Folic acid and B12 not effective in secondary prevention

The discussion of the Linus Pauling vitamin C/lysine invention for chronic scurvy

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godsilove

Folic acid and B12 not effective in secondary prevention

Post Number:#1  Post by godsilove » Tue Jun 22, 2010 11:30 am

In this week's JAMA:

Context Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal.

Objective To assess the effects of reducing homocysteine levels with folic acid and vitamin B12 on vascular and nonvascular outcomes.

Design, Setting, and Patients Double-blind randomized controlled trial of 12 064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008.

Interventions 2 mg folic acid plus 1 mg vitamin B12 daily vs matching placebo.

Main Outcome Measures First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization.

Results Allocation to the study vitamins reduced homocysteine by a mean of 3.8 µmol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B12 vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]).

Conclusion Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B12 supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence.


More information about the SEARCH trial can be found here:
http://www.searchinfo.org/

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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#2  Post by Johnwen » Tue Jun 22, 2010 3:51 pm

“This new work reinforces the fundamental importance of lowering LDL cholesterol as much as we can in our fight against heart disease and strokes.
“All the evidence now points to lower is better as far as LDL cholesterol is concerned, provided that this can be achieved safely.
For people who already have evidence of a circulatory problem and are at risk of further problems, doctors should now aim to get their LDL cholesterol as low as possible.
We have not found a lower limit of LDL cholesterol below which lowering it further isn’t worthwhile and safe.”


I hope the people who came to these conclusions actively and aggressively follow their own advice. In a short matter of time they will surely eliminate themselves from making such reckless and homicidal advice, Then the world will be free to understand the true cause of heart and circulatory disease. Free of these babbling idiots feeding their garbage, while trying to line their pockets with blood money.
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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#3  Post by godsilove » Tue Jun 22, 2010 5:49 pm

Johnwen wrote:
“This new work reinforces the fundamental importance of lowering LDL cholesterol as much as we can in our fight against heart disease and strokes.
“All the evidence now points to lower is better as far as LDL cholesterol is concerned, provided that this can be achieved safely.
For people who already have evidence of a circulatory problem and are at risk of further problems, doctors should now aim to get their LDL cholesterol as low as possible.
We have not found a lower limit of LDL cholesterol below which lowering it further isn’t worthwhile and safe.”


I hope the people who came to these conclusions actively and aggressively follow their own advice. In a short matter of time they will surely eliminate themselves from making such reckless and homicidal advice, Then the world will be free to understand the true cause of heart and circulatory disease. Free of these babbling idiots feeding their garbage, while trying to line their pockets with blood money.


Just because they have not found it does not mean it does not exist.

But what does this have to do with folic acid and B12?

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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#4  Post by ofonorow » Wed Jun 23, 2010 2:12 am

Wait a minute, this "new work on folic acid and B12" reinforces the importance of lowering cholesterol?? My brain hurts...

Just because they have not found it does not mean it does not exist.

But what does this have to do with folic acid and B12?


And what does folic acid and B12 have to do with heart disease? According to Pauling and Levy and Bush - not much.
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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#5  Post by Johnwen » Wed Jun 23, 2010 8:48 am

I don't know either but heres the results PDF of this study. It went from saying this to saying that about something not relavent to the study ??? I read it and my brain started hurting too!!


http://www.ctsu.ox.ac.uk/~search/result ... 091108.pdf
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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#6  Post by godsilove » Wed Jun 23, 2010 10:37 am

ofonorow wrote:Wait a minute, this "new work on folic acid and B12" reinforces the importance of lowering cholesterol?? My brain hurts...


The SEARCH trial had a factorial design, and aimed to answer two main questions: whether high-dose simvastatin is more effective than low-dose simvastatin in preventing coronary events, and whether folic acid + B12 is also effective in reducing coronary events. The JAMA paper from this week is addressing the latter question. The quote you have pulled is addressing the results from the statin portion of the study.

And what does folic acid and B12 have to do with heart disease? According to Pauling and Levy and Bush - not much.


Studies have shown that people with higher levels of homocysteine in their blood have a higher risk of coronary events. This study aimed to establish whether that link is causal, and if lowering homocysteine artificially would be beneficial.

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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#7  Post by ofonorow » Thu Jun 24, 2010 3:19 am

Studies have shown that people with higher levels of homocysteine in their blood have a higher risk of coronary events. This study aimed to establish whether that link is causal, and if lowering homocysteine artificially would be beneficial.


I have seen many studies, or at least reports, over the years, and none have shown that artificially lowering Hsc is all the beneficial. So if this is new, it isn't really news. (But if this got mixed up with a statin study, who knows how legit the results are?)

Hsc is apparently like cholesterol, that is, a SYMPTOM of CVD. We should all know that treating symptoms rarely cures anything. (Too bad all this work, money and effort can't be directed at finding out whether the Pauling therapy has any value. Why not spend the time and effort studying a theory proposed by the world's ONLY 2 -time unshared Nobel prize winner? Why not study what Pauling/Rath claim is the CAUSE of CVD, and his suggested treatment?!? Bizzaro world.)
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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#8  Post by bbtri » Thu Jun 24, 2010 3:46 am

Interesting that the study shows homocysteine is a marker for increased risk, but not a cause. It would be good to know what factor(s) raise homocysteine along with cardiovascular risk. Inflammation? The presumption also seems to be that cholesterol is causal rather than a marker for risk. Are there well designed studies proving causality rather than association for cholesterol?
Another interesting note: Since these studies love to trumpet big numbers, the higher statin dose had 17.7 times the incidence of the "‘myopathy’ muscle problem", or a relative risk increase of 1770%, vs. a cardiovascular risk reduction of 6%.

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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#9  Post by godsilove » Thu Jun 24, 2010 3:17 pm

ofonorow wrote:
Studies have shown that people with higher levels of homocysteine in their blood have a higher risk of coronary events. This study aimed to establish whether that link is causal, and if lowering homocysteine artificially would be beneficial.


I have seen many studies, or at least reports, over the years, and none have shown that artificially lowering Hsc is all the beneficial. So if this is new, it isn't really news. (But if this got mixed up with a statin study, who knows how legit the results are?)


Keep in mind that this study was started several years ago, and yes, in the time since it was started there have been other studies which have shown that lowering homocysteine through supplementation has not been an effective strategy. So yes, the outcome is not surprising, but I believe this is the longest and largest study to date looking at this issue and it probably puts the nail in that coffin. Also, it may not be "news" because the findings were reported at a medical conference about a year ago and you may have heard about it then.

Hsc is apparently like cholesterol, that is, a SYMPTOM of CVD. We should all know that treating symptoms rarely cures anything. (Too bad all this work, money and effort can't be directed at finding out whether the Pauling therapy has any value. Why not spend the time and effort studying a theory proposed by the world's ONLY 2 -time unshared Nobel prize winner? Why not study what Pauling/Rath claim is the CAUSE of CVD, and his suggested treatment?!? Bizzaro world.)


I came across this article which is an interesting read because it's an interview with someone who one of the pioneers of this hypothesis (and may have some parallels with the Pauling/Rath hypothesis):
http://www.chiro.org/nutrition/FULL/Kil ... y_MD.shtml


In science, determining causality is never an easy task, especially when complex biological systems are involved. There was some evidence to suggest that that the association between homocysteine levels could be causal, e.g. patients with homocystinuria often have thrombotic complications, as well as animal studies.

I should point out that even though a number of trials have failed to support the hypothesis that lowering homocysteine through B-vitamin supplementation can reduce cardiovascular events, they don't necessarily falsify the hypothesis that high levels of homocysteine can cause cardiovascular disease. It is still possible that chronic high levels of homocysteine can result in cardiovascular disease, but that the effects are irreversible (hence supplementation after the fact may not reduce risk). It is also possible that B vitamins increase CV risk through an independent mechanism which nullifies the benefit of lowering homocysteine. I'm not saying that any of these explanations are likely, but just to illustrate that it's not always straightforward (if new evidence convincingly showed that alternative explanations could account for the failure of these trials, the homocysteine issue may have to be approached with a different strategy).


Now with regards to Pauling's hypothesis that "chronic scurvy" is the cause of heart disease - the evidence is hardly compelling, in my view. Pauling has never shown that "chronic scurvy" actually exists in humans. Vitamin C has already been tested in randomized trials, and in doses of 500 mg it has not been effective in unselected populations (thus it suggests that epidemiological studies only show a correlation between low levels of ascorbate and heart disease and aren't showing a causal link). Of course, it doesn't mean that 18 grams of vitamin C per day isn't effective - but at this point, there's little published evidence to show that it would be. The fact that Pauling has two Nobel prizes is irrelevant.

Now, it's possible that vitamin C could be effective in a select group of patients (e.g. those with high Lp(a)). Maybe it needs to be given with lysine, and maybe it needs to be administered in high doses to have a substantial effect on Lp(a). But at this point - and correct me if I'm wrong - there is no published study showing that Pauling therapy substantially reduces Lp(a) levels. So at this moment in time, there's no justification for a large study in hundreds of patients. But given the recent evidence supporting the hypothesis that Lp(a) plays a causal role, there may be justification for a small trial designed to see if Lp(a) levels can be reduced with Pauling therapy. If the trial is positive, it may provide justification for a larger trial designed to see if using this strategy in patients with high Lp(a) levels will reduce the risk of cardiovascular events.

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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#10  Post by ofonorow » Fri Jun 25, 2010 4:46 am

bbtri - good find! I love the 1770 relative risk on high dose statins!

In science, determining causality is never an easy task, especially when complex biological systems are involved. There was some evidence to suggest that that the association between homocysteine levels could be causal, e.g. patients with homocystinuria often have thrombotic complications, as well as animal studies.

I should point out that even though a number of trials have failed to support the hypothesis that lowering homocysteine through B-vitamin supplementation can reduce cardiovascular events, they don't necessarily falsify the hypothesis that high levels of homocysteine can cause cardiovascular disease. It is still possible that chronic high levels of homocysteine can result in cardiovascular disease, but that the effects are irreversible (hence supplementation after the fact may not reduce risk). It is also possible that B vitamins increase CV risk through an independent mechanism which nullifies the benefit of lowering homocysteine. I'm not saying that any of these explanations are likely, but just to illustrate that it's not always straightforward (if new evidence convincingly showed that alternative explanations could account for the failure of these trials, the homocysteine issue may have to be approached with a different strategy).


Again, here is where a comprehensive theory helps make sense out of the data. If homocysteine (like cholesterol) was a cause of cardiovascular disease, one would expect the effect to be random and fairly distributed throughout the cardiovascular system. For example, one would expect to see higher levels of plaque/CVD where the blood pools and slows. But it is just the opposite. Plaque usually forms close to the heart, where the pressure and forces are the greatest. This is what made Willis (and later others) believe CVD was caused by physical stress (plaque is the body compensating for weakness) and this is the basis of the Pauling/Rath unified theory. It is based on the understanding of what would make the arteries weak (lack of collagen caused by a lack of vitamin C).



Now with regards to Pauling's hypothesis that "chronic scurvy" is the cause of heart disease - the evidence is hardly compelling, in my view. Pauling has never shown that "chronic scurvy" actually exists in humans. Vitamin C has already been tested in randomized trials, and in doses of 500 mg it has not been effective in unselected populations (thus it suggests that epidemiological studies only show a correlation between low levels of ascorbate and heart disease and aren't showing a causal link). Of course, it doesn't mean that 18 grams of vitamin C per day isn't effective - but at this point, there's little published evidence to show that it would be. The fact that Pauling has two Nobel prizes is irrelevant.

Now, it's possible that vitamin C could be effective in a select group of patients (e.g. those with high Lp(a)). Maybe it needs to be given with lysine, and maybe it needs to be administered in high doses to have a substantial effect on Lp(a). But at this point - and correct me if I'm wrong - there is no published study showing that Pauling therapy substantially reduces Lp(a) levels. So at this moment in time, there's no justification for a large study in hundreds of patients. But given the recent evidence supporting the hypothesis that Lp(a) plays a causal role, there may be justification for a small trial designed to see if Lp(a) levels can be reduced with Pauling therapy. If the trial is positive, it may provide justification for a larger trial designed to see if using this strategy in patients with high Lp(a) levels will reduce the risk of cardiovascular events.


You are entitled to your opinion, and your opinion is apparently shared by most everyone in medicine (who just happen to be part of a business making billions from the treatment of CVD.) Yes, Pauling's prizes are irrelevant, but it is a different thing for Linus Pauling to have made this claim, than for say, Owen Fonorow to make such a claim. He may have been wrong. Why has there been ABSOLUTELY NO PUBLICITY in the mainstream media that he made this claim?

I am confused. There is justification for a large study of vitamin B12 and folic acid, but not for investigating vitamin C? You seem pretty selective, considering that there is considerable evidence - when blood levels are actually measured - that low vitamin C does increase mortality, particularly cardiovascular mortality. http://www.ncbi.nlm.nih.gov/pubmed/14594788?dopt=Abstract I know of no such evidence for Hsc/B vitamins, for example.

As for chronic scurvy, take your head out of the sand. It is the number one killer in the United States, and probably the world! (I gather you haven't bothered to read Levy's STOP AMERICA'S #1 KILLER).

But of course, given the billions involved, one could argue that the livelihoods of almost everyone in medicine is at stake, thus I would expect you (and most doctors) to be thoroughly confused. That is apparently the intention of some very smart people.

Too bad this attitude dooms a lot of people, many of them all too young, to a lot of suffering.

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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#11  Post by Johnwen » Sat Jun 26, 2010 4:25 pm

Homocysteine plays a role in cadiovascular disease in that it blocks the production of Nitrous Oxide which prevents the arteries from relaxing causing stress on the endothiel lining which can break down any weakened areas causing the healing cascade of events to occur. So homocysteine dosen't directly cause the breakage but contributes to the chemical reactions which can lead to higher pressure traumas of the arteries. Homocysteine is a contributing factor in insulin resistance also. It's been discussed that this factor has cardiac implications also.
Doctors are bewildered by some people who they try all kinds of BP meds on and none seem to work within the prescriped guidelines and diruretics seem to be the only course of treatment only to find out after awhile they stop working also. L-Arginnine doesn't work either. Bewildering No! Lowering of the homcysteine stops the chain of events and allows the arteries to return to their responsive state. Homocysteine causes heart disease? NO! Contributes? YES!
Here's a couple of links that show how this happens. Very Techy but readable.

http://en.wikipedia.org/wiki/Asymmetric ... ylarginine

http://en.wikipedia.org/wiki/Dimethylar ... ohydrolase
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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#12  Post by bbtri » Sun Jun 27, 2010 5:16 am

Johnwen wrote: Doctors are bewildered by some people who they try all kinds of BP meds on and none seem to work within the prescriped guidelines and diruretics seem to be the only course of treatment only to find out after awhile they stop working also. L-Arginnine doesn't work either.

Actually, sustained release arginine does lower BP in hypertensive individuals, but doesn't lower normal BP.
http://www.ncbi.nlm.nih.gov/pubmed/16597191
Regular arginine gets metabolized so quickly the effect is only transient.

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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#13  Post by ofonorow » Sun Jun 27, 2010 5:18 am

Homocysteine plays a role in cadiovascular disease in that it blocks the production of Nitrous Oxide which prevents the arteries from relaxing causing stress on the endothiel lining which can break down any weakened areas causing the healing cascade of events to occur.


Thanks. Again, this illustrates how theory can help make sense of the data.
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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#14  Post by w6nrw » Sun Jun 27, 2010 6:12 am

For clarity--and my sub-optimal understanding--could someone
please break down the following sentence:

"Homocysteine plays a role in cadiovascular disease in that it blocks the production of Nitrous Oxide which prevents the arteries from relaxing causing stress on the endothiel lining which can break down any weakened areas causing the healing cascade of events to occur".

Thanks
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Re: Folic acid and B12 not effective in secondary prevention

Post Number:#15  Post by Johnwen » Sun Jun 27, 2010 11:19 am

Actually, sustained release arginine does lower BP in hypertensive individuals, but doesn't lower normal BP


In an ADMA + individual l-arginine will have no effect. If you read the article you posted you see that it says HEALTHY individuals with high Blood Pressure. This precludes individuals who have no responce to BP meds which presents as a problem. In a normal person with proper endothiel function L-Arginine will lower their BP.

http://www.ncbi.nlm.nih.gov/pubmed/19820234
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