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2017 Migraine Study

The End of Migraine?

Over the past ten years, the authors of the paper below have helped hundreds of patients with debilitating migraines using Advanced Wellness..

 

The paper describes success in patients who have failed conventional medical therapies and shows that the many associated symptoms found in migraine patients can also be benefited. You will note in the paper that we broke out our analysis into Groups I and II.   To hear a testimony of a Group I patient, watch Mandy’s video.  To watch a testimonial video of a Group II patient, watch Nannette’s video.  Group II were patients like Group I except had even more complexity to deal with.  Our results were so spectacular it has taught us that our Advanced Wellness method strikes at the root causes of migraine whereas conventional medicine merely attempts to suppress symptoms.

Mandy: Group I Patient

Nannette: Group II Patient

2017 Migraine Study

Multi-Modal Epigenetic Care Plans for Migraine

Brian Bakke, George W. Rozakis, Victoria Eaton, Les Emhof, Kim Allie, Vasili Rozakis, Scott Sedlacek

Abstract

Objective:  To evaluate the effectiveness of a multi-modal epigenetic care plan on the reduction in frequency (days per month), duration (hours), and severity (1-10) of migraine and headache in a population of adult patients in the United States and Canada.

Design: Multi-center, prospective migraine study that followed a cohort of 69 adult patients.

Setting: Patients in the United States and Canada were followed using a telemedicine system and were treated by their primary care physician in both clinic and remote settings.

Methods: Epigenetic-based care plans comprised of dietary, nutraceutical, and bioidentical hormone therapies were developed from a comprehensive health history evaluation; nutrigenomic based testing for single-nucleotide polymorphisms; IgG food sensitivity testing; methylation blood chemistry; and hormone blood chemistry testing. The patient’s migraine and headache scores were assessed at varying stages of treatment between 3 and 6 months of care.

Results: 54 out of a total of 69 participants completed 3 to 6-months of treatment and provided self-reported data on the reduction in frequency, duration, and severity of migraine. The average percentage reduction in frequency, duration, migraine hours per month (frequency x duration), and severity was 83%, 82%, 94% and 73%, respectively. 15 patients did not comply with the recommended care plans and were excluded from the study.

Conclusions: Personalised, multi-modal epigenetic care plans comprised of dietary, nutraceutical and hormonal interventions afforded a reduction in frequency, duration, and severity of migraine, headache and associated symptoms for a population consisting of migraine and headache patients. The results of this prospective study support the results of a prior, retrospective study and offer compelling evidence that multi-modal epigenetic care plans represent an effective intervention model in the management of migraine and associated co-morbidities.

Key Words: migraine, epigenetic care, telemedicine

Background

Migraine is believed to result from neurological abnormalities in the brain1 that are associated with genetic risk factors2,3 and influenced by a wide-range of possible biochemical,4,5 environmental,6,7 and emotional triggers.8 Over 10% of the population suffers from migraine.9 Three times as many women as men suffer from migraine in adulthood.10    Eighty percent of all migraine sufferers have their first attack before the age of 30 with many experiencing their first attack in childhood.11 Most sufferers experience attacks once or twice a month and approximately 4% of migraine sufferers report chronic migraine, defined as experiencing migraine at least 15 days per month.12-14

Migraine sufferers typically require higher levels of medical resources compared to non- migraine patients, which includes preventative and abortive pharmacological interventions, in office visits, diagnostic testing, and emergency room visits.15 Migraine also has an adverse impact on workplace absenteeism and presenteeism, accounting for billions of dollars in lost productivity annually.16,17

Some of the traditional pharmaceutical interventions for migraine are associated with side effects18 or the medications do not meet the expectations of the patient.19  As a result of the challenges associated with some of the traditional prophylactic and acute migraine management therapies, a significant percentage of migraine sufferers pursue complementary and alternative medicine (CAM) for managing their migraines.20,21Some of the CAM therapies that have been shown in studies to help lower the incidence and severity of migraine include riboflavin22, magnesium23, 24, estrogen25,26, butterbur, ubiquinol (CoQ10), feverfew, and various combinations of each supplement.27,28

The role of epigenetics in the development of migraine is an emerging area of focus in clinical research.29 Epigenetics involves non-inheritable alterations in the way genes function.30 Epigenetic processes are part of normal physiologic function and are essential for life; however, aberrant epigenetic modifications can contribute to adverse health outcomes. A significant number of chronic illnesses and other health factors have some level of evidence linking them with epigenetics.

