I don't get why the concept of chelation would be on the edge of some overton window when it comes to medical treatments. From my understanding of the development of the diptheria vaccine, the idea of using a substance to purify horse serum, or increase its production may have given the diea to experiment with aluminum as a type of adjuvant for those trying the vaccine route. So....conceptually aren't we talking about something that was intertwined with the development of modern vaccines? Why would there be such a hesitancy to explore such a treatment for substances we know aren't good for us being in our system?
TACT 1 was a scientific fraud and an ethical catastorphe. It's understandable that you wouldn't have known this if you hadn't investigated its history, as Dr. Gorski has previously written, but please do so now: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2438277/
So will the same logic be applied to Entresto? The Paradigm study was resoundingly positive for valsartan plus sacubitril, plus they compared its efficacy to a suboptimal dose of enalapril (10mg). Other clinical trials like Paradise-MI failed to show superiority for Entresto. Paragon-HF was not much better. So why has Entresto become the standard of care for heart failure?
1. Lead is a big issue even in the US, even at very low levels:
“we estimate that about 400 000 deaths are attributable to lead exposure every year in the USA, of which 250 000 are from cardiovascular disease. Concentrations of lead in blood lower than 5 μg/dL (<0·24 μmol/L) are an important, but largely ignored, risk factor for death in the USA, particularly from cardiovascular disease.”
2. Lead levels rise after stopping chelation because it constantly leeches from bones. When they measured lead levels after stopping therapy matters. How long was that gap?
3. One of the simplest ways to detox lead is take ascorbic acid as it blocks resorption. Been shown to plummet lead levels in ex-smokers. This and other chelating effects are likely a part of why vegetables are good for everything.
4. There are a ton of oral chelation approaches that make more sense than IV approaches. Cheaper, safer, easier, probably more effective. Including oral EDTA. And they facilitate ramping the dose to avoid bad reactions.
5. There absolutely is such a thing as a detox reaction and part of this is surely due to redistribution of heavy metals, as numerous chelators have been shown to do this in animals. I believe some of the old death reports from IV EDTA are because of this. The lack of safety issues in TACT2 to me is not generalizable. Plenty of people show up on forums with their lives wrecked from IV chelators - though usually from presumed mercury redistribution, not so much lead.
6. There are doctors who claim to have images of reversal of atherosclerosis. They claim Ca-EDTA pushes (not Na-EDTA drips) is the effective format.
sadly, there are some of us who don't believe much these days; certainly not from earnest "medical" journals. Has anyone read this paper; https://bmjopen.bmj.com/content/12/12/e060172 and then dived deep into what they say; and allowed themselves to be confronted by the hidden implications?
There seem to be deep and hidden hands behind every study? Can you publish anything that does not conform to someone else's narrative? (and likely they are much more powerful than you.)
Some find it hard to believe anything in a journal;
for me, the words of Marcia Angell ring incessantly in my ears "It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines";
You might be less impressed with the original TACT results if you had been following it from the beginning, as we at SBM have. Dr. R. W. Donnell did what I like to call a "magical mystery tour" of some of the clinical sites where TACT was carried out. He found a variety of quack clinics and made some observations that suggest that blinding might have been compromised at some of these sites.
The first stop on our tour is Tequesta Family Practice, Tequesta Florida. Among the alternative practices featured there are heavy metal analysis for chronic fatigue, intravenous infusion of vitamins and minerals for chronic fatigue, evaluation and treatment of “dysbiosis”, evaluation of colonic “ecology” by various culturing techniques, intravenous colchicine infusion for spinal disk herniation and, of course, chelation therapy.
<blockquote>The clinic’s uncritical promotion of chelation raises questions about the objectivity and scientific qualification of the investigators. Chelation therapy is touted by the clinic as “one of the premier anti-aging therapies” and as useful for scleroderma, Alzheimer’s disease, rheumatoid arthritis, multiple sclerosis and porphyria.</blockquote>
I wrote about it in 2006, as the study was being done, and my post includes links to all of Dr. RW's posts on individual sites.
"An initial P value between 0.001 and 0.005 in a trial implies only a 58% chance of getting P< 0.05 upon attempted replication. It’s even more unreliable in the stratum of -p-values of 0.01-0.05 is only 37%."
Did the Cochrane people find this out empirically by examining their database? I understand that probability experts have mathematical demonstrations that show that even a P-value itself has its own P-value. So maybe the conventional 0.05 is way too high for "statistical significance."
