A Review of Issues of Dietary Protein Intake in Humans
Considerable debate has taken place over the safety and validity of increased protein intakes for both weight control and muscle synthesis. The advice to consume diets high in protein by some health professionals, media and popular diet books is given despite a lack of scientific data on the safety of increasing protein consumption. The key issues are the rate at which the gastrointestinal tract can absorb amino acids from dietary proteins (1.3 to 10 g/h) and the liver's capacity to deaminate proteins and produce urea for excretion of excess nitrogen. The accepted level of protein requirement of 0.8g ∙ kg-1 ∙ d-1 is based on structural requirements and ignores the use of protein for energy metabolism. High protein diets on the other hand advocate excessive levels of protein intake on the order of 200 to 400 g/d, which can equate to levels of approximately 5 g ∙ kg-1 ∙ d-1, which may exceed the liver?s capacity to convert excess nitrogen to urea. Dangers of excessive protein, defined as when protein constitutes > 35% of total energy intake, include hyperaminoacidemia, hyperammonemia, hyperinsulinemia nausea, diarrhea, and even death (the ?rabbit starvation syndrome?). The three different measures of defining protein intake, which should be viewed together are: absolute intake (g/d), intake related to body weight (g ∙ kg-1 ∙ d-1) and intake as a fraction of total energy (percent energy). A suggested maximum protein intake based on bodily needs, weight control evidence, and avoiding protein toxicity would be approximately of 25% of energy requirements at approximately 2 to 2.5 g ∙ kg-1 ∙ d-1, corresponding to 176 g protein per day for an 80 kg individual on a 12,000kJ/d diet. This is well below the theoretical maximum safe intake range for an 80 kg person (285 to 365 g/d).
Amino acid catabolism must occur in a way that does not elevate blood ammonia (26). Catabolism of amino acids occurs in the liver, which contains the urea cycle (26), however the rate of conversion of amino acid derived ammonia to urea is limited. Rudman et al. (27)
Early findings suggest that rapidly absorbed proteins such as free amino acids and WP, transiently and moderately inhibit protein breakdown (39, 53), yet stimulate protein synthesis by 68% [using nonoxidative leucine disposal (NOLD) as an index of protein synthesis] (54). Casein protein has been shown to inhibit protein breakdown by 30% for a 7-h postprandial period, and only slightly increase protein synthesis (38, 54). Rapidly absorbed amino acids despite stimulating greater protein synthesis, also stimulate greater amino acid oxidation, and hence results in a lower net protein gain, than slowly absorbed protein (54). Leucine balance, a measurable endpoint for protein balance, is indicated in Figure 1, which shows slowly absorbed amino acids (~ 6 to 7 g/h), such as CAS and 2.3 g of WP repeatedly taken orally every 20 min (RPT-WP), provide significantly better protein balance than rapidly absorbed amino acids (39, 54).
The misconception in the fitness and sports industries is that rapidly absorbed protein, such as WP and AA promote better protein anabolism. As the graph shows, slowly absorbed protein such as CAS and small amounts of WP (RPT-WP) provide four and nine times more protein synthesis than WP.
This ?slow? and ?fast? protein concept provides some clearer evidence that although human physiology may allow for rapid and increased absorption rate of amino acids, as in the case of WP (8 to 10 g/h), this fast absorption is not strongly correlated with a ?maximal protein balance,? as incorrectly interpreted by fitness enthusiasts, athletes, and bodybuilders.
Using the findings of amino acid absorption rates shown in Table 2 (using leucine balance as a measurable endpoint for protein balance), a maximal amino acid intake measured by the inhibition of proteolysis and increase in postprandial protein gain, may only be ~ 6 to 7 g/h (as described by RPT-WP, and casein) (38), which corresponds to a maximal protein intake of 144 to 168 g/d.
The rate of amino acid absorption from protein is quite slow (~ 5 to 8 g/h, from Table 2) when compared to that of other macronutrients, with fatty acids at ~ 0.175 g ? kg-1 ? h-1 (~ 14 g/h) (55) and glucose 60 to 100 g/h (0.8 to 1.2 g carbohydrate ? kg-1 ? h-1) for an 80 kg individual (56). From our earlier calculations elucidating the maximal amounts of protein intake from MRUS, an 80 kg subject could theoretically tolerate up to 301 to 365 g of protein per day, but this would require an absorption rate of 12.5 to 15 g/h, an unlikely level given the results of the studies reported above.
