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History of a Vitamin

From: The Hospitalist, November 2006

Prelude to a forgotten hospital problem

by Michelle Schneider and Norman Egger, MD

flashback

What do the Japanese military, a Dutch microbiologist, sick chickens, and rice polishers have in common?

In the 1800s, Europeans colonizing Asia brought with them steam-powered machines that completely polished rice. This rice, which was thought to be superior to unpolished rice, became very popular. As Far Eastern society’s main source of thiamine was polished to oblivion, beriberi became more prevalent and problematic.

At that time, micronutrient deficiency states were still a mystery to physicians. Kanehiro Takaki (October 30, 1849–April 13, 1920), surgeon general of the Japanese Imperial Navy, noticed a connection between sailors’ diets and their development of beriberi. White rice was replaced with barley, vegetables, fish, and meat. The incidence of beriberi dropped swiftly and was eliminated in the Japanese Navy, within six years.

Kanehiro Takaki
Kanehiro Takaki

Meanwhile, in the Dutch Indies, beriberi was endemic and crippling. Christiaan Eijkman, a Dutch microbiologist (August 11, 1858–November 5, 1930) who had studied with bacteriologist Robert Koch (December 11, 1843-May 27, 1910) in Berlin, was sent to research the disease in Java. Eijkman was unaware of Takaki’s findings and was convinced that beriberi was an infection.

Eijkman tried to infect chickens with a microorganism isolated from the corpses of two beriberi-related deaths. While he was striving to find the causative pathogen, Eijkman noticed that all chickens, even those having no contact with either the microorganism or other chickens, developed “a disease, in many respects strikingly similar to beriberi in man.” In fact, they had developed polyneuritis. Then, miraculously, they recovered spontaneously.

Christiaan Eijkman
Christiaan Eijkman

Eijkman was bewildered by this sequence of events and set out to solve the poultry mystery. He discovered that the chickens, during the time that they had been ill, had been eating leftover cooked, polished white rice from the hospital kitchen. When the cook left, however, his replacement refused to relinquish leftover rice, and they were thereafter given raw, unpolished rice. After this dietary change, the chickens recovered. Eijkman concluded that a substance in unpolished rice protected chickens against infection—he was still searching for the elusive microscopic culprit—and he called this protective substance the “anti-beriberi factor.” He thought unpolished rice contained an antidote to a bacterial toxin.

In 1906, Frederick Hopkins (1861–1947) demonstrated “accessory factors” in food, those nutrients necessary to maintain good health in addition to the carbohydrates, fats, proteins, and minerals that had previously been acknowledged as vital. In 1912, a Polish biochemist, Casimir Funk (1884–1967), thought he had isolated the anti-beriberi factor and named his discovery vitamine, from “vital amine.” Although he hadn’t isolated anti-beriberi factor—it is believed that he isolated nicotinic acid—the name vitamine remained. Eventually, in 1926, researchers were able to isolate the anti-beriberi factor in rice bran extracts. In 1929, Hopkins and Eijkman were awarded the Nobel Prize in Physiology or Medicine for the discovery of vitamins.

Frederick Hopkins
Frederick Hopkins

Clinicians are now well aware of alcohol abuse and the development of Wernicke’s encephalopathy or Korsakoff amnestic syndrome. Phrases like wet (high output heart failure) and dry (peripheral neuropathy) beriberi were once commonly found on board exams. The clinical presentation of thiamine deficiency isn’t limited to alcoholics. For example, there is evidence that patients with end-stage renal disease on hemodialysis are at risk of becoming thiamine deficient and of developing “unexplained” encephalopathies.1 Patients who suffer congestive heart failure while on long-term diuretics are also at increased risk for thiamine deficiency.2

This account is a classic example of the fascinating way in which the discovery of these essential nutrients has evolved and serves as a wake-up call that emphasizes the current epidemic of malnutrition in hospitalized patients.

Protein energy malnutrition in hospitalized patients is very common. Many studies have demonstrated that the prevalence runs between 30% and 60%, depending on the patient population studied and the assessment tools used. Hospital malnutrition, independent of disease activity, has been linked to increased length of stay and heightened morbidity and mortality. It is disturbing to think that many patients are actually worse off at time of dismissal than they were at admission. Malnutrition often goes unrecognized and even when the problem is acknowledged adequate nutrition is often not provided. Patients are commonly permitted to subsist on very low nutrient intakes.3 The problem of malnutrition is likely grossly underestimated because most studies have not considered micronutrients such as trace elements and vitamins. In addition, the presence of subclinical, yet clinically important, deficiency is expected to be highly prevalent.

Eijkman tried to infect chickens with a microorganism isolated from the corpses of two beriberi-related deaths.

Early screening improves the recognition of malnourished patients and provides the opportunity to start treatment at an early stage of hospitalization. Nutritional therapy as part of a comprehensive treatment modality may result in improvement of healthcare quality. In some countries it is also a criterion for assessing the performance of hospitals. In the U.S., for example, nutritional screening in hospitals is required for accreditation by the Joint Commission on Accreditation of Healthcare Organizations and is part of the Minimal Data Set documentation in long-term care facilities.

In most institutions, nutritional screening refers to a rapid and general test that is undertaken by nursing, medical, and other staff, often at first contact with patients. This is in contrast to the detailed nutritional evaluation that is undertaken by nutrition specialists (e.g., dietitians, specialist nutrition nurses, or physicians with an interest in nutrition), often for complex problems and often following nutritional screening. The introduction of a nutrition screening program and documentation of nutritional status may also increase diagnosis-related group (DRG)-based reimbursement.

Unfortunately, a lack of standardized sensitive and specific methodologies to assess for macro- or micronutrient deficiencies makes it difficult to determine how best to screen patients. Recent literature suggests, however, that the use of a short nutrition questionnaire and an undemanding treatment plan improved nutritional care during a hospital stay.4 The use of this strategy reduced the duration of the hospital stay in a subgroup of frail malnourished patients, offering potential improvements in morbidity as well as financial benefits for the hospital.

The lessons of past discoveries should not be lost on modern medicine. Malnutrition can be made a condition of the past through the use of simple screening procedures and uncomplicated treatments. The results will benefit both patients and hospitals. TH

Michelle Schneider is a medical student at the Royal College of Surgeons in Dublin, Ireland. Dr. Egger is a senior associate consultant at the Mayo Clinic College of Medicine.

References

  1. Hung SC, Hung SH, Tarng DC, et al. Thiamine deficiency and unexplained encephalopathy in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis. 2001;38:941-947.
  2. Hanninen SA, Darling PB, Sole MJ, et al. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol. 2006 Jan 17;47(2):354-361.
  3. Sullivan DH, Sun S, Walls RC. Protein-energy undernutrition among elderly hospitalized patients: a prospective study. JAMA. 1999 Jun;281(21):2013-2019.
  4. Kruizenga HM, Van Tulder MW, Seidell JC, et al. Effectiveness and cost-effectiveness of early screening and treatment of malnourished patients. Am J Clin Nutr. 2005;82(5):1082-1089.

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