I am just back from a challenging (humbling) multiday backpack in the High Sierras of California. Very beautiful but drought conditions, dry stream water sources made it more difficult.
Here is a pre-note on my own regimen: After completing my two phase radiation treatments for oligometastatic PC: SBRT in April, followed a month later with two doses of Lu-PSMA-J591 radioligand treatments in May. Now, six weeks out from that, I am going on a 3-day Senolytic regimen. This is hopefully to "clear" treatment emergent senolytic cancer cells. These may make trouble down the line as "Senescence Associated Secretory Phenotypes", SASPs. My chosen senolytic regimen is Dasatinib 100mg, plus Quercetin 1600 mg, plus Fisetin 1000 mg daily for just three days.
On the long drive back to Oregon, I had downloaded a new and very good science podcast called "The Joy of Why" by Quanta online magazine. Every episode was excellent. One that especially engaged me was about why we (and every animal species) die if sufficiently sleep deprived. One experiment deprived fruit flies of sleep until they died. The normal controls lived 40 days average. Sleep deprived fruit flies started dying at 10 days and the average survival was just 20 days.
Then they did full microscopic autopsies on the dead flies and found that the major injury and cause of death was in the gut. Their stomach and intestines had severe injury from reactive oxygen species (ROS) causing widespread cellular injury, inflammation and death. In subsequent experiments they gave antioxidants (unspecified in the interview) to the flies being sleep deprived. This restored normal lifespan protecting them from the oxidative stress of sleep deprivation. How amazing.
It got me thinking about the role of excess ROS stress damaging our healthy cells as part of aging. And many other causes besides sleep loss. As many here are well aware, ROS play an important role also in the mechanisms of killing cancer cells in the through the of action of treatments such as radiation and chemotherapy. So we generally do not use anti-oxidants while actively undergoing these treatments. Not important with hormonal treatments such as ADT. We do not want to let ROS run rampant in our bodies causing cellular degradation and destruction when we are not actively on those cytoxic treatments.
What is the role of the gut microbiome (the types and activities of the various stomach and intestinal bacteria) in protecting against ROS? What probiotics are most helpful. Pro-biotics are the actual living bacteria that can form new colonies by the billions (CFU or colony forming units). And which prebiotics are most beneficial? Pre-biotics being nutritional supports to feed the most beneficial gut bacteria. And most mysteriously, what is the relationship to good sleep?I
I remembered great posts from our esteemed pjoshea13 on the gut bacterium called Akkermansia municiphila (A.mun). (Thank you Patrick.) This is a very favorable sub-population that is actually a marker of good microbiome health. It is associated with thicker intestinal mucin layer, protects against abnormal gut permeability, and is anti-inflammatory. Low counts of A.mun are associated with metabolic syndrome, obesity and type II diabetes. It seems a very good thing. However, there is curently only one probiotic product on the market that specifically provides high levels (CFUs) of A.mun. That is from Pendulum and is rather expensive, $115 for single month or $74 on subscription.
However, it turns out that you don't have to actually take A.mun as a probiotic to substantially increase their levels in the gut. Probiotics containing Lactobacilus rhamnosus, and most especially Bifidobacterium lactis (animalis, subspecies lactis) also strongly support building high A.mun counts, just as well as actually taking the A.mun product. These are much more common in good probiotics. Read the labels.
As for prebiotic support. By far the most effective dietary support for the favorable gut microbiome, including A.mun, is called FOS, fructo-oligosacharides. These are small polymer chains of fructose. But the bonds cannot be broken down by our human digestion. So we don't have to worry about the excess fructose. Rather, the bacteria ferment them for food. The most inexpensive and widely available form of FOS is inulin (not insulin!) that is derived from Chicory root fiber which is almost all inulin. There are some shorter chain FOS that might have advantages over the somewhat longer chain inulin, but these are harder to find.
Another interesting fact is that our old pal, Metformin, also strongly increases A.mun populations. And perhaps might mediate some of Metformin's beneficial effects on metabolism, glucose, insulin sensitivity and improving lipopolysaccharides. Rhubarb extract containing anthraquinones is another agent that increases A.mun.
The oral antibiotic Vancomycin also seems to preferentially favor A.mun whereas doxycycline is detrimental and degradess the microbiome even in low doses. We certainly don't want to take Vancomycin for this purpose due to emerging resistance of C. dificil and also renal toxicity.
A High Fat Diet is detrimental to the A.mun population. -Problematic for me on my ketogenic cycles. Also alcohol is detrimental to the gut microbiome.
Finally, I want to mention anti-oxidants that may be helpful. And I am not talking about the much studied and sometimes problematic Vitamins C, E and selenium. Rather, I am more interested in alpha-Lipoic Acid, a widely occuring natural substance called "the master antioxidant. It is widely distributed intracellularly to protect against ROS from mitochondrial "leakage". It restores Vitamin C activity, increases glutathione and SOD levels. I include it as part of my own supplement regimen, just hoping it does me some good. Poorly absorbed antioxidant phytochemicals such as Resveratrol, might be providing good gut antioxidants even though their absorption and bioavailability is notoriously low. I note that Melatonin also is aneffective antioxidant as well as being a regulator of circadian rhythms and sleep. Perhaps that is part of the complex interactions between sleep and oxidative stress recovery? -Paul
