Lowering Metastasis Risk

It’s crazy when you think about all of the different kinds of foods we eat.  We just swallow – and hope it all works out for the best. Well – as it turns out there are better ways to think about keeping our bodies humming healthfully along. Welcome to Nutrition Facts – I’m your host Dr. Michael Greger. 

Today – we try to help our bodies fight cancer that’s metastasized. And, we start with research about the powers of Palmitic acid.

Intro: This is the first in a three-part series on cancer metastasis. In this series, I’ll look at what dietary components contribute to the spread of cancer, and what dietary interventions—and even specific foods—can lessen the risk of spread, therefore increasing the chances of survival. Let’s go find out.

Metastasis formation is the leading cause of death in cancer patients. That’s how most people die of cancer. It’s not the primary tumor, but the cancer spreading through the body. “[It’s] estimated that metastasis is responsible for [90 percent] of cancer deaths”, with little progress made in stopping the spread despite our modern medical armamentarium. In fact, we can sometimes make it worse: Therapy-Induced Metastasis. All the typical cancer treatments: radiation, chemotherapy, surgery—even just poking the tumors with fine needle biopsies—have the potential to contribute to the problem. I mean, you can imagine how cutting around a tumor, severing the blood vessels, might lead to the migration of residual tumor cells. But why chemotherapy? How might chemo exacerbate metastases? Despite reducing the size of primary tumors, chemotherapy can change the surrounding tissues, resulting in an increased escape of cancer cells into the blood stream. Sometimes, chemo/surgery/radiation are entirely justified, but sometimes these treatments can make things worse. If only we had a way to treat the cause of the cancer spreading.

The development of antimetastatic therapies has been hampered by the fact that we haven’t been able to identity the cells that initiate metastasis. But then, this landmark study was published. Researchers found a subpopulation of human cancer cells “unique in their ability to initiate metastasis,” all expressing high levels of a fat receptor known as CD36, dubbed “the fat controller.” It turns out palmitic acid or a high-fat diet specifically boosts the metastatic potential of these cancer cells. Where do you find palmitic acid? Although originally discovered in palm oil, it’s most concentrated in meat and dairy. “Emerging evidence shows that palmitic acid…serves as a signaling molecule regulating the progression and development of many diseases at the molecular level”––and that’s the saturated fat that is recognized by the CD36 receptor on the cancer cells. And, we know that’s to blame, because if you block the CD36 receptor, you block the metastases.

Now, this was for a human cancer; however, it was a human cancer implanted into mice, but clinically (meaning in cancer patients), the presence of these CD36-studded metastasis-initiating cells does indeed correlate with a poor prognosis. For example, CD36 appears to drive the progression of brain tumors. If you look at the survival curves, those with tumors with less CD36 expression lived significantly longer. The same with breast cancer mortality. No surprise, since “CD36 [appears to play] a critical role in [the] proliferation, migration, and…growth of…breast cancer cells.” Inhibit CD36, and you can inhibit “the migration and invasion of the breast cancer cells.” Cancer cell migration and invasion before and after CD36 inhibition.

And not just in “human melanoma- and breast cancer-derived tumors.” Now we suspect that “…CD36…drives ovarian cancer progression and metastasis” too, since we can inhibit ovarian cancer cell invasion and migration and block both lymph node and blood-borne metastasis by blocking CD36. We see the same kind of effect with prostate cancer. Suppress the uptake of fat by prostate cancer cells, and you can suppress the tumor. This was all studied with receptor-blocking drugs and antibodies in a laboratory setting, though. If these metastasis-initiating cancer cells particularly rely on dietary fat to promote the spread of cancer, why not just block the dietary fat in the first place?

Cancer cells love fat and cholesterol. The reason why fat metabolism may fuel cancer’s spread is because there is so much energy stored in fat. “Hence, … metastatic cells might take advantage of this feature to obtain the high amount of energy that is likely to be required for them to anchor and [set up shop throughout the body].”

