and saffron to modulate HPA axis activity and preventing stress-induced elevation of cortisol, glutamate excitotoxicity and subsequent volumetric changes within the brain, which can contribute to depression in patients who experience chronic migraines.[123]

Mechanism of Action/Clinical Research:

  • Both saffron and turmeric  have been found to inhibit the activity of transcription factors, NFκB and mitogen activated protein kinase (MAPK).[124],[125] Saffron and turmeric also inhibit pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, all of which can affect neurotransmitter metabolism.
    • A randomised, double-blind, placebo-controlled study involving 123 participants prescribed 500 mg/d of BCM-95 Turmeric combined with 30 mg/d of saffron revealed significant reductions in depression and anxiety symptoms after 12 weeks.[126]
    • Safranal and crocin, present in saffron, have been shown to reduce HPA axis activity and decrease stress-induced plasma corticosterone levels.[127] Safranal has also been shown to have anxiolytic and sedative effects via innervation of the GABAergic pathway.[128]
    • Turmeric activates glutamate decarboxylase, which converts glutamate to GABA.[129]

 

If presenting with raised Hcy levels or MTHFR gene  mutations:

3.2 B12/Folate (5-MTHF) for Cellular Health

Dosage: Take 1 capsule daily with food.

Provides methylation cofactors including folate, vitamin B12, serine and vitamin B2 to support healthy Hcy metabolism, which is associated with enhanced patient outcomes for chronic headaches and migraines.

Mechanism of Action/Clinical Research:

  • Genetic polymorphisms have been associated with an increased prevalence of migraine, including MTHFR enzyme, which converts folate to its active form and promotes healthy homocysteine metabolism.[130] Elevated serum levels of homocysteine have been found to be elevated in migraine sufferers.[131]
    • In a study comparing 70 migraineurs with 70 healthy controls, serum vitamin B12 levels were significantly lower in those experiencing migraines. The highest B12 quartile had 80% less odds of having migraines.[132]
    • A 2020 review concluded that supplementation of vitamins B6, B12 and folate had a prophylactic effect in patients with migraine with aura.[133]
    • Six months of daily supplementation with 2 mg folic acid, 25 mg vitamin B6 and 400 µg B12 in 52 migraine with aura patients reduced homocysteine levels, migraine frequency and subjective pain severity, with a greater response in those with C677T genotype.[134]

 

If presenting with metabolic dysfunction:

3.3 Cocoa, Cinnamon and Chromium for Metabolic Syndrome

Dosage: To support healthy blood glucose and emotional wellbeing, take 1 tablet twice daily with food.

A combination of cocoa, cinnamon, gymnema, zinc and chromium to stimulate insulin secretion and stabilise metabolic health to support the management of headache and migraine symptoms associated with metabolic dysfunction.

Mechanism of Action/Clinical Research:

  • Cocoa polyphenols may assist in the maintenance of cellular redox states in pancreatic β-cell lines, thereby exerting a protective influence against β-cell dysfunction.[135]
    • Cocoa polyphenols, cinnamon,[136] chromium[137] and gymnema[138] may reduce fasting glucose and facilitate glucose uptake, in addition to down-regulating markers correlated with diminished glucose transport.
    • A randomised clinical trial in 66 subjects with type 2 diabetes given 4.8 g/d of cinnamon found significant reductions in fasting glucose and HbA1c after 12 weeks of treatment.[139]

 

If presenting with chronic sleep disorders such as insomnia or sleep apnoea:

3.4 Magnesium with Lutein and Zeaxanthin for Sleep Pattern Support

Dosage: Add 1 scoop (5.7 g) in 200 mL of water once daily in the evening.

Meta Mag magnesium bisglycinate, ornithine, ashwagandha, lutein, and zeaxanthin to address disrupted sleep cycle patterns, potentiate slow-wave sleep (SWS), enhance melatonin levels and reduce elevated cortisol. These ingredients may improve sleep quality and help to mitigate fatigue associated with sleep apnoea and sleep fragmentation (Figure 4).

Mechanism of Action/Clinical Research:

  • Magnesium has been shown to significantly decrease serum cortisol levels within hours of sleep initiation, resulting in increased in SWS (p<0.01).[140]
    • 500 mg/d of elemental magnesium over eight weeks was shown to significantly increase sleep time and sleep efficiency, while improving sleep onset latency (p<0.03).[141]Patient serum cortisol levels were shown to decrease (p<0.008) in correspondence with increased in melatonin (p<0.007), indicative of magnesium’s effect on improving sleep quality.[142]
  • Ornithine also improves sleep quality, as well as reducing stress markers through the regulation of cortisol and dehydroepiandrosterone sulfate (DHEAS) production.[143]
    • In a double-blind, randomised, placebo-controlled trial, 52 participants who received 400 mg/d of L-ornithine for eight weeks reported improved sleep quality, including enhanced sleep initiation and maintenance.[144] L-ornithine was shown to reduce serum cortisol and improve cortisol/DHEAS ratio supporting its beneficial effects on HPA axis function.[145]
  • Withania somnifera has been shown to simultaneously improve sleep quality and moderate cortisol levels, which may counteract stress induced HPA overactivity in insomnia.
    • In a study conducted in 60 healthy individuals receiving either 250 mg/d and 600 mg/d of withania over eight weeks, participants showed significant improvement in perceived stress scores, reductions in morning cortisol and enhanced sleep quality in both treatment groups (p<0.05).[146]
  • Lutein and zeaxanthin may assist sleep regulation by enhancing ocular macular pigment optic density (MPOD) levels, which is involved in filtering blue light. This in turn supports the production and release of melatonin.[147],[148] These carotenoids have been shown to reduce the effects of excessive screen time (i.e., six hours of screen time daily for six months) and improve sleep onset and maintenance.[149]
    • Supplementation of 20 mg/d of lutein and 4 mg/d of zeaxanthin in 48 healthy adults was shown to improve the incidence of sleep disturbances over six months, reduce the need for sleep-enhancing medications, and improve Pittsburgh Sleep Quality Index scores (p<0.05).[150] 
Figure 4: Ingredients within Magnesium with Lutein and Zeaxanthin for Sleep Pattern Support restores circadian rhythm and improves sleep quality.

 

4.0 Supportive Programs

 

The Metagenics Reducing Allergy and Reactivity Program is designed to address the core drivers of allergy and reactivity by managing the effects of dietary allergens, digestive enzymes, gut microbiota, intestinal barrier function and immune reactivity. The program outlines key evidence-based strategies to minimise symptom severity in addition to outlining specialised dietary approaches, including a Low Histamine Diet or a Custom Elimination Diet that may aid in the identification of food triggers and assist in the reduction of headache and migraine symptoms. Full instructions are available for free download.

 

5.0 Diet and Lifestyle Recommendations

 

5.1 Diet:

  • Ensure patients are adequately hydrated and are consuming a minimum of 2 litres of water daily, with an additional litre of water per hour of exercise.
  • Limit intake of common triggers of migraines and headaches, including cheese, chocolate, monosodium glutamate, artificial sweeteners, citrus, and wine.[151]
  • Foods that are rich in histamine including fish, cheese, cured meats, pickled vegetables, and alcohol are associated with a worsening of symptoms in patients suffering chronic headaches, with their reduced consumption shown to reduce headache frequency.[152]
    • To address dietary triggers, trial dietary elimination of suspected food triggers using the Metagenics Custom Elimination Diet or the Metagenics Low Histamine Diet outlined in the Metagenics Allergy and Reactivity Reduction Program Clinical Guide for two weeks, followed by reintroduction the foods and/or additives.
    • Advise patients to note their response following food re-introduction to help detect problematic foods.  Once the offending agents are identified, they may need to be eliminated for up to six months, prior to reintroduction.
  • If patient is overweight or obese, supporting successful weight loss to promote metabolic function may be achieved using either a hypocaloric ketogenic-style diet or a low-fat diet outlined in the Metagenics Shake It Practitioner Weight Management Program:
    • Both dietary options feature adequate protein for satiety, increased thermogenesis (i.e., promoting fat burning), which help maintain lean muscle mass.
    • A ketogenic diet has been shown to reduce the frequency of migraines in overweight patients[153]
  • The Low Histamine Diet, Custom Elimination Diet and Shake It Practitioner Weight Management Program Diet emphasise the minimisation of refined starches, sugar, saturated fats, and trans-fatty acids, which are generally of poor nutritional value. Further, due to their inflammatory nature, these may cause an activation of the innate immune system by excessive production of pro-inflammatory cytokines.[154]

 

5.2 Lifestyle:

  • For acute relief:
    • Cold compresses to forehead and eyes may help to relive pain.
    • Complete immobility, and minimisation of light, noise and odour can reduce symptom intensity.
    • Placing a heat pack across the back of the neck may help to relieve muscular tension.
    • Inhaling lavender essential oil for 15 minutes at the onset of headache symptoms has been shown to reduce the severity of headaches in migraine sufferers.[155]
  • Ensure adequate sleep, achieving approximately eight hours of sleep each night.[156]
  • Engage in regular physical activity to improve fitness, health and wellbeing, and reduce stress.[157]
  • Manual therapies and massage may help release exacerbating chronic neck and shoulder tension associated with headache and migraine onset.
  • Yoga in addition to conventional medical treatment in 114 patients over three months showed a significant reduction in headache frequency and intensity, and less need for pharmaceutical medications.[158]
  • Acupuncture is supported by research to reduce symptoms of headache and migraine. Twenty sessions of acupuncture over eight weeks have been shown to reduce migraine attacks in adults.[159]
  • Remote Electrical Neuromodulation (REN): A novel acute non-pharmacological migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation - an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. Clinical research has shown REN provides superior clinically meaningful relief of migraine pain compared to placebo, offering a safe and effective non-pharmacological alternative for acute migraine treatment.[160]