Medical Physiology, 3rd Edition

Nutritional Requirements

No absolute daily requirement for carbohydrate or fat intake exists

Nutritionists recommend that the daily intake of carbohydrate relative to fat should not differ with age, gender, or activity level. Of the total caloric intake in a Western diet, 55% to 60% is typically carbohydrate, 25% to 30% is fat, and the remaining 10% to 15% is protein.

The requirements for total caloric intake vary among individuals and depend on certain factors, including a person's ability to use and store energy (efficiency) and the daily activity level. Differences in the efficiency of energy use among individuals are the result, in part, of variations in muscle mass but also of genetic factors. Because adipose tissue has a low metabolic rate, people with a large fat mass require less caloric intake per kilogram of body weight. Stated differently, the requirement for energy intake is greater per kilogram of lean body mass than per kilogram of total body mass (which includes fat). Thus, men generally require a greater daily caloric intake per kilogram of body weight than do women, who have relatively less muscle and more fat.

Activity level is the primary factor determining the daily energy requirement, assuming a stable body weight. For example, in a steady state, athletes must consume more than nonathletes not only because of a higher muscle-to-fat ratio but also because of a higher energy expenditure. Manual labor necessitates greater energy intake than does sedentary activity, again to maintain energy balance and body weight. Excess energy intake over output, over time, causes weight gain in the form of fat (see p. 1173). Using 9.4 kcal/g as the conversion factor, 1 kg of fat stores 9400 kcal, sufficient energy to support the basal metabolic rate for 4 days.

In addition to serving as a source of energy, fatty acids are also important for membrane structure (see p. 8–9) as well as signal transduction by pathways such as those involving DAGs (see p. 60–61) and arachidonic acid (see p. 62). In mammalian cells, fatty-acid synthase produces two major fatty acids: palmitic acid and oleic acid. Palmitic acid, which has 16 carbons and is fully saturated, is referred to as 16 : 0. Oleic acid has 18 carbons and a single cis double bond between carbons 9 and 10. This unsaturated fatty acid is referred to as 18 : 1 cis9. Because mammals cannot insert double bonds beyond carbon 9, they need two fatty acids in the diet: linoleate (18 : 2 cis9Δ12) and linolenate (18 : 3 cis9Δ12Δ15). These essential fatty acids serve as precursors for other unsaturated fatty acids, including arachidonic acid, which is a precursor to prostaglandins, leukotrienes, and thromboxanes.

The current recommendations favoring low fat intake are based on the view that a high fat intake is associated with chronic diseases such as atherosclerosis and non–insulin-dependent diabetes (see Box 51-5). However, fats have a positive side. In addition to playing the roles we have discussed in this chapter, fats enhance satiety and aid in the absorption of certain vitamins (see p. 933). Finally, the so-called omega-3 polyunsaturated fatty acids—in which the first double bond is three carbons from the terminal methyl group (or “omega carbon”)—appear to protect against cardiovascular disease and some forms of cancer.

The daily protein requirement for adult humans is typically 0.8 g/kg body weight but is higher in pregnant women, postsurgical patients, and athletes

The diet must contain the nine essential amino acids (see Table 58-2) because the body cannot synthesize them. Eleven other amino acids are necessary for protein synthesis, but the body can synthesize their carbon skeletons from intermediates of carbohydrate metabolism. Vegetarian diets can meet the protein needs of the body provided the protein consumed contains adequate amounts of essential amino acids. Food protein is “scored” based on its content of essential amino acids compared with that of a reference protein, usually egg protein, which is given a score of 100. For example, a food containing protein with a score of 40 for threonine, 80 for phenylalanine, and 100 for lysine—all three of which are essential amino acids—receives a protein score of 40 because, relative to the standard, threonine is present in the lowest amount.

