Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Vitamins
History of the development of vitaminology and general concepts of vitamins

The Study of Vitamins—vitaminology—is now recognized as an independent scientific discipline, although as recently as 100 years ago it was widely believed that an adequate intake of Proteins, fats, CARBOHYDRATES, minerals, and Water was entirely sufficient to sustain normal life processes in humans and animals. Practice and experience, however, proved that these substances alone are not enough for normal Human and Animal GROWTH AND DEVELOPMENT. Travelogues, maritime history, and physicians' observations pointed to the existence of specific diseases whose development was directly linked to inadequate diets, even though those diets seemingly contained all the nutrients known at the time. Some illnesses caused by dietary deficiencies even assumed epidemic proportions. For instance, scurvy became widespread in the 19th century, with a mortality rate reaching 70–80%. Around the same period, beriberi became highly prevalent, particularly in Southeast Asian countries and Japan, where approximately 30% of the entire population was afflicted. The Japanese physician K. Takaki concluded that meat, milk, and fresh vegetables contained certain substances capable of preventing beriberi. Later, the Dutch physician C. Eijkman, working on the island of Java—where polished rice was the dietary staple—noticed that chickens fed the same polished rice developed a condition analogous to human beriberi. When Eijkman switched the chickens to unpolished rice, they recovered. Based on these findings, he concluded that the outer husk of the rice (rice bran) contained an unknown substance with a curative effect. Indeed, an extract prepared from rice husks exerted a therapeutic effect on patients suffering from beriberi. These observations indicated that rice husks contain specific nutrients essential for maintaining the normal physiological Functions of the human body.

Nevertheless, The Development of vitamin science is rightly associated with the Russian physician N.I. Lunin, who opened a new chapter in nutritional science. He concluded that, In addition to proteins (casein), fats, milk sugar, salts, and water, animals require other hitherto unknown substances that are indispensable for Nutrition. In his work "On The Significance of Mineral Salts for Animal Nutrition" (1880), N.I. Lunin wrote: "It is of great interest to investigate these substances and study their significance for nutrition." This important scientific discovery was later (in 1912) corroborated by the work of F. Hopkins. Because the first substance isolated in crystalline form by C. Funk (1912) from rice husk extracts—which protected against the development of beriberi—proved to be an organic compound containing an amino group, Funk proposed calling these unknown substances vitamins (from the Latin vita, meaning life), i.e., amines of life. Indeed, vitamins turned out to be essential dietary accessory factors, and although some of them contain no amino group or nitrogen whatsoever, the term "vitamins" has become firmly established in biology and medicine.

Thus, During the first third of the last century, the attention of physiological chemistry researchers was focused on isolating and identifying vitamins—dietary factors indispensable for humans and animals that cannot be synthesized within the body.

Disagreements still persist regarding the definition of "vitamins" because there are several instances where vitamins are indispensable nutritional factors for humans but not for certain animals. Specifically, it is known that scurvy develops in humans and guinea pigs, but not in rats, rabbits, and several other animals, when Vitamin C is absent from the diet; that is, in the latter case, vitamin C is not a dietary or indispensable factor. On the other hand, Certain Amino acids (see Chapter 2), as well as A number of plant-derived Unsaturated Fatty acids (linoleic, linolenic, etc.), have proven indispensable for humans because they cannot be synthesized in The Human Body. However, in the latter case, these substances are not classified as vitamins, since vitamins differ from all other organic nutrients by two characteristic features: 1) they are not incorporated into tissue structures; 2) they are not utilized by the body as an energy source.

Thus, Vitamins are essential dietary factors that, while present in foods in small amounts, ensure the normal development of animal and human organisms and maintain an adequate rate of biochemical and physiological processes. Disturbances in Metabolic Regulation and the development of pathology are frequently associated with an insufficient intake of vitamins, their complete absence from the diet, impaired absorption or transport, or, ultimately, altered coenzyme synthesis involving vitamins. This leads to avitaminoses—diseases arising from the complete absence of a specific vitamin in the diet or a total failure in its assimilation. There are also so-called hypovitaminoses, caused by an inadequate Dietary intake of vitamins or their incomplete assimilation. In clinical practice, humans most frequently present with these latter forms of the disease, representing states of relative vitamin deficiency. In certain regions of Asia, Africa, and South America, where populations subsist on monotonous, predominantly plant-based diets, cases of complete avitaminosis do occasionally occur. The literature also describes pathological states associated with the intake of excessively large quantities of vitamins (hypervitaminoses). These conditions are less common than hypovitaminoses, though cases of hypervitaminosis A, D, K, and others have been documented.

