High Fat Diet and Risk of Metastasis
I will frequently share articles or links that seem to be of interest to us all. This is a brief article from MedScape re the association between high fat diets and the risk of metastasis. Since there is so little really known about what we can do to maximize our chances of staying well (after we finish the recommended treatment), I am always glad to hear of something that might make difference. The bottom line of this particular study is that it may be wise for women who have had a diagnosis of breast cancer to eat a lower fat, or, at least, not a high fat, diet.
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High-Fat Diet Dramatically Increases Cancer Metastasis
Medscape Medical News 2009. © 2009 Medscape
March 5, 2009 Ñ Although the link between obesity and cancer is well established, exactly why there is a link remains unclear. Now, an animal study shows that a high-fat diet dramatically increases cancer metastasis, and offers a mechanistic explanation for what has been, up to now, anecdotal evidence.
The study was published online January 30 in BMC Cancer.
"These findings demonstrate than an increase in lipids leads directly to a rise in cancer metastasis", said senior author Ji-Xin Cheng, PhD, assistant professor at the Weldon School of Biomedical Engineering, Purdue University, in West Lafayette, Indiana.
The study was conducted in mice implanted with a tumor that metastasized, but there was a 300% increase in metastases in mice fed a high-fat diet, compared with those fed a lean diet. In addition, the researchers showed that the high-fat diet had a direct effect on cancer-cell membranes, which increased their aggressiveness.
The implication from this study is that patients who already have cancer could be increasing the risk of it spreading if they eat a high-fat diet, comments lead author Thuc Le, PhD, also from Weldon School of Biomedical Engineering. However, when asked whether physicians should advise their patients about this, Dr. Le told that there are "many caveats." "Firstly, our study was performed in laboratory animals," he noted. "It's unclear whether our observations hold true in humans."
"But, when our study is viewed in the context of many other clinical studies of human patients and the strong correlation between lipid-rich breast cancer and aggressive clinical behavior, including early death, then a link (albeit indirect) between high-fat diet and cancer aggressiveness should emerge," he added.
Dramatic Increase in Metastasis
The study was carried out in 32 mice implanted with a lung cancer cell line, injected subcutaneously into a hind leg.
One group of animals was fed a lean diet (4.2% fat and 3.82 kcal/g) and the other was fed a high-fat diet (34.9% fat and 5.24 kcal/g). The mice on the high-fat diet became "very sick" after 4 weeks, Dr. Le explained; this was "clearly due to a very high number of tumor colonies and very large tumor colonies in the lungs." These animals also "lost tremendous body weight and mobility. To minimize their suffering, they were euthanized on week 4."
In contrast, the mice fed a lean diet survived with normal weight and mobility until week 6, he added.
At 4 weeks after tumor implantation, there was a 3-fold increase in lung metastasis in mice on the high-fat diet, compared with mice on the lean diet. There was a strong correlation between the high-fat diet and increased cancer metastasis, Dr. Le noted.
However, there may also be a more general conclusion. The mice on the high-fat diet had elevated visceral adipose tissue weight (belly-fat weight) and elevated levels of free fatty acids, and "these conditions are normally observed in obesity," Dr. Le pointed out. This suggests that obesity or a high-fat diet might accelerate cancer spread, he commented.
Increase in Circulating Tumor Cells
In addition, mice on the high-fat diet also showed an early increase in circulating tumor cells, with levels 3-fold higher than those seen in the lean-diet mice 2 weeks after tumor implantation. However, this difference gradually declined and became indistinguishable by week 4, the researchers note.
"We don't know the exact reason because we don't have direct evidence showing the whereabouts of the circulating cancer cells at all times," Dr. Le explained. However, one speculative explanation is that, in the mice fed the high-fat diet, the cancer cells escaped from the primary tumor and into the bloodstream (intravasion) at a faster rate than in mice fed the lean diet.
A more detailed study of the cancer cells themselves revealed a direct effect of the diet on the cancer-cell membrane. The researchers studied this using an imaging method known as coherent anti-Stokes Raman scattering, and they found "physical perturbations" in the cancer-cell membrane, which contributed to increased cancer aggressiveness.
In mice fed a high-fat diet, the increased lipid levels resulted in increased membrane phase separation and membrane rounding in cancer cells, which enhanced their ability to separate and spread through the body. The more rounded shape leads to reduced cellÐcell adhesion and increased tissue invasion, the authors explain.
"If the cancer cells don't have excess lipids, they stick together and form very tight junctions in tumors, but increasing lipids causes them to take on a rounded shape and separate from each other," Dr. Le explained.
The team further demonstrated that linoleic acid, which is predominant in polyunsaturated fats, causes increasing membrane phase separation, whereas oleic acid, found in monounsaturated fats, does not.
The researchers have disclosed no relevant financial relationships.
BMC Cancer 2009; 9:42.