Creatine: Everything You Need To Know

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Hence the creatine graveyard, where various forms of creatine not CM go to die:


@Will Brink

As you are the expert: I still remain confused whether elevated creatinine with creatine use is a hazard. I have multiple health issues now, and have been having upper normal range creatinine, but low EGFR. I would love to use some kind of adjunct to gain some weight/muscle mass, but am leery of the effect of creatine on my creatinine and GFR. What can you tell me? Or have you already written about this?
 
@Will Brink

As you are the expert: I still remain confused whether elevated creatinine with creatine use is a hazard. I have multiple health issues now, and have been having upper normal range creatinine, but low EGFR. I would love to use some kind of adjunct to gain some weight/muscle mass, but am leery of the effect of creatine on my creatinine and GFR. What can you tell me? Or have you already written about this?

I do have a contraindication write up on creatine below. Elevated creatinine is not in itself an issue, and we know creatine is not "stressful" to the kidneys, but should not be ignored either. If it's elevated while on creatine, take a few weeks off, make sure to be well hydrated, and re test. If still elevated, then it's not the creatine and further tests should be done, but you already indicated you tested EGFR too.

 
I do have a contraindication write up on creatine below. Elevated creatinine is not in itself an issue, and we know creatine is not "stressful" to the kidneys, but should not be ignored either. If it's elevated while on creatine, take a few weeks off, make sure to be well hydrated, and re test. If still elevated, then it's not the creatine and further tests should be done, but you already indicated you tested EGFR too.


Thanks Will,

Yes, with my cancer and treatment, serial CMPs have shown decreasing trend in GFR, some under 60. This makes me very unconfident. I am not seeing this as safe for me.
 
Thanks Will,

Yes, with my cancer and treatment, serial CMPs have shown decreasing trend in GFR, some under 60. This makes me very unconfident. I am not seeing this as safe for me.

As always, risk/benefits exist. There's data to suggest creatine made cancar therapy more effective for example:


This is from a recent review also:

Does creatine cause kidney damage/renal dysfunction?​

Questions and concerns involving creatine supplementation and kidney damage/renal dysfunction are common. In terms of pervasive misinformation in the sport nutrition arena, the notion that creatine supplementation leads to kidney damage/renal dysfunction is perhaps second only to the myth that protein supplementation and high habitual protein intake causes kidney damage. Today, after > 20 years of research which demonstrates no adverse effects from recommended dosages of creatine supplements on kidney health, unfortunately, this concern persists. While the origin is unknown, the connection between creatine supplementation and kidney damage/renal dysfunction could be traced back to two things: a poor understanding of creatine and creatinine metabolism and a case study published in 1998.

In skeletal muscle, both creatine and PCr are degraded non-enzymatically to creatinine, which is exported to the blood and excreted in the urine []. Healthy kidneys filter creatinine, which would otherwise increase in the blood. Therefore, blood creatinine levels can be used as a proxy marker of kidney function. However, the amount of creatinine in the blood is related to muscle mass (i.e. males have higher blood creatinine than females) and both dietary creatine and creatinine intake []. Both blood and urinary creatinine may be increased by ingestion of creatine supplementation and creatine containing foods, such as meat. Creatine is normally not present in urine, but can reach very high levels (>10 g/day) during creatine supplementation []. There appears to be an unsubstantiated perspective that if the kidneys are “forced” to excrete higher than normal levels of creatine or creatinine, some sort of kidney “overload” will take place, causing kidney damage and/or renal dysfunction. In reality, transient increases in blood or urinary creatine or creatinine due to creatine supplementation are unlikely to reflect a decrease in kidney function. Additionally, one must exercise caution when using blood creatinine and estimated creatinine clearance/glomerular filtration rate in individuals who consume high meat intake or supplement with creatine. In a review of creatine supplementation studies, Persky and Rawson [] found no increase in serum creatinine in 12 studies, 8 studies showed an increase that remained within the normal range, and only 2 studies showed an increase above normal limits (although not different from the control group in one study).

In 1998, a case study of a young male with focal segmental glomerulosclerosis and relapsing nephrotic syndrome was reported []. The young male, who had kidney disease for 8 years and was treated with cyclosporine (i.e., immunosuppressant) for 5 years, had recently begun ingesting creatine supplementation (15 g/day for 7 days; followed by 2 g/day for 7 weeks). Based on increased blood levels of creatinine and subsequent estimate of calculated creatinine clearance, his kidney health was presumed to be deteriorating, although he was otherwise in good health. The patient was encouraged to discontinue creatine supplementation. At this time, it was already known that blood and urine creatinine levels can increase following ingestion of creatine containing food products, including creatine supplements []. This was ignored by the authors of this case study, as was the inclusion of two investigations which demonstrated that creatine supplementation did not negatively impact renal function [, ]. The dosage of creatine during the maintenance phase, which was also ignored, was only slightly higher than the daily creatine intake of a typical omnivore’s dietary intake, or in terms of food, a large hamburger or steak per day (meat contains about 0.7 g of creatine / 6 oz. serving; see []). In response to this case study, two separate teams of experts in creatine metabolism wrote letters to the editor of Lancet [, ]. However, the notion that creatine supplementation leads to kidney damage and/or renal dysfunction gained traction and momentum.

