thiamine deficiency hypertension Archives

Diet Induced Pseudo-Hypoxia and Hypertension

Published on March 18, 2024

7873 views

Although hypertension has become almost exclusively used to indicate high blood pressure, it is worth examining the true underlying meaning. The prefix “hyper” is from the Greek, meaning over or above. Tension is defined as “the state of being stretched tight”. Perhaps then it is worth looking at how this applies to blood pressure.

When a blood pressure is measured, there are always two figures represented. The higher number is known as “systolic” and the lower one as “diastolic”. The systolic is when the heart is contracting and indicates the ability of the arterial system to expand enough to accommodate the pressure from an increased volume of blood. The diastolic indicates the pressure in the arterial system when the heart is resting between beats. We are therefore looking at the highest and lowest pressures in a closed tube system that must be capable of expanding and contracting.

Since the system is made from live cells, it does not behave like a rubber tube with elastic recoil. The arteries where blood pressure is measured are lined with muscles. It is the contraction and relaxation of these muscles that control the capacity of the artery to accommodate the amount of blood arriving from the heart. The muscles are controlled by nerves carrying messages from the brain. These muscles are completely different from those that are activated willingly, such as those in the limbs. They are contracted and relaxed automatically by a part of the brain that acts more like a computer. The body muscles are activated by a nervous system known as “voluntary”. The arterial muscles are activated by a completely separate an involuntary nervous system known as autonomic (ANS). We therefore have to examine the control mechanisms.

Understanding the Autonomic Nervous System

I have discussed this nervous system many times in Hormones Matter because, when it goes wrong, it is a potent source of disease. The nerves of this system go to every organ within the body. The control system is in the lower part of the brain. It consists of two channels. One is known as sympathetic: the other is known as parasympathetic. Although they work together, their actions oppose each other and I will try briefly to outline this dichotomy.

Sympathetic. The sympathetic nervous system is designed for both physical and mental action through a reflex mechanism known as the fight-or-flight. It prepares us to meet an enemy or escape from danger. One of its actions is to raise the blood pressure. It does this by contracting the arterial muscles already described.

Parasympathetic. When the action is completed, the brain controls automatically withdraw the activity of the sympathetic and initiate those of the parasympathetic nervous system. When this happens, the body is prepared for resting.

Chronic Activation of the Sympathetic Nervous System

There is a large amount of evidence in the medical literature that this is the primary cause of chronically high blood pressure. If the system is healthy, the blood pressure will go down on completion of the action. If not, the blood pressure remains elevated. From here, I am going to hypothesize why this happens. Please remember as you read it that it is a hypothesis, not a proven fact.

Hypoxia. This word simply means lack of oxygen. Obviously, this is a dangerous state for the brain and it is not surprising that it will activate the sympathetic component described above, including raising the blood pressure.

Pseudo-hypoxia. The prefix “pseudo”, meaning false, or sham (from the Greek, lying, false) has been used in the medical literature to describe a state that is exactly like that of hypoxia when the presence of oxygen is normal. In order to understand this, focus on the fact that oxygen must be introduced to the body but is completely useless unless it is consumed. Therefore we must try to indicate how oxygen consumption occurs.

Oxidation and burning. All forms of burning are derived from oxygen combining with a fuel, liberating heat energy. That is why we are warm blooded, but other forms of energy are produced to drive physical and mental function. Because the burning is incomplete, ash is formed. Our cells derive their energy by the oxygen, delivered in the blood from the lung, combining with glucose. The “ash” is carbon dioxide and water, discarded in the breath. The oxidation of glucose is governed by a set of enzymes that require the vitamin B complex for their action. The leader of this orchestration appears to be vitamin B1 (thiamine). That is why many papers have appeared in the medical literature that describes thiamine deficiency as a cause of pseudo-hypoxia. Its function is to catalyze the enzymes essential for oxidation. Its deficiency results in lack of sufficient energy. It is therefore not surprising that one of the symptoms of thiamine deficiency is fatigue.

Calorie/thiamine ratio. A healthy diet provides us with calorie producing elements that are broken down to glucose and used as fuel. The amount of thiamine provides a normal calorie/thiamine ratio that enables efficient oxidation. If we load the diet with empty calories (calories without essential non-calorie nutrients that include thiamine) the calorie/thiamine ratio becomes abnormal. Measuring the concentration of thiamine in the blood would be normal for a healthy diet but inadequate to meet the demand of the empty calorie load. The laboratory method for identifying thiamine deficiency is by measuring it in the blood. If the result is reported by the laboratory as normal, the relevant symptoms produced by inadequate oxidation may well be ascribed to causes other than thiamine deficiency.

Hypothesis: High Calorie Malnutrition Induces Chronic Sympathetic Overdrive

I suspect that a common cause of hypertension is high calorie malnutrition, inducing a state of chronic sympathetic overdrive. It may be why obesity in children often foretells their rise in blood pressure. Perhaps another cause is the gradual diminution of oxidation associated with aging. There are genetic mechanisms that are turned on by hypoxia and these also may be activated by pseudo-hypoxia, e.g. thiamine deficiency.

