Osteoblast cells are known to express creatine kinase.[39][417] Bone growth factors such as IGF-1,[418] PTH,[419] and even Vitamin D[420][421] seem to induce bone growth alongside increases in creatine kinase activity. Vitamin D has been noted to work indirectly by increasing the cellular energy state (these hormones increase creatine kinase in order to do so) in order to make bone cells more responsive to estrogen.[420] This evidence, paired with enhanced growth rates of osteoblasts in the presence of higher than normal (10-20mM) concentrations of creatine[422] suggest a role of creatine in promoting osteoblastic and bone growth, secondary to increasing energy availability.
Creatine is an energy substrate: a small peptide serving as a reservoir for high-energy phosphate groups that can regenerate ATP, the main currency of cellular energy. An increase in creatine intake (through food or supplementation) increases cellular energy stores, promoting the regeneration of ATP in the short term. Stores are limited, however, and glucose or fatty acids are responsible for ATP replenishment over longer durations.
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!
That said, many people experience stomach cramps when they consume creatine monohydrate and it’s possible that taking a creatine with a different pH — usually creatine hydrochloride — can have a different effect on stomach acid and make for a creatine that digests more easily. As far as we know, the easier digestion doesn’t necessarily mean it’s more effective or that you need less of it to achieve the desired result.
Chwalbinska-Monteta [34] observed a significant decrease in blood lactate accumulation when exercising at lower intensities as well as an increase in lactate threshold in elite male endurance rowers after consuming a short loading (5 days 20 g/d) CM protocol. However, the effects of creatine supplementation on endurance performance have been questioned by some studies. Graef et al [35] examined the effects of four weeks of creatine citrate supplementation and high-intensity interval training on cardio respiratory fitness. A greater increase of the ventilatory threshold was observed in the creatine group respect to placebo; however, oxygen consumption showed no significant differences between the groups. The total work presented no interaction and no main effect for time for any of the groups. Thompson et al [36] reported no effects of a 6 week 2 g CM/d in aerobic and anaerobic endurance performance in female swimmers. In addition, of the concern related to the dosage used in these studies, it could be possible that the potential benefits of creatine supplementation on endurance performance were more related to effects of anaerobic threshold localization.

Creatine is involved indirectly in whole body methylation processes. This is due to creatine synthesis having a relatively large methyl cost, as the creatine precursor known as guanidinoacetate (GAA) requires a methyl donation from S-adenosyl methionine (SAMe) in order to produce creatine. This may require up to half of the methyl groups available in the human body.[35][122]
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]
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