Houston, Texas, USA : Mannose sugar, a nutritional supplement, can both slow tumour growth and enhance the effects of chemotherapy in mice with multiple types of cancer.
This lab study is a step towards understanding how mannose could be used to help treat cancer.
The results of the study, which was funded by Cancer Research UK and Worldwide Cancer Research, are published in Nature, today.
Tumours use more glucose than normal, healthy tissues. However, it is very hard to control the amount of glucose in your body through diet alone. In this study, the researchers found that mannose can interfere with glucose to reduce how much sugar cancer cells can use.
Professor Kevin Ryan, lead author from the Cancer Research UK Beatson Institute, said: “Tumours need a lot of glucose to grow, so limiting the amount they can use should slow cancer progression. The problem is that normal tissues need glucose as well, so we can’t completely remove it from the body. In our study, we found a dosage of mannose that could block enough glucose to slow tumour growth in mice, but not so much that normal tissues were affected. This is early research, but it is hoped that finding this perfect balance means that, in the future, mannose could be given to cancer patients to enhance chemotherapy without damaging their overall health.”
The researchers first examined how mice with pancreatic, lung or skin cancer responded when mannose was added to their drinking water and given as an oral treatment. They found that adding the supplement significantly slowed the growth of tumours and did not cause any obvious side effects.
To test how mannose could also affect cancer treatment, mice were treated with cisplatin and doxorubicin—two of the most widely used chemotherapy drugs. They found that mannose enhanced the effects of chemotherapy, slowing tumour growth, reducing the size of tumours and even increasing the lifespan of some mice.
Several other cancer types, including leukaemia, osteosarcoma, ovarian and bowel cancer, were also investigated. Researchers grew cancer cells in the lab and then treated them with mannose to see whether their growth was affected.
Some cells responded well to the treatment, while others did not. It was also found that the presence of an enzyme that breaks down mannose in cells was a good indicator of how effective treatment was.
Professor Kevin Ryan added: “Our next step is investigating why treatment only works in some cells, so that we can work out which patients might benefit the most from this approach. We hope to start clinical trials with mannose in people as soon as possible to determine its true potential as a new cancer therapy.”
Mannose is sometimes used for short periods to treat urinary tract infections, but its long-term effects have not been investigated. It’s important that more research is conducted before mannose can be used in cancer patients.
Martin Ledwick, Cancer Research UK’s head nurse, said: “Although these results are very promising for the future of some cancer treatments, this is very early research and has not yet been tested in humans. Patients should not self-prescribe mannose as there is a real risk of negative side effects that haven’t been tested for yet. It’s important to consult with a doctor before drastically changing your diet or taking new supplements.”
Citation: Pablo Sierra Gonzalez et al, Mannose impairs tumour growth and enhances chemotherapy, Nature. DOI: 10.1038/s41586-018-0729-3
A second study on Mannose’s unexpected effects on the microbiome and weight gain :
Mannose’s Unexpected Effects On The Microbiome And Weight Gain
Scientists continue to unravel links between body weight and the gut microbiome. Now, researchers from Sanford Burnham Prebys Medical Discovery Institute (SBP) report an unexpected finding: mice fed a fatty diet and mannose, a sugar, were protected from weight gain, leaner, and more fit—and this effect tracked with changes in the gut microbiome. The study published today in Cell Reports.
“Obesity and related diseases, such as nonalcoholic steatohepatitis (NASH), are on the rise—and scientists are on the hunt for new treatments, particularly for individuals who are unable to exercise,” says Hudson Freeze, Ph.D., senior author of the paper and director and professor of the Human Genetics Program at SBP. “Better understanding of mannose’s effects on the gut microbiome may lead to new therapies for treating obesity.”
Freeze and his team were studying mannose in the context of a rare disease called a congenital disorder of glycosylation (CDG). People with a specific form of the disease can be treated with mannose. While conducting their research, the scientists observed the anti-obesity effects of mannose feeding.
A closer look revealed the mice were also protected from typical negative effects of a fatty diet. They had less body fat, reduced fat in their liver, stable blood sugar—and even improved fitness. Surprisingly, these benefits were only seen when the mice received mannose early in life—older mice didn’t benefit from mannose.
“The gut microbiome is very dynamic in early life,” says Vandana Sharma, Ph.D., lead author of the paper and staff scientist in Freeze’s laboratory. “Because only young mice that received mannose exhibited leaness, we thought the microbiome might be involved.”
Despite eating the same amount of fatty food, mannose-fed mice absorbed fewer nutrients-and instead excreted them. Further work showed the gut microbial composition mirrored that of lean mice fed a regular diet. When mannose was removed, the mice on the fatty diet regained weight, and their gut microbiome composition shifted to resemble that of the obese mice that ate fatty food but didn’t receive mannose. The scientists also found that the gut microbes of the mannose-fed mice were less efficient at processing carbohydrates—an energy source.
“These findings further confirm the important role of the gut microbiome in metabolism,” says Freeze. “The microbiome partially explains the beneficial effects of mannose, but how exactly it affects the body’s metabolism remains a mystery.”
Citation: Cell Reports. DOI: 10.1016/j.celrep.2018.08.064
A third study linked mannose levels to diabetes risk, regardless of weight:
Regardless Of Weight, Mannose Levels Point To Diabetes Risk
Even if you are not overweight, your mannose levels may indicate whether you’re at risk for type 2 diabetes (T2D) or insulin resistance (IR), a Swedish study shows.
Mannose, a simple sugar that occurs as a component of many natural polysaccharides, has been identified as a biomarker for diabetes, says Adil Mardinoglu, a systems biologist at KTH Royal Institute of Technology in Stockholm and a fellow at SciLifeLab. The report was published June 24 in Cell Metabolism.
“We can measure mannose in the blood of lean or obese people and identify if they have increased risk for type 2 diabetes based on their mannose levels,” Mardinoglu says.
The researchers found that subjects with high mannose levels have a higher risk for T2D. Lead author Sunjae Lee, a researcher with SciLifeLab at KTH, says that mannose can be used as a biomarker since blood mannose levels are quite stable and not influenced by recent food intake, unlike glucose levels.
The study forces us to reconsider assumptions about the relationship between obesity and diabetes. “Although the prevalence of obesity and type 2 diabetes continues to dramatically increase worldwide, a clear understanding of the underlying molecular mechanisms involved in the progression of associated disorders has still been lacking,” Lee says. “So it is important to identify stable biomarkers that can be used for the early discovery of IR and future risk of T2D.”
Lee says the researchers used a systems biology-based approach and generated cell-specific integrated networks for liver, fat and muscle tissues.
They used these biological networks for analysis of clinical data to explain biological changes in response to obesity and IR, which provided comprehensive molecular clues.
“Based on our integrative analysis, we think that this knowledge can be useful in the clinic for detecting subjects at high risk for T2D,” Lee says. “However, larger studies are required for further clinical validation of our results.”
Citation for third study: Pablo Sierra Gonzalez et al, Mannose impairs tumour growth and enhances chemotherapy, Nature. DOI: 10.1038/s41586-018-0729-3