Printer Friendly

Asymmetric functional dysautonomia and the role of thiamine.


Asymmetric activity of the autonomic nervous system (ANS) is well known. Evidence has been published to show that this asymmetry can become exaggerated in association with clinically diagnosed dysautonomia. It has been hypothesized that this is due to inefficient oxidative metabolism in the limbic system and brainstem where the control mechanisms dominate. High calorie malnutrition, defined as an excess of empty calories, particularly those derived from simple sweet carbohydrates, is a major cause of dysfunction, giving rise to an extremely common form of dysautonomia. The normal asymmetry becomes exaggerated and gives rise to common symptoms that are often considered to represent conventional diagnostic phenomena erroneously. Because of the vital relationship of thiamine with glucose metabolism, the overload of carbohydrate results in relative deficiency of this vitamin that may be the rate limiting factor in oxidative processing of glucose. The use of erythrocyte transketolase activity is an easy way of observing deficiency of thiamine pyrophosphate (TPP), and it has been found to be a frequently abnormal laboratory test that is guarantee of the biochemical lesion. Apart from using it for clinical diagnosis, transketolase occurs twice in the hexose monophosphate shunt (HMS), and its occurrence in the brain is vital since the HMS is responsible for the production of reducing equivalents. Thus deficiency of TPP would be expected to result in brain oxidative stress apart from its role as cofactor in pyruvic and alpha-ketoglutarate dehydrogenases. Although it has been shown that thiamine triphosphate (TTP) is synthesized from TPP, using energy from the respiratory chain, its role is still largely unknown. It occurs in high concentration in the electric organ of Electrophorus electricus. The electric organ is an adaptation of a neuromuscular junction, and TTP may play a role in electrogenesis. Because the respiratory chain is in the inner mitochondrial membrane, any disruption of mitochondria will be expected to result in a deficiency of TTP, and its importance in brain thiamine deficiency is unknown. Beriberi is the prototype of dysautonomia in its early stages and its effects are reversible. As the disease progresses there is degeneration of autonomic ganglia and it becomes irreversible. It is hypothesized that the early diagnosis of modern nutrient deficiency dysautonomia is of vital importance to the clinician. Like beriberi, some irreversible brain disease may accrue if not recognized early enough. Alzheimer disease has responded only mildly to thiamine therapy, perhaps because treatment was offered too late.


Dysautonomia is a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome (POTS), inappropriate sinus tachycardia (1ST), vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic syncope (NCS), neurally mediated hypotension (NMH), autonomic instability, and a number of lesserknown disorders such as cerebral salt-wasting syndrome. Dysautonomia is associated with Lyme disease, primary biliary cirrhosis, multiple system atrophy (Shy-Drager syndrome), Ehlers-Danlos syndrome, and Marian syndrome for reasons that are not fully understood. (1) It has been hypothesized that its association with so many different diagnoses is because a common form of dysautonomia originates from high-calorie malnutrition. This leads to loss of oxidative efficiency and subsequent disorganization of ANS controls that are mediated through the limbic system and brainstem. Perhaps the associated organic disease is a result of years of "maladaptive wear and tear" or is itself a result of loss of oxidative efficiency in target organs. (2) The most definitive publication on autonomic failure was published in a comprehensive book in 1983. (3) It covered the various syndromes recognized at that time. Classification was presented as primary, secondary (associated with a number of diseases), and that caused by drugs. Although much discussion was given to symptomatology, pathology, and meticulous examination of histopathology, nowhere was there any reference to malnutrition as a potential cause, although much has been written about it since.


A Review of the Asymmetric Dysautonornic Literature

A review of the implications of autonomic nervous system asymmetry and its potential role in health and disease provides some interesting data that are relatively unknown, even by CAM physicians. A publication provides three methods for selectively activating one half of the autonomic nervous system (ANS). The first is an ancient yogic technique called unilateral forced nostril breathing (UFNB). The second is by stimulation of an autonomic reflex point in the fifth intercostal space near the axilla. The most modern method requires surgical implantation of a wire and pacemaker to stimulate the mid-inferior cervical branch of the vagus nerve (VNS). The noninvasive technique of UFNB, according to the author, seems to activate the ipsilateral branch of the sympathetic nervous system selectively, with a possible compensation effect leading to contralateral VNS." Both UFNB and VNS have been applied to treat psychiatric disorders. (4) Bob et al. concluded that their data suggested a relationship between left-hemispheric asymmetry and sympathetic overactivation in schizophrenia, and between right-hemispheric activity with sympathetic underactivity in depression. (5) Tanida et al. found a relationship between asymmetry of the prefrontal cortex activity and the ANS during a mental arithmetic task. The results, using quantitative electroencephalography in a group of women, provided support for a division of responsibility between the left and right frontal and temporal lobes in the regulation of heart rate and blood pressure. (6), (7) A study of 10 outpatients attending a cardiologic clinic highlighted a proximal brain basis for stress-induced arrhythmic vulnerability and risk for sudden death. (8)

