Examining the effects of creatine supplementation in augmenting adaptations to resistance training in patients with prostate cancer undergoing androgen deprivation therapy: a randomised, double-blind, placebo-controlled trial

Fairman, Ciaran M.; Kendall, Kristina L.; Newton, Robert U.; Hart, Nicholas; Taaffe, Dennis R.; Chee, Raphael; Tang, Colin; Galvão, Daniel A.

doi:10.1136/bmjopen-2019-030080

Cited by 15 publications

(11 citation statements)

References 59 publications

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“…Thus, research into RT variables, such as training frequency, load, and volume, is needed to optimize RT guidelines during ADT. Furthermore, knowledge of nutritional strategies to optimize RT-induced effects on lean body mass is currently scarce, but clinical trials are currently underway [ 48 , 49 , 50 ]. Specifically, creatine supplementation might lead to an increased training volume [ 51 ], and optimizing participants diets by ensuring sufficient protein content [ 52 ] holds the potential to further improve lean body mass responses to RT.…”

Section: Discussionmentioning

confidence: 99%

Does Androgen Deprivation for Prostate Cancer Affect Normal Adaptation to Resistance Exercise?

Nilsen

Johansen

Thorsen

et al. 2022

IJERPH

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Background: Loss of muscle mass and muscle function is a common side effect from androgen deprivation therapy (ADT) for prostate cancer (PCa). Here, we explored effects of heavy-load resistance training (RT) on lean body mass and muscle strength changes reported in randomized controlled trials (RCTs) among PCa patients on ADT and in healthy elderly men (HEM), by comparison of results in separate meta-analysis. Methods: RCTs were identified through databases and reference lists. Results: Seven RCTs in PCa patients (n = 449), and nine in HEM (n = 305) were included. The effects of RT in lean body mass change were similar among PCa patients (Standardized mean difference (SMD): 0.4, 95% CI: 0.2, 0.7) and HEM (SMD: 0.5, 95% CI: 0.2, 0.7). It is noteworthy that the within group changes showed different patterns in PCa patients (intervention: 0.2 kg; control: −0.6 kg) and HEM (intervention: 1.2 kg; control: 0.2 kg). The effects of RT on change in muscle strength (measured as 1 RM) were similar between PCa patients and HEM, both for lower body- (PCa: SMD: 1.9, 95% CI: 1.2, 2.5; HEM: SMD: 2.2, 95% CI: 1.0, 3.4), and for upper body exercises (PCa: SMD: 2.0, 95% CI: 1.3, 2.7; HEM: SMD: 1.9, 95% CI: 1.3, 2.6). Conclusions: The effects of RT on lean body mass and 1 RM were similar in PCa patients on ADT and HEM, but the mechanism for the intervention effect might differ between groups. It seems that RT counteracts loss of lean body mass during ADT in PCa patients, as opposed to increasing lean body mass in HEM.

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Section: Discussionmentioning

confidence: 99%

Does Androgen Deprivation for Prostate Cancer Affect Normal Adaptation to Resistance Exercise?

Nilsen

Johansen

Thorsen

et al. 2022

IJERPH

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“…The concept of resistance training is being considered as means to tackle ADT-induced loss of lean body mass. The idea of creatine supplement is studied as a component of ongoing lifestyle intervention clinical trial in prostate cancer (Fairman et al , 2019). Our observation of increased cellular proliferation in tumours from Pten pc-/- Spry2 pc-/- mice following creatine supplement for only eight weeks highlights the need to assess creatine supplement in patients with caution.…”

Section: Discussionmentioning

confidence: 99%

“…Our data implicate cyclocreatine treatment in suppressing both creatine uptake and biosynthesis, although it remains to be clarified whether the observed effect on creatine biosynthesis represents a consequence of reduced creatine utilisation due to functional inhibition of creatine kinases.The concept of resistance training is being considered as means to tackle ADTinduced loss of lean body mass. The idea of creatine supplement is studied as a component of ongoing lifestyle intervention clinical trial in prostate cancer(Fairman et al, 2019). Our observation of increased cellular proliferation in tumours from Pten pc-/-Spry2 pc-/mice following creatine supplement for only eight weeks highlights the need to assess creatine supplement in patients with caution.…”

mentioning

confidence: 99%

Cyclocreatine suppresses prostate tumorigenesis through dual effects on SAM and creatine metabolism

