What is protein cycling?
Before discussing the adaptations to varying protein intakes, a brief overview of the concept of protein cycling needs to be discussed. While far from a new concept, a recent trend in bodybuilding nutrition is the cycling of macronutrients in an attempt to cause specific physiological processes to take place. As an example, many are familiar with the cyclical ketogenic diet (CKD) which alternates periods of low-carbohydrate eating with periods of high-carbohydrate eating.
In the same vein, several authors have suggested that the intake of protein be cycled. The general premise is that chronically high intakes of protein lead to adaptive increases in protein oxidation and breakdown, which is deemed to be negative. By restricting protein for some periods of time (anywhere from 3 days to 1 month has been suggested), these authors suggest that oxidation and breakdown of AAs will be reduced, such that muscle can be gained more quickly when protein is refed at higher levels. One author has even suggested that AA oxidation rates will be permanently ‘reset’ at low levels after a month of low-protein intake. While there are other components to the theory of protein cycling, such as increased GH levels, the above serves as a good overview. The claims made above will be addressed in the following discussion of adaptations to varying protein intakes.
Mechanism of adaptation to changing protein intakes
The body has several potential mechanisms by which it can attempt to maintain protein stores. Arguably the primary method, other than growth, is via alterations in the rate of AA oxidation (17,43). When the intake of an AA is below what is required for maximal growth, oxidation of that AA remains low (43). When human AA intake is in excess of requirements, oxidation is increased. This adaptive response has been demonstrated in several studies on humans, with oxidation increasing or decreasing in response to high- or low-AA intakes (3-7).
In a study involving weight training, subjects received either 1.3 g/kg or 2 g/kg of protein per day (41). In the high protein group, AA oxidation was increased by 150% above normal levels. In addition, while there was no change in protein synthesis or breakdown in the low protein group, the high protein group increased synthesis by 105% and breakdown by 107%. Despite this increase in AA oxidation, there was a significant amount of lean body mass gained, approximately 3 lbs over a 4 week span, further supporting the concept that AA oxidation is not the negative it has been made out to be.
The second mechanism by which the body regulates protein stores is through alterations in protein synthesis and breakdown. In animal models, with as little as 12 hours without food, the rate of muscle protein synthesis falls although this can be reversed within 1 hour of refeeding (22). Although protein breakdown may increase initially (43), there is eventually a decrease in protein breakdown in protein deficient rats (43,44).
In humans, similar results occur: with increased protein intake, there is an overall increase in protein synthesis and breakdown. With decreased protein intake, protein synthesis and breakdown eventually fall so that the body can reattain balance (45,46). Ultimately this reflects an overall decrease in protein turnover (21). In a sense, AAs within the body are being more efficiently reutilized since there is decreased breakdown and oxidation.
A final potential mechanism by which the body can alter protein utilization is through the urea cycle. Recall from above that urea is generated when excesses of ammonium are produced through amino acid oxidation/catabolism. In that AA oxidation increases with increasing intake, we would expect urea production to increase with increased protein intake. Greater amounts of urea nitrogen being lost in the urine with increasing protein intakes. Similarly, decreased urea production is seen with decreasing protein intake (43).
With regards to the concept of protein cycling, the above data is more or less in keeping with the general concept. It is well-established that high-protein intakes (defined as above requirements) increases AA oxidation. As well, a reduction in protein leads over time to a reduction in AA oxidation. The only hole in the theory of protein cycling that we can see so far is represented in the study on weight training discussed above (41). What proponents of protein cycling seem to have forgotten is that only the excess protein is oxidized leaving the amount needed to support growth available to do so. Additionally, even in the face of increased oxidation, the body still maintains a net positive nitrogen balance.
The time course for changes
An important question regarding adaptation to changes in protein intake is how long it takes for the body to adapt. Once again, methodological problems prevent detailed human studies from being done although a few exist.
During protein deprivation in rats, both rates of protein turnover (synthesis and degradation) decrease as the length of time in starvation decreases (47). For example, in one study rats were given an essentially protein-free diet. After 1 day, protein synthesis had dropped by 25-40%. After 3 days, protein breakdown and oxidation had decreased by 30-45%. During refeeding, protein synthesis rose by 30% after 1 day and protein breakdown increased by 60% after day 3. The difference in changes of protein synthesis and breakdown during refeeding probably allows the rat to ‘catch-up’ to normal protein levels (48). In another study of protein deprivation, rats did not lose muscle protein until 9 days of protein deprivation had passed, while liver protein was lost almost immediately (44).
In humans, only a handful of studies have been done. Studies of complete starvation have found an increase in nitrogen losses (indicative of increased protein breakdown) during the first week or so followed by a decrease over the next several weeks (49). In another study, subjects were placed on varying levels of protein intake and a variety of measures were made after 7 days. With low protein intakes, protein breakdown dropped 24% within 7 days indicating the rapidity with which the body can adapt (46). In a third study, a reduction in protein breakdown was seen after only two low-protein meals (50). Overall, it appears that rates of protein and breakdown and synthesis can vary depending on protein intake as part of the overall adaptations.