Asymmetry of the ANS is reported in a number of diseases. Studies on the nasal cycle have demonstrated that autonomic tone to the nose is asymmetrical and oscillates in a regular cycle. Under stress or with hypothalamic instability, this balance might be disrupted, resulting in the asymmetry in migraine or Meniere's syndrome. (9) Brain autonomic control is asymmetrical, the left hemisphere affecting predominantly parasympathetic function and the right hemisphere affecting predominantly sympathetic function. The authors reported that left-side migraineurs had higher bilateral parasympathetic vasodilatation compared with right-side migraineurs. (10)

Asymmetry has been reported in the innervation of smooth muscle organs. (11) With use of electromyography, skin temperature, and skin conductance, asymmetries were found between the right and left sides of the body in patients with fibromyalgia syndrome The authors concluded that these asymmetries might be related to central, peripheral, and ANS dysfunctions. (12) Hemifacial sweating and flushing in patients with apparently abnormal ocular sympathetic innervation is defined as harlequin sign, used interchangeably with harlequin syndrome. (13) A case was reported in a woman in whom the symptoms were initiated by exercise. The authors suggested that the sympathetic impairment in the patient may lie on a spectrum of pre-and postgangl ionic autonomic dysfunction, which was observed in Holmes-Adie, Ross, and Guillain-Barre syndromes. (14) A 51-year-old man developed awake bruxism as he developed multiple system atrophy. Bruxism is usually nocturnal and automated. Electromyographic studies revealed side-to-side asymmetry in the bursts of motor activity. (15)

The reason for asymmetry in the ANS is unknown, but it may have important applications in both health and disease. We reported 17 patients with clinically diagnosed dysautonomia in whom asymmetry of brachial blood pressures was exaggerated in comparison with 13 age-matched healthy people. It is unknown whether the brachial blood pressures cycle. Additional evidence of this exaggerated asymmetry was that 13 of these dysautonomic patients had nasal congestion. All were asked whether they noticed recumbent alternating ipsilateral nasal congestion when lying in bed. Some of them admitted to this symptom, suggesting exaggerated asymmetry in the nasal cycle. (16) The nasal mucosa is a complex tissue that interacts with its environment and affects local and systemic changes. Receptors in the nose receive signals from stimuli and respond locally through afferent, nociceptive, type C neurons to elicit nasonasal reflex responses mediated via cholinergic neurons. (17)

Dysautonomia Associated with Other Diseases

Sleep problems in our 17 patients included insomnia, bruxism, night cough, sleep eating, and sleep apnea. (16) Chronic cough has been reported in 5 patients with the Holmes-Adie syndrome, associated with autonomic disturbances. The authors suggested that chronic cough may be part of the autonomic dysfunction. (18) An article in Polish recorded a 60-year-old woman with this syndrome who had experienced chronic dry cough for 4 years." The concept of organic disease as a separate entity divorced from brain action is changing. Studies have shown that the cholinergic anti-inflammatory pathway that inhibits innate immune responses provides evidence that innate immunity is reflexive. (20) Thus, in patients with recurrent infections, the fitness of this reflex mechanism must be taken into account as, for example, the virtual epidemic of recurrent ear infections in hosts of children seen by pediatricians today. Autonomic nervous system dysfunction may play a role in chronic upper airway inflammatory disease. (21) Obstructive sleep apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow. Impaired cerebral autoregulation appears to be an important part of either the etiology or the consequences. (22) Nicotinic acetylcholine receptors are expressed in brainstem and spinal cord regions involved in the control of breathing. Impairment of these mechanisms should be considered in neural control of automatic breathing such as sleep apnea and sudden infant death syndrome (SIDS). (23)

There is a diversity of diseases associated with autonomic dysfunction. Disturbances in the ANS are widely accepted in migraine that may also affect atrial and ventricular repolarization. (24) Adie syndrome, isolated or accompanied by other dysautonomic disorders, may reveal or precede the diagnosis of Sjogren's' syndrome. (25) Dysautonomia is commonly observed in GuiHain-Barre syndrome. (26) Several theories have been proposed to explain the underlying mechanisms of premenstrual syndrome, but it has been found that there is altered functioning of the ANS in the late luteal phase. (27) The role of the hypothalamus is sometimes neglected in disease, and it seems that this overlook is related to the present disease model in which organic disease is separated from brain disease. It is presently conventional to label a large number of seemingly unconnected symptoms as psychosomatic. This is particularly true if the laboratory studies and technological imaging do not support an organic disease. Laboratory studies can be superficially compared with a fishing expedition wherein the "net" has to be "where the fish are." Since nutritionally initiated pathology is still poorly considered, the right laboratory test can and will reveal the true etiology. Such tests, such as erythrocyte transketolase, need to be broadly expanded. Montagna notes that the hypothalamus is a key neural region in the regulation of sleep. (28) It forms part of the so-called central autonomic network, regulating body homeostasis by which we are able to adapt to the many physical and mental stresses encountered in the modern era. Our experience is that these adaptive mechanisms are commonly failing, and we have hypothesized that an easy way to produce this is through the dietary mayhem that flourishes in Western society.'

