Co-ingesting creatine with caffeine partially negated the benefits of creatine supplementation (at 5mg/kg bodyweight) during the loading phase in one study.[590] The exact mechanism responsible for this effect is not known, but might be related to opposing actions on muscle contraction time.[591] However, another study in trained men found that co-ingestion of 300mg caffeine per day during creatine loading at 20g per day (split into 4 doses) had no effect on bench press 1RM, time to fatigue, or sprinting ability.[592] However, this study also found that creatine alone or when combined with caffeine had no effect on any of these parameters over placebo, either. Thus, the study may have been underpowered or done in too short a time frame (the test was done after only 5 days of loading) to observe any possible effects.[592]
Once training is resumed under these conditions, there may be little in the way of caloric support to ensure that protein synthesis and muscle growth occurs. Muscle may even begin to cannibalize itself as the body enters into a catabolic state. Even with the best of diets this can sometimes happen if training demands override the nutritional balance or imbalance.

The maximum amount of creatine the body can store is about 0.3 gram per kilogram of body weight [6]. The creatine content of skeletal (voluntary) muscles averages 125 millimoles per kilogram of dry matter (mmol/kg/dm) and ranges from about 60 to 160 mmol/kg/dm. Approximately 60% of muscle creatine is in the form of PCr. Human muscle seems to have an upper limit of creatine storage of 150 to 160 mmol/kg/dm. Athletes with high creatine stores don't appear to benefit from supplementation, whereas individuals with the lowest levels, such as vegetarians, have the most pronounced increases following supplementation. Without supplementation, the body can replenish muscle creatine at the rate of about 2 g/day [7].

We hear this from 30 year olds and 60 year olds alike…and, like “I don’t have time,” it is a big fat lie! Even for the frail elderly, studies have shown that drastic results are possible in just 10 weeks of weightlifting (for both men and women in their 70s through their 90s). In fact, weight training has also been shown to delay Alzheimer’s and stave off dementia. So, if you think you might be “too old,” you’re probably the exact type of person that SHOULD be strength training!

It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio,[333][334] and when activated AMPK (active in states of low cellular energy[335] and colocalizes with creatine kinase in muscle tissue[336]) appears to inhibit creatine kinase via phosphorylation (preserving phosphocreatine stores but attenuating the rate that creatine buffers ATP). While phosphocreatine technically inhibits AMPK, this does not occur in the presence of creatine at a 2:1 ratio.[334] It seems that if the ratio of phosphocreatine:creatine increases (indicative of excess cellular energy status) that AMPK activity is then attenuated, since when a cell is in a high energy status, there is less AMP to directly activate AMPK.[334][336][337]