Some of us were not "stunned" by the TACT results. Using common sense analysis almost anyone could come to the conclusion that the results were meaningless. My advice on reading medical studies is to look at the raw numbers and use your common sense to decide whether the differences between outcomes for the control and experimental groups have any practical significance. Measures of statistical significance may be quite misleading. It is also very disappointing to see articles that repeatably use relative risk reduction figures and never mention actual risk reduction. Any person of average intelligence can employ this method in order to decide whether the study is of any practical use.
Some MDs have a financial stake in chelation; we have clinics here in Canada already promising it will cure positively everything & they're raking in the profits with off-label use. Thankfully the NIMH canceled the "chelation-autism" study on children before it ran, due to risks to participants. We need to consider risk for adult participants too. Time for funders to move on --& for regulators to take action on exploitative off-label clinics.
I hope Lamas will continue research based on his TACT 1 and 2 findings. He collected a lot of information this article wouldn't have space to share. Speaking of, I really enjoyed rradong it:) Thank you.
If TACT 2 was underpowered as you say, then that means that the results of TACT 2 are inconclusive. There may or may not be an effect! I liked the conclusion of yours:- "The main lessons here are humility and skepticism."
Very nice article John. I just take issue with the need to use the words 'positive' and 'negative'. To say that TACT 2 is negative or is not positive is minimally informative. The data are consistent with a 24% event rate reduction with chelation therapy, so the data in this too-small-N study are most consistent with the need for TACT 3 that should be combined with TACT 2 to provide a definitive answer. And trialists who continue to not think of learning as sequential but keep designing fixed-N studies need to take a close look at Bayesian sequential trials, e.g. at https://hbiostat.org/bayes/bet/design . Bayesian sequential designs do not pretend that we know the value of N.
The article would have been better had the confidence interval been in the first sentence.
In general, the medical literature is littered with poorly designed studies that have closed the doors on potential therapies. Some of them prematurely. Conversely the medical literature is littered with studies that are well funded and propelled treatments far beyond the science. Science is a winner when the pursuit of knowledge isn’t so deeply coupled with billion dollar interests.
I don't get why the concept of chelation would be on the edge of some overton window when it comes to medical treatments. From my understanding of the development of the diptheria vaccine, the idea of using a substance to purify horse serum, or increase its production may have given the diea to experiment with aluminum as a type of adjuvant for those trying the vaccine route. So....conceptually aren't we talking about something that was intertwined with the development of modern vaccines? Why would there be such a hesitancy to explore such a treatment for substances we know aren't good for us being in our system?
Dr. Mandrola,
TACT 1 was a scientific fraud and an ethical catastorphe. It's understandable that you wouldn't have known this if you hadn't investigated its history, as Dr. Gorski has previously written, but please do so now: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2438277/
You will be shocked and saddened.
So will the same logic be applied to Entresto? The Paradigm study was resoundingly positive for valsartan plus sacubitril, plus they compared its efficacy to a suboptimal dose of enalapril (10mg). Other clinical trials like Paradise-MI failed to show superiority for Entresto. Paragon-HF was not much better. So why has Entresto become the standard of care for heart failure?
1. Lead is a big issue even in the US, even at very low levels:
“we estimate that about 400 000 deaths are attributable to lead exposure every year in the USA, of which 250 000 are from cardiovascular disease. Concentrations of lead in blood lower than 5 μg/dL (<0·24 μmol/L) are an important, but largely ignored, risk factor for death in the USA, particularly from cardiovascular disease.”
https://www.sciencedirect.com/science/article/pii/S2468266718300252
2. Lead levels rise after stopping chelation because it constantly leeches from bones. When they measured lead levels after stopping therapy matters. How long was that gap?
3. One of the simplest ways to detox lead is take ascorbic acid as it blocks resorption. Been shown to plummet lead levels in ex-smokers. This and other chelating effects are likely a part of why vegetables are good for everything.
4. There are a ton of oral chelation approaches that make more sense than IV approaches. Cheaper, safer, easier, probably more effective. Including oral EDTA. And they facilitate ramping the dose to avoid bad reactions.
5. There absolutely is such a thing as a detox reaction and part of this is surely due to redistribution of heavy metals, as numerous chelators have been shown to do this in animals. I believe some of the old death reports from IV EDTA are because of this. The lack of safety issues in TACT2 to me is not generalizable. Plenty of people show up on forums with their lives wrecked from IV chelators - though usually from presumed mercury redistribution, not so much lead.
6. There are doctors who claim to have images of reversal of atherosclerosis. They claim Ca-EDTA pushes (not Na-EDTA drips) is the effective format.
Great example of the need for replication, and to only treat subgroups as hypothesis generating. Terrific object lesson for trialists and regulators.
sadly, there are some of us who don't believe much these days; certainly not from earnest "medical" journals. Has anyone read this paper; https://bmjopen.bmj.com/content/12/12/e060172 and then dived deep into what they say; and allowed themselves to be confronted by the hidden implications?
