thiamine - Page 13

Over the past year, I have written extensively about thiamine deficiency post Gardasil vaccination (here, here, here, here). We now have five cases where thiamine deficiency was identified and clinical symptoms remediated with supplementation. Many more are suspected but recognition and testing have been slow. Thiamine deficiency may not be limited to the post Gardasil population, although that is where we first recognized it. Symptoms of thiamine deficiency and dysfunctional oxidative metabolism have been observed amongst the post fluoroquinolone and post Lupron populations and likely other populations adversely affected by a vaccine or medication, though data are limited. For the current paper, I should like to offer an explanation of the effect of thiamine deficiency in relationship to the stress of the vaccination or medications.

Thiamine Deficiency and Diet

With the widespread ingestion of simple carbohydrates that is almost a hallmark of Western civilization I suggest that the Gardasil vaccination and certain other medications represent “the last straw to break the camel’s back”.  I have included a case report, from my clinical practice, as an example of the effect of a simple nutritional stressor – sugar – imposed on an individual who’s oxidative metabolism was marginal at the time. I have included the references for anybody that wishes to check on how much of this is published.

Cellular Energy and Diet

Present knowledge indicates that cellular energy arises only from oxidation of food sources. The prevalently common form of nutritional mayhem in the U.S. is a high calorie content from simple carbohydrates with insufficient vitamin/mineral content to catalyze efficient oxidation. This form of malnutrition might be compared with functional decline in a choked internal combustion engine. Evidence presented in this case report presented below indicates that simple carbohydrate ingestion can have far-reaching consequences.  A review indicates that a common manifestation of its effect is oxidative stress in the brain, particularly in the limbic system where emotional reflexes originate and where the controls of the autonomic and endocrine systems react automatically to sensory input. Beriberi is the classic example of high calorie carbohydrate malnutrition and is the prototype for dysautonomia (abnormal function of the autonomic nervous system [ANS] ) in its early stages. A later stage results in degeneration of autonomic ganglia and irreversible disease. Symptoms arising from thiamine deficiency or abnormal homeostasis are protean and diverse in nature.

Dysautonomia, Oxidative Stress and Thiamine

Dysautonomia, a common presentation of functional disease and often associated with variable organic diseases caused by loss of oxidative efficiency in the brain, has been reviewed. A hypothesis was presented that there is a combination of genetic risk, different forms of sensory input defined as stress, particularly those imposed by present civilization, and high calorie malnutrition that are collectively responsible. This was presented diagrammatically by the degree of overlap in the “three circles of health, named genetics, stress and nutrition” (1).  It is also known that mitral valve (a heart valve) prolapse (MVP) is widespread in the population and is associated with dysautonomia, although the cause and effect relationship is said to be unknown (2-4). MVP is associated with adrenergic overdrive (the well-known adrenalin rush) in the normally balanced adaptive reactions of the autonomic/endocrine axis (5-8). (The autonomic nervous system and the glands of the endocrine system are under the control of the brain).  Panic disorder, also sometimes associated with MVP, is seen as an example of falsely triggered fight-or-flight reflexes engendered in the limbic brain.  Pasternac and associates (6) showed that symptomatic patients with MVP demonstrated increased resting sympathetic tone and that supine bradycardia (slow heart rate) suggested increased vagal (the vagus is a nerve that runs from the brain to many parts of the body) tone at rest. Davies and associates (7) demonstrated physiologic and pharmacologic hypersensitivity of the sympathetic system in a group of patients with MVP. Sympathoadrenal responses were noted in rats exposed to low oxygen concentration (9) and impaired cerebral autoregulation has been reported in obstructive sleep apnea in human subjects (10). It has also been shown that thiamine deficiency produces traditionally accepted psychosomatic or functional disease (11,12).  A low oxygen concentration results in changes in brain structures similar to those induced in thiamine deficiency (13).

