Findings: In this double-blind, randomized, placebo-controlled trial involving 240 hospitalized patients with severe COVID-19, a single dose of 200,000 IU of vitamin D3 supplementation was safe and effective in increasing 25-hydroxyvitamin D levels, but did not significantly reduce hospital length of stay (hazard ratio, 1.12) or any other clinically-relevant outcomes compared with placebo.
Single dose is not the way other findings are using vD3. vD3 is used thought the body for many things and you need daily supplament to get and keep the concentration up over time
I'm not convinced the 2/3 dropout rate of the FMD didn't simply select for people with less aggressive tumors, given that the Intention-To-Treat analysis found no difference in response rate, and that this paper is telling a nice story that actually happens to reverse cause and effect.
Basically, this?
HAS AGGRESSIVE TUMOR ---> CANNOT DO THE FMD
HAS SLOW-GROWING TUMOR ---> ABLE TO MAINTAIN FMD
Since you're researcher in this field and I'm just a weirdo who likes watching scientists argue on Twitter, I'll ask: Anything you can see in the paper that would give a clearer picture regarding possible bias that might have snuck in?
That could very well be a possibility and something that researchers need to address if they wish to investigate this effect a bit further. We can make some educated guesses based on the supplemental table 3. Looking at the staging, grading, tumortype and the hormone receptor status, there don't seem to be any significant differences between the compliant and non-compliant groups. We know that those are the most important factors in assessing how aggressive a breast tumor is, with distinct treatment options and overall survival. So based on this information, I'm inclined to say the cause/effect is not reversed.
Of course, there could be some factors determining aggressiveness and response to chemotherapy that we do not know yet. Unfortunately I'm not in regular patient contact so can't say a whole lot about typical side effect profiles of chemotherapy, but I've heard some anecdotal evidence that for patients treated with immunotherapy, the more severe the side effects, the better the response.
Thanks for clarifying comments here, much appreciated.
I have to think my initial comment was overly harsh as well, given Supplement 3.
I think all I can say is that it may be possible for this issue to affect their data once they have OS stats accumulated in five years, but it was unlikely to do anything to yield differences in adherence with these kinds of patients over this kind of follow-up length.
"The main reason for non-adherence to the FMD was dislike of distinct components of the diet, perhaps induced by chemotherapy [...] The FMD is a 4-day plant-based low amino-acid substitution diet, consisting of soups, broths, liquids and tea"
Occam's razor, patients couldn't stick with the diet.
Also of note is tumor heterogenity. Not only are cancers different between cell origin and across different patients, cancer is not one uniform genetic entity even inside a single person.
Why? The cancer's ability to repair DNA mutations is crap, so different chunks of tumor can rapidly evolve different mutations.
You might be able to drug one portion of the tumor based on a fancy receptor/biomarker, but that tumor chunk will get outcompeted by a different cancer blob that doesn't express that.
Yes, and this was ignored for quite a while at least at the mainstream level.
I've read not too long ago that a tumor is actually mostly an outer layer of active cells, the inner is made up of dead tumors probably serving as nutrient (<= very blurry on this). yet another part of that strange anti-life living form named cancer.
Their "better response rate" touted at the top ignores the 2/3 of women who couldn't carry out the assigned FMD.
When you fold back in those 2/3 of people on that arm, the response rate is the same:
"The overall pCR rate was 11.7% and did not differ between the two groups (10.8% in FMD group versus 12.7% in control group; OR 0.830, 95% CI 0.282–2.442, P = 0.735)."
Almost no one reads these papers when stuff like this gets posted on HN.
And there is shameful statistical fuckery afoot in this paper. People are only repeating the hype statistics at the top of the paper.
Their "pathological response" rates touted at the top of paper only come from the 1/3 of women able to actually carry out the diet. This is the "per-protocol" language in the abstract. An honest evaluation here would be "intention to treat" and analyze chemo responses in every assigned to each arm.
And they do that evaulation, but bury it later in their paper. Turns out when you account for the 2/3 of women who can't do that fasting, there's NO DIFFERENCE in response rate:
"The overall pCR rate was 11.7% and did not differ between the two groups (10.8% in FMD group versus 12.7% in control group; OR 0.830, 95% CI 0.282–2.442, P = 0.735."
A lot of people might think "Ah, well, fasting is clearly effective for the 1/3 that are able to carry it out, just gotta make sure you have the willpower to be the 1/3."
But hold on. Slow down. There's a good chance the "women who fasted had better chemo responses" story completely REVERSES cause and effect. Here's how:
WOMEN 1 - Has indolent biology, slower growing tumor than your average breast cancer at this stage.
- Symptoms: Less pain, neuropathy, less swelling, tumors not affecting distant organs as much
WOMEN 2 - Has aggressive biology, faster growing tumor than your average breast cancer at this stage.
- Symptoms: More pain, neuropathy, more swelling, tumors begin to affect distant organs
So ask yourself: Which women is more likely to be able to follow a strictly regimented diet?
That's absolutely right and it's a major problem of this study. There is one caveat though, in the most common ER+ breast cancer, radiological response is more predictive of survival than pCR. And in this study, they do observe a better radiological response in the fasting group, even when looking at ITT (though just barely significant).
Welcome to every Vitamin D study done ever. I follow some PHD/RD combination researchers on Twitter and they all get together each time one of these studies is done and bang their heads against a wall.
Thank you thank you thank you. There is a craze for popping Vitamin D related to the raft of observational studies, here... so many of which never find a causal link.
Take my own particular condition: an inherited vascular dysplasia which causes frequent nose and GI bleeds. People with low Vitamin D seem to have a worse time of it in OBSERVATIONAL studies.
But people with GI bleeds so bad they have daily diarrhea from hemorrhages and anemia that disables them to the point they can't work aren't going to be out in the sun, and aren't going to be able to absorb as many vitamins in their gut due to the havoc the hemorrhaging is yielding.
Thinking really hard about the direction the arrow of causality runs here is massively important. Is it:
LOW VITAMIN D ---> BAD BLEEDING?
Or:
BAD BLEEDING ---> LOW VITAMIN D
And as the consequences of overdosing show, this isn't like popping an extra Metamucil cracker a day or something - dire stuff can happen.
There are seven results for American trials found on clinicaltrials.gov for Condition= "COIVD19" and Drug = "VitaminD" run by institutions like Harvard/MGH, Brigham, UNC, Arizona State University, etc.
PEP =/= PREP. PEP is after the fact treatment, there's more than just Truvada in that protocol.
PEP is typically much harder on the body than PREP.
Most every gay man I know takes PREP with few or no side effects.