University of Missouri researchers made the discovery using bioluminescence imaging technology to study how nicotinamide riboside supplements work inside the body. Commercial dietary supplements such as nicotinamide riboside (NR), a form of vitamin B3, have been linked to benefits related to cardiovascular, metabolic, and neurological health in previous studies. However, new research from the University of Missouri (MU) found that NR could actually increase the risk of serious diseases, including developing cancer. Supplements containing nicotinamide riboside are often marketed as NAD+ boosters that claim benefits such as increased energy, antiaging/longevity/healthy aging, improved cellular energy metabolism and repair, increased vitality, and improved heart health. Scientists discovered that high levels of NR could not only increase someone’s risk of developing triple-negative breast cancer, but could also cause the cancer to metastasize, or spread, to the brain. The international team of researchers was led by Elena Gunn, associate professor of chemistry at MU and corresponding author of the study. He said that once the cancer reaches the brain, the results are fatal because there are currently no viable treatment options. “Some people get them [vitamins and supplements] because they automatically assume that vitamins and supplements only have positive health benefits, but very little is known about how they actually work,” Goun said. “Because of this lack of knowledge, we were inspired to study the basic questions about how vitamins and supplements work in the body.” Following the death of her 59-year-old father, just three months after being diagnosed with colon cancer, Gunn was moved by her father’s death to pursue a better scientific understanding of cancer metabolism, or the energy through which cancer spreads in the body. Since NR is a known supplement that helps increase cellular energy levels, and cancer cells feed off of this energy with their increased metabolism, Goun wanted to investigate the role of NR in cancer growth and spread. Elena Gunn. Credit: University of Missouri “Our work is particularly important given the wide commercial availability and large number of ongoing human clinical trials where NR is used to mitigate the side effects of cancer treatment in patients,” said Goun. The researchers used this technology to compare and examine how much NR was present in cancer cells, T cells and healthy tissues. “While NR is already widely used in humans and is being explored in so many ongoing clinical trials for additional applications, much of how NR works is a black box – it’s not understood,” Goun said. This inspired us to come up with this novel imaging technique based on ultrasensitive bioluminescence imaging that allows quantification of NR levels in real time in a non-invasive manner. The presence of NR is seen with light, and the brighter the light, the more NR is present.” Gunn said the study’s findings underscore the importance of carefully investigating potential side effects for supplements like NR before using them in people who may have different types of health conditions. In the future, Goun would like to provide information that could potentially lead to the development of certain inhibitors to help make cancer treatments, such as chemotherapy, more effective in treating cancer. The key to this approach, Goun said, is to look at it from an individualized medical perspective. “Not all cancers are the same in every person, especially in terms of metabolic signatures,” Goun said. “Often cancers can even change their metabolism before or after chemotherapy.” Citation: “A bioluminescence-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism” by Tamara Maric, Arkadiy Bazhin, Pavlo Khodakivskyi, Georgy Mikhaylov, Ekaterina Solodnikova, Aleksander. Giordano Attianese, George Coukos, Melita Irving, Magali Joffraud, Carles Cantó and Elena Goun, 29 October 2022, Biosensors and Bioelectronics.DOI: 10.1016/j.bios.2022.114826 Other authors include Arkadiy Bazhin, Pavlo Khodakivsky, Ekaterina Solodnikova and Alexey Yevtodiyenko at MU. Tamara Maric at the Swiss Federal Institute of Technology. Greta Maria Paola Giordano Attianese, George Coukos and Melita Irving at The Ludwig Institute for Cancer Research in Switzerland. and Magali Joffraud and Carles Cantó at the Nestlé Institute of Health Sciences in Switzerland. Bazhin, Khodakivskyi, Mikhaylov, Solodnikova, Yevtodiyenko and Goun are also affiliated with the Swiss Federal Institute of Technology. Mikhaylov, Yevtodiyenko and Goun are also affiliated with SwissLumix SARL in Switzerland. Funding was provided by grants from the European Research Council (ERC-2019-COG, 866338) and the Swiss National Foundation (51NF40_185898), as well as support from NCCR Chemical Biology.
