Nutritional Recommendations

It is difficult to establish the amount of any vitamin that is essential to a human being. Even for animals the amount required for good health must exceed that needed for survival. The enormous individual variation among human beings ensures that any conclusion about the requirement for a nutrient will be incorrect for at least some individuals. The need for a vitamin will be affected by the age of the individual, by differences in the ability to take up the vitamin from the digestive tract, and by the ability to convert it to appropriate coenzyme forms. Also important is the ability of numerous enzymes to hold the coenzyme correctly into their active sites. With many thousands of possible sites for mutation of the DNA encoding these proteins, there are many possible reasons why some individuals may need larger amounts of a vitamin than does the average person. Recommended dietary allowances (Table I) are based on studies by panels of nutritional investigators. They vary somewhat from one country to another and are revised periodically. To put the needs for vitamins in a better perspective, Table II lists in concise form the other known human nutritional requirements.

Most of the B vitamins are synthesized by plants, fungi, and bacteria. Meat and dairy products also contain vitamins that have been obtained from these sources. As a consequence, a well-balanced human diet usually supplies adequate amounts of all of the vitamins. There are exceptions. Vitamin B₁₂ is not made by plants and strict vegetarians may become deficient if their diet does not contain yogurt or other products of fermentation. Thiamin is very labile, especially at high pH. Cooking at a pH above 8 quickly destroys this vitamin. Alcoholism is another cause of thiamin deficiency, sometimes leading to the characteristic Wernicke’s disease or Wernicke– Korsakoff syndrome, conditions with specific symptoms of encephalopathy. Because of the lability of thiamin, the number of turnovers, i.e., the number of times that a thiamin diphosphate molecule can pass through its catalytic cycle, seems to be limited. For this reason, the recommended daily allowance is increased by 0.5 mg for each 1000 kcal (Cal) consumed beyond that for an average person. Riboflavin is destroyed by light. Diets in many parts of the world are deficient in vitamin A and also in the plant carotenes, which can be converted into vitamin A in the body. Folate deficiency may occur if there is inadequate intake of fresh vegetables and fruit. Prolonged cooking can also destroy the vitamin.

Specific dietary deficiencies sometimes affect large populations. In the past, beriberi was a widespread consequence of consumption of polished rice without vitamin supplementation. During the early decades of the last century, pellagra was widespread in southern regions of the United States because the diet was low in protein and high in maize, a grain whose protein is deficient in tryptophan. Tryptophan can be converted to nicotinamide with an efficiency of about 1/60. Hence, most diets provide the necessary minimum. However, persons with pellagra often died after suffering from characteristic symptoms of dermatitis, diarrhea, and dementia. Deficiency of vitamin D was widespread, especially in northern regions, prior to the use of supplementation of milk. Deficiencies of the B vitamins, pantothenic acid, riboflavin, biotin, and vitamin B₆, are not often met in the human population. Except for the sensitivity of riboflavin to light, these compounds are quite stable. Nevertheless, some infants are born with unusually high requirements for specific vitamins. Some cases of sudden infant death have been attributed to biotin deficiency and convulsions in infants to a deficiency of vitamin B6 in a nutritional formula. Vitamin B₆ is a family of three forms, an alcohol pyridoxol, an amine pyridoxamine, and an aldehyde pyridoxal (Fig. 5). Of these, pyridoxol, a very stable compound, predominates in plants. More of the vitamin is present as the less stable pyridoxal and pyridoxamine in foods of animal origin.

TABLE I Approximate Nutritional Requirements (mg/day) for the Vitamins and Some Characteristic Deficiency Diseases or Symptoms

Vitamin	Approximate daily need (mg)	Deficiency diseases	Related coenzyme or function
Thiamin	0.8 or morea	Beriberi	Thiamin diphosphate
Pantothenic acid	10–15		Coenzyme A
Riboflavin	1.5		FMN, FAD
Nicotinamide (or nicotinic acid)	2.5b	Pellagra	NAD, NADP
Biotin	0.15–0.3		Bound as prosthetic group
Pyridoxine (vitamin B6) phosphate	1.5–2		Pyridoxal or pyridoxamine
Folic acid	0.2–0.4c		Tetrahydrofolate
Vitamin C	50–200	Scurvy	Antioxidant, electron carrier
Vitamin B12 (cobalamin)	0.002	Pernicious anemia	5´-Deoxycobalamin, 5´-methylcobalamin
Vitamin A (retinol)	0.7		Retinol, bound as prosthetic group
Vitamin D	0.02	Rickets	Hormonal role in calcium metabolism
Vitamin E	8–10		Antioxidant
Vitamin K	0.05–0.08	Bleeding	Blood clotting
a Amount should be at least 0.5 mg per 1000 kcal (Cal) of food energy.
b Some may be obtained from metabolism of the amino acid tryptophan, about 1/60 of which can be converted into this vitamin.
c The larger amount is recommended forwomen of child-bearing age.

