Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition

Derrick Lonsdale, Chandler Marrs

• Publisher: Academic Press
• Year: 2017
• ISBN:
  9780128103883
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition explores thiamine and how its deficiency affects the functions of the brainstem and autonomic nervous system by way of metabolic changes at the level of the mitochondria. Thiamine deficiency derails mitochondrial oxidative metabolism and gives rise to the classic disease of beriberi that, in its early stages, can be considered the prototype for a set of disorders that we now recognize as dysautonomia. This book represents the life's work of the senior author, Dr. Derrick Lonsdale, and a recent collaboration with his co-author Dr. Chandler Marrs.

• Presents clinical experience and animal research that have answered questions about thiamine chemistry
• Demonstrates that the consumption of empty calories can result in clinical effects that lead to misdiagnosis
• Addresses the biochemical changes induced by vitamin deficiency, particularly that of thiamine

Chapter 1

The History of Thiamine and Beriberi

Abstract

The history of the discovery of thiamine deficiency as the cause of beriberi is described. Its long morbidity, low mortality, relationship with environmental factors, and effect on the autonomic nervous system are emphasized. Because its appearance can be easily misdiagnosed as psychosomatic in the early stages, the clinical manifestations are provided. Long thought to be only of historical interest, brief case histories are outlined to illustrate the polysymptomatic presentation of abnormal thiamine homeostasis. Genetic predisposition, coupled with high calorie malnutrition, results in defective cellular energy metabolism. Some form of stress, requiring an adaptive and energy-consuming response, may therefore initiate the first symptoms of thiamine deficiency.

Keywords

Autonomic dysfunction; Beriberi; Dysautonomia; Mitochondria; Oxidative metabolism; Stress; Thiamine; Thiamine deficiency

Contents

From Kakke to Beriberi

Thiamine With Malnutrition: Navy Sailors Connect the Dots

Polished Rice, Pigeons, and the Catatorulin Effect

Clinical Features of Beriberi: Early Accounts

Historical Observations of Beriberi Symptoms

Appearance

Cardiovascular and Respiratory Disturbances

Gastrointestinal Dysmotility

Nervous System Disruption

Beriberi in Children

Infantile Beriberi

Juvenile Beriberi

Wet and Dry Beriberi and Wernicke’s Encephalopathy

Beriberi: The Great Imitator

Thiamine Deficiency and Autonomic Chaos

Toward a Broader Understanding of Stress and Autonomic Regulation

From Beriberi to Dysautonomia

Underlying Mechanisms of Autonomic Dysfunction: Thiamine, the Mitochondria, and Oxidative Metabolism

Thiamine as a Rate-Limiting Factor in Oxidative Metabolism

Thiamine and the Nervous System

Therapeutic Nutrition for Autonomic Balance

Stress and Nutrient Demands

Energy Production and Consumption

Oxidative Metabolism

Nutritional Versus Pharmaceutical Therapies

References

From Kakke to Beriberi

Evidence of thiamine deficiency syndromes in Japanese society dates back to as early as 808¹ where it was called “Kakke” or “leg disease” because of the large “proportion of cases of partial paraplegia, cases of edema of the legs, and cases of general dropsy.”² In the 18th and 19th centuries the term beriberi was adopted and remains with us today.² Much of the research on thiamine emanated from Japan where beriberi was rampant.

Until the 17th century the majority of the population in Japan took unpolished rice as the staple food. Polished rice was associated with relative affluence, since it looked better on the table when served. Epidemics of beriberi have been known to occur in association with increased affluence simply because it was expensive to take the rice to the mill. When white rice was served to friends, it became a signature of their newly acquired affluence. As the ingestion of well-milled white rice became nationwide, the incidence of the disease increased. This is because the B group vitamins were in the discarded husks. The pigs, to whom the rice polishings were thrown, were being fed better than the humans, who were unaware of the reason for this as the cause of their beriberi symptoms.

