Key Points:
- Undergoing intermittent fasting five days per week extends lifespan in mice with an aggressive form of ovarian cancer.
- Intermittent fasting suppresses tumor growth so that tumors are half the size of those from cancer-ridden mice fed a regular diet.
- Intermittent fasting modulates metabolism to increase levels of a blood metabolite called ꞵ-hydroxybutyrate (BHB) that increases lifespan in tumor-bearing mice.
Intermittent fasting encompasses not eating for a period of time, such as going at least 16 hours per day without eating, regardless of the calorie numbers consumed during the remaining eight hour period. Intriguingly, in various cancer models, this form of dietary intervention has been shown to inhibit tumor growth. However, no studies had examined whether intermittent fasting suppresses tumors in the most lethal gynecologic cancer — epithelial ovarian cancer (EOC).
Published in iScience, Rattan and colleagues from the Henry Ford Cancer Institute in Detroit, Michigan show that intermittent fasting significantly extends lifespan in mice with an aggressive form of EOC. The researchers also show that intermittent fasting inhibits tumor growth, limiting tumor sizes to less than half the volume of EOC mice fed a regular diet. Rattan and colleagues go on to show that intermittent fasting increases blood concentrations of a metabolite, BHB, that also extends lifespan in cancer-ridden mice without the intermittent fasting intervention. These findings suggest that intermittent fasting inhibits tumor growth and extends lifespan in EOC and that treating cancer with BHB partially mimics intermittent fasting’s benefits.
Intermittent Fasting Extends Remaining Lifespan and Suppresses Ovarian Tumor Growth
To find whether intermittent fasting influences lifespan with EOC, Rattan and colleagues injected mice with a highly aggressive form of the cancer. Interestingly, intermittent fasting conferred a ~53% increase in median remaining lifespan. These findings show that intermittent fasting extends lifespan in a mouse model for an aggressive form of EOC.
Since intermittent fasting extends lifespan in mice with EOC, Rattan and colleagues sought to measure this dietary intervention’s anticancer effects. To do so, they monitored how intermittent fasting affects tumor growth over the course of 100 days after cancer cell injections. As expected, intermittent fasting substantially inhibited tumor growth. Along those lines, tumor sizes were less than half the volume when compared to tumor-bearing mice fed a regular diet. These results show that intermittent fasting has tumor growth inhibiting effects.
To find how intermittent fasting confers anticancer properties and extends lifespan in mice with EOC, Rattan and colleagues measured blood inflammatory factors and metabolites. In line with previous studies, the Michigan-based researchers found that intermittent fasting reduced blood inflammatory proteins like interleukin-6. These findings suggest that intermittent fasting confers anticancer benefits, in part, by suppressing cancer-promoting inflammation.
The researchers also found that the blood metabolite BHB showed markedly increased levels in tumor-bearing mice that underwent intermittent fasting. BHB is a molecule that provides cellular energy when not enough carbohydrates are available, and its increased concentrations indicate that the body has metabolically switched to a state of ketosis — when the body burns fat for energy.
To find whether BHB alone could recapitulate the lifespan-extending effects of intermittent fasting, Rattan and colleagues injected tumor-bearing mice with BHB. Intriguingly, BHB significantly increased median remaining lifespan. BHB didn’t extend remaining lifespan to the degree that intermittent fasting did, though, likely because intermittent fasting increases other ketosis-related metabolites along with BHB. These data suggest that BHB plays a key role in intermittent fasting’s lifespan-extending effects in EOC and that injecting it can confer some of the same anticancer impacts as intermittent fasting in EOC mice.
“Here, we emphasize [intermittent fasting]’s capacity to induce anti-tumor immunostimulatory effects via one of its metabolic mediator BHB, which can be leveraged to limit EOC and increase patient survival,” say Rattan and colleagues.
Intermittent Fasting as a Dietary Intervention to Fight Cancer
The findings presented here add to the list of studies showing that intermittent fasting limits tumor growth to suppress cancer. Previous research has linked intermittent fasting to tumor growth inhibition in breast, colon, and brain cancers in rodents. Human trials examining intermittent fasting in cancer suggest that this dietary intervention may improve chemotherapy efficacy and reduce pain. Whether intermittent fasting’s anticancer benefits apply to humans requires more research, though.
A key finding from the study was that BHB recapitulates some of the remaining lifespan extension from intermittent fasting. As such, BHB may be used as an adjuvant treatment for cancers like EOC to extend lifespan. Along those lines, supplements for BHB can be purchased for about $20 for a month’s supply.
Whether one has cancer or not, supplementing with BHB may be a way to acquire some of the benefits of intermittent fasting without implementing this dietary intervention. Supplementing with BHB may be especially helpful for those who have trouble adhering to an intermittent fasting eating schedule.
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