Protein intake is most important to meet the needs for tissue maintenance and repair, for muscle and neural function, and for maintenance of host defense mechanisms. The daily requirement for protein intake depends on one's nutritional status. The average human needs ~0.6 g of protein per kilogram of body weight per day to maintain nitrogen balance. The RDA for protein is ~0.8 g/kg of body weight for adults, ~1 g/kg for adolescents, and ~2 g/kg in the first 6 months of life. Pregnant and lactating women require extra protein intake to ensure adequate fetal development and milk production. Athletes require >1 g/kg to maintain a greater lean body mass and to fuel a highly active metabolism. Well-balanced but larger meals usually provide adequate protein for those with a greater need. Burn victims, patients recovering from surgery, and patients with disorders of protein absorption all require increased daily protein intake.

The distribution of amino acids required for protein accretion by growing infants and children is different from that for tissue maintenance. Moreover, the requirements change throughout development. The child uses 25% of amino-acid intake for protein accretion at 6 months of age but only 10% by 18 months of age. More than 40% of a child's protein intake must consist of essential amino acids versus only 20% of an adult's.

Proteins play a key role in host defenses. For example, proteins provide the structural backbone for skin and mucus. Protein synthesis is essential for phagocytes and lymphocytes that are responsible for antibody and cell-mediated immunity. The skin, lungs, and intestinal tract are the main structural defenses against invading organisms. In both the lungs and the gastrointestinal tract, mucus (containing glycoproteins) coats the surface of the passageways and aids in defending against disease by catching most foreign particles. Protein-depleted individuals, regardless of age, have impaired immune competence. Protein depletion limits the availability of amino acids for synthesis of the cellular proteins of the immune system, including glutathione, mucus glycoproteins, and metallothreonine. The acute-phase response to invading organisms is suboptimal in a protein-deficient state.

The impaired immune competence of patients with acquired immunodeficiency syndrome (AIDS) is a function of poor nutrition in addition to the effects of the virus itself. During infection, the body mobilizes amino acids to synthesize proteins for defense against invading organisms. Thus, improving protein and energy intake may be beneficial for some AIDS patients.

Aside from being the backbone of proteins, amino acids play a variety of physiological roles. For example, arginine is a precursor to nitric oxide (see p. 66). Glutamate is a major excitatory neurotransmitter in the brain (see pp. 318–319), whereas glycine is a major inhibitory neurotransmitter (see p. 319). Glutamine is a major source of NH3 production in the kidney (see pp. 829–831) and it also regulates protein turnover in muscle. The decrease in muscle glutamine concentration that occurs during trauma and infection is associated with a general decline of muscle function. Research in anorectic patients shows that the most important factor affecting muscle function is insufficient nutrient intake. Increasing total nutrient intake in these patients by total parenteral nutrition increases muscle function before it has a measurable effect on muscle mass.

Minerals and vitamins are not energy sources but are necessary for certain enzymatic reactions, for protein complexes, or as precursors for biomolecules

Vitamins and minerals do not provide energy but are essential for such functions as metabolism, immune competence, muscle-force production, and blood clotting.


Table 45-4 lists the essential minerals. The current recommendations for daily mineral intake are based on a mix of balance studies and usual dietary intakes in the United States. The recommendation for copper, for example, is based on balance studies, whereas those for manganese, chromium, and molybdenum are based on dietary intakes.

Assigning daily mineral intakes is problematic because some methods of determining mineral status do not always expose functional deficiencies. For example, a frank deficiency in Ca2+ intake leads to bone loss even though blood Ca2+ levels remain normal. Iron deficiency is difficult to detect because no clinical signs appear until iron stores are depleted. It is difficult to base recommendations simply on absorption because, for some minerals, absorption varies with intake. For example, copper deficiency or toxicity is unlikely in humans because absorption is inversely related to intake. Furthermore, interactions among minerals must be taken into account when establishing recommendations.

The goal is to base recommendations on scientific evidence. Radioisotopes can be used to monitor storage, absorption, and excretion. Another approach is to establish the physiological role of the mineral and then determine the mineral intake required for maintaining that physiological role. However, because of redundancy in function, it is often difficult to assess which mineral is deficient when function is compromised. For example, both iron and copper are involved in energy metabolism at the level of the electron transport chain. The blood clotting cascade involves Ca2+, copper, and vitamin K. Zinc, selenium, and manganese all have antioxidant activities.


