![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 17 to 41 of 54. Go back in thread:
Posted by Klavot on March 26, 2007, at 11:06:27
In reply to Re: correction » Squiggles, posted by Larry Hoover on March 26, 2007, at 8:52:26
> With respect to your assertions vis a vis morbidities associated with the two realms, standard and alternative medicines, there is no comparison at all. I know of no deaths attributed to anything but intentional overdose associated with any alternative product, except those cases associated with contaminants arising from the greed of fast-buck operators (e.g. kava kava products with hepatic toxins, the contaminated tryptophan from the early 90's). Contrast the latter with Internet drug sellers, if you want a valid comparison. A woman just died in B.C. from Internet anxiety meds. Mainstream alternative medicine is safer than mainstream medical science, IMHO, and by a great margin. Consider the withdrawal of Serzone due to fulminant liver failure. Yet, that is still listed as a side effect, rather than a toxic effect. Semantics influence the comprehension and interpretation of the event. We allow pharmaceutical drugs to have side effects, yet we assert toxic effects to nutrients. That's bias, plain and simple.
Perhaps there are very few sequelae and mortalities in orthomolecular medicine simply because very few people actually use true megadose quantities of micronutrients. If millions of people had to start taking intravenous Vitamin C at doses of 150 g / day, as some orthomolecular therapists advocate, I suspect things might be different.
I agree that orthodox treatments have more side-effects and carry greater risks than alternative treatments. But this argument does not factor the greater efficacy of orthodox medicine. I believe that given two populations, one of which uses exclusively orthodox medicine and the other using exclusively alternative medicine, the population using orthodox medicine would have a far superior health profile. It is misleading to suggest that alternative medicine is safer than orthodox medicine. It's like saying vitamin C has fewer side-effects than chemotherapy and then trying to demonise chemotherapy for having so many side-effects. Yet it is the cancer patient receiving chemotherapy who has the greater likelihood of survival, rather than the patient opting for Vitamin C supplementation.
Klavot
Posted by Larry Hoover on March 26, 2007, at 11:10:18
In reply to Re: correction, posted by Klavot on March 26, 2007, at 10:35:32
> > All I hear in your intent to go silent is the sound of a closed mind.
>
> Asking for evidence of safety and efficacy before pursuing a particular treatment modality is not closed minded.
>
> KlavotI agree. If there is a pursuit taking place. And if the evidence is considered.
Lar
Posted by Larry Hoover on March 26, 2007, at 11:37:26
In reply to Re: correction, posted by Klavot on March 26, 2007, at 11:06:27
> > With respect to your assertions vis a vis morbidities associated with the two realms, standard and alternative medicines, there is no comparison at all. I know of no deaths attributed to anything but intentional overdose associated with any alternative product, except those cases associated with contaminants arising from the greed of fast-buck operators (e.g. kava kava products with hepatic toxins, the contaminated tryptophan from the early 90's). Contrast the latter with Internet drug sellers, if you want a valid comparison. A woman just died in B.C. from Internet anxiety meds. Mainstream alternative medicine is safer than mainstream medical science, IMHO, and by a great margin. Consider the withdrawal of Serzone due to fulminant liver failure. Yet, that is still listed as a side effect, rather than a toxic effect. Semantics influence the comprehension and interpretation of the event. We allow pharmaceutical drugs to have side effects, yet we assert toxic effects to nutrients. That's bias, plain and simple.
>
> Perhaps there are very few sequelae and mortalities in orthomolecular medicine simply because very few people actually use true megadose quantities of micronutrients.Orthomolecular is not synonymous with megadose. Quite the contrary. First coined by Pauling, it was originally defined as "the right molecule, in the right dose". He later expanded the meaning to "the treatment of disease by the provision of the optimum molecular environment, especially the optimum concentrations of substances normally present in the human body" or as "the preservation of good health and the treatment of disease by varying the concentrations in the human body of substances that are normally present in the body and are required for health."