Spontaneously Hypertensive Rats

Lipothiamin is a synthetic derivative of thiamine. Its biologic properties enable it to be used as a drug. A rat known as SHR (spontaneously hypertensive rat) is used as the animal model for studying the effect of antihypertensive drugs. Many years ago I took a group of these rats and treated them with Lipothiamin to see if it would prevent the rise in blood pressure that always occurs in these animals. There was a statistically significant difference between the experimental rats and the controls, indicating that this thiamine derivative did indeed prevent the spontaneous rise in blood pressure. This experiment is published in our book (Lonsdale D, Marrs C. Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition). It obviously requires human subjects to research the use of this completely non-toxic, nutrient/drug derivative but nevertheless provides us with solid clues about hypertension.

Conclusion: Diet Matters

It has been said that simplicity must be distilled out of complexity in order to make complex issues usable. The brain/body, whether we like to recognize it or not, is an “electrochemical machine” that must obey all the physical laws designed by Mother Nature. Health is governed by only three factors:

Genetics: the enormous complexity is dictated by a code written in DNA. Passage from generation to generation makes mistakes and represents our inheritance.
Stress: defined as anything that requires physical/mental defensive response. The response, designed for relatively short term action, demands a huge consumption of energy.
Nutrition: this is the only one of the three issues that we can control. It must supply both fuel and the multiple factors that enable the fuel to be turned into energy.

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Hypertension, the Autonomic System, and Thiamine

by Derrick Lonsdale MD, FACN, CNS

Published on February 2, 2022

14556 views

hypertension, autonomic system and thiamine

Physiological studies have long demonstrated the vital role of the autonomic nervous system in controlling blood pressure values. Beriberi, the classical disease due to thiamine deficiency, is the prototype example of dysautonomia in its early stages. The limbic system and brainstem are peculiarly sensitive to thiamine deficiency. Hypoxia is known to initiate sympathetic nervous system activity. Because thiamine deficiency has effects similar to those of hypoxia, these effects have been referred to in the literature as arising from pseudo-hypoxia.

There is much evidence that the common indulgence of empty calories, particularly those derived from simple carbohydrates and processed fats, is producing pathophysiologic brain effects due to what has been termed high calorie malnutrition. This form of malnutrition is totally different from that produced by starvation, the traditional form of malnutrition. Although the concentration of thiamine in the blood may be considered to be normal, it is only normal in the presence of a healthy diet. The excess of empty calories results in a high calorie/thiamine ratio that overwhelms the normal oxidative capacity associated with the presence of thiamine.

Patients suffering from high calorie malnutrition represent the “walking sick” of America. In its early stages it results in a polysymptomatic disease that defies our present concept of diagnosis. Traditional laboratory results may be quite normal or nonspecifically abnormal and the symptoms “written off” as psychosomatic. It may well be that some cases of hypertension, affecting millions, is part of the clinical effect produced by the dysautonomia of thiamine deficiency. The text that follows provides support for this hypothesis. It may also be true that failure to recognize the true etiology may lead over time to chronic brain disease in the untreated patient.

Autonomic Control of Blood Pressure

It has been well documented that the autonomic nervous system plays a key role in controlling blood pressure values. The hypothesis has been put forward that the origin, progression, and outcome of human hypertension are related to dysfunctional autonomic cardiovascular control, especially to abnormal activation of the sympathetic division. There is a consistent association between hypertension and pro-inflammatory cytokines of the innate and adaptive immune system. The sympathetic nervous system, a major determinant of hypertension, is pro-inflammatory, whereas the parasympathetic nerve activity dampens the inflammatory response through α7-nicotinic acetylcholine receptors. In the Goldblatt model of renal hypertension and the use of renal denervation in the treatment of drug-resistant hypertensive patients, autonomic mechanisms underpin the maintenance of this hypertension. Autonomic mechanisms initiate the development and maintenance of renal vascular hypertension. Obesity-associated overnutrition leads to neural inflammatory molecular changes, particularly in the hypothalamus, leading to elements of the metabolic syndrome. Increased sympathetic activation is a critical mediator.

Children, Hypertension, and Obesity

There are an increasing number of children diagnosed with primary hypertension, mainly in association with obesity. One of the factors considered is dysregulation of the autonomic nervous system. Emerging evidence suggests that the sympathetic branch plays a much broader role in the regulation of blood pressure, including the development and maintenance of sustained hypertension by a chronically elevated central sympathetic tone. A recent study examined the relationship between the autonomic nervous system dysfunction, anxiety and depression in hypertension. The sympathetic nervous system and arterial baroreceptor reflex control of renal sympathetic nerve activity has been proposed to play a role in long-term control of arterial pressure.

Abundant evidence supports the role of the sympathetic nervous system in the pathogenesis of obesity -related hypertension. The mechanisms are incompletely understood. A study supports the concept that increased renal sympathetic activity is the critical mechanism by which increased central sympathetic outflow initiates and maintains reductions in renal excretion function, resulting in obesity hypertension. Hypertension and obesity are risk factors for coronary heart disease in adults. Childhood weight problems and high blood pressure increase the risk of subsequent obesity and hypertension as an adult.