A Case Study of Thiamine Deficiency and Dietary Influence: The Sugar Problem

The Table below shows laboratory results from an 84-year old man who had begun to experience severe insomnia for the first time in his life. He also had painful tenosynovitis (also known as “trigger finger”) in the index finger of the left hand.  He had edited a journal for some 14 years and for several years, had been a member of a bell choir in which he played a heavy base bell in each hand, involving repetitive trauma to the index fingers.  He did not crave sugar, his ingestion of simple carbohydrates being minimal to moderate. The only treatment offered was complete withdrawal from all forms of simple carbohydrates.

Serial laboratory studies revealed a gradual improvement over six months and his weight decreased from 182 to 170 pounds without any other change in diet. Insomnia and tenosynovitis gradually improved. The Table shows that serial laboratory tests over a period of six months, from February to August, showed continued gradual improvement. In September, the day after a minimal ingestion of simple carbohydrate, there was an increase in triglycerides and TPPE.

Understanding the Labs

Notice that the triglycerides dropped from 206 in February to 124 in August, then rose again in September only one day after a minimal amount of sugar.  Triglycerides are part of the routine lipid profile test done by doctors and are well known to be related to the ingestion of simple carbohydrates.  Fibrinogen and HsCRP are both recognized as markers of inflammation.  Notice that both of them decreased between February and August but HsCRP rose again in September like the triglycerides.  The TPPE is the important part of the transketolase test.  The higher the percentage, the greater is the degree of thiamine deficiency.  Notice that it dropped from 35% to zero between February and August, but that it jumped to 8% in September, the day after the ingestion of sweets.  I have provided the normal laboratory values for the discerning reader.

The abnormal TPPE indicated thiamine deficiency in this patient (14). The increased triglycerides and their steady decrease over time indicated that sugar ingestion was a potent cause of his symptoms. An increase in fibrinogen and hypersensitive CRP are both laboratory markers of inflammation, although the site is not indicated.  Recent studies in mice (15) have shown that high calorie malnutrition activates a normally silent genetically determined mechanism in the hypothalamus, causing either obesity, inflammation or both. The potential association of thiamine with electrogenesis (formation of electrical energy) (16) may have some relationship with brain metabolism and the complex functions of sleep.

Compromised Oxidative Function: Thiamine Deficiency, Beriberi and Diet

It has long been known that beriberi is a classic disease caused by high consumption of simple carbohydrate with insufficient thiamine to process glucose into the citric acid cycle. (This complex chemistry represents the engine of the cell, meaning that it produces the energy for function).  Widespread thiamine deficiency has been reported in many publications(17-20), producing the same brain effects as low oxygen concentration (13,21). In rat studies, this produces an imbalance in the autonomic nervous system (9). Thiamine  deficiency is easily recognized in a clinical laboratory by measuring TKA and TPPE (14).

Thiamine and the Brain

Thiamine triphosphate (TTP) (this is synthesized from thiamine in the brain) is known to be important in energy metabolism. Although its action is still unknown, the work with electric eels has revealed that the electric organ has a high concentration of TTP and may have a part to play in electrogenesis, the transduction of chemical to electrical energy (16,22). The energy for its synthesis from thiamine comes from the respiratory chain. This is also complex chemistry in the formation of energy synthesized within mitochondria, the “engines” of the cell (23), so that any form of disruption of mitochondria would be expected to reduce adequate synthesis of this thiamine ester. Although slowing of the citric acid cycle appears to be the main cause of the biochemical lesion in brain thiamine deficiency (24), the part played by TTP is not yet known. Alzheimer’s disease has been helped by the use of therapeutic doses of thiamin tetrahydrofurfuryl disulfide (TTFD) (25), a more efficient method of administering pharmacologic doses of thiamine (26).

Acetylcholine, the neurotransmitter used by both branches of the autonomic nervous system, is generated from glucose metabolism, requiring  B vitamins, particularly thiamine. Choline is a “conditional nutrient”, meaning that it is derived mainly from diet but is also made in the body. The presence of all these nutrients leads to the synthesis of this neurotransmitter.  It’s depletion would affect both branches of the autonomic nervous system, resulting in dysautonomia.