Vitamin C is made not only by plants but also by most animals who use the sugar glucose as the starting material. However, human beings, guinea pigs, and a few other species are unable to synthesize this important antioxidant compound. The need for ascorbic acid is high, but the optimum amount needed for good nutrition is uncertain. Furthermore, there has been some concern that excessive intake of vitamin C, especially in combination with iron ions, may generate damaging free radicals. However, ascorbic acid seems to have predominantly an antioxidative effect in animals.

Vitamin B₁₂ is required in minute amounts, one microgram per day supplying the needs for the human body. However, absorption of this small amount of vitamin from the gut and transport to its sites of action requires special transport proteins. One of these, the “intrinsic factor,” is synthesized by cells of the intestinal mucosa and is utilized for absorption of vitamin B₁₂. Synthesis of the intrinsic factor is defective in some individuals, and is often inadequate in persons older than about 60 years. If untreated, this deficiency leads to pernicious anemia, a condition in which red blood cells do not mature normally and in which dementia develops as a result of the lack of vitamin B12 in the brain. If treated in time, a monthly injection of one milligram of the vitamin is curative.

Nutrient			Approximate daily need (mg or g)Variable			Major biological function
Water			Variable			Solvent
Energy			A. Basal need ∼1800 kcal (Cal)/day B. Additional needed for work:			Metabolism
				240 g carbohydrate or 108 g fat per 1000 additional kilocalories (Cal)
	Major energy sources
		Carbohydrates (4.1 kcal/g)	300 g*		230 kcal (Cal)	*These amounts together will supply
		Fat (9.3 kcal/g)	65 g*		605 kcal (Cal)		typical basal need
		Protein (4.1 kcal/g)
	Protein for biosynthesis		∼0.44g/kg body weight			Must include the nine essential amino
							acids plus 11 other amino acids needed for protein synthesis and other purposes or other suitable nitrogen source for their synthesis.
Essential amino acids				(for 70 kg person, 31 g)		All of these, as well as the
							“nonessential” amino acids, are needed for formation of specific proteins in the body. Several are also required for synthesis of nucleotides, coenzymes, hormones, and neurotransmitters.
			Infants		Adults (older)
	Valine		93		20 (10)
	Leucine		160		39 (14)
	Isoleucine		70		23 (10)
	Methionine (+cysteine)b		58		15 (13)
	Phenylalanine (+tyrosine)b		125		39 (14)
	Tryptophan		17		6 (4)
	Threonine		87		15 (7)
	Lysine		103		30 (12)
	Histidine		28		8–12
Essential fatty acids						Absolutely required. Enter cell
							membranes and affect many biochemical processes. The C20 acids are also converted to eicosanoids, signaling molecules that include prostaglandins and leukotrienes. Essential fatty acids protect against cardiovascular disease, disease, inflammation, and autoimmune reactions.
Omega 6 (ω6 or n-6)			1–4 % of total calories
	Linoleic acid (C 18:2,
		18 carbon atoms,
		2 cis double bonds) and
		arachidonic acid (C 20:4)
Omega 3 (ω3 or n-3)				0.1–0.3% of total calories
	Linolenic acid (C18:3),
	eicosapentaenoic (C20:5), and
	docosahexaenoic acid (C22:6) acids
Mineral elements
			Infants		Adults
	Sodium Na+						Electrolyte
	Potassium K+						Electrolyte
	Chlorine Cl−						Electrolyte
	Calcium Ca2+		270		1000	Structural in proteins, carbohydrates,
							bone; signaling ion
	Phosphorus P		275		700	Present in nucleic acids, proteins, coenzymes
	Magnesium as Mg2+		75		300	Enzyme activator, often associated with
							organic phosphate groups; electrolyte
	Zinc as Zn2+		5		15	Structural; catalytic component in active
							sites of enzymes
	Iron Fe		1		1 (men) 2 (young women)	Active sites of oxidative enzymes, electron transport proteins
	Copper Cu		1.5–3 mg			Oxidative enzymes, electron-
							transferring proteins
	Manganese Mn		2–5 mg			Component of enzymes
	Iodine I		150 µg			Formation of thyroxine, triiodothyronine
	Sulfur S					Largely supplied as cysteine or
							methionine (above)
	Selenium Se		50 µg			Formation of selenocysteine,
							component of active sites of several enzymes and other proteins
	Molybdenum Mo		25 µg			Formation of sulfite oxidase and other
							molybdoenzymes
	Chromium Cr		50 µg			Utilization of glucose
	Cobalt Co		as vitamin B12 (Table I)
Ultratrace elements, probably needed or beneficial						Most functions are uncertain
	Boron B		1–10 mg			Crosslinking?
	Fluorine F		1.5–4 mg			Protective component of hydroxyapatite
							in teeth, bones
	Arsenic As		15 µg
	Silicon Si		5–30 µg			Crosslinking in connective tissue
	Nickel Ni		25-30 µg			Uncertain
	Vanadium V					Component of thyroid peroxidase
Possibly needed			Typical dietary intake			Functions are unknown
	Aluminium Al		2 mg
	Bromine Br		2–8 mg
	Cadmium Cd		0–20 µg (toxic in excess)
	Germanium Ge		0.4–1.5 mg (toxic in excess)
	Lead Pb		15–100 μg (toxic in excess)
	Lithium Li		0.2–0.6 mg
	Rubidium Rb		1–5 mg
	Tin Sn		1–40 mg
a Data are from Shils, M. E., et al., eds. (1999). Modern Nutrition in Health and Disease, 9th ed., Williams & Wilkins, Baltimore. This book can be consulted for detailed discussions of all of the listed dietary components.
b The need for methionine is decreased if cysteine (or cystine) is present. Likewise, tyrosine decreases the need for phenylalanine. Persons with phenylketonuria must have tyrosine.