The list of some of the more prominent modulators of epigenetic processes includes environmental toxins, medications, foods, tobacco, hormones, physical and emotional stressors and pathogens.  Many mechanisms of epigenetic regulation have been identified, including methylation, phosphorylation, and acetylation, among others. Given the prominent role that diet and environment have in influencing epigenetic regulation, the personalized epigenetic care plans were crafted to support healthy functioning of cells and tissues, which in turn, serves as an effective preventative strategy for migraine.

Materials and Methods

Personalized epigenetic care plans were rendered to migraine patients by their treating physician through a telemedicine system in the United States and Canada.  The epigenetic care plans were constructed from the patient self-reporting included in a comprehensive health history evaluation; nutrigenomic based testing for single-nucleotide polymorphisms; IgG food sensitivity testing; methylation blood chemistry; and hormone blood chemistry testing.  Therapeutic interventions included in the care plan consisted of dietary counseling with meal planning, nutraceuticals, and bioidentical hormones.

Patients were coached to update their symptom record by accessing their chart in the xRMD telemedicine portal once per week.  Patients also completed a phone consultation with an xRMD dietitian every two weeks for the first 3 months of care. The enhanced accessibility of the xRMD telemedicine model is thought to promote greater levels of compliance and allows the practitioner to dynamically adjust the patients’ program to help resolve symptoms more efficiently, which in turn, enables the patient to achieve more rapid resolution of their symptoms.

Improvement in migraine was defined by the self-reported, subjective scoring system for frequency (days per month), duration (hours), and severity of migraine (0-10).

Associated co-morbidities were tracked using a subjective scoring system (0-4). Notable symptoms reported by patients included depression, anxiety, chronic fatigue, fibromyalgia pain, irritable bowel syndrome, joint pain, sleep disturbances, hot flashes, night sweats, low libido, sugar cravings, and constipation.

Patient progress was evaluated on a continual basis and once the patient had been in treatment for at least 3 months and their migraines and associated symptoms had improved by at least 50% from baseline, they transitioned to a new phase of their program where they were tracked monthly, rather than weekly.  Patients were assigned a non-compliant designation if they were unable or unwilling to adhere to the dietary, nutraceutical or hormonal recommendations.

Participants in the xRMD migraine program failed to derive sufficient benefit from either conventional or complementary migraine therapies prior to enrollment.  Examples of interventions reported by patients included abortive and preventative strategies encompassing OTC analgesics, SSRIs, anticonvulsants, beta blockers, triptans, narcotics, botox, surgery, nerve stimulators, eastern medicine, supplements, bioidentical hormones, hormone and non-hormone based contraceptives, massage, acupuncture and cognitive behavioral therapy (CBT), among others.

Results

A total of 54 participants completed a 3 to 6-month treatment phase of their program and provided self-reported data on the reduction in frequency, duration, and severity of migraine. The average percentage reduction in frequency (days per month), duration (hours), migraine hours per month (frequency x duration), and severity (0-10) was 83%, 82%, 94% and 73%, respectively (Table 1). 

Table 1. Improvement in Frequency, Duration, and Severity of Migraine (n = 54)

Percent Reduction in:

Frequency    Duration    Hrs/Month    Severity      
        83%          82%           94%              73%   

Two Groups of migraine patients were identified.

Group 1 Patients

Group I consisted of patients who had migraine of any frequency, duration, and severity along with symptoms or conditions that generally respond favorably to dietary, nutraceutical and hormonal clinical interventions (Table 2).

Table 2. Associated Conditions and Symptoms (n = 54)
Fatigue (31)
Anxiety (22)    
Hyperlipidemia (8)
IBS (8)    
ADHD (2)
Memory Deficit (2)
Depression (20)
Joint Pain (12)    
Allergies (5)
Hypothyroid (4)    
Diabetes (2)
ED (1)
Menopause (11)
Low Libido (11)    
Constipation (4)
Hypertension (4)    
Acid Reflux (1)
Osteoporosis (1)
Insomnia (9)    
Acne (2)

Group I also included patients with the following characteristics:
1.  Adult male or female with no history of head, neck or back trauma associated with onset or progression of migraine.
2.  Conversion from birth control to bioidentical hormones (female only) within first 3 months of starting the program.
3.  Prospective patient uses less than the maximum amount of prescription pain medication that qualifies for overuse (10 or less days per month). 