“The time when sugar was considered as the major, if not only, fuel to support cancer cell proliferation is over.” There appears to be “a fatter way to metastasize”. No wonder “…high-fat [diets may]…play a crucial role in increasing the risk of different cancer types,…[including] several advanced cancers.” Okay, if dietary fat may be “greasing the wheels of the cancer machine,” might there be specific dietary regimens we could use to starve cancers of dietary fat?

In our next story we look at how randomized controlled trials show lowering saturated fat intake can lead to improved breast cancer survival. 

“Metastasis is the leading cause of cancer-[related death].” Cancer kills, because cancer spreads. For example, the five-year survival rate for women with localized breast cancer is nearly 99 percent, but that drops to just 27 percent in those with metastasized cancer. Yet “our ability to effectively treat metastatic disease has not changed significantly in the past few decades.” You know things are getting desperate when there are papers like this: “Targeting Metastasis with Snake Toxins.”

Now, we do have built-in defenses––natural killer cells that roam the body killing off budding tumors, and I have videos on boosting natural killer cell activity. But as I explained in the last video, there’s a fat receptor called CD36 that appears to be essential for cancer cells to spread, and these cancer cells respond to dietary fat intake. But not all fat.

CD36 is upregulated by palmitic acid, as much as a 50-fold increase within 12 hours. Palmitic acid is a saturated fat found in junk food made from palm oil, but it is most concentrated in meat and dairy. This may explain why, if you look at “dietary fat and breast cancer mortality,” there was no difference in risk of breast-cancer-specific death for women in the highest versus lowest category of total fat intake. But, you’re about 50 percent more likely to die of breast cancer if you eat a lot of saturated fat. The systematic review and “…meta-analyses [conclude]… that saturated fat intake negatively impacts upon breast cancer survival.”

This may explain why “intake of high-fat dairy, but not low-fat dairy, was related to a higher risk of mortality after breast cancer diagnosis.” If it was the dairy protein, like casein, that was a problem; the skim milk might be even worse. But no, it was the saturated butterfat, maybe because it triggered that CD36-induced cancer-spreading mechanism. “…Women who consumed one or more servings per day of high-fat dairy had…[about a 50] percent higher risk of dying from breast cancer.”

We see the same thing with “dairy intake in relation to prostate cancer survival.” “…Drinking high-fat milk [appeared to increase] the risk of dying from prostate cancer by as much as 600 percent in patients with localized prostate cancer,” but “low-fat milk was not associated with such an increase in risk.” So, it seemed to be the animal fat, rather than the animal protein, and this is consistent with what Harvard researchers found in the United States.

More evidence that the fat receptor CD36 is involved is “…that the risk of colorectal cancer for meat consumption increased from [just doubling risk to octupling risk]”—multiplying the odds of getting cancer eight-fold for those who carry a specific type of CD36 gene. So, “Is It Time to Give Breast Cancer Patients a Prescription for a Low-Fat Diet?” A cancer diagnosis is a “teachable moment” if there ever was one to motivate people to make changes to their lifestyle. But provision of  evidence-based guidelines is essential, and you don’t know, until you put it to the test.

 “A randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer…” (meaning the women had their breast cancer surgically removed and were praying it doesn’t come back). The dietary intervention group dropped their fat intake from about 30 percent of calories down to 20 percent of calories, dropping saturated fat intake about 40 percent, and maintained that 40 percent lower intake after one year, three years, five years. And…,“after approximately five years of follow-up, [the] women in the dietary intervention group had a 24 percent lower risk of relapse…”, a 24 percent lower risk of the cancer coming back.

That was the WINS study, the Women’s Intervention Nutrition Study. Then, there was the Women’s Health Initiative Study, where again, women were randomized to drop their fat intake down to about 20 percent of calories, and again, those in the dietary intervention group experienced increased breast cancer survival, meaning “a dietary change may be able to influence breast cancer outcome[s].” And, not only was breast cancer survival significantly greater; the women also experienced a reduction in heart disease and a reduction in diabetes as a little side bonus.

Finally today – the mighty power of cruciferous vegetables – in fighting cancer.

