How cutting carbs may benefit men on hormonal therapy

Stephen J. Freedland, MDRecent data show that a low-carbohydrate diet may have significant positive effects in men on hormonal therapy for prostate cancer, including metabolic effects. In this interview, study author Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, discusses his group’s findings, ongoing research on diet and lifestyle changes in men with prostate cancer, and how he counsels patients. Dr. Freedland is professor of surgery (urology), director of the Center for Integrative Research in Cancer and Lifestyle, and the Warschaw Robertson Law Families Chair in Prostate Cancer at Cedars-Sinai Medical Center in Los Angeles. He was interviewed by Urology Times Editorial Council member Stacy Loeb, MD, MSc, assistant professor of urology and population health at New York University School of Medicine, New York.

At the 2016 AUA annual meeting, you presented results from a prospective, randomized trial of dietary carbohydrate restriction for men initiating androgen deprivation therapy called the Carbohydrate and Prostate Study 1, CAPS1. Please give us a little bit of background on your study.

We know hormonal therapy, when used in the right patient, is life extending. But the problem with hormonal therapy is it comes with side effects, many of which are familiar to urologists: erectile dysfunction, fatigue, loss of libido, osteoporosis. What’s becoming increasingly clear is that hormonal therapy also has metabolic effects. Some very nice studies show the risk of diabetes increases 40% when you start hormonal therapy.

How did you get the idea that you might be able to reverse some of these changes through diet and exercise?

I’ve been working with low-carbohydrate diets in the laboratory as an approach to slow cancer. In mice, balanced calorie for calorie, eating a low-carbohydrate diet actually slows their cancer growth. I have also been working with an investigator at Duke University who is performing clinical trials showing that a low-carbohydrate diet in non-cancer patients improves insulin sensitivity. When they’re on a low-carb diet, a lot of diabetic patients completely get off their medication and they lose weight, and it seemed like this diet could prevent the side effects of hormonal therapy.

Next: How the study was carried out

How was your study carried out?

We conducted a prospective, randomized trial of extreme low-carbohydrates-20 grams of carbohydrates a day-versus control. The study group was restricted from anything that you would think of as a carbohydrate: no bread, pasta, rice, or fruits. The diet included a lot of cheeses, meats, eggs, and select vegetables.

And you also recommended that the men exercise along with this diet?

Correct. We recommended that the men exercise for 30 minutes a day, 5 days a week. The obvious question is, what role did exercise play in the results? When we look at other studies that have examined the effect of exercise only in men starting hormonal therapy, they don’t see prevention of osteoporosis and weight loss, and they don’t see changes in insulin. Men get stronger and feel better, but a lot of the metabolic effects don’t occur. The more we’ve been doing this, the more I think diet is the driver of our results.

But aren’t the two synergistic, in that the exercise component can add more energy and the diet change is what helps with the other metabolic effects?

Exercise certainly has a role to play, and I’m not trying to downplay the importance of exercise. I don’t think it played as large a role in our results, but we do certainly encourage men to exercise, particularly to do weight-bearing exercise.

Next: "The changes were very dramatic"

Were the men in your study actually able to adhere to the low-carb diet?

That’s a great question, and the answer is in the results. We’ve actually not analyzed the dietary data yet, so I can’t tell you what the men actually ate. But I can tell you we saw changes on the metabolic effect including a significant weight loss, which basically imply they were doing something correctly. The changes were very dramatic.

How many men dropped out of the study?

We did have a few dropouts, but overall 75% of the men on the low-carbohydrate diet were able to finish the 6-month study. The reason for one or two of the dropouts we had is that they were losing too much weight and weren’t happy. You go through a little adjustment in the first week or two of the low-carbohydrate diet, and the men require a lot of hand-holding. If they lose too much weight-a lot of it is water initially-they get a little light-headed and experience a little fatigue in that first week or two. Once you get them past that, they actually tend to have more energy, they’re losing weight, and they’re happy about things. Thus, a couple of patients dropped out during this early extreme weight loss phase.

Please summarize the take-home message of your study findings with respect to the impact of a low-carb diet plus exercise for men on hormonal therapy for prostate cancer.

When you do a dietary study, one of the keys is to tell subjects the diet may be really important. If it’s a randomized trial and then you suddenly flip a coin and it comes up they are randomized to the control arm, the question always is whether the control arm actually made changes. In the control group in our study, we saw that at 6 months they gained 1.3 kg, their insulin resistance went up 36%, and they added 11% new fat mass. They experienced the effects that hormones generally have. In that sense, we had a good control group.

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Compared to the control group, rather than going up 36%, insulin resistance went down 4% in the diet group. So we completely prevented insulin resistance from happening. At 6 months, that wasn’t statistically significant. It was significant at 3 months and the 6 months actually looked better, but there was more variability so it wasn’t statistically significant. PSA levels went down 99% in both groups, indicating that hormonal therapy is good cancer therapy. The bone loss, which was about 2% in the control group, was completely blocked in the low-carbohydrate group. They did not lose any bone; they actually put on a tiny bit of bone.

Rather than gaining 11% of their fat mass, the low-carb group lost 16% of their fat mass at 6 months. And the body weight difference between the arms at 6 months was about 23 pounds of weight lost in the low-carb group relative to the control group.