Oxidative Stress and the Role of Thiamine

Although it is obvious that thiamine deficiency is not the only cofactor to be implicated in oxidative function, its vital importance in many aspects of energy metabolism can be used as a model for discussion. The prototype for dysautonomia is beriberi in its early stages when it is treatable with large doses of thiamine. In its later stages the autonomic ganglia and the nerves that flow from them degenerate and the condition is irreversible. (29) The disease is clearly related to metabolic rate, since the acuity of symptoms is greatest in infants, in whom sudden death is a common disaster. It is less acute in older children and is usually most chronic in adults, although a peracute form was recognized in Japan and called Shoshin. The extraordinary multiplicity of symptoms recorded in this chapter should be known by physicians, since they are occurring in the modern era? There is an outstanding collective psychological problem in the medicine of today, for we have assumed that the diseases associated with vitamin deficiency have been eradicated and that they are only of historical interest. When patients today have some of the symptoms that would have been readily recognized 70 years ago for what they represent, the potential underlying cause of malnutrition is not even considered in the differential diagnosis.

Unfortunately, malnutrition is often considered only in the worldwide incidence of starvation. Little thought has been given to an excess of calories that produces a relative vitamin deficiency. Even a rough estimate of dietary habits often reveals nutritional mayhem, particularly in the young. Beriberi is now well accepted as a thiamine deficiency disease. Symptoms arise from loss of oxidative efficiency, primarily affecting brain, heart, and nervous systems, particularly the ANS. Most importantly, beriberi reflects a high-carbohydrate diet, for centuries represented in Eastern cultures by the consumption of polished rice. Epidemics were related to increased affluence when peasants could afford milling of their rice crops. The rice polishings contained the vitamins, and they were given to pigs. Thus the pigs were better fed than the people. In spite of this knowledge, the disease made its reappearance in 23 Japanese patients, 17 of whom were teenagers consuming sweet carbonated soft drinks, instant noodles, and polished rice. (30)

I have compared the disease to a "choked engine" in a car wherein there is an excess of fuel that cannot be efficiently oxidized, resulting in increased carbon from the exhaust. This is an appropriate analogy, since relative thiamine deficiency is easily induced by an excess of simple carbohydrate. (31)

Symptoms Affecting the Heart and ANS in Beriberi

These symptoms are numerous, and it is immediately obvious that many of them occur in the patients who represent the diseases of the modern era. The data are extracted from the chapter already referred to. (28) The book was published in Tokyo in 1965, so it might easily be regarded as too old a reference. The nature of the clinical presentation has not changed, however, and the observations made by those who had a particular interest in solving a disease that had been in epidemic form for centuries have to be taken seriously.

Cardiovascular symptoms. These symptoms were regarded among the most important. Heart palpitation on exertion or mental excitement gave rise to palpitation and dyspnea at rest as the disease progressed. The characteristic cardiac enlargement may easily be mistaken for a more modern concept of cardiomyopathy. As the disease advanced, there were characteristic changes in the electrocardiogram, involving high P and QRS and abnormal T waves, and prolongation of PQ intervals, all of which became more conspicuous with physical exercise. Ventricular ectopic beats were sometimes noted. The pulse was usually fast but could be slow in some cases, but accelerated with exercise. Low diastolic blood pressure, usually below 60 mm/Hg, could reach 0. I have often witnessed a diastolic pressure of 0 in children with ADD or ADHD, together with an audible femoral pulse by auscultation. Many of these patients had laboratory evidence of thiamine deficiency and responded to supplementation. (32) The patients reported with asymmetric dysautonomia whose erythrocyte transketolase revealed evidence of thiamine deficiency had higher pulse pressures than those without this evidence. (16) It has already been stated that a high systolic/low diastolic pressure is a feature that is seen in beriberi.

ANS symptoms. The labile excitability of the ANS has a large influence on the cardiovascular system, and there was some evidence of increased sympathetic tone. In some moderately severe cases, there was an exaggerated response to injection of adrenalin, including tachycardia, substernal oppression, nausea, and vomiting. In some cases, there was increased parasympathetic tone in the early stages, revealed by bradycardia, low diastolic blood pressure, and changes in body temperature, while this was replaced by increased sympathetic tone in the later stages. The state of the ANS therefore depends on the stage of the disease. A young patient was reported with many "psychosomatic" symptoms whose dysautonomia was asymmetric. Exposure to injection of norepinephrine produced asymmetric pupillary dilatation, headache, vomiting, and widely different pulse pressures in the brachial blood pressure measurements. She was classified as asymmetric functional dysautonomia. Her diet was standard American diet (SAD). With thiamine supplementation and strict adherence to a sugar-free diet, the symptoms gradually improved; and testing again a year later revealed that the asymmetry had disappeared.