There is evidence that high-dose thiamin increases the effect of acetylcholine (27). Animal studies have shown that TTFD improves long term memory in mice (28) and it has been shown that it extends the duration of  neonatal seizures in DBA/J2 mice, seizures that normally cease in a few days with normal maturation (29).  These seizures are naturally related to a prolonged effect of this neurotransmitter in this strain of mouse.  The experimental prolongation of the seizures by administration of TTFD indicated that it enhanced the effect of the neurotransmitter. A pilot study in autistic spectrum disorder showed clinical improvement in 8 of the 10 children treated with TTFD (30), a disease that has been shown to have reduced  parasympathetic activity in the heart (31,32). Neural reflexes regulate immunity (33).  Dysautonomia was found in a large number of patients with cancer at Mayo Clinic (34).

Dysautonomia and Thiamine Deficiency         

Evidence has been presented that a common connection exists between dysautonomia, inefficient oxidative metabolism produced mainly by high calorie malnutrition, and organic disease (1). Thiamine enters the equation in terms of its relationship with carbohydrate ingestion and its use by the brain as fuel (35). Decreased transketolase activity in brain cells induced by thiamine deficiency contributes to impaired function of the hippocampus (36) each, part of the limbic system control mechanisms that affect autonomic sympathetic/parasympathetic balance. Erythrocyte (red cells) transketolase indicates abnormal thiamine homeostasis that is commonly achieved by carbohydrate ingestion and deficiency of vitamin B (14).  Beriberi gives rise to functional changes in the autonomic nervous system in its early stages and produces irreversible degeneration in its later stages (37). This, because it represents a largely forgotten aspect of disease, might equate with the wide use of simple carbohydrates in Western civilization. Deficiency of other essential non-caloric nutrients has been associated with dysautonomia (1).

The Role of Nutritional Stress in Post Vaccination and Medication Reactions

Two results of post- Gardasil vaccination have been reported, Postural Orthostatic Tachycardia Syndrome (POTS) and cerebellar ataxia.  POTS, a disease easily confused with beriberi, is one of the many syndromes reported under the general heading of dysautonomia and stress related intermittent episodes of cerebellar ataxia were reported in thiamin dependency (38).  Since the inflammatory reflex has recently been found to be involved with the sympathetic branch of the ANS (39), enhancement of its dysfunction by TD might explain some of the Gardasil affected illnesses.

Conclusion

Thiamine deficiency is now accepted as the major cause of the ancient scourge of beriberi. The underlying mechanisms are still not fully understood for we do not yet know the complete roles of thiamine. The clinical effects are protean and unpredictable. It is, however, clear that thiamine has a vital effect on many aspects of oxidative metabolism and its deficiency can be used as a model for the clinical effects produced by disruption in energy synthesis. It can be summed up under the general heading of dysoxegenosis and thiamine is certainly not the only component that governs this vital life process. The example of beriberi indicates that the brain, peripheral nervous system and the heart are the tissues most affected by the disease, the tissues that rapidly consume oxygen.

The limbic system is a complex computer that organizes all our adaptive survival reflexes and its sensitivity to hypoxia is well known. It is evident that non-caloric nutrient deficiency, especially thiamine, gives rise to the same symptoms and histopathology as mild to moderate hypoxia (oxygen deficiency) and that the leading symptomology is that of dysautonomia. Since the limbic system gives rise to emotional reflexes and mild to moderate hypoxia enhances sympathoadrenal response, it can be expected that an affected individual would be more aggressive and more likely to experience exaggerated fight-or-flight reflexes. A “nursed” emotional grievance might be expected to explode in violence that would otherwise be curtailed or suppressed by normal brain metabolism. It suggests that high calorie malnutrition, particularly that provided by excessive consumption of simple carbohydrates, gives rise to uncontrolled pathophysiological actions that might explain some of the widespread incidence of emotional and psychosomatic disease in contemporary society. It may also explain some of the “hot” juvenile crime and vandalism, much of which is poorly understood in our present civilization. It is also hypothesized that a marginal state of oxidative metabolism, perhaps asymptomatic or with only mild symptoms that are ignored, might be precipitated into clinical expression with a mild degree of stress imposed by a vaccination. The individual in the case reported above appeared to be unusually sensitive to sugar ingestion and this may be an additional genetically determined risk.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

Image created using Canva AI.