Group 2 Patients

Group 2 patients suffered from similar symptoms as Group 1 but had additional complex co-morbidities (table 3), which slowed the rate of response of the treatment plans in most cases. Generally, this cohort transitioned from treatment at 6 months or longer and
were deemed long term cases.

Table 3. Complex Conditions and Co-Morbidities (n = 27)
Daily Narcotic Pain Medication Use (15)    
Hashimoto’s (2)
Multiple Sclerosis (2) 
Lyme’s Disease (1)
Alcoholism (1)
Fibromyalgia (6)
Head Trauma (2)
Bipolar (2)    Rheumatoid Arthritis (1)
Trauma, Neck, or Spine (4)
Obesity (3)  
 Heart Disease (2)
Cancer (2)    
Epilepsy (1)

 

Discussion
Patients that transitioned from the treatment to improvement phase at 3 or 6 months comprised groups I and II. Of the 54 patients who successfully transitioned to the improvement phase of our program, half (27/54) were in Group II.  The 54 patients that completed the study reported an average of 21 migraine days per month of varying duration and severity prior to participating in the migraine program. We calculated migraine hours per month as the product of frequency and duration. Success was defined as at least 75% reduction in frequency or migraine hours per month within 6 months of care.

An assessment of associated symptoms will be described in a separate paper using patient reported scoring system (0-4).  The overwhelming majority of associated symptoms improved, and in some cases resolved. This finding is consistent with a prior retrospective data analysis, where a xRMD migraine cohort consisting of 34 migraine patients were treated with Epigenetic Care plans derived from genetic testing. Many of the patients from this cohort had migraines for decades impacting 50 % or more of their month; after the treatment, many of the patients reported a significant reduction in migraine occurrence. A noteworthy observation from the analysis of the present cohort was that associated symptom improvement often precedes measurable improvement in migraine. This is likely owed to the complexity of migraine pathogenesis and the myriad of underlying triggers that can precipitate an attack.

Time to Symptom Resolution
In general, Group I achieved symptom resolution more rapidly than Group II.  The time to > 75% migraine improvement for Group I ranged from 5 days to 3 months. Group II patients generally required 6 months or longer to achieve comparable levels of improvement with migraine.

Non-Compliance
Fifteen patients were unable to complete their treatment phase and were deemed non- compliant with the program. One patient was improving and then suddenly discontinued his regimen and dropped out of the program. The patient reported that he was “tired of taking supplements”. He was later diagnosed as bipolar.  Seven patients were unable or unwilling to comply with the dietary regimen.  One of these patients was an active smoker. In 7 instances, the patient was unable to comply with the hormone portion of the care plan due to an unsupportive local physician.  In 3 of these instances, the provider was concerned about the safety of bioidentical hormone use.

Side Effects
Side effects were generally tolerable, self-limited and resolved with program adjustment. The most common reported side effect was GI upset.  In some cases, migraines, anxiety, acne, and insomnia worsened transiently as dosages were adjusted.  No patients reported stopping their program due to side-effects.

Conclusions
Personalized, multi-modal epigenetic care plans comprised of dietary, nutraceutical and hormonal interventions afforded a reduction in frequency, duration, and severity of migraine, headache and associated symptoms for a population migraine and headache patients. The results of this prospective study support the results of a prior, retrospective study and offer compelling evidence that multi-modal epigenetic care plans represent an effective intervention model in the management of migraine and associated co-morbidities.

Prior to participating in the migraine treatment protocol many of the patients reported that their migraines and associated co-morbidities were poorly controlled or unresponsive to conventional or CAM therapies. The cohort of patients in the present study reported >20 migraine days per month on average and numerous, complex co- morbidities were present in the population including a history of head, neck, and/or back trauma; obesity; multiple sclerosis; Lyme’s disease; bi-polar disorder; cancer; and polypharmacy.

Patient compliance was a critical determinant of success. The most common reason for non-compliance was the patient’s inability or unwillingness to adhere to the dietitian directed nutritional plan.  A secondary reason for non-compliance was due to an unsupportive primary care physician that was unwilling to provide prescriptions for bioidentical hormones. Improving outcomes in future investigations will require the development of a comprehensive provider network to fully support the bio-identical hormone and nutritional requirements of the xR patient population.

