by raylad on 6/8/25, 7:19 PM
My father was on chemotherapy with fludarabine, a dna base analog. The way it functions is that it is used in DNA replication, but then doesn’t work, and the daughter cells die.
Typically, patients who get this drug experience a lot of adverse effects, including a highly suppressed immune system and risk of serious infections.
I researched whether there was a circadian rhythm in replication of either the cancer cells or the immune cells: lymphocyte and other progenitors, and found papers indicating that the cancer cells replicated continuously, but the progenitor cells replicated primarily during the day.
Based on this, we arranged for him to get the chemotherapy infusion in the evening, which took some doing, and the result was that his immune system was not suppressed in the subsequent rounds of chemo given using that schedule.
His doctor was very impressed, but said that since there was no clinical study, and it was inconvenient to do this, they would not be changing their protocol for other patients.
This was around 1995.
by unnamed76ri on 6/8/25, 6:11 PM
I used to be on a chemo drug and had to take folic acid every day to stop it from doing bad things to me.
I had awful ulcers in my mouth from the chemo drug and had been taking the folic acid in the morning. Through forgetfulness I ended up shifting the folic acid to the afternoon and the ulcers went away and never came back.
by levocardia on 6/8/25, 6:47 PM
Hazard ratio of 0.45 seems implausibly high, especially when it's just the exact same treatment dichotomized to before/after 3pm. My money is on something other than a real circadian effect: either the result of a 'fishing expedition' in the data, or some other variable that incidentally varies by time of day. Maybe breaking randomization, leaving the drugs out for too long at room temp, etc. If you really believe this is an important and biologically plausible effect it should be a top candidate for a replication attempt.
by EricPhy on 6/9/25, 6:37 AM
“Let’s pretend you have very early-stage cancer. The dendritic cells are in their normal cycle of desperately presenting tumor fragments to T cells, the T-cells rightfully getting upset, activating themselves, and going off to hunt the cancer. But cancer simply shuts them down by expressing an immune blocker protein: PD-L1. In response, the T-cell mostly shuts down, wanders back to the lymphatic system, and gets a little bit more ‘exhausted’. It believes that it activated itself for no reason, and thus will require a much higher bar for doing anything else in the future. The more times this occurs, the more exhausted the T-cell becomes, the more unwilling to ever activate again. In the limit, it will simply kill itself. Hence why you need immunotherapy to revitalize these cells!”
That’s a powerful analog for depression and burnout in humans.
by jmward01 on 6/8/25, 5:57 PM
I wonder if other basic processes could be at play here like when patients go to the bathroom. If you do this in the morning they may be more likely to not need that for a while while in the evening they may do that immediately. I'm not saying this is the mechanism, just pointing out that there are a lot of timing dependent things in a person's schedule that could be a factor here. It is a great thing to point out though. I hope a lot more research goes into the idea of timing and integrating medication into a schedule most effectively.
by rendaw on 6/8/25, 5:55 PM
I'm doing CedarCure. You're required to not exercise or bath/shower for 2h after taking, which is fairly difficult in the morning, so I asked the doc if I could do it in the evening instead (despite explicit instructions to do it in the morning). The doc said it was fine, confirmed by the pharmacist.
I should know better by now than to trust doctors to act based on research and not gut feeling, but I hope this doesn't mean the last year of taking it was a wash...
by BDGC on 6/8/25, 8:16 PM
If you’re interested in circadian biology, which underlies chronoimmunotherapy, please check out UCSD’s BioClock Studio. We create tutorial videos and other media to teach circadian biology concepts:
https://bioclock.ucsd.edu/by NotGMan on 6/8/25, 6:22 PM
Perhaps it's due to overnight fasting, that people in the morning don't eat yet/as much?
Autophagy is increased during fasting, it usually takes 3 days of water fasting to fully ramp up to its maximum, so no food overnight might just slightly start it up.
I watched a youtube video of guy who did low carb and fasted at least 24h before and after chemo (or even 48h, forgot which) and he didn't experience the negative side effects of chemo as much.
by egocodedinsol on 6/8/25, 6:51 PM
by aitchnyu on 6/9/25, 10:15 AM
If a hospital cannot serve everybody in the morning, should they create a dorm with only artificial light that has sunrise at 12 pm and sunset at 12 am to shift circardian rythms?
by Kiyo-Lynn on 6/9/25, 1:47 AM
I once accompanied a family member through immunotherapy. The treatment times were mostly arranged by the hospital, and the doctor suggested doing it in the morning.
We just thought it was to avoid the afternoon rush.
Looking back, though, they really did seem to feel better with morning treatments.
Now I realize the timing itself might actually affect how well it works.
I really hope that in the future, doctors will consider not just the drug and the dosage, but also when it’s given.
by OrderlyTiamat on 6/9/25, 9:25 AM
They changed the study target effect (which hour range), design (interventional vs observational) and inclusion/ exclusion criteria multiple times.
I don't really care at that point what their conclusion says, because I have no idea how to interpret the statistics in a theoretically sound way now.
by parsabg on 6/8/25, 10:46 PM
I wonder if the same would also be true for immunosuppressants administered for autoimmune conditions. Given they mostly interact with the signaling pathways, I guess in theory they should also be more effective in the morning if there is more immune cell activity going on.
by Laaas on 6/8/25, 6:22 PM
Light affects us deeply. Very probably true for more than immunotherapy.
by more_corn on 6/8/25, 11:18 PM
Because the immune system sleeps at night and wakes up in the morning?
by HexPhantom on 6/9/25, 7:02 AM
In a way it feels like we're scratching the surface of a new layer of treatment optimization
by georgeburdell on 6/8/25, 10:19 PM
Not a medical doctor. Does this also have implications for other immunotherapy like allergy shots?
by pmlnr on 6/9/25, 11:17 AM
Body meridian clock, that's why.
by owenthejumper on 6/8/25, 8:56 PM
Sicker patients get emergency treatment in the hospital in the afternoon while healthier ones in the morning in the clinic
by s1mplicissimus on 6/9/25, 12:48 PM
tl;dr
Administering immune system related drugs in the morning improves success rate. This is because the immune system is more receptive in the morning, due to evolutionary adaptation. The authors even seem to have isolated the gene sequence that leads to the "sensor" which generates the necessary "data" for the immune system to optimize on.
Really cool research imo
by ImHereToVote on 6/9/25, 7:06 PM
Fasted state?
by Noelia- on 6/9/25, 10:10 AM
A while back, a colleague told me his doctor always scheduled his immunotherapy infusions for the morning, saying it would be more effective. I thought it was just something they said, but seeing all this new data, I’m realizing there’s actually real science behind it.
by zevets on 6/8/25, 5:46 PM
This is bad science. Patients schedule when they go to immunotherapy appointments. People who go in the morning are still working/doing things, where once you get _really_ sick, you end up scheduling mid-day, because its such a hassle to do anything at all.