References

1. Lonsdale D. Dysautonomia, a heuristic approach to a revised etiology for disease. eCAM 2009;6(1):3-10.
2. Orhan A L, Sayar N, Nurkalem Z, Uslu N, Erdem I, Erdem E C, Assessment of autonomic dysfunction and anxiety levels in patients with mitral valve prolapase. Turk Kardiyol Dern Ars 2009;37(4):226-233.
3. Alpert M A, Murkerji V, Sabeti M, Russell J L, Beitman B D. Mitral valve prolapse, panic disorder, and chest pain. Med Clin North Am 1991;75(5):1119-1133.
4. Raj A, Sheehan D V. Mitral valve prolapse and panic disorder. Bull Menninger Clin 1990;54(2):199-208.
5. Di Salvo G, Pergola V, Ratti G, Tedesco M A, Giordano C, Scialdone A, et al. Atrial natriuretic factor and mitral valve prolapse syndrome. Minerva Cardioangiol 2001;49(5):317-325.
6. Pasternac A, Tubau J F, Puddu P E, Krol R B, de Champlain J. Increased plasma catecholamine levels in patients with symptomatic mitral valve prolapse. Am J Med. 1982;73(6):783-790.
7. Davies A O. Mares A, Pool J L, Taylor A A. Mitral valve prolapse with symptoms of beta-adrenergic hypersensitivity. Beta 2-adrenergic receptor supercoupling with desensitization on isoproterenol exposure. Am J Med 1987;82(2):193-201.
8. Boudoulas H, Wooley C F. Mitral valve prolapse syndrome: neuro-endocrinological aspects. Herz 1988;13(4):249-258.
9. Johnson T S, Young J B, Landsberg L, Dana C A. Sympathoadrenal responses to acute and chronic hypoxia in the rat. J Clin Invest 1983;71:1263-1272.
10. Urbano F, Roux F, Schindler J, Mohsenin V. Impaired cerebral autoregulation in obstructive sleep apnea. J Appl Physiol 2008;105(6):1852-1857.
11. Lonsdale D, Shamberger R J. Red cell transketolase as an indicator of nutritional deficiency. Am J Clin Nutr 1980;33:205-211.
12. Lonsdale D. Three case reports to illustrate clinical applications in the use of erythrocyte transketolase. eCAM 2006;4(2):247-250.
13. Macey P M, Woo M A, Macey K E, Keens T G, Saeed M M, Alger J R et al. Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital hypoventilation syndrome. J Appl Physiol 2005;98(3):958-969.
14. Massod M F, McGuire S L, Werner W R. Analysis of blood transketolase activity.Am J ClinPathol 1971;55:465-470.
15. Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamc 1KKbeta/N-kB and ER stress link overnutrition to energy imbalance and obesity. Cell   2008;135(1):61-73.
16. Bettendorff L, Michel-Cahay C, Grandfils C, De Rycker C, Schoffeniels E. Thiamine triphosphate and membrane-associated thiamine phosphatases in the electric organ of Electrophorus electricus. J Neurochem 1987;49(2):495-502.
17. O’Keefe S T, Tormey W P, Glasgow R, Lavan J N. Thiamine deficiency in hospitalized elderly patients. Gerontology 1994;40(1):18-24.
18. Macias-Matos C, Rodriguez-Ojea A, Chi N, .Zulueta D, Bates C J. Biochemical evidence of thiamine depletion during the Cuban neuropathy epidemic, 1992-1993. Am J Clin Nutr 1996;64(3):347-353.
19. Mazavet D. Vassilev K, Perrigot M. Neuropathy with non-alcoholic thiamine deficiency: two cases of bladder disorders [article in French]. Ann Readapt Med Phys 2005;48(1):43-47.
20. Hazell A S, Butterworth R F. Update of cell damage mechanisms in thiamine deficiency: focus on oxidative stress, excitotoxicity and inflammation. Alcohol Alcohol 2009;44(2):141-147.
