Proteins participate in virtually every cellular process and are essential to life. They perform a range of biological functions, including enzymatic catalysis of biochemical reactions, cell signalling, immune response, mechanical functions and structural support. Proteins may also serve as a fuel source under some circumstances, providing 17kJ/g (4 kcal/g) of energy. They are composed of polymer chains of amino acids linked together by peptide bonds. Following digestion, consumed protein is broken down into its constituent amino acids, typically by denaturation through exposure to acid and the action of proteolytic enzymes.
There are 20 different amino acids found in humans, nine of which are unable to be synthesised de novo from other compounds. These nine are considered essential, meaning they must be supplied in the diet. Failure to obtain sufficient quantities of these essential amino acids can lead to protein-energy malnutrition and ultimately death. The essential amino acids are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine. Additionally, six amino acids are conditionally essential, with certain pathophysiological states such as severe catabolic distress limiting their synthesis.
Unlike fatty acids and glucose, which can be stored as triglyceride or glucagon respectively, amino acids cannot be stored. The total concentration of free amino acids in plasma is only about 2.5 mM(77). Amino acids which are digested in amounts exceeding the need for biosynthesis are rapidly catabolised. All amino acids contain at least one nitrogen atom. While some nitrogen is used in biosynthesis, most is not needed and is eliminated as urea in the urine. The removal of nitrogen occurs early in the degradation of amino acids, leaving behind a carbon skeleton which may then be used for energy; producing glucose, ketone bodies, or both depending on the specific amino acid.
There is ongoing debate regarding ideal protein intake requirements. Many different factors determine protein requirements, such as stage of life, body weight, body composition, activity level, other macronutrient consumption and the presence of illness or injury. The Australian Dietary Guidelines recommend different levels of protein intake based on age, sex, and for females, pregnancy and breast feeding status. The Australian recommended daily intake (RDI) for adult males between 19-70 years is 0.84 g/kg, increasing to 1.07g/kg for those over 70 years. The equivalent recommendation for females is 0.75 g/kg between 19-70 years, and 0.94g/kg over 70 years. The recommended daily allowance provided for in the Dietary Guidelines for Americans is similar, recommending 0.8 g/kg for both males and females.
Current dietary guidelines on protein intake were largely derived from nitrogen balance studies based on the structural requirement for protein. However, this approach neglects the role of protein in other metabolic processes. Further, nitrogen balance studies to collect this data were usually performed on college-aged males, with findings extrapolated to female and the elderly populations. Consequently, there are substantial questions regarding the validity of current dietary guideline recommendations regarding optimal protein intake.
One reanalysis of existing nitrogen balance data, based on an improved biological understanding of protein found the mean requirement in adult males was 0.93g/kg/day, 41% higher than the current American recommendation.
Recommended protein intake for special populations
The elderly have an increased need for dietary protein due to a reduced anabolic response to dietary amino acids. While current guidelines do recommend higher protein intakes in those over 70 years, this is still likely to be insufficient. Available research suggests that 1.5 g protein/kg/day, or about 15-20% of total caloric intake, is a reasonable dietary protein target optimising health and function in the elderly.
Participation in both endurance and strength exercise increases protein requirements compared to sedentary controls, albeit for different reasons. Amino acids can serve as substrate for energy production in endurance athletes and serve a structural function in strength athletes. Experimental data from studies on strength and power athletes suggest that optimal protein intake may be up to 2.4g/kg/day(85). The rate of oxidation of amino acids during endurance exercise is largely dependent on exercise intensity. A daily protein intake of 1.5g/kg has been estimated as sufficient to meet the needs of most endurance distance runners.
Individuals following restrictive diets or who have digestive issues may find it more difficult to obtain sufficient dietary protein. In most cases however, protein supplementation is unnecessary, with sufficient quantities able to be obtained from the diet.
Too much or too little protein?
The optimal level of protein intake for good health probably exceeds the recommended intakes in dietary guidelines. Excess protein intake is often cited as leading to increased risk of osteoporosis, with concerns arising from studies demonstrating a transient increase in calcium excretion with higher protein intakes. There is no convincing evidence to support these concerns. The authors of a 2017 systematic review concluded that increased dietary protein was associated with improved bone mineral density, while higher protein intakes have also been linked to a reduced risk of hip fracture in the elderly.
Protein restriction is frequently advised in the setting of renal disease. However, again, this recommendation does not appear to be supported by the best available evidence. One long-term follow-up of 585 patients with renal disease demonstrated no beneficial effects of a low protein diet (0.58 g/kg/day) when compared to a high protein control group (1.3 g/kg/day)(91).
Additionally, there is no evidence that high protein diets are detrimental to renal function in those without renal disease, including in diabetics. Multiple studies have failed to find association between high protein intake and renal impairment. Further, a 2016 study evaluating very high protein intakes (3g/kg/day) in resistance-trained men found no harmful effects on blood lipids, liver or kidney function.
The Australian Dietary Guidelines recommend that protein ought to provide 15-25% of total energy intake to minimise the risk of chronic disease. Adherence to this recommendation is likely to lead to a protein intake significantly exceeding the RDI. The upper limit of this recommendation, based on an average resting metabolic rate of 3.61 kJ/kg/hr, represents a protein intake equivalent to 1.32 g/kg/day to solely meet basal energy needs. This contrasts with the Australian (RDI) for adult males and females of 0.84 g/kg and 0.75 g/kg respectively.
It is important to consider the source of dietary protein when considering its impact on health.
Animal sources of protein provide a complete complement of all essential amino acids, including meat, eggs, dairy and fish. Plant sources, with the exception of soy and certain seeds, generally lack one or more of the essential amino acids, and have a reduced content of essential amino acids in comparison to animal proteins. Many health professionals hold concerns regarding the consumption of animal-sourced protein due to the concurrent consumption of saturated fat, however these concerns are yet to be substantiated.
Multiple systems exist to rate proteins by their biological utility. Factors considered include the digestibility and subsequent absorption of the protein, as well as amino acid composition which is a major determinant of nutritional quality. The Protein Digestibility Corrected Amino Acids Score (PDCAAS) has been widely adopted as the standard method for determining the quality of dietary protein(98). It does have several limitations however, such as failing to account for anti-nutrient factors like phytic acid and trypsin inhibitors, both found in plant foods, which limit the absorption of protein. Recently, the Digestible Indispensable Amino Acid Score (DIAAS) has been proposed as an alternative measure which addresses these shortcomings.
Most measures of protein quality of foods rank whey protein isolate first. It has a complete complement of the 20 amino acids seen in humans, is rapidly absorbed, and has the highest PDCAAS score possible of 1.0. It has a DIAAS score of 1.25 which is second only to that of whole milk with 1.32. Casein and egg proteins are also complete proteins, both obtaining a PCDAAS score of 1.0. Plant based sources of proteins are generally considered to be inferior to animal proteins due to incomplete amino acid profiles and reduced absorption profiles, often secondary to the previously mentioned anti-nutrient factors such as phytic acid and trypsin inhibitors.