> If millions of people had to start taking intravenous Vitamin C at doses of 150 g / day, as some orthomolecular therapists advocate, I suspect things might be different.
Considering the proper definition of orthomolecular medicine, this then becomes a straw man argument. Millions of people would not be candidates for such treatment.
> I agree that orthodox treatments have more side-effects and carry greater risks than alternative treatments. But this argument does not factor the greater efficacy of orthodox medicine. I believe that given two populations, one of which uses exclusively orthodox medicine and the other using exclusively alternative medicine, the population using orthodox medicine would have a far superior health profile.
Please permit us to reach different conclusions. Moreover, this dichotomy is really a false dilemma, as orthomolecular medicine does not exclude pharmaceuticals, and conventional medicine does not preclude the precepts of orthomolecular practise.
> It is misleading to suggest that alternative medicine is safer than orthodox medicine. It's like saying vitamin C has fewer side-effects than chemotherapy and then trying to demonise chemotherapy for having so many side-effects. Yet it is the cancer patient receiving chemotherapy who has the greater likelihood of survival, rather than the patient opting for Vitamin C supplementation.
Orthomolecular approaches are best seen as complimentary practises. It needn't be seen as an either/or proposition.
Lar
Posted by Larry Hoover on March 26, 2007, at 11:50:09
In reply to Re: correction, posted by Klavot on March 26, 2007, at 10:48:10
> Medical science vilifies alternative medicine because it is unscientific. As and when alternative practitioners provide empirical evidence that their treatments work and are safe, those treatments cease being alternative and become evidence-based and orthodox.
>
> KlavotIt's not that simple or straight-forward, as I've tried to demonstrate. The graphical representation of the AROI curves was intended to demontrate that there are different rules being applied to nutrients than to other substances. Nutrient intake recommendations are based on symptoms of clinical deficiency, whereas pharmaceutical drugs are judged on symptoms of toxicity. The whole concept of orthomolecular medicine is based on getting into the AROI. Properly applied, toxicity is not relevant. That there are improper (i.e. toxic) applications does not invalidate the AROI concept.
Standard medical wisdom has it that a balanced diet will provide the RDA of all essential nutrients. As I expressed quite clearly, the RDA is itself based on clinical signs of deficiency syndromes, rather than optimal functioning. However, simply ignoring that issue, upon spending many years of effort, I have yet to find evidence that any diet (restricted to reasonable caloric intake) can even meet the nutrient RDAs. I have posted this as a challenge on newsgroups such as sci.med.nutrition, and no one has ever shown that I am wrong. There is no such thing as a balanced diet that meets all known RDAs. It cannot be done even for a single day, let alone providing for a diet with choices of menu items.
One poster developed a spreadsheet of the entire USDA nutrient database, and failed to find even one combination that met the 17 RDAs that were in the database. There are now over 30 nutrients with RDA values.
Lar
Posted by Squiggles on March 26, 2007, at 19:37:13
In reply to Re: neighbourhood, posted by Klavot on March 25, 2007, at 9:08:28
I'll have to read up on it; it's an
extremely complex field, beyond my
scientific background to understand. In cases
of deficiency, disabilities are much
easier to understand. I am sure I am not
the only one who sees this as an experimental
enterprise, and there's the rub. Over and out,
honest; :-)Squiggles
Posted by teejay on March 26, 2007, at 20:54:16
In reply to Re: neighbourhood, posted by Squiggles on March 26, 2007, at 19:37:13
Squiggles,
I gave you the benefit of the doubt when you first posted, but after two lengthy threads I've come to the conclusion that you came to this board purely to stir up a reaction of some kind.
Clearly nobody comes to the alternative board to question it with such weak arguments as you did, and more importantly without a solid grounding in the subject matter at hand which you clearly lack.
No offence intended and whatever it is you are looking for, I hope you find it and hope it delivers you all the pleasure you desire (apart from stiring it up on here of course).
TJ
Posted by Squiggles on March 26, 2007, at 21:09:32
In reply to Re: neighbourhood, posted by teejay on March 26, 2007, at 20:54:16
One triple chocolate fudge sundae,
with orthomolecular smarties-
hold the whipped cream!:-)Squiggles
Posted by Klavot on March 27, 2007, at 9:03:34
In reply to Re: neighbourhood, posted by teejay on March 26, 2007, at 20:54:16
I belive the following article is interesting in the context of the present discussion:
http://jama.ama-assn.org/cgi/content/abstract/297/8/842
Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention
Systematic Review and Meta-analysisGoran Bjelakovic, MD, DrMedSci; Dimitrinka Nikolova, MA; Lise Lotte Gluud, MD, DrMedSci; Rosa G. Simonetti, MD; Christian Gluud, MD, DrMedSci
JAMA. 2007;297:842-857.Context Antioxidant supplements are used for prevention of several diseases.
Objective To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials.
Data Sources and Trial Selection We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.
Data Extraction We included 68 randomized trials with 232 606 participants (385 publications).
Data Synthesis When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.
Conclusions Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.
Author Affiliations: The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Bjelakovic, L. L. Gluud, Simonetti, and C. Gluud and Ms Nikolova); Department of Internal Medicine, Gastroenterology and Hepatology, University of Nis, Nis, Serbia (Dr Bjelakovic); and Divisione di Medicina, Ospedale V. Cervello, Palermo, Italy (Dr Simonetti).Klavot
Posted by Meri-Tuuli on March 27, 2007, at 13:40:28
In reply to Re: neighbourhood, posted by Klavot on March 27, 2007, at 9:03:34
I've read that study was flawed in someway (see the text below I've copied and pasted). I personally have no opinion on the matter - I don't have time to check it all out etc etc.
__________________
Today's review of trials on antioxidants in the Journal of the American Medical Association fails the four key tests of 'publication bias'. For the following reasons I suspect it's an attempt to demote vitamin therapy so we keep taking the drugs.The first way to investigate whether an analysis of studies is biased is to read the summary, and see if it correlates with the actual result. The conclusion of this study says 'treatment with beta carotene, vitamin A, and vitamin E may increase mortality' creating the impression these antioxidants are no good. What it fails to say, all of which are clearly shown in the results, is that 'vitamin C given singly, or in combination with other antioxidants, and selenium given singly or in combination with other antioxidant supplements may reduce mortality'. It also fails to say that 'beta-carotene or vitamin A did not show increase in mortality if given in combination with other antioxidants', or that 'vitamin E given singly or combined with 4 other antioxidants did not significantly influence mortality'. If you can have one take home message it is that antioxidants are team players and reduce mortality in combination, and that vitamin C and selenium are more beneficial than beta-carotene or vitamin A.
The next way to investigate whether an analysis is a stitch up is to see if all trials are included, how trials are excluded, and what the trials actually say. Two classic primary prevention studies, where vitamin E is given to healthy people, are those of Stampfer et al, published in the New England Journal of Medicine, the first of which gave 87,200 nurses were given 67mg of vitamin E daily for more than two years. A 40 per cent drop in fatal and non-fatal heart attacks was reported compared to those not taking vitamin E supplements (1). In another study, 39,000 male health professionals were given 67mg of vitamin E for the same length of time and achieved a 39 per cent reduction in heart attacks (2). Guess what? They are not included.
Bjelakovic's analysis goes on to further degrade antioxidants by deciding which trials (usually the positive ones) are high bias, then excluding them, and which trials are low bias (usually the negative ones) and only adding these together. I don't agree with how this is done. For example, it is well known that taking statin drugs, that lower cholesterol and induce CoQ10 deficiency, make vitamin E harmful by turning it into an oxidant. This is an obvious bias but the authors don't even mention this. Once you exclude these trials vitamin E has an overall positive effect.
The next test is to see if the most negative studies were actually negative. These studies can skew results on an overall analysis. One the studies most cited to show increase risk of gastrointestinal cancer is that of Correa et al. So I read the actual paper and contacted the author, Dr Pelayo Correa from the pathology department at the Louisiana State University Health Sciences Centre in New Orleans, and asked about the increased risk he had supposedly found. He was amazed, he said, because his research, far from being negative, had shown clear benefit from taking vitamins.
His study, published in the Journal of the National Cancer Institute, had involved giving people with gastric cancer either beta-carotene, vitamin C or antibiotics to kill off the stomach bacterium Helicobacter pylori. All three interventions produced highly significantly improvements, causing substantial regression of gastric cancer. Correa and his colleagues had concluded: 'dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma'. No evidence of increased mortality there.
In fact, as Correa told us, there was no way the study could show anything about mortality. 'Our study was designed for evaluation of the progress of precancerous lesions,' he said. 'It did not intend, and did not have the power, to study mortality and has no value to examine mortality of cancer.' Without this study the main conclusion, that antioxidants may increase gastrointestinal cancer, becomes completely invalid.
So, I'm afraid this 'meta-analysis' fails all four tests of publication bias. The summary at the front refers to negative results only, not the positive results. Some key positive studies have not been included. Positive studies have become negative studies by jiggling the statistics. Known dynamics that would bias some studies towards a negative effect have been ignored. In conclusion, I will keep doing what I've always been doing, because this study confirms it - and that is to supplement a combination of antioxidants, including selenium and high dose vitamin C, because, as this study says, it seems to make you live longer and reduce your risk of premature death.
Posted by Klavot on March 27, 2007, at 13:52:26
In reply to Re: neighbourhood » Klavot, posted by Meri-Tuuli on March 27, 2007, at 13:40:28
OK OK OK, I give up, you got me.
Posted by Meri-Tuuli on March 27, 2007, at 13:57:16
In reply to Re: neighbourhood, posted by Klavot on March 27, 2007, at 9:03:34
I just want to say some things. My other half is a respected research scientist in his particular field of study. His research area is relatively small - he knows alot of his fellow scientists and has published many papers, including several in Science. I used to work in the scientific journals publishing business too - I had to find reviewers and authors etc.
So. I have come to get to know the academic world somewhat. There are several things I want to point out.
1) One study/published paper does not prove anything - okay it might be true but in general, it takes alot of papers reaching the same conclusions to 'prove' something. Papers can be badly written, with pretty trashy science in them, particulary of the lessor known journals, which can be pretty desperate for material. The so called studies can be made up too - or sort of doctored if you know what I mean. Good journals generally vet this sort of stuff out with good reviewers, but again, reviewers work for free, and often the lessor know journals make do with third rate reviewers, which means that papers get through which shouldn't really make it.
2) Just because an academic researcher is on the faculty of a fancy university doesn't mean he's not a quack. In the field my bf works in, there is a well know prof at Harvard, who is considered a complete Quack by the rest of the scientific community - yet to the layman he isn't.
Conversely, just because a researcher doesn't belong to a uni/whatever, doesn't make him/her any less credible or whatever.
And perhaps people who are considered Quacks now, perhaps some of them just have ideas that aren't accepted by the mainstream? Don't most scientific ideas/theories etc start out as relatively Quack-like? I mean, people laughed when they heard that the Earth revolves around the Sun. People laughed at Darwin, etc etc.
And finally, you probably have to consider the background to which the paper is written - is it funded by Big Pharma? Are the researchers reputable? What other papers have they published?
And so on.Just some thoughts.
Kind regards
Meri
Posted by Meri-Tuuli on March 27, 2007, at 14:04:07
In reply to Re: neighbourhood, posted by Klavot on March 27, 2007, at 9:03:34
I don't know why we can't think of these things as a spectrum - the alternative stuff and the conventional stuff are not so far removed from one another, its just our mindset (and that of the practitioners) is.
I mean, both alternative stuff and conventional stuff should be both practised and should be both intertwined - clearly the altnerative stuff for prevention and general health and the conventional stuff for 'crisis intervention' like a heart attack. But if we can stop the crisis in the first place, by say, eating garlic, being healthy and taking ginkgo, for example, I don't see why this is so hard to comprehend or preach or practise.
Plus I don't see why alternative compounds in plants should be considered so different from conventional drugs -- I think Big Pharma has a big say in this and the subsequent brain washing of Doctors.
I follow the Lar school on this.
Posted by Squiggles on March 27, 2007, at 14:06:59
In reply to Orthomolecular medicine, posted by Klavot on March 27, 2007, at 13:52:26
> OK OK OK, I give up, you got me.
LOL-- i'm sorry to interrupt, but it just
occurred to me that scientific dispute should
not be confused with arm-wrestling.And one more thing -- with one and a half million kids starving in Africa, i think a meal with water, approximating the average nutritional needs, would be scientifically acceptable to them, thank you very much -- you can go to Oxfam.org for that. The orthomolecular research is for the future benefit of mankind - very future.
Squiggles
Posted by teejay on March 28, 2007, at 9:21:09
In reply to Re: Orthomolecular medicine, posted by Squiggles on March 27, 2007, at 14:06:59
You sure do have a lot of 'last words' ;-)
Posted by Larry Hoover on March 28, 2007, at 10:58:36
In reply to Re: neighbourhood, posted by Klavot on March 27, 2007, at 9:03:34
> http://jama.ama-assn.org/cgi/content/abstract/297/8/842
>
> Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention
> Systematic Review and Meta-analysis> Conclusions Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.
I found the full-text version.
http://www.jhsph.edu/welchcenter/_pdf/3_6_07.pdf
Where to start? I cannot believe stuff like this gets published. This product is so biased, it does not even support its published conclusions within its own text. Its basic premises are fatally flawed, methodologically. It's junk science.
A priori assumptions for meta-analysis require that the study groups and study methodology are similar. That's the whole point, to create something of the sort of a larger homogenous group than was available through separate and smaller subject pools, subject to similar control of variables, to increase the power of the discriminant measure(s). Here, primary (healthy people) and secondary (those with diagnosed disease/pathology) prevention trials are lumped together without any rationale for doing so. Disease prevention and disease recurrence are different entities, certainly. Also, a prevention trial is disease-specific. They didn't look at disease outcomes, they looked at all-cause mortality. A car accident would count. Using other people's data for purposes not within the bounds of the intent of the original data collection constitutes the derivation of a new hypothesis. It is not a test of the hypothesis, however, as no control of variables is possible. It is purely speculative.
Another disturbing methodological flaw is the a priori exclusion of all studies in which no subject died. As the analysis was (supposedly) to find correlations between antioxidant supplementation and mortality, excluding 747 trials with no mortality, and analyzing only 68 trials with mortality seems illogical, at best. But apart from a single paragraph in the preamble, I didn't see it mentioned in the discussion. Maybe I missed it.
Another a priori discriminant (with subsequent effects on the statistics), a completely arbitrary separation of trials into two groups which they call low-risk and high-risk, is without any realistic relevance. Does it really matter if subjects took vitamin E or whatever in a double-blind trial environment (as one of the four criteria for risk was applied)? No, it doesn't. So long as some people took it and some people didn't, whether they died or not can't be attributed to placebo effect. All this arbitrary distinction does is provide you with yet another form of data exclusion, which permits derivation of new statistics. If you divide a heterogenous group without significant variation enough times, you will find statistical significance, eventually. This is called data mining, pejoratively, amongst scientists.
Consider yet another a priori decision, with subsequent profound effect on mortality stats....the lumping together of chronic vs. acute exposure. For example, one study in which bed-ridden geriatric patients were given a single injection of 200,000 IU vitamin A is lumped together with data from long-term oral supplementation of healthy people with 2,000 IU/day. Remember, meta-analysis requires similarity of subject pools and methodology, yet the obtained statistical relative risk for vitamin A, by dose, was 1.000006. That was found to be significant, but with the underlying assumptions (or ignorance, as you might alternatively conclude), does that have any relevance to others? Does it warrant inclusion in the abstract?
Now, within the obtained statistics, there is a hierarchy of groups. There is the statistic derived from all data. That would be the main outcome of the study. There are then statistics for the individual antioxidants, but with all data included. Then analyses within those groups for factors influencing the outcomes. And only at the end, was the high-risk/low-risk data exclusion criterion applied. Way down the relevance/validity tree. Here are the study outcomes, in order of validity (notwithstanding the methodological flaws):
"The pooled effect of all supplements vs placebo or no intervention in all randomized trials was not significant (RR, 1.02; 95% CI, 0.98-1.06)."
No harm done. Where is that in the abstract?
Next in line, the individual antioxidants, with dose alone amongst lone variables that led to significant statistics....
"Univariate meta-regression analyses revealed significant influences of dose of beta carotene (RR, 1.004; 95% CI, 1.001-1.007; P = .012), dose of vitamin A (RR, 1.000006; 95% CI, 1.000002-1.000009; P = .003), dose of selenium (RR, 0.998; 95% CI, 0.997-0.999; P = .002), and bias-risk (RR, 1.16; 95% CI, 1.05-1.29; P = .004) on mortality. None of the other covariates (dose of vitamin C; dose of vitamin E; single or combined antioxidant regimen; duration of supplementation; and primary or secondary prevention) were significantly associated with mortality."
So, beta carotene (a single form of provitamin A)/Vitamin A have statistical mortality risk, of 0.4% and .0006%, respectively, *by dose*. Selenium significantly reduced mortality. Do you see that in the abstract? No, it "needs further study". And vitamin E has yet to be implicated. Please also note the other variables which did not obtain significance when regressed alone (i.e. by univariate analysis).
Next, you have the multivariate analyses, which attempt to tease out the variables which significantly influence the collective statistic, from those that don't seem to make a difference one way or the other. We're getting into data mining territory, here. This is where you typically obtain rationale for conducting future hypothesis-testing. We're already beyond the true scope of meta-analysis available from this diverse data-set, but lets see what they find, anyway.
"In multivariate meta-regression analysis including all covariates, dose of selenium was associated with significantly lower mortality (RR 0.998; 95% CI, 0.997-0.999, P=0.005) and low-bias risk trials with significantly higher mortality, (RR, 1.16; 1.05-1.29; P=.005). None of the other covariates was significantly associated with mortality."
Let's start at the last sentence. The mortality risk of beta-carotene and vitamin A do not survive data-mining, no matter how they slice it. No evidence against vitamins C or E, by any measure. Selenium still looks golden, except when the arbitrary data exclusion of "bias risk" is applied. Look at the expansion of the 95% confidence interval following this data exclusion. Heterogeneity has gone way up (larger CI), so the subject pool was drastically reduced, or they were dissimilar in some way.
When bias risk itself was examined, we find significant effects.
"In trials with low-bias risk mortality was significantly increased in the supplemented group (RR, 1.05; 95% CI, 1.02-1.08)", whereas in high-bias trials, "...mortality was significantly decreased in the supplemented group (RR, 0.91; 95% CI, 0.83-1.00)."
What does this mean? One possible variable (of four; they never say which one(s) were applied) is 'absence of blindedness'. Is it inconceivable that people who take a supplement knowing it is good for their health might have a state of mind that is different from someone who is being given a supplement that may be a placebo? I still contend that this data exclusion criterion is arbitrary, and in any case, it has not yet had any influence on the obtained statistics, save that one adverse finding for selenium trials.
The researchers continue to massage the data, however, and obtain some further statistics. Now they consider only whether a supp was used alone or in combination, but not dose.
When we examine the stats, we find that beta-carotene used alone is bad: RR 1.06 (CI = 1.01-1.11), but when combined with other antioxidants, it's okay: RR 1.01 (CI = 0.94-1.08). Only when you further exclude data, i.e. combinations which include selenium, *and* they apply the arbitrary risk criterion, is there any significant risk found in combinatory analyses: RR 1.07 (CI = 1.02-1.11). We already knew you shouldn't take beta-carotene alone. Why were such studies even conducted? Anyway....
When we look at vitamin A, there is no significant risk of using it alone or in combination. That is the main finding. Only when data are excluded, do you see any significant risk. Again, it is when the risk bias is applied, *and* selenium combinations are excluded. Why don't they say that?
I've still yet to see anything about vitamin E being bad. Oh, wait. Vitamin E, alone, in combination, in arbitrarily low or high dose, had no effect on mortality. However, when data are excluded, specifically when the risk criterion *and* selenium combinations are excluded, we see a significant finding of increased mortality. Are you starting to see a pattern here?
Vitamin C? They couldn't find anything. Even when they excluded any data they could. So why does it "need further study"?
Selenium? When used alone and/or in combination, it significantly reduced mortality: RR 0.91 (CI 0.84-0.99), and survived the risk criterion. And they conclude further study is required?
Here, once again, is the published conclusion in the abstract:
"Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study."
In fact, their own evidence shows that selenium reduces mortality, and is an essential component of any antioxidant supplementation regime. Beta-carotene should never be taken alone, but in a combination of antioxidants, it is safe to use. That would be a valid abstract conclusion.
The interdependence of antioxidants is worthy of an entirely separate discussion. For example, vitamin C is required to regenerate oxidized vitamin E. And I've totally ignored the fact that d-alpha-tocopherol (synthetic) is *not* a surrogate for natural vitamin E. d-alpha-tocopherol displaces d-gamma-tocopherol (one of eight structural variations of vitamin E), but fails to accept electrons in the chain reaction in which d-gamma protects membranes from oxidation. It is thus toxic, if absorbed in this synthetic unnatural form, without simultaneous increases in gamma-tocopherol. We haven't even considered beta- and delta-tocopherols, or the tocotrienols (eight more, which some include with tocopherols under the term vitamin E).
Nothing was said here about the absence of cofactors, which explain *why* beta-carotene is toxic if taken alone. It is reductionist science in the extreme, reductio ad adsurdum, to isolate a nutrient and manipulate that sole variable.
Nutrients act like instruments in an orchestra. You can't give cellos to the violinists and expect them to play their role, nor silence all but the percussionists, and expect to hear the melody. What are they thinking? Moreover, what do these experiments collectively demonstrate? That is the real question. If all experiments are methodologically suspect, then GIGO is the only conclusion. We got garbage out, here, without even considering if it was garbage going in.
Lar
Posted by Larry Hoover on March 28, 2007, at 11:02:18
In reply to Re: neighbourhood, posted by Squiggles on March 26, 2007, at 19:37:13
> I'll have to read up on it; it's an
> extremely complex field, beyond my
> scientific background to understand.Then why do you have so much to say?
Lar
Posted by Larry Hoover on March 28, 2007, at 11:05:36
In reply to Re: neighbourhood » Klavot, posted by Meri-Tuuli on March 27, 2007, at 13:40:28
> So, I'm afraid this 'meta-analysis' fails all four tests of publication bias.
Even more reason to dismiss this propaganda out of hand.
Thanks,
Lar
Posted by Larry Hoover on March 28, 2007, at 11:13:45
In reply to A word about Quacks etc, posted by Meri-Tuuli on March 27, 2007, at 13:57:16
> I just want to say some things.
And good things they were.
I've done substantial lit reviews, professionally, and I'd have to say I'm astounded by what gets published. Or how often the abstract is unsupported by the experimental outcomes.
Thanks for your input.
Lar
Posted by Larry Hoover on March 28, 2007, at 11:19:51
In reply to Re: neighbourhood, posted by Meri-Tuuli on March 27, 2007, at 14:04:07
> I mean, both alternative stuff and conventional stuff should be both practised and should be both intertwined - clearly the altnerative stuff for prevention and general health and the conventional stuff for 'crisis intervention' like a heart attack.