Hypokalemia occurred in proportion to the degree of paralysis in beriberi, and hypokalemia is a common and important finding in hospitalized patients in the modern era. The differential diagnosis rarely includes thiamine deficiency. (33) The same is true for the long QT syndrome. (34) Perhaps we are simply looking at various cellular energy syndromes that require a biochemical diagnosis rather than a symptom/ sign/laboratory method of diagnosis. (2) This would simplify the extraordinary diversity of diseases as they are presently coded.

The Role of Thiamine in Disease

Perhaps the commonest form of dysautonomia is that associated with diabetes. Recent research in experimental diabetes points to the potential of thiamine in preventing diabetic complications. (35), (36) It must be an important reminder of nutrient deficiency or innate oxidative dysfunction that is often overlooked. Oxidative stress is commonly thought of as an excess of unquenched oxidative species. But hypoxia or its equivalent, inefficient use of oxygen in oxidative metabolism, is an obvious source of oxidative stress. Too little oxygen or its equivalent in the form of inefficient oxidation (IO) is as bad as too much, referred to as unquenched oxidative species (UAS). Thiamine pyrophosphate has its wellknown oxidant function, but it has been shown that it has UAS function because of its cofactor status in transketolase that occurs twice in the hexose monophosphate shunt (HMS). This shunt is of vital importance, since it supplies reducing equivalents. It is particularly important in the brain. (37) Benfotiamine, the agent used in this study, is an open ring, S-acyl lipophilic thiamine pyrophosphate (TPP) pro-drug. A number of thiamine derivatives have been synthesized and are superior to the use of the water soluble thiamine salts readily available in health food stores.38 A great deal of research in Japan started after the discovery of allithiamine, a disulfide derivative of thiamine that occurs in garlic after naturally occurring enzymatic action. The use of the word allithiamine should be reserved for this naturally occurring homologue. Although allithiamine is itself a disulfide, it is unstable, and all the available disulfides and S-acyl thiamine derivatives are synthetic. Japanese investigators produced a series of both types of homologue. All of them are superior to thiamine in their affinity to tissue. The disulfides are, however, readily reduced at the cell membrane nonenzymatically, whereas the S-acyl derivatives require enzymatic action to separate thiamine from the prosthetic group. Neither do the S-acyl compounds protect against cyanide and carbon tetrachloride poisoning as do the disulfides. (39) The anti-inflammatory effect of S-acyl homologues is unknown whereas thiamine tetrahydrofurfuryl disulfide (TTFD) has been shown to have this property. (40) A pilot study showed that TTFD had benefit in the treatment of autism spectrum disorder, a disease that is in epidemic form. (41) Its benefit has been shown in nutritional polyneuropathy. (42) High dose thiamine (3-8 g/day) and TTFD (100 mg/day) have both been shown to have some benefit in Alzheimer's disease. (43), (44) In experimental diabetes, high-dose thiamine and benfotiamine stimulated the HMS and countered accumulation of triosephosphates that lead to the development of diabetic nephropathy, suggesting a potential novel strategy for the prevention of clinical diabetic nephropathy. (44) With the virtually unheard-of toxicity at high doses, surely thiamine or one of its available homologues should be a routine supplement for all diabetics.

Altitude sickness is an obvious effect of oxygen deprivation in the untrained individual. A 72-year-old woman had recurrent "flu-like" symptoms after exercise. She had evidence of thiamine deficiency and hemoconcentration. Symptoms ceased and hemoconcentration was corrected by thiamine and magnesium supplementation. (46) Erythrocytosis has been produced in thiamine-deficient rats. Reticulocytosis and plasma erythropoietin increases indicated that this was similar to the mechanism in this patient. (47) Oxygen chemosensitive sites are distributed throughout the brainstem from the thalamus to the medulla and may form an oxygen-sensitive network. (48) Experimentally induced hypoxia in rats induced polycythemia, suggesting that symptoms from mild to moderate hypoxia and thiamine deficiency are the same. (49)

Panic disorder is a very common symptom and is treated traditionally as a psychological problem. That it can be a too easily sympathetically induced fight-or-flight reflex is suggested by the fact that it is triggered by carbon dioxide enriched air. (50) In a study of the brains of 49 patients who had died at least 4 days after an event of severe hypoxia, the findings demonstrated that the morphological changes in the mamillary bodies due to thiamine deficiency and those due to hypoxia-ischemia may be identical. (51) Congenital central hypoventilation syndrome patients subjected to hypoxic challenge suggested significant participation of limbic structures in their responses. (52) A review of the metabolism and clinical benefits of thiamine and its derivatives includes some of the more unusual and comparatively unknown conditions that respond to its pharmacological uses. (53)

