Now we have more reason than ever to focus on bicarbonate therapy for cancer. A new Ludwig Cancer Research study said, “If you want to clean cancer’s clock—that is, defeat it decisively—you may want to really clean it—that is, restore it to proper working order. Only cancer cells that remain active, in sympathy with the tick-tock of their internal circadian mechanisms, remain susceptible to cancer therapies. So, how might these circadian mechanisms be kept in motion? Sodium bicarbonate now promises to awaken cancer cells that have gone to sleep deep inside tumors, where oxygen deprivation and acidic conditions go hand in hand. By buffering against acidification, sodium bicarbonate rescues circadian oscillation.”
“You can think of the circadian cycle as a sort of internal clock of your body that regulates many different mechanisms. The cycle starts over about every 24 hours (hence the term “circadian”, coming from Latin circa “about” and dies “day”), and among its many functions, it tells cells when they’re supposed to produce and consume nutrients. Healthy cells are normally allowed to do so for about 12 hours a day, in order to prevent them from being overwhelmed by a flood of excessive nutrients.”
“In order to keep dividing indefinitely, cancer cells cannot afford the periodic fasting imposed by the circadian rhythm; before they can divide, they need to grow, and in order to grow, they need nutrients. Therefore, furiously paced division requires furiously paced nutrient intake. Hence, all cancers evolve strategies to get around the circadian limitation.”
Acidification, the Ludwig researchers report, essentially disengages some of the elements that keep the cell’s circadian clock ticking. This acid-mediated effect, the researchers assert, can be reversed by sodium bicarbonate. When they gave tumor-xenografted mice water that had been supplemented with sodium bicarbonate, the acidity of hypoxic patches in the tumors was neutralized.
The study, presented May 31 2018, in the journal Cell, in an article entitled ‘Acid Suspends the Circadian Clock in Hypoxia through Inhibition of mTOR’. “Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome when hypoxic cells are permitted to acidify to recapitulate the tumor micro-environment,” the article states. “Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation.”
The study’s authors, led by Chi Van Dang, M.D., Ph.D., scientific director of the Ludwig Institute for Cancer Research, conclude that acid produced during the cellular metabolic response to hypoxia suppresses the circadian clock through diminished translation of clock constituents. Dr. Dang, who is also a professor in the Molecular and Cellular Oncogenesis Program at The Wistar Institute said, “But if you add baking soda to the drinking water given to those mice, the entire tumor lights up with mTOR activity. The prediction would be that by reawakening these cells, you could make the tumor far more sensitive to therapy.”
“We started out with a question about oxygen starvation and the circadian clock, and we ended up discovering a new mechanism by which acidic conditions in tissues shut off a lot of things—including the cell’s molecular clock,” muses Dang.
The finding that something as simple as baking soda could reverse this effect and render quiescent cancer cells susceptible to cancer therapies excites Dang. “The concept is so easy,” he says. “It’s not some $100,000 per year drug. It’s literally just baking soda.” Using MRI, medical scientists have seen how much of tagged bicarbonate is converted into carbon dioxide within tumors. In more acidic tumors, more bicarbonate is converted into carbon dioxide.