The Role of Hypoxia in Blood Pressure Regulation

Obstructive sleep apnea is one of the most common causes of hypertension in Western societies, causing chronic intermittent hypoxia. The normal homeostatic balance between HIF-1α-dependent pro-oxidant and HIF-2α dependent antioxidant enzymes is disrupted. Hypertension affects one in three United States adults and involves the integration of the actions of multiple organ systems, including the central nervous system, driving enhanced sympathetic outflow and increased blood pressure. There is increased understanding of hypothalamic activity in hypertension. Changes in the baroreflex and chemoreflex may contribute to the development of chronic hypertension observed in obstructive sleep apnea patients. Animal studies have identified induced hypoxic hypertension, but this is still conjectural in humans.

Thiamine Deficiency and Pseudo-hypoxia

Because mild to moderate thiamine deficiency results in pseudo-hypoxia in the limbic system and brainstem, emotional and stress reflexes of the autonomic nervous system are stimulated and exaggerated. Like chronic intermittent hypoxia that activates HIF-1 and suppresses HIF-2-mediated transcription, thiamine deficiency induces HIF-1α mediated gene expression similar to that observed in hypoxic stress. Thiamine deficiency induces an early, functionally significant central muscarinic cholinergic lesion that may be at least part of the reason for sympathetic overdrive. Details of the genetic determination in hypertension are poorly understood. A novel blood pressure locus that encodes a previously uncharacterized thiamine transporter has been reported, again perhaps emphasizing the importance of thiamine deficiency in hypertension. Evidence supports the likelihood that an increased cytosolic ratio of NADH/NAD+, caused by hyperglycemia, results in playing an important role in the pathogenesis of diabetic complications. Thiamine deficiency occurs in individuals with diabetes, leading to hyperglycemic-induced damage and oxidative stress. The potential benefit of long-term replacement is not yet known but may well reduce the cardiovascular risk and angioplasty complications. Thiamine deficiency should be considered in all patients with pulmonary hypertension of unknown origin.

Maternal hypertension is the most common medical disorder of pregnancy, varying from 4 to 6% of all pregnancies. The daily dose of 100 mg of thiamine has been given to over 1000 non-selected prenatals starting in the second and third trimesters. The expected number of toxemia patients in this group was well over 150, but the actual occurrence was zero.

Hypertension and High Calorie Malnutrition

Optimum nutrition is the level of intake that should promote the highest level of health. A deficit in nutrition may result in tissue depletion of essential nutrients that can lead to biochemical changes and eventually to clinical signs and symptoms. Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Obstructive sleep apnea increases over the course of pregnancy and is common during the third trimester. These adverse conditions have reportedly been completely prevented by the use of 100 mg of thiamine beginning even before pregnancy is confirmed. Thiamine deficiency, resulting in impaired oxidative metabolism, leads to a multifactorial cascade of events in the brain that include focal decreases in energy status, oxidative stress, blood-brain barrier disruption, glutamate-mediated excitotoxicity, amyloid deposition, immediate-early gene induction and inflammation.

Thiamine Tetrahydrofurfuryl Disulfide and Hypertension

This disulfide derivative of thiamine is the synthetic counterpart of allithiamine that occurs naturally in garlic. Allithiamine was discovered in Japan in 1951 and extensively researched by Japanese scientists. Experimental work in animals and human subjects revealed that its metabolic effect was much more powerful than the thiamine from which it was derived. Almost unknown in America, its therapeutic actions have been reviewed.

SHR rats are widely studied as a model of hypertension, exhibiting metabolic abnormalities that share features with the human metabolic syndrome. The SHR rat becomes hypertensive early in life and blood pressure continues to increase with age, often resulting in a cardiovascular event. Over the course of four months, blood pressure and body weight of two groups of SHR rats were monitored. The control group was fed normally and the TTFD group was given increasing doses of TTFD from 5 to 15 mg. There was a statistically significant reducing effect on the treated rats as compared with the controls. Of the 13 TTFD-supplemented rats, five showed a definite response with no rise in the expected blood pressure measurements, while the control group showed a 20 to 25 mm Hg increase in blood pressure across the experiment. The results showed that TTFD has a preventive effect on blood pressure in these genetically abnormal rats.

Thiamine Deficiency > Hypoxia > Hypertension

It has been shown in the above text that hypoxia and pseudo-hypoxia have virtually identical effects in the area of the brain that is peculiarly sensitive to thiamine deficiency. Since any phenomenon that causes inefficient oxygen consumption is dangerous to the organism, activation of the fight-or-flight reflex seems to be entirely logical. Repeated hypoxia in sleep apnea syndrome induces persistent chronic sympathetic dominance and is obviously an abnormal state of metabolism. It is possible that sleep apnea represents a combination of brainstem thiamine deficiency and recurrent obstructive hypoxia. Lonsdale and Marrs have published evidence that thiamine deficiency is widespread in the American population and that its effects in the brain are diverse and the resulting morbidity prolonged. Evidence could be accumulated by proving thiamine deficiency and attempting clinical trials with TTFD.