Preface to the Fifth Edition
Understanding the vitamins is key to understanding nutrition. The history of their discovery and the continuing elucidation of their roles in health is the history of the emergence of nutrition as a science from the areas of physiology, biochemistry, medicine, and agriculture.
Capturing the understanding that grew out of that history is both a challenge and a privilege. For us, it involved months of reviewing thousands of publications and looking for clear ways to present complex information without overstating present understanding.
Producing this fifth edition of The Vitamins benefitted from the inclusion of a coauthor, which we believe brought a new prospective to the text. James studied the first edition of the The Vitamins as a masters student at the University of New Hampshire in 1997. He encountered the second edition of the text as Jerry’s student at Cornell University in 2001. We are hopeful that the dynamic relationship we have enjoyed, as student/mentor, colleagues, friends, and now coauthors, has resulted in the most effective edition of this text, as both a reference and a teaching aid.
In writing this fifth edition of The Vitamins, we were mindful of comments from users of previous editions,
which prompted several changes that we believe enhanced the book. We reorganized several chapters, which reduced their number. We emphasized roles of the gut microbiome in several places of importance. We added sections on biomarkers of vitamin status and modestly expanded the section on biofortification. We added, redrew, and updated several tables and figures. We used extensive footnoting as a means of including explanatory notes as well as for citing primary sources.
We are grateful for the professional assistance from editors, Ms. Jaclyn Truesdell, Ms. Megan Ball, and Ms. Caroline Johnson of Elsevier.
We enjoyed writing this fifth edition of The Vitamins together. We hope you will find it useful.
Gerald F. Combs, Jr. Topsham, Maine
James P. McClung Westborough, Massachusetts
June 2016
knowledge that it involved any particular nutrient, much less a certain vitamin. The Case Study in Chapter 21 is different; it is a fictional but highly plausible scenario that calls for a nonobvious decision. Additional case studies are listed in Appendix B.
Take sometime and go through the Study Questions and Exercises at the end of each chapter. These, too, are designed to direct your thinking back to the key concepts of the respective chapter and to facilitate integration of those concepts with those you already have.
We have made a point in Chapter 1 of using the technique of concept mapping do demonstrate the integration of complex subject matter. We have found the concept map to be a powerful teaching/learning tool. If you have had no previous experience with this device, then it will be worth your while to consult Learning How to Learn. 1
When you have done all of this for a chapter, then deal with your questions. Discuss them with fellow students or look them up. To assist you in the latter, a short reading list is included at the end of each chapter. With the exception of Chapter 2, which lists papers of landmark significance to the discovery of the vitamins, the reading lists consist of key reviews in prominent scientific journals. These reviews and the papers cited in the footnotes will help you find primary research papers on topics of specific interest.
After you have followed all of these steps, reread the chapter. You will find this last step to be extraordinarily useful in gaining a command of the material.
Last, but certainly not least, have fun with this fascinating aspect of the field of nutrition!
To the instructor The format of this text reflects the way GFC taught a course called “The Vitamins” for some 29 years at Cornell University. To that end, some experiences in using The Vitamins as a text for my course may be of interest to you.
I have found that every student comes to the study of the vitamins with some background knowledge of the subject, although those backgrounds are generally incomplete and frequently include areas of misinformation. This is true for upper-level nutrition majors and for students from other fields, the difference being largely one of magnitude. This is also true for instructors, most of whom come to the field with specific expertise that relates to only a subset of the subject matter.