There seem to be deep and hidden hands behind every study? Can you publish anything that does not conform to someone else's narrative? (and likely they are much more powerful than you.)
Some find it hard to believe anything in a journal;
for me, the words of Marcia Angell ring incessantly in my ears "It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines";
and she wrote that in 2009.
You might be less impressed with the original TACT results if you had been following it from the beginning, as we at SBM have. Dr. R. W. Donnell did what I like to call a "magical mystery tour" of some of the clinical sites where TACT was carried out. He found a variety of quack clinics and made some observations that suggest that blinding might have been compromised at some of these sites.
For example:
https://doctorrw.blogspot.com/2006/08/magical-mystery-tour-of-nccam.html
An excerpt:
The first stop on our tour is Tequesta Family Practice, Tequesta Florida. Among the alternative practices featured there are heavy metal analysis for chronic fatigue, intravenous infusion of vitamins and minerals for chronic fatigue, evaluation and treatment of “dysbiosis”, evaluation of colonic “ecology” by various culturing techniques, intravenous colchicine infusion for spinal disk herniation and, of course, chelation therapy.
<blockquote>The clinic’s uncritical promotion of chelation raises questions about the objectivity and scientific qualification of the investigators. Chelation therapy is touted by the clinic as “one of the premier anti-aging therapies” and as useful for scleroderma, Alzheimer’s disease, rheumatoid arthritis, multiple sclerosis and porphyria.</blockquote>
I wrote about it in 2006, as the study was being done, and my post includes links to all of Dr. RW's posts on individual sites.
https://sciencebasedmedicine.org/the-result-of-the-trial-to-assess-chelation-therapy-tact-as-underwhelming-as-expected/
Seriously, we at SBM predicted that the results would be equivocal. Kimball Atwood, for instance:
https://sciencebasedmedicine.org/the-trial-to-assess-chelation-therapy-equivocal-as-predicted/
This is really interesting:
"An initial P value between 0.001 and 0.005 in a trial implies only a 58% chance of getting P< 0.05 upon attempted replication. It’s even more unreliable in the stratum of -p-values of 0.01-0.05 is only 37%."
Did the Cochrane people find this out empirically by examining their database? I understand that probability experts have mathematical demonstrations that show that even a P-value itself has its own P-value. So maybe the conventional 0.05 is way too high for "statistical significance."
Cool story that a layman can understand. Thanks!
Some of us were not "stunned" by the TACT results. Using common sense analysis almost anyone could come to the conclusion that the results were meaningless. My advice on reading medical studies is to look at the raw numbers and use your common sense to decide whether the differences between outcomes for the control and experimental groups have any practical significance. Measures of statistical significance may be quite misleading. It is also very disappointing to see articles that repeatably use relative risk reduction figures and never mention actual risk reduction. Any person of average intelligence can employ this method in order to decide whether the study is of any practical use.
Some MDs have a financial stake in chelation; we have clinics here in Canada already promising it will cure positively everything & they're raking in the profits with off-label use. Thankfully the NIMH canceled the "chelation-autism" study on children before it ran, due to risks to participants. We need to consider risk for adult participants too. Time for funders to move on --& for regulators to take action on exploitative off-label clinics.
I hope Lamas will continue research based on his TACT 1 and 2 findings. He collected a lot of information this article wouldn't have space to share. Speaking of, I really enjoyed rradong it:) Thank you.
If TACT 2 was underpowered as you say, then that means that the results of TACT 2 are inconclusive. There may or may not be an effect! I liked the conclusion of yours:- "The main lessons here are humility and skepticism."
Very nice article John. I just take issue with the need to use the words 'positive' and 'negative'. To say that TACT 2 is negative or is not positive is minimally informative. The data are consistent with a 24% event rate reduction with chelation therapy, so the data in this too-small-N study are most consistent with the need for TACT 3 that should be combined with TACT 2 to provide a definitive answer. And trialists who continue to not think of learning as sequential but keep designing fixed-N studies need to take a close look at Bayesian sequential trials, e.g. at https://hbiostat.org/bayes/bet/design . Bayesian sequential designs do not pretend that we know the value of N.
The article would have been better had the confidence interval been in the first sentence.
In general, the medical literature is littered with poorly designed studies that have closed the doors on potential therapies. Some of them prematurely. Conversely the medical literature is littered with studies that are well funded and propelled treatments far beyond the science. Science is a winner when the pursuit of knowledge isn’t so deeply coupled with billion dollar interests.
I think I need the 'Chelation For Dummies' version. 🤔🥴🤣