migraine mitochondria Archives

Migraine Energy Metabolism: Connecting Some Dots

Published on October 10, 2023

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I have been reading some of the fascinating posts by Angela Stanton PhD concerning her research in migraine headaches. I regard the substance of her discussions as somewhat like dots on a chart that need to be connected. I learned a great deal about the chemistry involved in migraine. One of her comments that involves ion homeostasis in brain metabolism is fascinating. She noted that “serotonin is created by a normally functioning brain. Why it decreases or increases in the brains of migraineurs has always puzzled me. Should we not try to find out why?” That simple three letter word is the heart and soul of research and I believe that I may be able to add some information that might provide an answer.

Ehlers Danlos and Migraine

In one of Angela’s posts she discusses a subject which has been of interest to me for many years, the overlap of symptoms in disease. She noted that 60% of migraineurs have one type of Ehlers Danlos syndrome (EDS) and 43% of EDS have minor changes in DNA (SNPs) found in migraineurs. She concludes that they must be related. Over 70% of migraineurs have Raynaud’s disease and there is an overlap with EDS and Raynaud’s. Therefore, she concludes that these three diseases are variants. In fact, there is an association between EDS, Postural Othostatic Tachycardia Syndrome (POTS) and a group of conditions known as mast cell disorders. EDS-HT, (one of the manifestations of this disease), is considered to be a multisystemic disorder, involving cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic and psychiatric manifestations, including joint hypermobility. Many non-musculoskeletal complaints in EDS-HT appear to be related to dysautonomia, consisting of cardiovascular and sudomotor dysfunction. Many of the clinical features of patients with mitral valve prolapse can logically be attributed to abnormal autonomic function. Myxomatous degeneration of valve leaflets with varying degree of severity is reported in the common condition of mitral valve prolapse.

A woman, with what was described as a “new” type of EDS, died after rupture of a thoracic aortic aneurysm. Autopsy revealed myxomatous degeneration and elongation of the mitral and tricuspid valves. Patients with POTS, a relatively common autonomic disorder, may have EDS, mitral valve prolapse, or chronic fatigue syndrome and are sensitive to various forms of stress, as depicted in the clinical treatment of a dental patient affected by the syndrome. Dysautonomia has been described in the pathogenesis of migraine, featured by nausea, vomiting, diarrhea, polyuria, eyelid edema, conjunctival injection, lacrimation, nasal congestion and ptosis. In general, there is an imbalance between sympathetic and parasympathetic tone.

Energy Metabolism and Migraine

Technological studies have confirmed the presence of deficient energy production together with an increment of energy consumption in migraine patients. An energy demand over a certain threshold creates metabolic and biochemical preconditions for the onset of the migraine attack. Common migraine triggers are capable of generating oxidative stress and its association with thiamine homeostasis suggests that thiamine may act as a site-directed antioxidant. It strongly suggests that migraine is a reflection of an inefficient use of brain oxygen. An intermediate consumption of oxygen between deficiency and excess appears to be a necessity at all times. In fact,” moderation in all things” is an important proverb

Backing up energy deficiency, two cases of chronic migraine responded clinically to intravenous administration of thiamine. However, the authors are in error when they state in the abstract that “nausea, vomiting and anorexia of migraine may lead to mild to moderate thiamine deficiency”. An otherwise healthy 30-year-old male acquired gastrointestinal beriberi after one session of heavy drinking. Nausea, vomiting and anorexia relentlessly progressed. He had undergone 11 emergency room visits, 3 hospital admissions and laparoscopy within 2 months but the gastrointestinal symptoms continued to progress, unrecognized for what these symptoms represented. When he eventually developed external ophthalmoplegia (eye divergence), he received an intravenous injection of thiamine which reversed both the neurologic and gastrointestinal symptoms within hours.

In other words it is important to be aware that nausea, vomiting and anorexia are primary symptoms of beriberi due to pseudohypoxia in the brainstem where the vomiting center is located. Chronic migraine has a well documented association with insulin resistance and metabolic syndrome. The hypothalamus may play a role. One of Angela’s comments concerns ion homeostasis in migraines. Thiamine triphosphate (TTP) can be found in most tissues at very low levels. However, organs and muscles that generate electrical impulses are particularly rich in this compound. Furthermore, TTP increases chloride (ion) uptake in membrane vesicles prepared from rat brain, suggesting that it could play an important role in the regulation of chloride permeability. Although this research was published in 1991, the exact role of TTP is still unknown. It has been hypothesized that thiamine and magnesium deficiency are keys to disease.