You can demonstrate this in the following exercise, best done of the first day of class. Raise your index finger (best done with a bit of dramatic flair) and say “vitamin A.” Hold that pose for 10 s and then ask “What came to mind when I said ‘vitamin A’?” Without fail, someone will say “vision” or “carrots,” and then an older graduate student may add “toxic.” When it looks safe to chime in, others will add what
1. Novak, J.D., Gowin, D.B., 1984. Learning How to Learn. Cambridge, University Press, New York, NY, pp. 199
will build to an array of descriptors that, collectively, are more relevant to vitamin A than any is individually. Most of the answers, by far, will relate to the clinical symptoms of vitamin A deficiency and the sources of vitamin A in diets. Catch each answer by dashing it on to a large sticky note and then stick the note haphazardly to a blackboard or wall. If you hear something complex or a cluster of concepts, make sure to question the contributor until you hear one or more individual concepts, which you can record on individual sticky notes. This approach never fails to stimulate further answers, and it is common that a group of 15–20 students will generate a list of twice that number of concepts before the momentum fades. Having used sticky notes, it is easy to move them into clusters and, thus, to use the activity to construct a concept map of “Vitamin A” based solely on the knowledge that the students, collectively, brought into the room. This exercise can demonstrate an empowering idea that, having at least some background on the subject and being motivated (by any of a number of reasons) to learn more, every learner brings to the study of the vitamins a unique perspective which may not be readily apparent. We are convinced that meaningful learning is served when both instructor and students come to understand each others’ various perspectives. This has two benefits in teaching the vitamins. First, it is in the instructor’s interest to know the students’ ideas and levels of understanding concerning issues of vitamin need, vitamin function, etc., such that these can be built upon and modified as may be appropriate. Second, many upper-level students have interesting experiences (through personal or family histories, their own research, information from other courses, etc.) that can be valuable contributions to classroom discussions. These experiences are assets that can reduce the temptation to fall back on the “instructor knows all” notion, which we all know to be false. To identify student perspectives, it is useful to assign on the first class period, for submission at the second class, a written autobiographical sketch. Distribute your own as a model, and ask each student to write “as much or as little” as he or she cares to, recognizing that you will distribute to the class copies of whatever is submitted. The biographical sketches will range from a few sentences that reveal little of a personal nature to longer ones that provide many good insights about their authors; everyone will help you to get to know your students personally and to get a better idea of their understandings of the vitamins and of their expectations of the course. The exercise serves the students in a similar manner, thus promoting a group dynamic that facilitates classroom discussions.
The Vitamins can be used as a typical text from which you can make regular reading assignments as preparation for each class. This will free you of the need for lecturing in favor of an open discussion format. In fact, this approach allows more information to be covered, as even a brilliant lecturer simply cannot cover the vitamins in any real depth
Perspectives on the Vitamins in Nutrition
addition, some (e.g., the chick) do not develop that capacity completely until they are several weeks of age. Thus, for the young chick and for individuals of other species fed diets providing limited methyl groups, choline is a vitamin.
Niacin: All animal species can synthesize nicotinic acid mononucleotide from the amino acid tryptophan. Only those for which this metabolic conversion is particularly inefficient (e.g., the cat, fishes) and others fed low dietary levels of tryptophan require a dietary source of niacin
With these counterexamples in mind, the definition of a vitamin has specific connotations for animal species, stage of development, diet or nutritional status, and physical environmental conditions.5
4. THE RECOGNIZED VITAMINS
Thirteen substances or groups of substances are now generally recognized as vitamins (Table 1.1); others have been proposed.6 In some cases, the familiar name is actually the generic descriptor for a family of chemically related compounds having qualitatively comparable metabolic activities. For example, the term vitamin E refers to those analogs of tocol or tocotrienol7 that are active in preventing such syndromes as fetal resorption in the rat and myopathies in the chick. In these cases, the members of the same vitamin family are called vitamers. Some carotenoids can be metabolized to yield the metabolically active form of vitamin A; such a precursor of an actual vitamin is called a provitamin.
The “Vitamin Caveat”
l Some compounds are vitamins for one species and not another.
l Some compounds are vitamins only under specific dietary or environmental conditions.
4. The concept map can be a useful device for organizing thought, as its discipline can serve to assist in identifying the nature and extent of concepts related to the one in question. A concept map should be laid out as a hierarchy of related concepts with the superordinate concept at the top and all relationships between concepts identified with a verb phrase. Thus, it can be “read” from top to bottom. One of the authors (GFC) has used concept mapping in graduate-level teaching, both as a group exercise and testing device. For a useful discussion of the educational value of the concept map, the reader is referred to Learning How to Learn, 1984, J.D. Novak and D.B. Gowin, Cornell University Press, Ithaca, NY, pp. 199.