The actions of the S-acyl derivative benfotiamine were compared with those of TTFD in mice. It was concluded that although benfotiamine strongly increased thiamine levels in blood and liver, it had no significant effect on brain. This, the investigators said, explains why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutamine (TTFD) increases thiamine derivatives in the brain as well as in cultured cells, acting as a central nervous system drug. (54)


Decreased transketolase (TK) activity contributes to impaired hippocampal neurogenesis induced by thiamine deficiency. (55) Up to now, one TK gene and two TK-like genes have been identified in the human genome. One of them (TKTL1) is reported to play a pivotal role in carcinogenesis and TK variants, and reduced activities of the enzyme have been found in patients with neurodegenerative diseases. (56) TK activators and polymerase inhibitors block major biochemical pathways of hyperglycemic change, hence its potential role in iabetes. (57) Glyoxals, reactive alpha-oxoaldehydes formed endogenously from sugars, are increased in various pathological conditions associated with hyperglycemia. Glyoxal toxicity, long an unknown question in understanding TD, was prevented in animal studies using thiamine. (58) A non-cofactor role of thiamine derivatives in excitable cells probably involves further knowledge about the role of thiamine triphosphate (TTP). Known to be of importance in brain and nervous system, its role is stil largely unknown. (59), (60)

Erythrocyte transketolase measurement is an easy way of ascertaining nutritional deficiency of thiamine pyrophosphate or loss of its homeostasis. (61) The cornea contains a particularly high transketolase concentration, consistent with the proposal that pentose phosphate pathway activity has a role in the removal of light-generated radicals. (62)

The Potential for Later Irreversible Disease

There is a possibility that our asymmetric dysautonomic patients reported with a variety of symptoms related to dietary indiscretion might represent aging continuation of unrecognized symptomatology affecting our adolescent patients reported in 1980. (16), (61) Abnormal oxidative processes including a reduction in thiamine-dependent enzymes accompany many neurodegenerative diseases. (63) Further evidence indicates that oxidative stress, glutamate-mediated excitotoxicity and inflammation are major contributors to the neuropathology resulting from thiamine deficiency. (64) Zhang et al have suggested that the activation of hypothalamic IKK [beta]/NF-KB could underlie the entire family of modern diseases induced by overnutrition and obesity. (65) The term multiple system atrophy (MSA) was proposed to cover a whole array of "disease entities" which, according to the author, are in fact merely the expression of neuronal atrophy in a variety of overlapping combinations, including progressive autonomic failure. One of the striking features of MSA is the preservation of intellect in the face of severe motor disability. Dementia seems therefore not to be an integral feature of the disease. For practical purposes, dementia rules out uncomplicated MSA. (66) This concept supports the hypothesis offered here that it is the lower, highly oxygensensitive, more primitive parts of the brain that are responsible and that thiamine-dependent metabolism and other noncaloric nutritionally derived factors may well be a common etiological component.


We have shown evidence from the published literature that thiamine plays a huge part in the healthy functions of the heart, brain, and nervous systems. Its deficiency gives rise to brain pathology that is similar to that produced by mild to moderate hypoxia. A relative deficiency is incurred by an excess of carbohydrate as in the ingestion of white rice in the etiology of beriberi, and we have suggested the analogy of a choked engine in a car. The widespread ingestion of simple carbohydrates is a major cause of dysautonomia that is easily corrected by completely discontinuing the common "junk" foods, particularly those that are sweet tasting, and supplementing the diet with thiamine and magnesium. The symptoms are collectively those that have been reported in dysautonomia but they must be recognized for their true etiology. We have hypothesized that the frequent association of dysautonomia with recognizable disease entities is related to defective oxidative metabolism that affects the limbic system control mechanisms first because it has a well known high oxygen requirement. We hypothesize another potentially important etiologic factor. The normal taste mechanism is from permutations and combinations of 6 stimuli. Like the spectrum of white light, they are sweet, salt, sour, bitter, astringent, and metal. All natural food provides flavor, representing those mixes of taste stimuli. If the signal from the tongue to brain taste perception is singled out as in sugar or salt, it is being used as a drug and it may be this that gives rise to a jolt of pleasure that forms the addictive mechanism. My experience with PMS and children with various forms of brain confusion clearly shows that a fundamental part of the etiology is commonly related to the sweet taste of sugar in all its different forms. This provides an explanation for why women with PMS express their craving for chocolate and/or sweets in the premenstrual week. Less commonly, children and PMS patients confess to salt craving. Since our adaptation to the perception of environmental stress factors depends on the automatic executive signals via the hypothalamic/autonomic/ endocrine axis, we are witnessing a massive incidence of maladaptation that is widespread through Western cultures. Although we know very little about thought processes and consciousness, it is clear that the limbic system is a computer that relies on oxidative metabolism for its efficient function. To put oft its recognition and relatively easy treatment may be risking the development of much more serious and untreatable disease. Perhaps the diagnostic confusion surrounding multiple system atrophy might be simplified if the biochemical lesion were to be discovered early in the continued progress of this group of diseases that have so far confounded their individual etiology. (66)