Footnotes

Competing interests: Brian Bakke, George W. Rozakis , Victoria Eaton, Kim Allie and Vasili Rozakis are members of the xRMD Personalized Health, LLC. The other authors have no competing interests.

References

1.  Olesen J, Burstein R, Ashina M, Tfelt-Hansen P.  Origin of pain   in migraine: evidence for peripheral sensitization.  Lancet Neurol  2009;8:679-90.

2.  Gormley p, Anttila V, Winsvold G, Palta P, Esko T, Pers T, Farh K, Cuenca-Leon E, Muona M, Furlotte N, et al.  Meta-analysis of 375,00 individuals identifies 38 susceptibility loci for migraine.  Nature Genetics 2016;48:856-866.

3.  Gervil M, Ulrich V, Kaprio J, Olesen J, Russell M.  The relative role of genetic and environmental factors in migraine without aura.  Neurology  1999;53:995.

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10. Stewart W, Lipton, R, Celentano D.  Prevalence of Migraine Headache in the United States: Relation to Age, Income, Race, and Other Sociodemographic Factors. JAMA 1992;267:64-69.

11. Victor T, Campbell J, Buse D, Lipton R.  Migraine prevalence by age and sex in the United States: a life-span study.  Cephalagia  2010;30:1065-1072.

12. Johannes C, Le T, Zhou X, Johnston J, Dworkin R.  The Prevalence of Chronic Pain in the United States Adults:  Results of an Internet-Based Survey.  The Journal of Pain 2010;11:1230-1239.

13. Smitherman T, Burch R, Sheikh H, Loder E.  The Prevalence, Impact, and Treatment of Migraine and Severe Headaches in the United States:  A Review of the Statistics From National Surveillance Studies.  2013;53:427-436.

14. Weatherall M. The diagnosis and treatment of chronic migraine.  Ther Adv Chronic Dis 2015;6:115-123.

15. Lipton R, Scher A, Kolodner K, Liberman J, Steiner J, Stewart W.  Migraine in the United States: Epidemiology and patterns of health care use.  Neurology 2002;58:885-894.

16. Hu X, Markson L, Lipton R, et al.  Burden of Migraine in the United States: Disability and Economic Costs.  Arch Intern Med  1999:159:813-818.

17. Stewart W, Lipton R, Simon D.  Work-Related Disability:  Results From the American Migraine Study.  Cepthalalgia.  1996;16:231-238.

18. Gallagher R, Kunkel R.  Headache.  Migraine Medication Attributes Important for Patient Compliance: Concerns About Side Effects May Delay Treatment. Headache 2003;43:36-43.

19. Lipton R, Stewart W.  Acute Migraine Therapy:  Do Doctors Understand What Patients With Migraine Want From Therapy?  Headache  1999;39:20-26.

20. Gaul C, Eismann R, Schmidt T, May A, Leinisch E, Wieser T, Evers S, Henkel K, Franz G, Zierz S. Use of complementary and alternative medicine in patients suffering from primary headache disorders.  Cephalagia  2009;29:1069-1078.

21. Wells R, Bertisch S, Buettner C, Phillips R, McCarthy E.  Complementary and Alternative Medicine Use Among Adults With Migraines/Severe Headaches. Headache 2011;51:1087-1097.

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23. Mauskop A, Altura B.  Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci 1998;5:24-27.

24. Mauskop A, Varughese J.  Why all migraine patients should be treated with magnesium. J Neural Transm  2012;119:575-579.

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Appendix 1

xRMD Overview
xRMD utilizes a patient-centered approach in addressing the underlying cause of disease. xRMD doctors meticulously review the patient’s detailed health history; comprehensive hormonal, methylation, inflammatory and blood chemistry; and nutrigenomic profiles to create a personalized care plan specifically designed to meet the patient’s unique health needs.

Our advanced telemedicine system enables us to leverage cutting edge science and serve as the interface between the practitioner and patient anywhere in the world.  We partner with our patients and their doctors, so that they feel empowered to take an active role in managing their health outcomes through lifestyle and dietary modification.

What makes xRMD’s approach to multi-modal therapies unique is that our care plans not only address biochemical and genetic deficiencies with hormones, supplements, lifestyle and/or dietary modification, but we also restore optimal levels of deficient biologically active substances via numerous routes of delivery (eg oral, sublingual, and/or transdermal).  This multi-modal delivery approach enables us to overcome GI challenges that often accompany chronic illness and enables us to more efficiently ameliorate the patient’s symptoms.

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