5. For this reason, it is correct to refer to vitamin C for the nutrition of humans but ascorbic acid for the nutrition of livestock.
5. STUDY QUESTIONS AND EXERCISES
1. What are the key features that define a vitamin?
2. What are the fundamental differences between vitamins and other classes of nutrients between vitamins and hormones?
3. Detail, citing a specific example, a situation in which a vitamin may be nutritionally essential for one species but not another.
4. Using key words and phrases, list briefly what you know about each of the recognized vitamins.
6. These include such factors as inositol, carnitine, bioflavonoids, pangamic acid, and laetrile, for some of which there is evidence of vitamin-like activity (Chapter 19).
7. Tocol is 3,4-dihydro-2-methyl-2-(4,8,12-trimethyltridecyl)-6-chromanol; tocotrienol is the analog with double bonds at the 3, 7, and 11′ positions on the phytol side chain (Chapter 7).
FIGURE 1.1 Concept map of a Vitamin.4
TABLE 1.1 The Vitamins: Their Vitamers, Provitamins, and Functions
Group Vitamers
Vitamin A Retinol Retinal Retinoic acid
Vitamin D Cholecalciferol (D3) Ergocalciferol (D2)
Vitamin E α-Tocopherol γ-Tocopherol
Vitamin K Phylloquinones (K1) Menaquinones (K2) Menadione (K3)
Vitamin C Ascorbic acid Dehydroascorbic acid
Vitamin B1 Thiamin
Vitamin B2 Riboflavin
Niacin Nicotinic acid Nicotinamide
Vitamin B6 Pyridoxol Pyridoxal Pyridoxamine
Folic acid Folic acid Polyglutamyl folacins
Biotin Biotin
Pantothenic acid Pantothenic acid
Vitamin B12 Cobalamin
Provitamins
β-Carotene Cryptoxanthin
Physiological functions
Visual pigments; epithelial cell differentiation
Calcium homeostasis; bone metabolism; transcription factor
Membrane antioxidant
Blood clotting; calcium metabolism
Reductant in hydroxylations in the formation of collagen and carnitine, and in the metabolism of drugs and steroids
Coenzyme for decarboxylations of 2-keto acids (e.g., pyruvate) and transketolations
Coenzyme in redox reactions of fatty acids and the tricarboxylic acid (TCA) cycle
Coenzyme for several dehydrogenases
Coenzyme in amino acid metabolism
Coenzyme in single-carbon metabolism
Coenzyme for carboxylations
Coenzyme in fatty acid metabolism
Coenzyme in the metabolism of propionate, amino acids, and single-carbon units
the French scientist Antoine Lavoisier,2 started probing the elemental components and metabolic fates of these nutrients, the widely read ideas of the German chemist Justus von Liebig3 resulted in protein being recognized as the only essential nutrient, supporting both tissue growth and repair as well as energy production. In the middle part of the century, attention was drawn further from potential relationships of diet and health by the major discoveries of Pasteur,4 Liebig,5 Koch,6 and others in microbiology. For the first time, several diseases, first anthrax and then others, could be understood in terms of a microbial etiology. By the end of the century, germ theory, which proved to be of immense value in medicine, directed hypotheses for the etiologies of most diseases. The impact of this understanding as a barrier to entering the inductive phase of nutritional discovery is illustrated by the case of the Dutch physician Christiaan Eijkman,7 who found a water-soluble factor from rice bran to prevent a beriberi-like disease in chickens (now known to be the vitamin thiamin) and concluded that he had discovered a “pharmacological antidote” against the beriberi “microbe” presumed to be present in rice.
Diseases Linked to Diet
Nevertheless, while they appeared to have little effect on the prevailing views concerning the etiology of human disease, by the late 1800s empirical associations had been made
2. Antoine-Laurent de Lavoisier (1743–1794) is often considered the “father of modern chemistry”, as his work changed that science from a qualitative to a quantitative one. He is best known for his discovery of oxygen and its role in combustion.
3. In his widely read book, Animal Chemistry, or Organic Chemistry in its Application to Physiology and Pathology, Liebig argued that the energy needed for the contraction of muscles, in which he was able to find no carbohydrate or fat, must come only from the breakdown of protein. Protein, therefore, was the only true nutrient.