Even though vitamins are not energy sources themselves, they play an integral role as cofactors in many metabolic processes. Some vitamins are involved in group-transfer reactions, such as decarboxylations and carboxylations in fatty-acid and glucose metabolism, and transaminations in amino-acid metabolism. Vitamins act as oxidizing and reducing agents in the generation of ATP and also as antioxidants to quench free radicals produced as a byproduct of oxidation.

Of the 13 identified vitamins, RDAs have been established for 11 (see Table 45-3). Safe and allowable ranges are estimated for the remaining two—biotin and pantothenic acid. Recommendations differ widely among countries. Lower recommendations are generally based on scientific evidence. For each vitamin, a person's nutritional status falls into one of five categories: deficient, marginal, satisfactory, excessive, and toxic. Although “marginal” and “excessive” are not usually associated with overt clinical signs, people whose vitamin status falls into one of these categories are at increased risk of various diseases.

In the past, recommendations for the intake of vitamins and minerals were based largely on levels necessary to promote normal growth and development. However, the role of vitamins and minerals in optimizing body function and in promoting longevity is becoming an area of intense interest both to researchers and to the general public. Older people generally have a less vigorous immune response than do young people, in large part because of deficiencies in iron, zinc, and vitamin C. Correcting these deficiencies improves immune competence significantly. In addition, older people with poor dietary habits may have inadequate intake of Ca2+, vitamin D, and other nutrients involved in bone deposition and strength (see pp. 1056–1058), which puts them at greater risk of hip fracture.

Mineral deficiencies usually do not occur without extreme abnormalities in diet, and even then, a mineral deficiency may not impair function (see Table 45-4). However, a deficiency of almost any vitamin can cause functional impairment (see Table 45-3).

Excessive intake of vitamins and minerals has mixed effects on bodily function

A current controversy surrounds the use of so-called megadoses of certain vitamins and minerals. Such excessive intake has mixed effects. Slight excesses of vitamins A and E, zinc, and selenium are associated with an enhanced immune response, especially in patients with burns, trauma, or sepsis. In these conditions, “excess” intake may not be an excess at all but rather the intake that meets the greater need. Increased intake of fruits and vegetables—which contain a variety of vitamins as well as “fiber”—clearly decreases the risk of various cancers. However, efforts to link these effects specifically to dietary carotenoid levels have failed to show a correlation; indeed, the excessive intake of β-carotene supplements may even increase the risk of some cancers. Antioxidants (e.g., β-carotene, vitamins C and E) quench peroxyl radicals of lipids, suppress tumor growth, and decrease atherosclerotic lesions in rabbits. Enhanced vitamin E intake lowers the risk of coronary heart disease by nearly one half.

The excessive intake of certain minerals and vitamins may compromise the immune response. Excess vitamin E intake in infants may increase the risk of infection, possibly by quenching superoxide radicals that are important for leukocytes to kill bacteria. Excess lipids can impair the immune response, too. High intake of saturated and polyunsaturated fatty acids leads to decreases in cell-mediated immunity. Excessive Ca2+ intake interferes with the ability to use iron, zinc, and Mg2+, whereas high dietary copper affects zinc absorption and excretion.

Because the kidneys readily excrete water-soluble vitamins in the urine, toxicity from excessive intake is not common. Because fat-soluble vitamins are not easily excreted in the urine, it is easier to develop toxicity for these vitamins. In particular, polar bear liver, a component of the Inuit diet, contains extraordinarily high levels of vitamin A (35,000 IU/g versus the RDA of 5000 IU), which can lead to acute hypervitaminosis A and death.




Length (m)



Area of apical plasma membrane (m2)









Crypts or glands






Nutrient absorption



Active Na+ absorption



Active K+ secretion