New paper added below – Creatine metabolism: energy homeostasis, immunity and cancer biology – is a potentially ground break paper. It’s very dense paper if you can get your hands on a copy and covers in depth creatine as it pertains to immunity, cancer, and fat cell metabolism. One study I posted not long ago looks at the possibility of creatine for potentiating weight loss. Creatine has a long list of potential benefits, and much of that only just being recognized and researched. Yet another potential benefit of creatine is that of an essential immune support supplement via energy for antitumor immunity. While this is a mouse model, there’s no reason to think it does not apply to humans as the cellular mechanisms are essential the same:
“...our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell–based cancer immunotherapies.”
So what does that mean? T cells need large amounts of energy to fight cancer, and it’s known they can suffer what’s called T-cell exhaustion. They literally run out of energy while attempting to fight cancer. 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. More data is needed to be sure, but as it has such a long list of known benefits, this may be yet one more. The data also suggests that creatine may improve outcomes for those with cancer being treated via T cell–based cancer immunotherapies. Amazingly, feeding mice the dose of creatine typical of what humans ingest, they demonstrated the mice then had ability to suppress both colon and skin cancer growth. Creatine is of course just one of several key ingredients in my Bomb Proof Coffee recipe and continues to demonstrate a wide range of potential benefits, much of which is discussed on this web site as i was one on of the very first people to write about the non athletic/performance benefits in the lay publications.
Creatine uptake regulates CD8 T cell antitumor immunity
T cells demand massive energy to combat cancer; however, the metabolic regulators controlling antitumor T cell immunity have just begun to be unveiled. When studying nutrient usage of tumor-infiltrating immune cells in mice, we detected a sharp increase of the expression of a CrT (Slc6a8) gene, which encodes a surface transporter controlling the uptake of creatine into a cell.
Using CrT knockout mice, we showed that creatine uptake deficiency severely impaired antitumor T cell immunity. Supplementing creatine to WT mice significantly suppressed tumor growth in multiple mouse tumor models, and the combination of creatine supplementation with a PD-1/PD-L1 blockade treatment showed synergistic tumor suppression efficacy.
We further demonstrated that creatine acts as a “molecular battery” conserving bioenergy to power T cell activities. Therefore, our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell–based cancer immunotherapies.
Full Paper HERE
Creatine metabolism: energy homeostasis, immunity and cancer biology
Nature Reviews Endocrinology volume 16, pages421–436(2020)
Perturbations in metabolic processes are associated with diseases such as obesity, type 2 diabetes mellitus, certain infections and some cancers. A resurgence of interest in creatine biology is developing, with new insights into a diverse set of regulatory functions for creatine. This resurgence is primarily driven by technological advances in genetic engineering and metabolism as well as by the realization that this metabolite has key roles in cells beyond the muscle and brain.
Herein, we highlight the latest advances in creatine biology in tissues and cell types that have historically received little attention in the field. In adipose tissue, creatine controls thermogenic respiration and loss of this metabolite impairs whole-body energy expenditure, leading to obesity. We also cover the various roles that creatine metabolism has in cancer cell survival and the function of the immune system. Renewed interest in this area has begun to showcase the therapeutic potential that lies in understanding how changes in creatine metabolism lead to metabolic disease.
Mitochondria in brown adipose tissue are capable of normal oxidative phosphorylation, with P:O ratios similar to those of other tissues. Atypical actions of creatine involve phosphocreatine transport into colorectal cancer cells, super-stoichiometric ADP liberation to trigger respiration in thermogenic adipocytes and chromatin remodelling to modulate macrophage polarity. Cyclocreatine and creatine can both inhibit tumour progression, suggesting that the pro-cancer role of creatine is independent of its function in energy buffering. The mitochondrial network transduces energy over long distances, thus minimizing the requirement for metabolite diffusion, whereas cells with a disrupted mitochondrial network might buffer energy via the creatine kinase–phosphocreatine circuit.
Will Brink is the owner of the Brinkzone Blog. Will has over 30 years experience as a respected author, columnist and consultant, to the supplement, fitness, bodybuilding, and weight loss industry and has been extensively published. Will graduated from Harvard University with a concentration in the natural sciences, and is a consultant to major supplement, dairy, and pharmaceutical companies.
His often ground breaking articles can be found in publications such as Lets Live, Muscle Media 2000, MuscleMag International, The Life Extension Magazine, Muscle n Fitness, Inside Karate, Exercise For Men Only, Body International, Power, Oxygen, Penthouse, Women’s World and The Townsend Letter For Doctors.
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