Since this case study was reported in 1998, experimental and controlled research trials investigating the effects of creatine supplementation on kidney/renal function has substantially increased [, –]. Overall, in healthy individuals, there appears to be no adverse effects from consuming recommended doses of creatine supplements on kidney/renal function [, –]. Interestingly, Gualano et al. [] reviewed a small number of case studies which reported renal dysfunction in individuals who were supplementing with creatine. Similar to the case report by Pritchard and Kalra [], these additional case reports were confounded by medications, pre-existing kidney disease, concomitant supplement ingestion, inappropriate creatine dosages (e.g., 100 X recommended dose), and anabolic androgenic steroid use.

It is prudent to be cautious when ingesting any dietary supplement or medication. Survey data indicates that creatine supplementation usage ranges between 8-74% in athletes and other exercising individuals (reviewed in Rawson et al. []). Even with a low estimate of 8% of exercising individuals using creatine supplements, this indicates thousands of exposures across several decades. If the link between creatine supplementation and kidney health was valid, there would be an expected increase in kidney damage / renal dysfunction in low risk (i.e. young, physically fit, healthy) individuals since 1992 after Harris et al. published their seminal work []. After nearly 30 years of post-marketing surveillance, thousands of exposures, and multiple clinical trials, no such evidence exists.

In summary, experimental and controlled research indicates that creatine supplementation, when ingested at recommended dosages, does not result in kidney damage and/or renal dysfunction in healthy individuals.


 
Thanks again @Will Brink

Do you know if creatine has immune boosting effect on B-cells?

We need more data but from my write up "...As creatine is an essential molecule in energy production for all cells, it also acts as “molecular battery,” wherein stored energy helps these essential immune cells from simply running out of steam to fight on."

The “molecular battery" aspect no doubt applies to B-cells.
 
We need more data but from my write up "...As creatine is an essential molecule in energy production for all cells, it also acts as “molecular battery,” wherein stored energy helps these essential immune cells from simply running out of steam to fight on."

The “molecular battery" aspect no doubt applies to B-cells.

My B-cells need to die, not fight on. It's really messed up. Any immune boosting substance that increases B-cell proliferation, increases my cancer.
 
Blackhawk, you know that eGFR is calculated almost entirely on the creatinine concentration in blood, which is increased if you take creatine or a lot of protein. There is another test for kidney function that doesn't use creatinine to estimate GFR:

Cystatin C

Cystatin C is a low-molecular-weight protein that functions as a protease inhibitor produced by all nucleated cells in the body. It is formed at a constant rate and freely filtered by the kidneys. Serum levels of cystatin C are inversely correlated with the glomerular filtration rate (GFR). In other words, high values indicate low GFRs, while lower values indicate higher GFRs, similar to creatinine. The renal handling of cystatin C differs from creatinine. While glomeruli freely filter both, once cystatin C is filtered, it is reabsorbed and metabolized by proximal renal tubules, unlike creatinine. Thus, under normal conditions, cystatin C does not enter the final excreted urine to any significant degree. Cystatin C is measured in serum and urine. The advantages of cystatin C over creatinine are that it is not affected by age, muscle bulk, or diet, and various reports have indicated that it is a more reliable marker of GFR than creatinine, particularly in early renal impairment. Cystatin C has also been incorporated into eGFR equations, such as the combined creatinine-cystatin KDIGO CKD-EPI equation.

Cystatin C concentration may be affected by the presence of cancer, thyroid disease, and smoking.
 
If you have been on the same drugs, same protein and creatine consumption daily and your creatinine in blood starts increasing, that may signify a worsening kidney function.

On the other hand, if you have changed your drugs or have increased protein or creatine consumption, that by itself may cause increase of creatinine in blood which then is not a signal of decreasing kidney function.

Some drugs compete with creatinine filtration at the kidneys which increases creatinine concentration in blood but is not a sign of worsening kidney function. Some HIV drugs that I use do that and depending on the drug my creatinine concentration jumps up or down, with the corresponding jumps in the calculated eGFR. Because eGFR is just calculated from creatinine, I pay attention only to the creatinine concentration and I know what is the normal concentration for a particular HIV drug, so I am not worried if it jumps to that concentration. When I take another HIV drug that doesn't compete with creatinine that much, it's concentration in the blood drops, which means there was no real change in the kidney function.
 
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Also, creatinine is produced by the breakdown of creatine or phosphocreatine by your muscles. During intense, short-duration exercise — such as weightlifting or sprinting — phosphocreatine is used to rapidly regenerate muscle energy, but is exhausted within approximately 10 seconds as seen below. Creatinine is the by product of the PCr energy system. After 10 seconds of exercise we revert to the glycogen system. Its kind of like shifting from 1st gear to 2nd gear.

atpbreakdown.gif


So lifting weight will naturally cause your blood creatine levels to be much higher. This in turn will cause your eGFR to be higher. Most doctors are totally unaware of this so you may have to lear to expain it to them. On average, it takes the body around 24 hours to clear the creatine produced in intense exercise back to base line. This time greatly depends on the amount of muscle mass you have as well.
 
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