Laboratory Assessment of Vitamin Status

Dominic J. Harrington

• Publisher: Academic Press
• Year: 2018
• ISBN:
  9780128130513
• Topic: Médecine
• Subtopic: Pathologie

Laboratory Assessment of Vitamin Status provides a comprehensive understanding of the limitations of commonly used approaches used for the evaluation of vitamin status, reducing harm in the general health setting. It outlines the application of 'Best Practice' approaches to the evaluation of vitamin status, giving physicians and other healthcare professionals the opportunity to make evidence-based interventions. Nearly every metabolic and developmental pathway in the human body has a dependency on at least one micronutrient. Currently, the clinical utility of approaches taken by laboratories for the assessment of vitamin status is generally poorly understood, missing the opportunity to diagnosis vitamin deficiencies. This essential reference gives clinical and biomedical scientists an understanding of the limitations of commonly used approaches to the evaluation of vitamin status in the general health setting through change in practice. Nutritionists and dietitians gain an understanding of more sophisticated markers of vitamin status.

• Describes specialist assays in sufficient detail to enable laboratories to replicate what is being performed by expert groups
• Provides detailed information that supports laboratories in the setting up of methods for the evaluation of vitamin status
• Informs laboratories looking for third party providers of specialist investigations
• Provides an essential overview of reference ranges for each vitamin

Chapter 1

Discovery to diagnosis

Krutika Deuchande*; Dominic J. Harrington*^{,† *} Nutristasis Unit, Viapath, St. Thomas' Hospital, London, United Kingdom
^† Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom

Abstract

The idea that food may contain small quantities of life-important substances is an old one. Yet, the substances that play such a vital role in health and disease eluded discovery until the 20th century. Their elusiveness appears wholly disproportionate to the importance of their function, and reflects not only the minute quantities in which they are required, but also the degree of analytical sophistication necessary for their detection and characterization.

Keywords

Beriberi; Scurvy; Nutrition; Vitamins; HPLC; Anemia; Rickets; Pellagra; Pernicious Anemia; Xerophthalmia

Chapter Outline

• Essential Nutrients for Life
  • The Advent of Biochemistry
  • Germ Theory and the Great Diversion
  • Nutrition at the Beginning of the 20th Century
• Biological Assays and the Path to Discovery
  • Fat- and Water-Soluble Vitamins
• Standardization of the Novel Methods
• Historic Methods 1912–80—A Journey Toward Clinical Utility
  • Biological Methods
  • Microbiological Methods
  • Physiochemical Methods
• The Arrival of High Performance Liquid Chromatography
  • Sample Type
• References

Essential Nutrients for Life

The idea that food may contain small quantities of life-important substances is an old one. Yet, the substances that play such a vital role in health and disease eluded discovery until the 20th century. Their elusiveness appears wholly disproportionate to the importance of their function, and reflects not only the minute quantities in which they are required, but also the degree of analytical sophistication necessary for their detection and characterization.

Early scientific studies of living things were dependent on observation using the human eye. This approach proved sufficient for ancient Greek, Roman, and Arab physicians to conclude that diet plays a role in the prevention and cure of some diseases. Ultimately it was attempts to better understand the causes of beriberi and scurvy, and the innovative interpretation of experimental findings, that eventually revealed our dependence on an exogenous supply of micronutrients to support development and maintain health.

Beriberi (a disorder now known to be caused by vitamin B₁ deficiency) was endemic during the 19th century in Japan.¹ In 1872, Takaki Kanehiro joined the Imperial Japanese Navy and observed that the disease was uncommon among the crewmen of Western and Japanese navies whose diet consisted of various vegetables and meat—yet common in those crewmen whose diet consisted almost exclusively of white rice. Low-ranking crewman ate white rice because it was provided free of charge.

While working in Malay, Englishman W Leonard Braddon reported in 1907 that more than 150,000 cases of beriberi had been treated in Government hospitals and infirmaries during the preceding twenty years from a population of one million people. Of these, 30,000 people had died.² Since approximately only one-third of the deaths took place in hospitals, Braddon estimated that the total deaths from beriberi were 100,000. No drug showed any promise in alleviating the disease. Braddon noted that patients remaining under the conditions in which they became ill rarely recovered, yet removal to a different environment or a change of food remedied the disorder.

