A meta analysis pools results from many studies into one number. A meta regression goes a step further and asks which features of those studies predicted how large each individual result was.
That is what makes this paper unusual here. It lets a protocol variable, such as how much carbohydrate was fed or how empty the muscle was before loading started, be tested against the whole literature at once rather than one trial at a time.
Drawn from background method, not from this paper.
Many studies had confirmed that glycogen overshoots after exercise and a carbohydrate rich diet, but they used different exercise and different diets and reached very different sized answers, and the authors write that the mechanisms behind the elevated glycogen remain unclear.
Their aim was to put a single number on the size of the overshoot for cycling and for running, and then to run meta regressions to find which factors were influencing it.
Drawn from the paper's introduction.
Thirty studies published between 1966 and 2020 were included, covering 319 participants, of whom 271 were male and 48 were female. Muscle glycogen rose by 269.7 millimoles per kilogram of dry weight after cycling and by 156.5 after running.
Three moderators reached significance in the cycling studies. Carbohydrate as a percentage of total energy intake was positively associated with the overshoot and explained the largest share of the variation. Glycogen measured immediately after the depleting exercise was negatively associated with it, and so was glycogen before loading began. The last two are the same headroom story told twice: the emptier the muscle, the bigger the subsequent overshoot.
Three moderators came out flat. Carbohydrate intake in grams per kilogram per day was not associated with the overshoot. Neither was the amount of glycogen broken down during the exercise bout. Neither was maximal oxygen uptake, which explained none of the variation at all.
Heterogeneity was very high, above 90 percent for both cycling and running. Adding the two significant moderators to a single model brought it down from 92.4 percent to 66.1 percent, which is the clearest evidence in the paper that protocol differences are what the trials have been disagreeing about.
| Glycogen increase after cycling | 269.7 +/- 29.2 mmol/kg dw, 95% CI 212.4 to 327.0, p<0.001, I2 92.4% |
| Glycogen increase after running | 156.5 +/- 48.6 mmol/kg dw, 95% CI 61.3 to 251.7, p=0.001, I2 93.5% |
| Males | 294.3 +/- 32.0 mmol/kg dw, n=168 |
| Females | 151.6 +/- 70.9 mmol/kg dw, 95% CI 12.8 to 290.5, p=0.032, n=32 |
| Moderator: carbohydrate as percent of total energy | estimate 15.25, 95% CI 9.86 to 20.65, p<0.001, R2 0.56 |
| Moderator: glycogen immediately after exercise | estimate -2.25, 95% CI -3.42 to -1.09, p<0.001, R2 0.49 |
| Moderator: basal glycogen | estimate -0.80, 95% CI -1.42 to -0.18, p=0.011, R2 0.18 |
| Moderator: carbohydrate in g/kg/day | p=0.177, R2 0.03, not significant |
| Moderator: glycogen broken down during exercise | p=0.574, R2 0.00, not significant |
| Moderator: maximal oxygen uptake | p=0.949, R2 0.00, not significant |
| Heterogeneity after adding the two significant moderators | I2 fell from 92.4% to 66.1%, p<0.001 |
Proposed by the authors This is the explanation the authors offer in their discussion. This study did not test it.
The authors read the gram dose null as a ceiling rather than an absence. Every study in the pool fed enough carbohydrate to saturate resynthesis, so there was no low dose left in the literature for the regression to detect, and they put the threshold at more than eight grams per kilogram per day being sufficient when no further exercise is done.
They read the depletion association as a matter of headroom. Muscle glycogen appears to have an upper limit, since the supercompensated values cluster far more tightly than the increases do, so a muscle that starts emptier has further to travel and shows a larger overshoot without necessarily ending up any fuller.
On the sex comparison they point at energy rather than biology: the one study that found supercompensation in men and not women had fed the women far less energy, and its own authors found no difference once energy intake was raised.
Drawn from Discussion, PMC12399638.
Three procedural factors move muscle glycogen and three do not. How carbohydrate rich the diet is matters, and how much headroom the muscle has matters, which shows up twice as the glycogen left after the bout and the glycogen there before it. Grams per kilogram per day, the size of the depleting bout, and the athlete's maximal oxygen uptake all came out flat. That last one is the one worth sitting with, because the received idea is that better trained athletes have less to gain, and across sixty years of these trials aerobic fitness predicted none of the difference in how much glycogen was stored.
Thirty studies of cycling and running published between 1966 and 2020, with the moderator analysis run on the cycling studies alone.
The same analysis with performance as the outcome and the depletion phase, the loading duration and the dose coded as moderators. It does not exist, and the paper that examined the performance literature most closely argues the underlying evidence may not currently support one.
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