4. Louis Pasteur (1822–1895) was a French pioneering microbiologist. He disproved the doctrine of “spontaneous generation” of microbial life and advanced “germ theory.” He discovered the principles of vaccination, fermentation and developed the process of heat-killing of microbes in liquids is now called “pasteurization”.
5. Justus von Liebig (1803–1873) was a German chemist who made major contributions to agricultural and biological chemistry, elucidated the importance of nitrogen in plant nutrition, and introduced laboratory experience in teaching chemistry.
6. Robert Koch (1843–1910) was a German physician who identified the causative agents of tuberculosis, cholera and anthrax, and formulated the general principles (“Koch’s Postulates”) for linking specific microorganisms to specific diseases. In 1905, he received the Nobel Prize for Physiology or Medicine.
7. Christiaan Eijkman (1858–1930) was trained in the Netherlands and served as a medical officer in the Dutch Indies. After contracting malaria in 1885, he returned to Amsterdam where he worked in the laboratories of Forster and, then, Kock (Berlin). In Koch’s laboratory he met another Dutch physician C.A. Pekelharing whom he assisted in a second period of service in the Indies investigating beriberi. They proposed establishing a medical laboratory of which Eijkman was named director and Director of the Javanese Medical School, which ultimately became the University of Indonesia.
between diet and the diseases scurvy, rickets, pellagra, and night blindness.
Scurvy has been known that scurvy, the disease involving apathy, weakness, sore gums, painful joints, and multiple hemorrhages, could be prevented by including in the diet green vegetables or fruits. Descriptions of cases in such sources as the Eber papyrus (c.1150 BCE) and writings of Hippocrates (c.420 BCE) are often cited to indicate that scurvy was prevalent in those ancient populations. Indeed, signs of the disease are said to have been found in the skeletal remains of primitive humans. Scurvy was common in northern Europe during the Middle Ages, a time when local agriculture provided few sources of vitamin C that lasted through the winter. In northern Europe, it was treated by eating cresses and spruce leaves. Scurvy was very highly prevalent among seamen, particularly those on ocean voyages to Asia during which they subsisted for months at a time on dried and salted foods. The Portuguese explorer Vasco da Gama reported losing more than 60% of his crew of 160 sailors in his voyage around the Cape of Good Hope in 1498. In 1535–1536, the French explorer Jacques Cartier reported that signs of scurvy were present in all but three of his crew of 103 men (25 of whom died) during his second Newfoundland expedition. In 1595–1597, the first Dutch East Indies fleet lost two-thirds of its seamen due to scurvy. In 1593, the British admiral Richard Hawkins wrote that, during his career, he had seen some 10,000 seamen die of the disease.
The link between scurvy and preserved foods was long evident to seafarers. The first report of a cure for the disease appears to have been Cartier’s description of the rapidly successful treatment of his crew with an infusion of the bark of Arborvitae (Thuja occidentalis) prepared by the indigenous Hurons of Newfoundland. By 1601, the consumption of berries, vegetables, scurvy-grass (Cochlearia officinalis, which contains as much ascorbic acid as orange juice), and citrus fruits or juices was recognized as effective in preventing the disease. In that year, the English privateer Sir James Lancaster introduced regular issues of lemon juice (three spoonfuls each morning) on one of his found ships, finding significantly less scurvy among treated sailors. Nevertheless, the prestigious London College of Physicians viewed scurvy as a “putrid” disease in which affected tissues became alkaline and stated that other acids could be as effective as lemon juice in treating the disease. Accordingly, in the mid-1600s British ship’s surgeons were supplied with vitriol (dilute sulfuric acid).
Against this background, in 1747, James Lind, a Scottish physician serving in the British Royal Navy, conducted what has been cited as the first controlled clinical trial to compare various therapies recommended for scurvy in British sailors at sea. Lind’s report, published 6 years later, described 12 sailors with scurvy whom he assigned in pairs to 2-week regimens including either lemons and oranges, vitriol, vinegar, or other putative remedies. His results were