As has now been established, many Metabolic Disorders in avitaminoses are caused by impairments in the activity or function of enzyme systems, given that numerous vitamins form part of the prosthetic groups of Enzymes (see Chapter 4). The Link Between vitamins and enzymes was first pointed out in 1922 by Academician N.D. Zelinsky. He maintained that vitamins regulate METABOLISM not directly, but indirectly through the enzyme systems of which they are a part. This viewpoint has been confirmed in modern science.

The discovery of vitamins played an exceptional role in the Prevention and Treatment of many infectious diseases. Because Bacteria also require the presence of many vitamins for their GROWTH AND REPRODUCTION in order to synthesize Coenzymes, the Introduction of structural analogues of vitamins—known as Antivitamins—into the body leads to the death of microorganisms. Antivitamins typically block the active sites of enzymes by displacing the corresponding vitamin derivative (coenzyme), thereby causing competitive Enzyme Inhibition (see Chapter 4). Antivitamins are defined as substances capable of inducing the classic clinical picture of hypo- or avitaminosis following their introduction into an animal Organism.

The causes of hypo- and avitaminoses in humans and animals are conventionally divided into exogenous and endogenous. The former include insufficient vitamin intake or their complete absence from the diet; consequently, inadequate and poor nutrition is most often the cause of exogenous avitaminoses. Endogenous causes, which are arguably more significant, include: a) an increased requirement for vitamins during certain physiological and pathological states (Pregnancy, Lactation, thyrotoxicosis, cachectic diseases, etc.); b) enhanced degradation of vitamins in the gut due to overgrowth of intestinal microflora; c) impaired vitamin absorption resulting from compromised secretory and motor functions of the intestines in gastrointestinal diseases, in which a relative vitamin deficiency develops even on a full diet; d) Liver and pancreatic disorders that cause obstruction of the common Bile duct and are accompanied by impaired absorption of fats, their breakdown products (fatty acids), and consequently Fat-soluble vitamins; in these instances, secondary or endogenous avitaminoses likewise develop.

Thus, an understanding of the patterns of development of hypo- and avitaminoses, their Clinical presentation, and the Biological Role of vitamins in metabolism is essential for every practicing physician. This knowledge dictates their clinical approach in devising Methods for the prevention and treatment of hypovitaminoses. If an avitaminosis (hypovitaminosis) has an exogenous origin, the missing vitamin is supplied via the diet or as a pure pharmacological preparation. If the cause is endogenous, then alongside treating the underlying disease, the corresponding vitamin is administered parenterally, i.e., bypassing the digestive tract.

One cannot disagree with the view of several leading vitaminologists (R. Harris, C. Scriver, V.B. Spirichev, and others) that DISEASES ASSOCIATED WITH inadequate vitamin intake have nowadays become rare thanks to "dietary rationalization" and represent a socio-economic problem rather than a purely medical one. At the same time, over the past three decades, A large number of previously unknown congenital disorders have been described whose clinical presentation resembles typical avitaminoses. They manifest in early childhood regardless of the body's adequacy in all known vitamins. In some instances, these diseases can be cured by megavitamin therapy, i.e., administering the relevant vitamin in amounts 50 to 100 times exceeding physiological requirements (so-called vitamin-dependent states). In other cases, the illness cannot be resolved even through the administration of high doses of vitamins (vitamin-resistant states). These conditions run a severe course and frequently result in the patient's death. For example, cases of vitamin D-resistant Rickets, vitamin D-dependent rickets, thiamine-responsive megaloblastic anemia, pyridoxine-dependent seizure syndrome and pyridoxine-dependent anemia, pernicious anemia, and others have been described.

Accumulated clinical data alongside detailed genetic and biochemical studies have made it possible to classify such disorders as inborn errors of vitamin metabolism and function, which have already been described for thiamine, pyridoxine, biotin, Folic acid, vitamin B₁₂, nicotinic acid, vitamins A, D, E, K, and others. Currently, there is sufficient evidence to consider that the underlying cause of these diseases is genetic defects associated either with impaired intestinal Absorption of Vitamins, disrupted transport to target Organs, or, ultimately, defects in The conversion of vitamins into coenzymes (or active forms in the case of group D vitamins). There is also evidence of hereditary defects in the Synthesis of the protein moiety of the enzyme (apoenzyme) in the Pathogenesis of certain congenital metabolic and functional disorders of vitamins, as well as impaired interaction (binding) between the coenzyme (or active vitamin form) and the specific protein—the apoenzyme—representing a defect in holoenzyme assembly.

The clinical picture of congenital disorders of vitamin metabolism and function differs little, if at all, from the true picture of dietary avitaminosis and a number of inherited metabolic defects. Therefore, prompt Differential Diagnosis and Pathogenetic Therapy are of paramount importance. Depending on the Etiology of the defect, therapeutic approaches include replacement therapy, parenteral administration of high doses of the respective vitamin (megavitamin therapy), and, in cases of congenital defects in its absorption and transport, the administration of the coenzyme, and so forth.