Commentary

Even Intentional Weight Loss Linked With Cancer


 

This transcript has been edited for clarity.

As anyone who has been through medical training will tell you, some little scenes just stick with you. I had been seeing a patient in our resident clinic in West Philly for a couple of years. She was in her mid-60s with diabetes and hypertension and a distant smoking history. She was overweight and had been trying to improve her diet and lose weight since I started seeing her. One day she came in and was delighted to report that she had finally started shedding some pounds — about 15 in the past 2 months.

I enthusiastically told my preceptor that my careful dietary counseling had finally done the job. She looked through the chart for a moment and asked, “Is she up to date on her cancer screening?” A workup revealed adenocarcinoma of the lung. The patient did well, actually, but the story stuck with me.

The textbooks call it “unintentional weight loss,” often in big, scary letters, and every doctor will go just a bit pale if a patient tells them that, despite efforts not to, they are losing weight. But true unintentional weight loss is not that common. After all, most of us are at least half-heartedly trying to lose weight all the time. Should doctors be worried when we are successful?

A new study suggests that perhaps they should. We’re talking about this study, appearing in JAMA, which combined participants from two long-running observational cohorts: 120,000 women from the Nurses’ Health Study, and 50,000 men from the Health Professionals Follow-Up Study. (These cohorts started in the 1970s and 1980s, so we’ll give them a pass on the gender-specific study designs.)

The rationale of enrolling healthcare providers in these cohort studies is that they would be reliable witnesses of their own health status. If a nurse or doctor says they have pancreatic cancer, it’s likely that they truly have pancreatic cancer. Detailed health surveys were distributed to the participants every other year, and the average follow-up was more than a decade.

JAMA

Participants recorded their weight — as an aside, a nested study found that self-reported rate was extremely well correlated with professionally measured weight — and whether they had received a cancer diagnosis since the last survey.

This allowed researchers to look at the phenomenon described above. Would weight loss precede a new diagnosis of cancer? And, more interestingly, would intentional weight loss precede a new diagnosis of cancer.

I don’t think it will surprise you to hear that individuals in the highest category of weight loss, those who lost more than 10% of their body weight over a 2-year period, had a larger risk of being diagnosed with cancer in the next year. That’s the yellow line in this graph. In fact, they had about a 40% higher risk than those who did not lose weight.

JAMA

Increased risk was found across multiple cancer types, though cancers of the gastrointestinal tract, not surprisingly, were most strongly associated with antecedent weight loss.

JAMA

What about intentionality of weight loss? Unfortunately, the surveys did not ask participants whether they were trying to lose weight. Rather, the surveys asked about exercise and dietary habits. The researchers leveraged these responses to create three categories of participants: those who seemed to be trying to lose weight (defined as people who had increased their exercise and dietary quality); those who didn’t seem to be trying to lose weight (they changed neither exercise nor dietary behaviors); and a middle group, which changed one or the other of these behaviors but not both.

Let’s look at those who really seemed to be trying to lose weight. Over 2 years, they got more exercise and improved their diet.

If they succeeded in losing 10% or more of their body weight, they still had a higher risk for cancer than those who had not lost weight — about 30% higher, which is not that different from the 40% increased risk when you include those folks who weren’t changing their lifestyle.

JAMA

This is why this study is important. The classic teaching is that unintentional weight loss is a bad thing and needs a workup. That’s fine. But we live in a world where perhaps the majority of people are, at any given time, trying to lose weight. The truth is that losing weight only with lifestyle modifications — exercise and diet — is actually really hard. So “success” could be a sign that something else is going on.

We need to be careful here. I am not by any means trying to say that people who have successfully lost weight have cancer. Both of the following statements can be true:

Significant weight loss, whether intentional or not, is associated with a higher risk for cancer.

Most people with significant weight loss will not have cancer.

Both of these can be true because cancer is, fortunately, rare. Of people who lose weight, the vast majority will lose weight because they are engaging in healthier behaviors. A small number may lose weight because something else is wrong. It’s just hard to tell the two apart.

Out of the nearly 200,000 people in this study, only around 16,000 developed cancer during follow-up. Again, although the chance of having cancer is slightly higher if someone has experienced weight loss, the chance is still very low.

We also need to avoid suggesting that weight loss causes cancer. Some people lose weight because of an existing, as of yet undiagnosed cancer and its metabolic effects. This is borne out if you look at the risk of being diagnosed with cancer as you move further away from the interval of weight loss.

Total Cancers JAMA

The further you get from the year of that 10% weight loss, the less likely you are to be diagnosed with cancer. Most of these cancers are diagnosed within a year of losing weight. In other words, if you’re reading this and getting worried that you lost weight 10 years ago, you’re probably out of the woods. That was, most likely, just you getting healthier.

Last thing: We have methods for weight loss now that are way more effective than diet or exercise. I’m looking at you, Ozempic. But aside from the weight loss wonder drugs, we have surgery and other interventions. This study did not capture any of that data. Ozempic wasn’t even on the market during this study, so we can’t say anything about the relationship between weight loss and cancer among people using nonlifestyle mechanisms to lose weight.

It’s a complicated system. But the clinically actionable point here is to notice if patients have lost weight. If they’ve lost it without trying, further workup is reasonable. If they’ve lost it but were trying to lose it, tell them “good job.” And consider a workup anyway.

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

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