The first national statistics for the disease appeared in 1899 and showed a death rate of 20 per 100,000, a surprisingly low mortality. This dropped to 0.5 in 1959 after its nutritional association was discovered. Of considerable interest to us today is that the peak incidence of beriberi occurs in August and September every year. Although the reason for this is obscure, it might have been associated with the stress of ultraviolet light. For example, factory workers would take their lunch between factory buildings. If the sun came round so that it shone into the corridor between the buildings, some workers would show the first symptoms of the disease. When the underlying cause became known, it had to be concluded that the sun’s rays would stress them sufficiently to initiate the symptoms in individuals who were in a state of hitherto asymptomatic marginal malnutrition. Perhaps before sun exposure their symptoms, if any, were relatively trivial, or perhaps ascribed to other factors. It was therefore hardly surprising that the etiology in the early 1900s, before its nutritional association became common knowledge, was considered to be from infection.

Thiamine With Malnutrition: Navy Sailors Connect the Dots

The discovery of the relationship between thiamine and malnutrition came in the last decades of the 19th century, but it was many years before scientific knowledge caught up. A Japanese naval surgeon by the name of Takaki studied in England from 1875 to 1880. He noted that beriberi was less common in the British Royal Navy than in navy personnel in Japan where the diet on ships was very different. In 1882 a Japanese naval vessel sailed on a 272-day voyage. On its return, 61% of the crew had succumbed to beriberi. Two years later, Takaki sent another ship that completed the same voyage, but was provided with an ample supply of dried milk and meat, giving a carbon-to-nitrogen ratio of 16:1. Only 14 crew members had developed beriberi. Takaki concluded that the lack of nitrogenous food was the cause of the disease, a notable contribution before vitamins were known. Protein and calorie deficiency is still relevant in beriberi in countries where this disease is still endemic.

Polished Rice, Pigeons, and the Catatorulin Effect

In 1890, Eijkman found that polished rice given to pigeons caused polyneuritis, and the histopathology was similar to that seen in humans with beriberi. Funk and Cooper isolated an “antiberiberi factor” from rice polishings in 1910 and this was crystallized in 1926 and called Vitamine.³ It was not until 1936 that thiamine was synthesized,⁴ leading to an explosion of basic science and clinical experimentation. The work of Sir Rudolph Peters⁵ exposed the vitally important association of thiamine with what was later to become the science of oxidative metabolism. He was the first to discover that respiration in a brain cell from thiamine-deficient pigeons was no different from the respiration in thiamine-sufficient cells until glucose was added to the preparation. The effect of failure of the thiamine-deficient cells to respond like the thiamine-sufficient cells was immediately obvious and he referred this as the catatorulin effect. He even noted that this effect was more prominent in cells from the lower part of the pigeon brain, a fact that later became important in a better understanding of thiamine deficiency in the human brain.

Clinical Features of Beriberi: Early Accounts

After the discovery of thiamine and its application to the treatment of a scourge that had existed for thousands of years and still occurs, particularly where white rice is a staple food, it was natural that a vast amount of research was initiated. In 1962 a symposium was published to commemorate the synthesis of the vitamin. At that time there were 696 published papers where thiamine therapy had been attempted in more than 230 different diseases with varying degrees of success.⁶ It should be noted that although a great many symptoms of beriberi have been described, none of them is considered to be pathognomonic.¹

At that time, beriberi was classified into “wet” or edematous type and “dry” type, both being chronic in their course. Those categories have since been expanded to include neuritic beriberi (sensorimotor polyneuropathy) and gastrointestinal beriberi (gastrointestinal dysmotility), although the vestiges of the original framework remain. A peracute and extremely lethal form is known in Japan as “Shoshin” where “Sho” means acute damage and “shin” means heart. Shoshin denotes acute cardiac collapse and is believed to develop in approximately 5% of beriberi cases.⁷ Shoshin has also been referred to as acute pernicious beriberi.⁸

Despite the original classification of beriberi based on cardiac symptoms, reading through clinical observations made in the 1960s we see a far more expansive pattern of symptoms emerging: symptoms that are difficult to account for unless one looks beyond the specific organ systems involved. What follows are the historical observations of beriberi symptoms as reported in an English translation of a book written in 1965 in Japan.¹

Historical Observations of Beriberi Symptoms

Appearance

The general appearance of an individual affected by thiamine deficiency did not always suggest malnutrition, at least in the early stages. Thiamine deficiency was more common in robust manual laborers. Edema was one of the important signs and was always present in early s...