Angela wondered why serotonin might be increased or decreased in migraineurs. I strongly suspect that it is due to brain thiamine deficiency as the ultimate underlying cause of the migraine. In a review of thiamine metabolism, it was pointed out that metabolites could be high or low according to the degree of the deficiency. Victims of beriberi were found to have either a low or a high potassium according to the stage of the disease. If they were found to have a low acid content in the stomach, treatment with thiamine resulted in a high acid content before it became normal. If the stomach acid was high it would become low before it became normal. Since low and/or high potassium levels may be found in the blood of critically ill patients, thiamine deficiency should be a serious consideration in the emergency room or ICU Thiamine deficiency may be the answer for the fluctuations of serotonin observed in migraine.

Redefining Disease Models

According to the present medical model, each disease is described as a constellation of symptoms, physical signs and laboratory studies, each with a separate etiology. The overlap discussed by Angela suggests that the various conditions nominated have a common cause and that they are indeed nothing more than variations. If energy metabolism is the culprit, it would make sense of the infinite variations according to the degree and distribution of cellular energy deficiency. EDS-HT, described above is reported as a multi-system disease, exhibiting cardiovascular, autonomic gastrointestinal, hematologic, ocular, gynecological and psychiatric symptoms as well as the joint mobility. It seems to be impossible to explain this multiplicity without invoking energy deficiency as the cause. People with prolapsed mitral valve and a patient with a “new” form of EDS, reportedly have myxomatous degeneration as part of their pathology and it is tempting to suggest that such an important loss of structure might well be because of energy deficit.

The controls of the autonomic nervous system are located in the lower part of the brain that is particularly sensitive to thiamine deficiency and beriberi is a prototype for thiamine deficiency in its early stages. Dysautonomia is frequently reported as part of many different diseases, offering energy deficiency as the etiology in common. Yes, it is true that thiamine is not the only substance that enables the production of ATP. Nevertheless, it seems to dominate the overall picture of energy metabolism. It has long been considered the essential focus in the cause of beriberi, even though all the B complex vitamins are found in the rice polishings. Milling and the consumption of white rice was the prime etiology of the disease when it was common in rice consuming cultures.

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This article was published originally on June 22, 2020.

Migraine, Diet, and Thiamine

by Derrick Lonsdale MD, FACN, CNS

Published on August 15, 2018

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In US population studies, the prevalence of migraine is approximately 18% in women and 6% in men. About 90% of sufferers have moderate or severe pain and 75% have a reduced ability to function during the headache attacks. One third require bed rest during an attack. A study at the Mayo Clinic showed the incidence in women increased 56% during the 1980s and 34% during the same period in men. Although the term “migraine” is often used to describe any severe headache, a migraine headache is the result of specific physiologic changes that occur within the brain leading to the characteristic pain and associated symptoms. They are usually accompanied by sensitivity to sound, light and odors and there may be nausea or vomiting. Typically, the headache involves only one side of the head but in some cases it may be bilateral. The pain is often described as throbbing, pounding and maybe made worse with physical exertion. Silent migraine is a variant where the patient may experience aura, nausea, vomiting and other nervous symptoms without headache.

Migraine headache is estimated to affect up to 28% of adolescents, most of whom are female. It has been associated with reduced quality of life and academic disruption due to missed school days. In 2014 the US Food and Drug Administration approved an existing medication called topiramate for prophylaxis in adolescents between the ages of 12 and 17 years. There are several possible adverse effects from this drug, some potentially serious. Prophylactic drugs are unpromising and unpredictable. A mild degree of prevention could be obtained from the use of acupuncture.

Migraine Precipitants

Of 171 patients who fully completed a survey, 49.7% reported alcohol as a precipitating factor of headache other than migraine. Only 8.2% reported aspartame and 2.3% reported carbohydrate. Patients with migraine were significantly more likely to report alcohol as a trigger. They also reported aspartame as a precipitant three times more often than those having other types of headache. Non-nutritive sweeteners, including aspartame, saccharin, sucralose, neotame, acesulfame-K and stevia have all been questioned as to their safety. Pregnant and lactating women, children, diabetics, migraine and epilepsy patients, represent the susceptible population. Although sucralose is not considered to be a migraine trigger, a patient was reported with attacks of migraine consistently triggered by this sweetener.

Hypoxia, Pseudo-hypoxia, and Migraine

Migraine with aura is prevalent in high-altitude populations, suggesting that hypoxia has a part to play in etiology. Of 15 patients with migraine headaches, artificially induced hypoxia triggered migraine attacks in eight patients.