Both the Women’s Intervention Nutrition Study and the Women’s Health Initiative Study showed that women randomized to a lower-fat diet enjoyed improved breast-cancer-free survival. But, wait a second. What about the Women’s Healthy Eating and Living Study, where women with breast cancer were also randomized to drop their fat intake down to 15 to 20 percent of calories, yet after seven years there was no difference in breast cancer relapse or death? Any time you get an unexpected result, you always have to question whether people actually followed through with the instructions. Like if you randomized people to a stop-smoking group, and they ended up with the same lung cancer rates as the group not instructed to stop smoking, one likely explanation is that the group told to stop smoking didn’t actually stop. In the Women’s Healthy Eating and Living Study, both the dietary intervention group and the control group started out at about 30 percent of calories from fat. Then, the diet group was told to drop down to 15 to 20 percent. And, by the end of the study, they dropped from 28.5 percent fat all the way down to 28.9 percent fat! They didn’t change at all. No wonder they didn’t experience any breast cancer benefit.

But even if you include that flawed study and put all the trials together on the effect of lower-fat diets on breast cancer survival, you see a reduced risk of breast cancer relapse and a reduced risk of death. Conclusion: Going on a low-fat diet after a breast cancer diagnosis can improve breast cancer survival by reducing risk of cancer recurrence. And now, perhaps, we know why: by targeting metastasis-initiating cancer cells through the fat receptor CD36, which I covered in my last two videos.

We know that the cancer-spreading receptor is upregulated by saturated fat. Is there anything in our diet that can downregulate it? Broccoli. Broccoli appeared to decrease CD36 expression by as much as 35 percent, but that was in mice. But, of all fruits and vegetables, cruciferous vegetables like broccoli were the only ones associated with significantly less total cancer risk, and not just getting cancer in the first place. Those with bladder cancer who eat broccoli appear to live longer than those who don’t. Those with lung cancer who eat more cruciferous veggies appear to survive longer as well. For example, one year out, about 75 percent of lung cancer patients eating more than one serving of cruciferous vegetables a day were still alive, whereas, by then, most who had been getting less than a half serving a day were already dead––killed off by their cancer.

Ovarian cancer. “Cruciferous vegetable…[intake] significantly favor[ed] survival,” whereas “a survival disadvantage was shown for meats.” Milk also appeared to double the risk of dying. Here are the survival graphs. Eight years out, for example, about 40 percent of ovarian cancer patients who averaged meat or milk every day were dead, compared to only about 20 percent who just had meat or milk a few times a week at most.

Now, it could just be that the fat and cholesterol in the meat increased circulating estrogen levels, or because of meat’s growth hormones, or all the carcinogens. And galactose, the sugar naturally found in milk, may also be directly toxic to the ovary, and dairy has got all the hormones too. However, the lowering of risk with broccoli and the increasing of risk with meat and dairy are also consistent with the CD36 mechanism of cancer spread we’ve been talking about.

So, how about putting it to the test for patients with advanced pancreatic cancer, given pulverized broccoli sprouts or a placebo. “Compared to those [in] the placebo group, the [average] death rate was lower in the [broccoli] group…”. After a month, 18 percent of the placebo group was dead, but none in the broccoli group. By three months, another quarter of the placebo group had died, but still not a single death in the broccoli group. By six months, 43 percent of the remaining patients in the placebo group were dead, along with the first 25 percent of the broccoli group. Unfortunately, the patients knew which group they were in because they were evidently getting broccoli burps which gave it away; so, you can’t discount the placebo effect. And, they weren’t even properly randomized, since many of the patients refused to participate unless they were placed in the active treatment group––which is understandable, but it makes for a less rigorous result. But hey, a little broccoli can’t hurt. And, it’s the no downsides that leads to “Advising Women Undergoing Treatment for Breast Cancer,” for example, to include the “liberal culinary use of cruciferous vegetables…” And, the same for reducing saturated fat.

“Is it time to give breast cancer patients a prescription for a low-fat diet?” “Although counseling women to consume a healthy diet after breast cancer diagnosis is certainly warranted for general health,” read an editorial in a journal of the National Cancer Institute, “the existing data still fall a bit short of proving this will help reduce the risk of breast cancer recurrence and mortality.” But, what do you have to lose? After all, it’s still certainly warranted for general health.

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