21. Vortmeyer A O, Hagel C, Laas R. Hypoxia-ischemia and thiamine deficiency. Clin Neuropathol 1993;12(4):184-190.
22. Nghiem H O, Bettendorff  L,Changeux J P. Specific phosphorylation of Torpedo 43K raspsyn by endogenous kinase(s) with thiamine triphosphate as the phosphate donor. FASEB J 2000;14(3):543-554.
23. Gangolf M, Wins P, Thiry M. Thiamine triphosphate synthesis in the rat brain is mitochondrial and coupled to the respiratory chain. J Biol Chem 2010;285(1):583-594.
24. Bettendorff  L, Sluse F, Goessens G,  Wins P, Grisar T. Thiamine deficiency-induced partial necrosis and mitochondrial uncoupling in neuroblastoma cells are rapidly reversed by addition of thiamine. J Neurochem 1995;65(5):2178-2184.
25. Mimori Y, Katsuoka H, Nakamura S. Thiamine therapy in Alzheimer’s disease. Matab Brain Dis 1996;11(1):89-94.
26. Lonsdale D. Thiamine tetrahydrofurfuryl disulfide: a little known therapeutic agent. Med Sci Monit 2004;10(9):RA199-203.
27. Meador K J. Nichols M E, Franke P, Durbin M W. Evidence for a central cholinergic effect of high-dose thiamine. Ann Neurol 1993;34:724-726.
28. Micheau J, Durkin D P, Destrade D C, Rolland Y, Jaffard R. Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation.  Pharacol Biochem Behav 1985;23(2):1
29. Lonsdale D. Effect of thiamine tetrahydrofurfuryl disulfide on audiogenic seizures in DBA/2J mice. Dev Pharmacol Ther 1982;4(1):28-36.
30. Lonsdale D, Shamberger R J, Audhya T. Treatment of autism spectrum children with thiamine tetrahyhdrofurfuryl disulfide: a pilot study. Neuro Endocrinol Lett 2002;23(4):303-308.
31. Ming X,  Julu P O O, Brimacombe M, Connor S, Daniels M L. Reduced cardiac parasympathetic activity in children with autism. Brain Dev 2005;27:509-516.
32. Palmieri L Persico A M. Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochem Biopys Acta 2010; May 1 [Epub ahead of print].
33. Rosas-Ballina M, Tracey K J. The neurology of the immune system: neural reflexes regulate immunity. Neuron 2009;64(1):28-32.
34. McKeon A, Lennon V A, Lachance D H, Fealey R D, Pittock S J. Ganglionic acetylcholine receptor autoantibody: oncological, neurological and serological accompaniments. Arch Neurol 2009;66(6)(:735-741.
35. Elmadfa I Majchrzak D, Rust P Genser D. The thiamine status of adult humans depends on carbohydrate intake. Int J Vitam Nutr Res 2001;71(4):217-221.
36. Zhao Y, Pan X, Zhao J, Wang Y, Peng Y, Zhong C. Decreased transketolase activity contributes to impaired hippocampal neurogenesis induced by thiamine deficiency. J Neurochem 2009;111(2):537-546.
37. Inouye K, Katsura E. Etiology and pathology of beriberi. In: Thiamine and
38. Beriberi. Igaku Shoin Ltd. Tokyo;1965:1-28.
39. Lonsdale D. Faulkner W R, Price J W, Smeby R R. Intermittent cerebellar ataxia associated with hyperpyruvic academia,hyperalaninemia and hyperalaninuria. Pediatrics 1969;43:1025-34.
40. Martelli D, Yao S T,McKinley M J,McAllen R M. Reflex control of inflammation by sympathetic  nerves, not the vagus. J Physiol 2014; Jan 13 [Epub ahead of print].

Related posts:

How Can Something As Simple as Thiamine Cause So Many Problems? It All Comes Down to Energy Childhood Trauma, Diet, and Behavior Marginally Insufficient Thiamine Intake and Oxalates