Patel

Rodgers

et al. 2021

Preprint

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Prostate cancer is highly prevalent, being the second most common cause of cancer mortality in men worldwide. Applying a novel genetically engineered mouse model (GEMM) of aggressive prostate cancer driven by deficiency of PTEN and SPRY2 (Sprouty 2) tumour suppressors, we identified enhanced creatine metabolism within the phosphagen system in progressive disease. Altered creatine metabolism was validated in in vitro and in vivo prostate cancer models and in clinical cases. Upregulated creatine levels were due to increased uptake through the SLC6A8 creatine transporter and de novo synthesis, resulting in enhanced cellular basal respiration. Treatment with cyclocreatine (a creatine analogue that potently and specifically blocks the phosphagen system) dramatically reduces creatine and phosphocreatine levels. Blockade of creatine biosynthesis by cyclocreatine leads to cellular accumulation of S-adenosyl methionine (SAM), an intermediary of creatine biosynthesis, and suppresses prostate cancer growth in vitro. Furthermore, cyclocreatine treatment impairs cancer progression in our GEMM and in a xenograft liver metastasis model. Hence, by targeting the phosphagen system, cyclocreatine results in anti-tumourigenic effects from both SAM accumulation and suppressed phosphagen system.

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“…These details and any deviations from the exercise protocol will be reported in the final manuscript. This programmme was chosen in accordance with our exercise facilities and resources available and has been utilised in prior studies with individuals with cancer [29,30].…”

Section: Exercisementioning

confidence: 99%

Rehabilitation strategies following oesophagogastric and Hepatopancreaticobiliary cancer (ReStOre II): a protocol for a randomized controlled trial

et al. 2020

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Background: Curative treatment for upper gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) cancers, involves complex surgical resection often in combination with neoadjuvant/adjuvant chemo/chemoradiotherapy. With advancing survival rates, there is an emergent cohort of UGI and HPB cancer survivors with physical and nutritional deficits, resultant from both the cancer and its treatments. Therefore, rehabilitation to counteract these impairments is required to maximise health related quality of life (HRQOL) in survivorship. The initial feasibility of a multidisciplinary rehabilitation programme for UGI survivors was established in the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) feasibility study and pilot randomised controlled trial (RCT). ReStOre II will now further investigate the efficacy of that programme as it applies to a wider cohort of UGI and HPB cancer survivors, namely survivors of cancer of the oesophagus, stomach, pancreas, and liver. Methods: The ReStOre II RCT will compare a 12-week multidisciplinary rehabilitation programme of supervised and self-managed exercise, dietary counselling, and education to standard survivorship care in a cohort of UGI and HPB cancer survivors who are > 3-months post-oesophagectomy/ gastrectomy/ pancreaticoduodenectomy, or major liver resection. One hundred twenty participants (60 per study arm) will be recruited to establish a mean increase in the primary outcome (cardiorespiratory fitness) of 3.5 ml/min/kg with 90% power, 5% significance allowing for 20% drop out. Study outcomes of physical function, body composition, nutritional status, HRQOL, and fatigue will be measured at baseline (T0), post-intervention (T1), and 3-months follow-up (T2). At 1-year follow-up (T3), HRQOL alone will be measured. The impact of ReStOre II on well-being will be examined qualitatively with focus groups/ interviews (T1, T2). Bio-samples will be collected from T0-T2 to establish a national UGI and HPB cancer survivorship biobank. The cost effectiveness of ReStOre II will also be analysed.

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Examining the effects of creatine supplementation in augmenting adaptations to resistance training in patients with prostate cancer undergoing androgen deprivation therapy: a randomised, double-blind, placebo-controlled trial

Cited by 15 publications

References 59 publications

Does Androgen Deprivation for Prostate Cancer Affect Normal Adaptation to Resistance Exercise?

Does Androgen Deprivation for Prostate Cancer Affect Normal Adaptation to Resistance Exercise?

Cyclocreatine suppresses prostate tumorigenesis through dual effects on SAM and creatine metabolism

Rehabilitation strategies following oesophagogastric and Hepatopancreaticobiliary cancer (ReStOre II): a protocol for a randomized controlled trial

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