A deficit of vitamin A causes night blindness and loss of proper differentiation of epithelial cells. A dangerous symptom is the dry eye condition xerophthalmia, which can cause blindness. In fact, thousands of children in developing countries become blind from this condition each year. Fortunately, the problem can be alleviated inexpensively. A single oral dose of vitamin A provides a store in the liver adequate for 4–6 months. An international effort to eradicate vitaminA deficiency as a cause of blindness is in progress. Deficiency also interferes with reproduction. The yellowbeta-carotene and some related plant pigments can be converted by the human body into vitamin A. About six micrograms of all-trans beta-carotene yields one microgram of the vitamin. In large excess, vitamin A, especially in the form of retinoic acid, is toxic. About 3 mg per day of retinol or naturally occurring retinol esters is a safe limit. Amounts of vitamin A are often given in international units (IU). One IU is provided by 0.3 µg of all-trans retinol.

Deficiency of vitamin K is rare in adults but more frequent in breast-fed infants. The characteristic symptom of slow blood clotting may also arise, rarely, because of a hereditary lack of vitamin K-dependent processing of blood clotting proteins. The exact functions of vitamin E have been hard to define, but a deficiency can cause neurological and reproductive problems and muscular dystrophy in some animals. Although symptoms are rare in humans, they appear in various hereditary conditions such as the lack of a liver tocopherol transport protein. There are eight naturally occurring isomeric forms of vitamin E (Fig. 3) with differing potencies. The most active is the natural R, R, R-isomer of α-tocopherol for which 0.67 mg = 1 IU. At high levels, e.g., 1200 IU per day, vitamin E may compete with vitamin K and cause bleeding.

Figure 11 The vitamin biotin and the vitamin-like compound lipoic acid and their covalent attachments to selected lysine side chains in proteins (polypeptides). Both of these compounds function as catalytic prosthetic groups, biotin for CO2 and lipoic acid for hydrogen. The fragment biocytin was isolated from autolysates of rapidly growing yeast.

Figure 12 The use of five different vitamin-containing coenzymes in an important metabolic process, the oxidation of fatty acids (beta oxidation) to carbon dioxide and water.