Thiamine deficiency produces abnormal gene expression in brain exactly like that induced by true hypoxia. Migraine is a risk factor for thiamine deficiency and Wernicke encephalopathy (WE), the classic thiamine deficiency disease that affects the brain. Two female patients have been reported with chronic migraine. They also had clinical signs and laboratory support for WE. Both patients received intravenous thiamine supplementation, leading to improvement of both WE and the associated headache. The authors suggested that nausea and vomiting, occurring with migraine, may lead to the thiamine deficiency. However, headache, nausea, vomiting and loss of appetite are symptoms that occur in the early stages of WE, thus simulating migrainous features and the association is by no means clear. The authors suggest that thiamine supplementation might be a promising therapy in a subset of patients with chronic migraine.

Also, the range of pathologies associated with magnesium deficiency is staggering, including migraine, multiple sclerosis, glaucoma and many other disorders. It is important to emphasize once more that magnesium and thiamine work together in the cellular machinery that produces energy and deficiency of either is critical. Chronic recurrent nausea in childhood is a poorly described symptom and in a study of 45 affected children, 62% had migraine headaches. They also suffered from dizziness, anxiety, fatigue and sleep problems. The exact incidence of dizziness and vertigo during adolescence is not known. For those few adolescents who seek outpatient evaluation, the majority are diagnosed with migraine headaches and many suffer from postural orthostatic tachycardia syndrome (POTS), a condition that has been reportedly due to thiamine deficiency in some cases.

Autonomic Asymmetry

Normally there is a balance between the autonomic tone of the right and left half of the body. However, under stress or with hypothalamic instability this balance may be disrupted and result in the marked autonomic asymmetry seen in migraine. Abnormal regulation of the large cranial arteries appears to play a significant role in the mechanisms of migraine pain, also reflecting abnormal autonomic function.

Migraine and Diet

Attack frequency of migraine in children was associated with higher intake of high fat or sugar. The processing of both is dependent on thiamine. With these strong associations in the medical literature, it is impossible not to contemplate that the sweet sensory input from the tongue to the brain is an important trigger for migraine. There has been a steady increase in sugar consumption in America over the past few decades, suggesting the possibility that it represents the published increased incidence of migraine in the 1980s as mentioned above. It also suggests the possible implication of artificial sweeteners as migraine triggers.

The association of migraine with alcohol ingestion might be an important observation, since alcohol has long been known to be a cause of thiamine deficiency in the part of the brain that controls the autonomic nervous system. It has also long been known that beriberi, the classical thiamine deficiency disease, causes autonomic dysfunction in its early stages. One of the most important observations that I observed in practice was that a mild degree of this deficiency makes the brain extremely sensitive to many different input stimuli. It results in a high degree of sympathetic nervous system activity, hence so-called panic attacks that are really distorted fight-or-flight reflexes. Patients complain of constant anxiety, heart palpitations, unusual sweating, nausea, vomiting, dizziness and brief fainting attacks known as syncope. This collection of symptoms, thought by many physicians to be psychological in nature, is also referred to as postural orthostatic (positional) tachycardia (rapid heart) syndrome (POTS).

In a person who is in a marginal state of malnutrition, any mild stress such as a vaccination, a mild infection or some form of trauma may initiate POTS. A reader might conclude that this diversity of symptoms, that include the incidence of migraine, cannot be caused by a deficiency of a single nutritional element. In order to understand, it is necessary to be aware that a deficiency of energy in the brain resulting from a common form of malnutrition creates a multiplicity of cellular dysfunction according to the distribution of the deficiency. If this is the truth, it makes a mockery of the present medical model in which each described disease is thought to have a specific underlying cause. Hence, money is collected to find the cause of Alzheimer’s disease and is probably a pipe dream. It is well known a published association with thiamine metabolism strongly suggests that we should be looking for prevention rather than spending millions in trying to find a curative drug.

Conclusion

The clues that alcohol, sugar and artificial sweeteners are major triggers for producing migraine headaches are so strong, their avoidance would appear to be mandatory. However, it is almost certainly true that many sufferers know this, but make no attempt at avoidance, marking the taste of sweeteners as addictive. I became aware that there were millions of people in America suffering from symptoms that are constantly being unrecognized in medical clinics. Even if they are recognized as nutritional in nature, the doctor and patient are likely to ignore the appropriate prevention by adopting the consumption of an appropriate diet. Since most of the population is ingesting pills of one sort or another, perhaps advising the use of vitamin supplements as part of the dietary discretion might at least partially serve in the reversal of these common symptoms.