RELATED ARTICLE: Glucosamine Synergy Combines Glucosamine with Boswellia to Support Joint Health

Glucosamine Synergy, from Standard Process, combines glucosamine sulfate with Boswellia serrata extract, vitamins, and minerals to help maintain healthy joint function and relieve discomfort in affected areas. *

Glucosamine is a natural compound involved in forming cartilage, while boswellia helps support joint tissue by maintaining the body's normal inflammation-response function. Omega-3s from flaxseed oil help promote bone growth and restoration. Calcium and magnesium, also included in the formula, are essential in the maintenance of bone structure and function. This combination supports joint health and the body's normal connective-tissue repair process. *

For additional information or to order, see or call 800-558-8740.

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.


(1.) Kollensberger M, Stampfer-Kountchev M, Seppi K, et al. Progression of dysautonornia in multiple system atrophy: a prospective study of self-perceived impairment. Fur f Neural. 2007;14(1):66-72.

(2.) Lonsdale D. Dysautonornia, a heuristic approach to a revised model for etiology of disease. eCAM 2009;6(1):3-10;doi:10.1093lecaminem064.

(3.) Bannister R, ed. Autonomic Failure. Oxford University Press; 1984:666.

(4.) Shannahof-Khalsa D S. Selective unilateral autonomic activation: implications for psychiatry. CN.5 Spam 2007;12(8):625-634.

(5.) Bob P, Susta M, Glaslova K, et al. Dissociation, epilepticlike activity and lateralized dysfunction in patients with schizophrenia and depression. Neura Endocrin UM. 2007;28(6):868-874.

(6.) Tanida M, Sakatani K. I akano R, Tagai K. Relation between asymmetry or prefrontal cortex activities and the autonomic nervous system during a mental arithmetic task: near infrared spectroscopy study. Neurosci !Ott. 2004;369(11:69-74.

(7.) Foster P S, Harrison D W. Magnitude of cerebral asymmetry at rest: covarialion with baseline cardiovascular activity. Brain Cogn. 2006;61(3):286-297.

(8.) Critch ley H D, Taggart P, Sutton P M, et al. Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism. Brain, 2005;128(Pi1);75-85.

9. Eccles R, Eccles K S. Asymmetry in the autonomic nervous system with reference to the nasal cycle, migraine, anisocoria and Meniere's syndrome. Rhinology 1981;19(3):121-125.

(10.) Avnon Y, Nitzan M, Sprecher E, et al. Autonomic asymmetry in migraine: augmented parasympathetic activation in loll unilateral migraineurs. Brain. 2004;127(Pt9):2099-2108.

(11.) Ivchkova AE. Functional asymmetry in the innervation of smooth muscle organs. Bull Exp Riot Mod. 2005;139(2):163 167.

(12.) Mitani Y, Fukunaga N4, Kanbara K, et al. Evaluation of psychophysiological asymmetry in patients with fibromyalgia syndrome. App? Psychophysiol Biofeedback. 2006;31(3):217-225.

(13.) Tascilar N, Tekin NS, 12rdem L, et al. Unnoticed (lysoutonomic: syndrome of the face: harlequin syndrome. Auton Neurosci. 2007;137(1-21:1-9.

(14.) Moon St Shin DI, Park SH, Kim JS. Harlequin syndrome with crossed sympathetic deficit of the face and arm. Korean Med Sci. 2005;20(23):329-330.

(15.) Wali GM. Asymmetrical awake bruxism associated with multiple system atrophy. Mov Disord. 2004;19(3):352355.

(16.) Lonsdale D, Shamberger R J, Obrenovich M E. Exaggerated autonomic asymmetry: a clue to nutrient deficiency dysautonomia [online article]. Webmed Central. 2011:2(4):WMC001854.

(17.) Baraniuk J N, Kim D. Nasonasal reflexes, the nasals cycle, and sneeze. Curr Allergy Asthma Rep. 2007;7(21:105-111

(18.) Kimber J, Mitchell D, Mathias C. Chronic cough in the Holmes-Adie syndrome: association in five cases with autonomic dysfunction. 1 Neuroi Neurosurg Psychiatry. 1998;65(4):583-586.

(19.) Kosztyla-Hojna B, Popko M. [A rare case of Holmes-Adie syndrome in a 60-year old patient with a chronic cough cured in a laryngological way]. Poi Merkur Lekarski. 2007;23(137):371-374.

(20.) Rosas-Bellina M. Tracey K J. The neurology of the immune system: neural reflexes regulate immunity. Neuron. 2009;64(1 ):28-32.

(21.) Loehri T.A. Autonomic dysfunction, allergy and the upper airway. Curr Opin Otolaryngol Head Neck Surg. 2007;15(4):264-267.

