Low-carbohydrate Diet Plus Walking to Reduce ADT-induced Metabolic Disturbances Among Prostate Cancer Patients - Commentary

Androgen deprivation therapy (ADT) is standard treatment for advanced and metastatic prostate cancer. While it is very effective for cancer control, it has many side effects. Commonly known side effects include loss of libido, fatigue, osteoporosis, and hot flashes. Additionally, ADT has metabolic side effects. Imagine a young athlete using steroids to have a competitive advantage. They gain muscle mass and lose fat. Now imagine the same man 50 years later undergoing ADT for his prostate cancer – it will have the exact opposite effects – gain of fat mass and loss of muscle mass.

These changes are coupled with a ~40% increased relative risk of diabetes. While exercise can help preserve muscle mass, to date, no treatment has been shown to prevent this metabolic sequela. Given one of the fundamental problems from ADT is problems with controlling sugar, what if people simply didn’t eat sugar?

There is tremendous growth in interest in the ketogenic diet, an extreme form on a low carbohydrate (i.e. sugar) diet. Proponents often tout it as the cure-all for diabetes, obesity, and possibly even cancer. Opponents argue that it is not sustainable, is bad for the environment, and it simply can’t be healthy to eat all that fat. Where is the truth? To date, a small, but growing number of studies, do show that low-carbohydrate diets help with weight loss and diabetes control. However, the opponents are correct in that long-term studies are generally lacking. However, the impact on cancer is largely unexplored.

Within this void in the literature, our team tested whether a 6-month dietary intervention of extreme low-carbohydrate diet (20 grams/carbs/day) plus walking advice (walk 30 min/day x 5 days/week) could do what exercise had failed to do – prevent the metabolic sequelae from ADT. There were multiple reasons we chose a low-carb diet. First, we had already shown this diet slowed tumor growth in mice. Thus, in the long run (not tested in this study), we hoped this diet would be “good” for cancer. As such, this study would give us some experience with the diet in prostate cancer patients, which could be used to help design a second study testing the anti-cancer effects (now completed – to be submitted for publication soon). Second, we were well aware of the aforementioned data linking this diet with weight loss and improved diabetes. Thus, we were hopeful similar results would be seen in men on ADT. Finally, a meta-analysis published in JAMA in 2014 suggested low-carb diets result in the greatest weight loss – further supporting their use in this study.

All told, though we aimed to enroll 100, we ultimately had final data on only 29. This was in large part due to our struggles to enroll. In hindsight, the biggest challenge was requiring a baseline study visit prior to starting ADT. Men who were told they had progressing cancer were unwilling to wait a week or 2 for a baseline study visit and to capture baseline diet information before starting ADT. Despite the small numbers, we showed that the diet + walking advice could reduce metabolic effects from ADT, with the caveat being that because we had markedly fewer men than we planned, the primary outcome did not reach statistical significance. Importantly, we saw no downside to the diet beyond some fatigue, headaches, and constipation – all well-known low carb side effects. In short, while the low carb diet in this small study was not the cure all for everything (given our primary outcome was not significant), there was almost no downside. Thus, for men who want to consume the diet while on ADT – go ahead! At the least it will lower your weight and raise your good cholesterol. Whether it has other benefits requires a larger study.

One final caveat – the opponents of a low-carb diet argue that compliance is not perfect. While true, compliance in drug trials is not perfect too. Nonetheless, despite imperfect compliance – we saw real benefits. If compliance had been better – perhaps the benefits would have been greater. However, our study shows – imperfect compliance still beats doing nothing.

Written by: Stephen J. Freedland, MD, Editor-in-Chief, Prostate Cancer and Prostatic Diseases Cedars-Sinai Medical Center, Los Angeles, CA

Read the Full-Text Article: A Lifestyle Intervention of Weight Loss via a Low-Carbohydrate Diet Plus Walking to Reduce Metabolic Disturbances Caused by Androgen Deprivation Therapy Among Prostate Cancer Patients: Carbohydrate and Prostate Study 1 (CAPS1) Randomized Controlled Trial 
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