In one detailed study, subjects were placed on either a low (96 gram/day) or high (260 gram/day) protein diet, which was maintained for 50 days (51). At that time, the groups switched from either high- to low-protein or vice versa. While only nitrogen balance was measured (i.e. no measurement of protein synthesis, breakdown or oxidation were performed), the results are interesting and applicable to the idea of protein cycling (discussed below). After the switch from low to high protein intakes, there was a large positive nitrogen balance persisting for 9-12 days before adaptation had occurred. by the same token, when subjects switched from high to low protein intakes, there was a large negative nitrogen balance which lasted for about 9-12 days before the body adapted. This has important implications for protein cycling, discussed below.
With regards to protein cycling, the above data supports the idea of short (3-12 day cycles of alternating protein intake) far more than it does the idea of a full month of low-protein. It appears that the majority of adaptations has taken place in a fairly short time period. Longer periods of low-protein would only serve to further deplete protein stores. Additionally, there is no evidence in humans to support the idea that AA oxidation remains low permanently. In fact, this would run quite contrary to the body’s goal of maintaining homeostasis.
Where does the protein come from/go to?
Perhaps the most important consideration when examining the adaptations to different protein intakes is where the protein is being lost (during protein deprivation) and gained (during protein refeeding). Once again, we must look at animal studies although they provide an incomplete picture for humans.
Recall from above that tissues vary in their rates of turnover. Liver proteins may be broken down and replaced completely within several hours, while muscle protein may take several days. Tendons and ligaments may take months to a year to turnover. Because of these differences, we would expect there to be differences in the site of protein synthesis and breakdown. Due to their short turnover time (several minutes), liver proteins are thought to be the site of short-term synthesis (after meals) and breakdown (during fasting) (1,22,34).
Unfortunately, it is methodologically difficult to determine where protein is being lost in humans so we must look at animal models. It should be noted that there are significant differences between animal and human protein metabolism so extrapolation should be made with care. During starvation in rats, the first proteins to be lost are from the liver, with 25-40% of liver protein being lost after 48 hours (34,47). Decreases in the size of other organs such as the heart and brain has also been noted. Muscle protein is not lost until several days later. Considering differences in the rate of protein turnover (see above), it makes sense that proteins with the fastest rates of turnover would be lost first. Readers should note that 48 hours of starvation in the rat corresponds to longer periods of starvation in man.
By corollary, during refeeding, we would expect that the first proteins to be repleted are liver proteins, with muscle protein being rebuilt afterwards. So while it has been suggested that the low-protein days will cause the loss of liver proteins while the high-protein days will cause the gain of mainly muscle proteins, this seems a highly illogical path for the body to take as it would allow the progressive depletion of organ proteins with the progressive growth of muscle protein. This would most likely eventually result in the death of the organism.
In addition, the studies cited above demonstrate perhaps the biggest problem with the whole concept of protein cycling, as the body’s protein stores are repleted (sometimes referred to as ‘catch-up’ growth), rates of oxidation, synthesis and breakdown return to the levels they were at prior to the low-protein phase. So not only does the body appear to first replete those proteins which were first lost (liver and other organ proteins), but by the time those proteins are repleted, the body has readapted to the current level of protein intake. In all likelihood, the net result of protein cycling will be no change in total body protein stores. This should be contrasted to simply keeping protein intake at appropriate levels (at or slightly less than 1 g/lb as discussed in Part 1) to allow gains to occur at their normal rate.
Summary
There are a number of mechanisms by which the body can adapt to increasing and decreasing protein intakes. Arguably the most important is rates of oxidation, which can increase or decrease rapidly to compensate for increasing and decreasing protein intakes. In addition, rates of protein synthesis and breakdown can be altered, with both typically decreasing with lowered protein intakes, and increasing with raised protein intakes. Finally, the amount of urea produced, which is related to AA oxidation, may be altered.
Although comprehensive data is lacking, it appears that the major adaptations to altered protein intakes take place fairly rapidly, within a number of days. In rats, this may be 3-7 days, in humans 9-12 days or slightly longer.
While more research is needed, it appears the the first proteins lost during protein deprivation are liver and other organ proteins. By the same token, during protein refeeding (or simply high protein feeding) it appears that liver proteins are the first to be synthesized.
With regards to the concept of protein cycling, while the general idea is somewhat logical, in that decreasing protein intake can cause a transient decrease in oxidation and turnover, there is little indication that there will be a net gain in body protein when protein intake is increased again. In the same way that liver proteins are the first lost, they will likely be the first regained. And by the time liver proteins have been rebuilt, rates of oxidation and turnover will have returned to normal, leaving the individual with no net gains.