(22.) Urbano F, Roux F, Schindler J, Mohsenin V. Impaired cerebral autoregulation in obstructive sleep apnea. J Appl Physiol. 2008;105(6):1852-1857.

23. Shao XM, Feldman JL. Central cholinergic regulation of respiration: nicotinic receptors. Acta Pharmacol Sin. 2009;30(6):761-770.

24. Melek IM, Seyfell E, Duru M, et al. Autonomic dysfunction and cardiac repolarization abnormalities in patients with migraine attacks. Med Monk Sci. 2007;13(3):RA47-RA49.

25. Vermersch P, Dufourd-Delalande S, Defoort-Dhellemmes S, et al. Tonic pupils in Sjogren's syndrome. [In French.] Rev Neuroi (Paris). 2005;161(10):963-966.

(26.) Zhang Q, Gu Z, Jiang J, et it Orthostatic hypotension as a presenting symptom of the Guillain-Barre syndrome. Clin Auton Res. 2010;20(3):209-210.

(27.) Matsumoto T Ushiroyama T, Kimura T, et al. Altered autonomic nervous system activity as a potential etiological factor of premenstrual syndrome and premenstrual dysphoric disorder. Biopsychosoc Med. 2007; Dec 20;1:24.doi 10.1186/1751-0759-1-24.

(28.) Montagna P. Hypothalamus, sleep and headaches. Neurol Sci. 2006; May 27 Suppl 2:S138-143.

(29.) Inouye K, Katsura E. Clinical signs and metabolism of beriberi patients. In: Shimazono N, eds. Review of Japanese Literature on Thiamine and Beriberi. Tokyo: Igaku Shoin Ltd; 1965:29-63.

(30.) Kawai C, Wakabayashi A, Matsamura T, Yui Y. Reappearance of beriberi heart disease in Japan. A study of 23 cases. Am f Med. 1980;69(3):383-386.

(31.) Elmadfa I, Majchrzak, D, Rust P, Genser D. The thiamine status of adult humans depends on carbohydrate intake. Mt J Vitam Nutr Res. 2001;71(4):217-221.

(32.) Lonsdale D. A Nutritionist's Guide to the Clinical Use of Vitamin 8-1. Tacoma: Life Sciences Press; 1987:209.

(33.) Lin SH, Halperin ML. Hypokalemia: a practical approach to diagnosis and its genetic basis. Curr Med Chem. 2007;14(14)1 551-1565.

(34.) Homer JM, Horner MM, Ackerman MI. The diagnostic utility of recovery phase QTc during treadmill exercise stress testing in the evaluation of long QT syndrome. Heart Rhythm. Epub May 30.

(35.) Thornalley PJ. The potential role of thiamine (vitamin B1) in diabetic complications. Curr Diabetes Rev. 2005;1(3):287-298.

(36.) Beltramo E, Berrone E, Buttiglieri S, Porta M. Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose. Diabetes Metab Res Rev. 2004;20(4):330-336.

(37.) Schmid U, Stopper H, Heidland A, Schupp N. Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro. Diabetes Metab Res Rev. 2008;24(5):371-377.

(38.) Lonsdale D. Thiamine tetrahydrofurfuryl disulfide; a little known therapeutic agent. Med Sci Monk. 2004;10(9): RA 199-203.Epub 2004 Aug 20.

(39.) Fujiwara M. Absorption, excretion and fate of thiamine and its derivatives in [the] human body. In: Shimazono N, Katsura E. Review of Japanese Literature on Thiamine and Beriberi Tokyo: Igaku Shoin Ltd; 1965:29-63.

(40.) Matsui K, Nakahara 1i, Watanabe H, et al. Inhibition by thiamine tetrahydrofurfuryl disulfide (TTFD) of the arachidonic acid cascade-line activation as evidenced in the heart-lung preparation of the dog. Jpn J Pharmacol. 1985:39(3):375-379.

(41.) Lonsdale D, Shamberger R J, Audhya T. Treatment of autism spectrum children with thiamine tetrahyhdrofurfuryl disulfide; a pilot study. Neura Endocrinol Lett. 2002;23(4):303-308.

(42.) Djoenaidi W, Notermans S L. Thiamine tetrahydrofurfuryl disulfide in nutritional polyneuropathy Eur Arch Psychiatry Neural Sci 1990;239(4):218-220.

(43.) Meador K, Loring D, Nichols M, et al. Preliminary finding of high dose thiamine in dementia of Alzheimer's type. J Ccriat Psychiatry Neural 1993;5(4):222-229.

(44.) Mimori V. Katsuoka K, Nakamura S. Thiamine therapy in Alzheimer's disease. Metabo! Brain Dis 1996;11(1):89-94.

(45.) Babaei-Jadidi R, Karachalias N, Ahmed N, et al. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes. 2003;52(8):2110-2120.

(46.) Lonsdale D. Three case reports to illustrate clinical application in the use of erythrocyte transketoIase. eCAM. 2006;4(2):247-250.