The consumption of large amounts of protein by athletes and bodybuilders is not a new practice (13). Recent evidence suggests that increased protein intakes for endurance and strength-trained athletes can increase strength and recovery from exercise (14, 80, 81). In healthy adult men consuming small frequent meals providing protein at 2.5 g ? kg-1 ? d-1, there was a decreased protein breakdown, and increased protein synthesis of up to 63%, compared with intakes of 1g ? kg-1 ? d-1 (16). Subjects receiving 1g ? kg-1 ? d-1 underwent muscle protein breakdown with less evident changes in muscle protein synthesis. Some evidence suggests, however, that a high protein diet increases leucine oxidation (82, 83), while other data demonstrate that the slower digestion rate of protein (38, 54), and the timing of protein ingestion (with resistance training) (84) promote muscle protein synthesis.
Absorption rates of amino acids from the gut can vary from 1.4 g/h for raw egg white to 8 to 10 g/h for whey protein isolate. Slowly absorbed amino acids such as casein (~ 6 g/h) and repeated small doses of whey protein (2.9 g per 20 min, totaling ~ 7 g/h) promote leucine balance, a marker of protein balance, superior to that of a single dose of 30 g of whey protein or free amino acids which are both rapidly absorbed (8 to 10 g/h), and enhance amino acid oxidation. This gives us an initial understanding that although higher protein intakes are physiologically possible, and tolerable by the human body, they may not be functionally optimal in terms of building and preserving body protein. The general, although incorrect consensus among athletes and bodybuilders, is that rapid protein absorption corresponds to greater muscle building.
From the limited data available on amino acid absorption rates, and the physiological parameters of urea synthesis, the maximal safe protein intakes for humans have been estimated at ~ 285 g/d for an 80 kg male. It is not the intention of this article, however, to promote the consumption of large amounts of protein, but rather to prompt an investigation into what are the parameters of human amino acid kinetics. In the face of the rising tide of obesity in the Western world where energy consumption overrides energy expenditure, a more prudent and practical approach, which may still provide favorable outcomes, is a 25% protein energy diet, which would provide 118 g protein on an 8000 kJ/d diet at 1.5 g ? kg-1 ? d-1 for an 80 kg individual (Table 2).
Little data exists on the comprehensive metabolic effects of large amounts of dietary protein in the order of 300 to 400 g/d. Intakes of this magnitude would result in some degree of prolonged hyperaminoacidemia, hyperammonemia, hyperinsulinemia, and hyperglucagonemia, and some conversion to fat, but the metabolic and physiological consequences of such states are currently unknown. The upper limit of protein intake is widely debated, with many experts advocating levels up to 2.0 g ? kg-1 ? d-1 being quite safe (102, 117, 118) and that renal considerations are not an issue at this level in individuals with normal renal function.
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Abstract
Considerable debate has taken place over the safety and validity of increased protein intakes for both weight control and muscle synthesis. The advice to consume diets high in protein by some health professionals, media and popular diet books is given despite a lack of scientific data on the safety of increasing protein consumption. The key issues are the rate at which the gastrointestinal tract can absorb amino acids from dietary proteins (1.3 to 10 g/h) and the liver's capacity to deaminate proteins and produce urea for excretion of excess nitrogen. The accepted level of protein requirement of 0.8g x kg(-1) x d(-1) is based on structural requirements and ignores the use of protein for energy metabolism. High protein diets on the other hand advocate excessive levels of protein intake on the order of 200 to 400 g/d, which can equate to levels of approximately 5 g x kg(-1) x d(-1), which may exceed the liver's capacity to convert excess nitrogen to urea. Dangers of excessive protein, defined as when protein constitutes > 35% of total energy intake, include hyperaminoacidemia, hyperammonemia, hyperinsulinemia nausea, diarrhea, and even death (the "rabbit starvation syndrome"). The three different measures of defining protein intake, which should be viewed together are: absolute intake (g/d), intake related to body weight (g x kg(-1) x d(-1)) and intake as a fraction of total energy (percent energy). A suggested maximum protein intake based on bodily needs, weight control evidence, and avoiding protein toxicity would be approximately of 25% of energy requirements at approximately 2 to 2.5 g x kg(-1) x d(-1), corresponding to 176 g protein per day for an 80 kg individual on a 12,000kJ/d diet. This is well below the theoretical maximum safe intake range for an 80 kg person (285 to 365 g/d).