For the poor, scurvy (now known to be caused by vitamin C deficiency) had been an annual winter affliction in England for hundreds of years. It was not until the devastating impact of the disease on the productivity of crewman, and the subsequent negative commercial implications for trade by sea were recognized, that advances were made towards a cure. Scurvy had successfully been treated by teas, brews and beer made from spruce needles,^3,4 and by giving oranges and lemons.⁵ In 1601 Sir James Lancaster introduced the regular use of oranges and lemons into the ships of the East India Company.¹ Others in the 17th and 18th centuries also confirmed that fresh fruit and vegetables were effective in preventing or curing scurvy: Woodall (in 1639),^6,7 Kramer (1739),⁸ Lind (1757),⁸ and Captain Cook (1772).⁹

The Advent of Biochemistry

The discovery and study of vitamins marks the advent of biochemistry. Until the second half of the 19th century there had been very little collaboration between exponents of biology and chemistry or physics. Scientists were strongly biased in favor of one science or the other until some physiologists began to realize that it should be possible to think about organisms in terms of chemical mechanisms and started to adapt methods from chemistry and physics.

Chemists had learnt how to analyze foods, and ascertained that they were composed of proteins, carbohydrates, and fats, together with certain mineral elements and water. Together these components accounted for nearly 100% of the chemical analysis. One of the foremost investigators of nutrition, Carl von Voit (1831–1908), mentioned that the outcome of feeding pure foodstuffs—preparations of protein, fat, sugar, starch, and inorganic compounds would be no different from that achieved by feeding naturally occurring food mixtures. Indeed, the accomplished investigator Röhmann claimed to have been able to satisfy the nutritive requirements of mice with rations prepared by mixing a number of isolated and purified food components. Not only did the mice put on weight, but they were sufficiently nourished to produce young. Later, scrutiny of this work suggests that insufficient care was taken in ensuring the purity of the components of his food mixture.

In 1881, the Russian student N. Lunin published a paper concerning the significance of inorganic salts for animal nutrition.¹⁰ Working in Prof Gustav von Bunge’s laboratory in Basle, he was the first to produce experimental evidence, and came very near to discovering the vitamins, when he failed in his attempt to rear young mice on a mixture of purified proteins, carbohydrates, fats and minerals, he compounded to resemble the composition of milk, and which according to contemporary theories, should have provided all that was required for the mice to thrive. Others in Central Europe reported similar results. Among them was Carl Socin, also from Bunge's laboratory, who concluded that unknown substances were “present in egg yolk and milk” and which it was “the first task of the future to discover.” The question was approached in a different way in Germany by Wilhelm Stepp. Rather than use synthetic diets, he explored the effect of subjecting a natural diet such as bread and milk to an extraction process using alcohol and ether. The mice died when fed the diet but others flourished when the extracts were put back. To some extent these findings were not novel. As early as 1873 Forster had reported that washed meat is not an adequate diet for dogs. He had also observed that pigeons fed an artificial diet food mixture developed symptoms similar to that later to be described by Eijkman.

Germ Theory and the Great Diversion

In 1883 the Dutch Government sent a Commission to Java (part of the Dutch East Indies) to investigate the worryingly high prevalence of beriberi.¹¹ So shortly after the wide acceptance of Pasteur's “germ theory” and the disproving of the “spontaneous generation doctrine” it was natural for the leaders of the Commission, Professors Winkler and Pekelharing, to think of beriberi in terms of germs and infectivity. They were assisted by the young Army doctor Christian Eijkman. Having discovered a micrococcus, which they suspected to be the cause of beriberi, Winkler and Pekelharing returned to the Netherlands, leaving Eijkman behind as the institute's director. Eijkman concentrated all of his attention on the infective agent and the possibility of it causing beriberi, until a chance observation was made. Financial constraints at the institute led his laboratory assistant to feed the experimental chickens surplus food from the hospital kitchen. Eijkman observed that some of the chickens developed an inability to walk and showed symptoms of beriberi.¹¹ He initially thought that the birds had become infected by the responsible germ, but when the diet was changed the chickens recovered. Eijkman observed that while the chicken feed used in the laboratory had been unpolished rice, the hospital kitchen rice was polished. In 1897 Eijkman concluded that a polyneuritis gallinarum in fowls and pigeons is analogous to the human beriberi and induced by a diet of polished rice.

Eijkman's colleague, Gerrit Grijns, discovered that the addition of ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Chapter 1: Discovery to diagnosis
• Chapter 2: Methods for assessment of Vitamin A (Retinoids) and carotenoids
• Chapter 3: Methods for assessment of Vitamin D
• Chapter 4: Methods for assessment of Vitamin E
• Chapter 5: Methods for assessment of Vitamin K
• Chapter 6: Methods for assessment of Thiamine (Vitamin B1)
• Chapter 7: Methods for assessment of Vitamin B2
• Chapter 8: Methods for assessment of pantothenic acid (Vitamin B5)
• Chapter 9: Methods for assessment of Vitamin B6
• Chapter 10: Methods for assessment of biotin (Vitamin B7)
• Chapter 11: Methods for assessment of folate (Vitamin B9)
• Chapter 12: Methods for assessment of Vitamin B12
• Chapter 13: Methods for assessment of vitamin C
• Index