(47.) Habara R, Yasuhara H. Erythrocytosis in thiamine deficient rats. Jpn I Pharmacol 1981;31:985-993.

(48.) Neubauer JA, Sunderram J. Oxygen-sensing neurons in the central nervous system. J Appl Physiot 2004;96:367-374.

(49.) Zucali JR, Lee M, Mirand EA. Carbon dioxide effects on erythropoietin and erythropoiesis. f Lab Clin Med 1978;92:648-655.

(50.) Blechert J, Wilhelm FH, Meuret AE, et al. Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO(2) enriched air in panic disorder, social phobia, and healthy controls. Biol Psychol. 2010;84(1):104-111. Epub Jan 11.

(51.) Vortmeyer AO, Hager C, Laes R. Hypoxia-ischemia and thiamine deficiency. Clin Neuropthol. 1993;12(4):184190.

(52.) Macey PM, Woo MA, Macey KE, et al. Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome. I Appl Physiol. 2005;98(3):958-969.

(53.) Lonsdale D. A review of the biochemistry, metabolism and clinical benefits of thiaminte) and its derivatives. eCAM 3006;3(121:49-59.

(54.) Volvert M-L, Seyen S, Piette M, et al. Benfotiamine, a synthetic 5-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. BMC Pharmacol. 2008 June 12;8:10;doi:10.1186/1471-2210-8-10.

(55.) Zhao Y, Pan X, Zhao J, et al. Decreased transketolase activity contributes to impaired hippocampal neurogenesis induced by thiamine deficiency. Neurochem. 2009;111(21:537-546.

(56.) Zhao J, Zhong C J. A review on research progress of transketolase Neurosci Bull. 2009;25(2):94-99.

(57.) Lee FIB, Seo jY, Yu MR, et al. Radical approach to diabetic nephropathy. Kidney lot Stippl. 2007;(1 06):S67-S 70.

(58.) Shangari N, Bruce WR, Poon R, O'Brien PJ. Toxicity of glyoxals - role of oxidative stress, metabolic detoxification and thiamine deficiency. Biochemrt Soc Trans. 2003; Dec;31(pt6):1390-1393.

(59.) Bettendorff LA. non-cofactor role of thiamine derivatives in excitable cells. Arch Physic), Blochem.1996(6).75-751.

(60.) Bettendorff L, Wins P. Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors. FEBS Journal. 276;2009:2917-2925.

(61.) Lonsdale D, Shamberger R J. Red cell transketolase as an indicator of nutritional deficiency. Am J Clio Nutr. 1980;33:205-211.

(62.) Schenk G, Duggleby RG, Nixon PF. Properties and functions of the thiamin diphosphate dependent enzyme transketolase. lot J Biochem Cell Biol 1998;Dec 30(12):1297-1318.

(63.) Calingasan NY, Park L CH, Calo IL, et al. Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism. Am Pathol 1998;153(2):599-610.

(64.) Hazell AS, Butterworth RF. Update of cell damage mechanisms in thiamine deficiency: focus on oxidative stress, excitotoxicity and inflammation. Alcohol Alcohol. 2009;44(2):141-147.

(65.) Zhang X, Zhang G, Zhang H, et al. Hypothalamic 1KKbeta/NF-kB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008;135(1)161-73.

(66.) Quinn N. Multiple system atrophy - the nature of the beast. J Neural Neurosurg Psychiat. 1989 Jun(Suppl):78-89.

by Derrick Lonsdale, MD, FAAP, FACAM

Derrick Lonsdale received his degree MBBS in 1948 from London University. After service in the Royal Air Force, he was a family physician under the British Health Service until 1957, when he immigrated to Canada as a medical officer in the Royal Canadian Air Force. After residency and board certification in pediatrics at Cleveland Clinic Foundation, he joined the staff in the Pediatric Department from 1962 to 1982, when he went into private CAM practice. He is a Fellow of the American College of Nutrition and the American College for Advancement in Medicine and a Certified Nutrition Specialist, and edited the now discontinued ACAM Journal for 14 years. He has maintained interest and written widely on the metabolism of thiamine and its therapeutic value for 39 years.

Derrick Lansdale, MD, FAAP, FACAM 24700 Center Ridge Road Westlake, Ohio 44145 440-835-0104; fax 440-871-1404 dlonsdale@poLnet Physician in private practice of complementary alternative medicine Associate Emeritus Pediatrician, Cleveland Clinic Foundation, Cleveland, Ohio
COPYRIGHT 2012 The Townsend Letter Group
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2012 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Lonsdale, Derrick
Publication:Townsend Letter
Article Type:Report
Geographic Code:1USA
Date:Oct 1, 2012
Previous Article:Depression, fibromyalgia, chronic fatigue, and pain: shared neurobiological pathways and treatment.
Next Article:Multiple chemical sensitivity: etiology, mechanism, and epigenomic manifestations.

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters