Chelation therapy reduces cardiovascular events for older patients with diabetes

In My Humble Opinion
41

You could also look at Dr. Gorsi’s April 2013 followup and examine the problems he documented with the TACT study. He notes that the study investigators initially cited a barely statistically significant overall effect of chelation on cardiovascular outcomes. Now we have a statement from the study authors indicating they went back and combed the data to find a particular subgroup (diabetics) who supposedly had a more impressive decline in negative cardiovascular events. This announcement does not address other criticisms of TACT methodology, including the fact that heparin and other substances contained in chelation fluid were not present in control fluid. It also does not explain any mechanism by which diabetics might benefit but others wouldn’t. This increases the possibility of an anomalous result which may not be repeated in followup studies (a phenomenon we have seen for multiple other interventions). So the cautionary comments by other observers seem prudent to me as well.

Remember that prior reviewers have found no significant benefit in chelation for cardiovascular disease, including the respected independent Cochrane Collaboration. From a review published in 2008:

“Chelation therapy for atherosclerotic cardiovascular disease
Not enough evidence about the effects of chelation therapy to reduce blockages in the blood vessels of people with atherosclerotic cardiovascular (heart and circulation) disease. Atherosclerosis is caused by fatty deposits sticking to the inside of people’s arteries and restricting blood flow. People with blocked arteries are more likely to have strokes and heart attacks, and can often only walk short distances before their legs begin to ache. Chelation therapy involves infusions into the bloodstream of substances believed to remove metals from the blood. This is promoted to people with atherosclerotic heart and circulation disease as a way of breaking down the blockages in their blood vessels. However, the review found there is not enough evidence from trials about the effects of this treatment.”

Beyond the limited evidence presented in the latest TACT re-review and the need to confirm these findings in subsequent research by other investigators, it should be remembered that chelation is a potentially risky therapy that has been abused by quack practitioners who claim benefits beyond its known usefulness in heavy metal toxicity. Before giving these people added license to promote their quackery, it is necessary to be cautious about cardiovascular uses which remain unproven for general practice. It’s not as if we are totally bereft of interventions to lower cardiovascular diseases risk, or other promising avenues of research.

42

First of all, I’m pretty sure that comment is in error. Fat doesn’t ‘stick’ or get deposited on arterial walls. My understanding is that macrophage cells infiltrate the epithelium and they’re the one’s that contain the oxidized lipids that make up the fatty deposits - but I could be wrong about that. It’s been a while since I’ve seen anything about the precise mechanism behind atherosclerosis so if anyone has something on that, please contribute.

Aside from that though, certainly the mechanism behind this result has to be sussed out. It may well be, as I’ve already said, that the connection to chelation therapy is only tangential. But there seems to be a solid result here. I don’t think there’s any way to avoid that conclusion.

43

Actually, it does.

“The clinical events resulting from atherosclerosis are directly related to the oxidation of lipids in LDLs that become trapped in the extracellular matrix of the subendothelial space. These oxidized lipids activate an NFκB-like transcription factor and induce the expression of genes containing NFκB binding sites. The protein products of these genes initiate an inflammatory response that initially leads to the development of the fatty streak. The progression of the lesion is associated with the activation of genes that induce arterial calcification, which changes the mechanical characteristics of the artery wall and predisposes to plaque rupture at sites of monocytic infiltration.”

http://circ.ahajournals.org/content/91/9/2488.long

I find it striking that even though multiple previous studies and a recent independent review found no significant benefit for chelation in cardiovascular disease, you’re sure that this one study interpretation changes everything and don’t seem to concede the possibility that further research will debunk it.

44

That article is 20 years old and I understand that the beginnings of arterial deposits are due to cellular damage (inflammation). That’s why I believe immune cells like macrophages are involved.

45

Here you go. This from Nature Medicine and from May of this year. I was a little off the mark but not by much. Note the bolded text, emphasis supplied. From the abstract:

46

Yes inflammation is involved early … and atherosclerotic plaques contain lipid (fat) compounds deposited within (stuck to) the vessel wall.

There are plenty of ways to avoid the conclusion that this is a solid result. The critiques are reasonable. Combing data after the fact looking for subgroups that hit 95% confidence interval will find that 1 out of 20 subgroups randomly do that. As pointed out with the control used the study may merely show the effect of heparinization. The data is very weak, not striking. It may be true and it is suggestive. The fact that it fits with a body of research showing the benefit of decreasing iron stores by other, less risky and less costly, means, does lend it some credence. Of course it also lends some WTF to it as well: if you can accomplish the same benefit in a no cost much lower risk means that also provides benefits to others why even consider this riskier more costly stuff?

47

You’re talking about statistical significance and that’s not very impressive. After all, there are lies, damned lies and statistics. A 50% reduction in any subgroup unless you’ve obviously and deliberately done some gerrymandering is.

48

No, it is not. What’s the confidence interval?

Put it this way - flipping two sets of coins 4 times. One I have sprinkled special dust on. One comes up all heads. the other comes up two of each. Does that 50% reduction in one arm mean that my special dust is effective?

Now take that one step further. I’ve flipped 16 sets of those sets of coins 4 times each, each with a different dust sprinkled on them. I find one that came up all heads. Is that any sort of proof that the dust sprinkled on that set caused the result that was twice as many heads as the average? That’s what they are doing when they retrospectively comb through data. You can do that to generate a hypothesis but it is not testing one.

Again, I find it interesting, suggestive even. And consistent with other data about iron marker levels and lowering iron by blood donation and insulin sensitivity and endothelial reactivity. But that is as far as it goes.

Donating blood based on suggestive data is one thing, the cost is nil, the risk quite low, and the benefits to others real. Chelation therapy on the basis of suggestive data, especially when donation would likely do the same thing if the effect is real, that would be reckless.

49

What exactly are you trying to argue against here, just out of curiosity? Because the fact of the matter is that no matter how you slice it this is a gross anomaly in the data and once you admit to that you have, de facto, admitted to its significance - right?

50

I am arguing against overinterpreting it, against misinterpreting it as a “gross anomaly in the data” when we have no reason to believe it is any such thing. It may be true and it even makes sense to me (in context of lowering iron levels and consistency with the blood donation studies) that it would be. But this study as reported IMHO is not enough to make that case by itself. And if true that would not be enough to advise chelation therapy for that subgroup until it was, in a large enough study, compared head to head with regular blood donation as a lower risk lower cost alternative.

51

I don’t think any responsible physician will recommend something based on one study, so that’s an irrelevant point in my opinion.

And this is incredibly significant. It’s like saying you did a placebo controlled study and the active compound resulted in a 50% decline in cardiovascular events in a certain group and then trying to write that off as an artifact. That just bullshit.

52

You may not be familiar with research into vitamin E and prevention of cardiovascular disease (though I’m sure DSeid is). It was believed that vitamin E supplementation offered significant (or even “incredibly significant”) protection, but studies have offered conflicting results and now suggest a lack of significant beneficial effect (or even enhanced disease risk). For example:

*"The HOPE and HOPE-TOO trials provide compelling evidence that moderately high doses of vitamin E supplements do not reduce the risk of serious cardiovascular events among men and women >50 years of age with established heart disease or diabetes [21]. These findings are supported by evidence from the Women’s Angiographic Vitamin and Estrogen study, in which 423 postmenopausal women with some degree of coronary stenosis took supplements with 400 IU vitamin E (type not specified) and 500 mg vitamin C twice a day or placebo for >4 years [22]. Not only did the supplements provide no cardiovascular benefits, but all-cause mortality was significantly higher in the women taking the supplements.

The latest published clinical trial of vitamin E’s effects on the heart and blood vessels of women included almost 40,000 healthy women ≥45 years of age who were randomly assigned to receive either 600 IU of natural vitamin E on alternate days or placebo and who were followed for an average of 10 years [23]. The investigators found no significant differences in rates of overall cardiovascular events (combined nonfatal heart attacks, strokes, and cardiovascular deaths) or all-cause mortality between the groups. However, the study did find two positive and significant results for women taking vitamin E: they had a 24% reduction in cardiovascular death rates, and those ≥65 years of age had a 26% decrease in nonfatal heart attack and a 49% decrease in cardiovascular death rates.

The most recent published clinical trial of vitamin E and men’s cardiovascular health included almost 15,000 healthy physicians ≥50 years of age who were randomly assigned to receive 400 IU synthetic alpha-tocopherol every other day, 500 mg vitamin C daily, both vitamins, or placebo [24]. During a mean followup period of 8 years, intake of vitamin E (and/or vitamin C) had no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, or cardiovascular morality. Furthermore, use of vitamin E was associated with a significantly increased risk of hemorrhagic stroke."*

Regarding chelation for cardiovascular indications, results from one clinical trial that differ markedly from previous findings and lack an explanatory mechanism (why would only diabetics benefit from chelation?) are not to be relied upon as the final word, and certainly not for changing clinical practice.

Sorry deltasigma, but you’re beginning to sound like JKander in the GD cannabis thread, cherry-picking research fragments and touting them as far more than they actually are.

53

I know I am just repeating myself at this point but really no it is not (bullshit). And this coming from someone who believes that the result is likely real and likely due to the mechanism that causes the same suggestive findings when iron and likely other metals as reduced by means of regular blood donation.
The point deltasigma is that some irresponsible physicians (quacks) are already using this costly risky procedure on real people … it was that fact that apparently motivated the study being funded. So it is not so irrelevant.

54

Then what is with the stats lecture. Don’t talk to me like I’m some ignorant HS freshman. I’ve followed the science press long enough to understand the difference between bullshit press announcement and something significant. So don’t give me bogus examples with flipping coins because THAT is completely inapposite and you know it. That is nothing like a double blind placebo controlled drug trial.

In addition, you of all people should know that all drugs don’t affect all people the same way. So filtering out results by sub-group is not polishing the apple, or however you put it. It would be like saying there is no basis for individualized cancer therapies - which medical science did actually believe for a long time but I guess you guys are finally waking up on that score.

So taking the results and only looking at how diabetics were affected is completely valid and when you do that and see a 40-50% reduction, that is simply extraordinary - as the people at the NIH, not some bunch of quacks have openly stated. So forgive me if I ignore your skepticism and share a drink and happy dance with them.

55

“The people at the NIH” have not said anything about “extraordinary” or “incredibly significant” results. I can’t see where they’ve endorsed that study’s reported findings in any way. All the NIH (or more properly speaking, its alt med division) did is to provide funding for the study, which was carried out by others.

And it apparently needs to be pointed out to you again that even the lead investigator and cheerleader for the study is using caveats like “if supported by future research" and “could point the way towards new treatments to prevent complications of diabetes”.

Real scientists do not go out for drinks and happy dances on the basis of one study. They get back to work. Others examine the data, challenge defects in its interpretation and collection, and if time and money permit, do their own studies to confirm or refute the findings. If you comprehended how the process works and were more familiar with past instances where people were too quick to draw conclusions, you wouldn’t be so fervently jumping on the bandwagon in this particular case.

56

I guess you didn’t read my link very carefully or post 9. As for the rest of your post, I guess you’re not familiar with the phrase ‘waxing poetic.’ :smack:

57

Your post #9 quotes the lead investigator, who is not an employee of the NIH or NCCAM.

The director of NCCAM (quoted in the news release) is even more cautious than the lead investigator, saying “Although subgroup analyses of clinical trials do not provide definitive answers, they are very useful in identifying future research questions”.

If she is boozing it up and dancing the can-can, it’s too subtle for me. :slight_smile:

58

Since you don’t think the chief of cardiology at Miami Mount Sinai is worth a quote, how about these 2 from the article which you also must have over looked.

And now the bullshit quote you want to overlook

So yeah. I’m going to go party with these guys. See ya. :stuck_out_tongue:

59

And by the way, that’s all as if to say that a FORTY TO FIFTY PERCENT REDUCTION by itself wasn’t enough of a wake up call. Unbelievable. Because despite all the bullshit I’m reading from you gurus here, guess what. IT IS. :smack: :smack: :smack:

60

If you walk like a duck …

Post hoc analysis is not the same as a double blind placebo trial.

Let’s highlight your quotes a bit differently:

Your second is not an experts quote but the article writer. The next is the author of the paper who does not count as a potential critic of it. Yes, Lamas thinks his research is great. News at 11.

And then the other quote in the article,

I get that you think this is an amazing finding and will brook no critical analysis of it, believing that our shared skepticism is bullshit. You are welcome to ignore the skepticism that many of the rest of us have regarding the significance of this study. Dance happily. I am, I believe, the closest to believing that it is most likely true. The unfortunate thing being that this “finding” will be used by quacks to justify putting more people at risk and fleecing them of their money when, IMHO, likely donating a pint of blood two or three times a year would do them more good and help others in the process. I personally see no value in drinking to that but YMMV. I think the people you’ll find in the bar with you are those who will be using this to sell their snake oil but hey, have fun!