Next: The next steps

What are the next steps for your group on this research?

One of the key questions for me is whether eating a lot of fats and cheeses may actually make the cancer grow faster, and there is some literature that suggests this. Again, our animal data suggests that’s not true. If anything, this is a good diet for cancer, and PSA declines were very impressive in both groups. That’s something we want to explore: Is this safe, and could this actually be a good diet for cancer patients?

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We are currently carrying out a study called Carbohydrate and Prostate Study 2 (CAPS2), which is looking at men who have a rising PSA after surgery or radiation. At some point, these patients are going to be ready for hormones, but there’s a window where we can calculate a PSA doubling time and we’ll carry out the same randomization as CAPS1-half of the group will have no dietary changes and half will receive a low-carb diet. The idea is to see if we can slow the rate of PSA rise and delay the time to hormonal therapy. That study is ongoing now. We’ve enrolled about 30 patients. Hopefully, we’ll have some preliminary data at next year’s AUA meeting.

We would also like to study how else a weight-loss, low-carb diet could have a benefit. We have a few ideas, and we’re talking to different sources and companies about research on the possible benefit of this intervention in preventing side effects from some of the newer prostate cancer drugs or in combining this intervention with their drugs to slow cancer growth. So we have a lot of ideas for CAPS3, but nothing firm yet.

Next: Strategies for patients

A lot of patients ask if there are any dietary strategies that can actually prevent prostate cancer or slow prostate cancer growth. Do you have any suggestions?

Yes. For patients who ask me that question, one of the things I talk to them about is simple carbohydrates and the fact that cookies, cakes, candies, etc. really have no nutritional value whatsoever. Getting those types of foods out of the diet, in and of itself, will drive a fair amount of weight loss. I think that’s probably the most important dietary advice that we give our patients-to lose weight.

You’ve done a lot of work on body mass index and the impact of obesity on prostate cancer. Can you describe that?

We’ve looked at this question in patients undergoing surgery, and obese patients are much more likely to develop a cancer recurrence. Men starting hormonal therapy are more likely to develop castrate-resistant disease if they are obese. Some of the best data we have comes from the American Cancer Society, which has followed 800,000 men for 10 to 20 years. Obese men are about 30% more likely to die from prostate cancer. The link is there, and it’s real. I don’t think we’re going to prevent all cancers, but I think we can prevent some and slow the aggressiveness of others with diet changes and in particular weight loss.

Patients always like to have strategies that they can execute themselves, so congratulations on finding interventions that patients can do to be proactive.

I think that’s so important. In so much of what we do for patients with prostate cancer-the surgery, the radiation, the chemo, the hormones-the patient is very passive. I tell patients that we’re going to work as a team. I’m going to do surgery, the hormones, or whatever is appropriate for that patient, but I tell them, “This is what you need to do. We’re going to work together, and I want you to lose 5 or 10 pounds by the time you see me next time.” I actually have them sign a contract and write in their notes, “I will lose 10 pounds by the next visit.” Usually the first topic we discuss is diet and weight, and then we get into the PSA and other things.

Next: More dietary tips for patients

Do you have any other dietary tips for patients?

The number one question I get from patients is, what should I eat? We do talk about cutting out simple carbohydrates, but there’s a lot more that can be done. We talk about the data concerning the role of eating fish in reducing prostate cancer risk. There’s some controversy with the omega-3s and some studies show that blood levels may increase risk, so I don’t recommend the supplements. But there are pretty good data about eating fish. I point out that the reason for eating fish is for the fish oil, and there’s one particular type of fish-tilapia-that has almost no fish oil in it. So I recommend against eating tilapia.

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There are benefits associated with eating tomatoes, but keep in mind that lycopene and other products within tomatoes are fat soluble. The best data on tomatoes comes from tomato paste because it’s usually on a pizza with cheese and grease or it’s served with meatballs. If you’re just eating a dry salad with tomatoes, you’re not absorbing a whole lot of the nutrients in it. If you think of the Mediterranean diet, the tomatoes are usually in a sauce or with cheese and olive oil dribbled over it. So it’s important to think about not just the foods patients eat, but the context in which they eat them.

Nuts tend to be high in fat, but it tends to be good fat. Walnuts have been studied a little more than others, but I wouldn’t distinguish good nuts from bad ones; I think they’re all in that “good” category.

Finally, we can preach to our patients that they need to tomatoes and broccoli and fish all day, but that’s just not the reality. My goal is to help them make better choices. It’s not about making the perfect choice every time. It’s about making a better choice-switching to more complex carbohydrates and getting away from simple sugars, for example. A granola bar may not be perfect, but it’s better than a cookie. If patients can consistently make better choices at every meal, we’re going to move the needle in the right direction.

You may also end up reducing patients’ risk of cardiovascular disease and other competing conditions using the prostate cancer diagnosis as a teachable moment.

Absolutely. We know for the average man diagnosed with prostate cancer, 85% will die of something other than prostate cancer. The number one thing men with prostate cancer die of is heart disease. We know losing weight and getting exercise are good for that, and now it may be good for the prostate as well.

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