Indeed. Who says orthomolecular approaches were to replace anything?
> I follow the Lar school on this.
<grin>
Lar
Posted by Squiggles on March 28, 2007, at 12:21:41
In reply to Re: neighbourhood » Squiggles, posted by Larry Hoover on March 28, 2007, at 11:02:18
It is not I who have so much to say
but you who have so little. Look, I'm a
simple person. Show me the proof that
orthomolecular medicine is superiour
to what we presently practice for affective
disorders (or cancer), and I will say that
you have made a scientific breakthrough in
mental health.Squiggles
Posted by Klavot on March 28, 2007, at 13:01:12
In reply to Re: neighbourhood, posted by Meri-Tuuli on March 27, 2007, at 14:04:07
> I mean, both alternative stuff and conventional stuff should be both practised and should be both intertwined - clearly the altnerative stuff for prevention and general health and the conventional stuff for 'crisis intervention' like a heart attack.
Forget for a moment the issue of orthomolecular medicine. I do not agree with implementing alternative treatments simply for the sake of using alternative treatments. What does "alternative" mean? I would understand "alternative" to be the complement of "conventional", which is to say "evidence-based". Conventional medicine is not static; alternative treatments may become conventional as and when there is evidence to support their safety and efficacy. Likewise conventional treatments may be relegated to the status of "alternative" as and when they are found to be bogus. It is wrong to encourage the use of treatments which have no evidence to back up their safety or efficacy.
Some alternative treatments, for example homeopathy, simply do not work. The principles which underlie homeopathy violate some of the basic laws of chemistry and physics.
If a treatment works beyond placebo, then it should be possible to demonstrate that fact. Most alternative treatments are alternative simply because their practitioners are consistently unable to demonstrate efficacy.
Klavot
Posted by Larry Hoover on March 28, 2007, at 13:14:56
In reply to Re: neighbourhood, posted by Squiggles on March 28, 2007, at 12:21:41
> It is not I who have so much to say
> but you who have so little.Eh? I don't believe I've ever heard anyone say that about me, before this.
> Look, I'm a
> simple person.I'll take your word for it.
> Show me the proof that
> orthomolecular medicine is superiour
> to what we presently practice for affective
> disorders (or cancer)....I've got nothing to say about something I didn't say.
Lar
Posted by Meri-Tuuli on March 28, 2007, at 16:32:42
In reply to Alternative treatments, posted by Klavot on March 28, 2007, at 13:01:12
Well I meant more straightforward 'alternative' practices, like eating garlic to help heart health, taking exercise, or taking ginkgo or fish oils or eating lots of fruits and vegetables, taking vitamin supplements and yes, taking herbs.
Just because something hasn't been documented by the research literature doesn't mean it doesn't have a helpful effect. For instance, lypocene in tomatoes protects against prostate cancer - so if you're worried about that, eat more tomatoes - but this effect was only discovered relatively recently. But tomatoes have been helping people for centuries.....okay tomatoes are hardly an 'alternative' treatment, you see what I'm saying.
I'm not sure where I stand on homopathy. I think in some instances it might be useful - a friend of mine was helped a great deal by homopathy with a skin complaint - but I took some pills for warts and they didn't do a thing! It took a trip to Iceland and bathing in these hydrothermal springs to kill off a nasty wart on my thumb. Anyway I'm rambling!
Kind regards
Meri
Posted by teejay on April 1, 2007, at 19:16:22
In reply to Re: antioxidants and mortality » Klavot, posted by Larry Hoover on March 28, 2007, at 10:58:36
From this months VRP newsletter.........
http://www.vrp.com/art/2067.asp
JAMA’s Antioxidant Study:
An In-Depth Examination of a Flawed Report
VRP Staff
There’s an old saying in statistics: if you torture the data long enough, statisticians can “prove” almost anything. This means that if you exclude certain studies, lump differing kinds of studies together into the same data pool, set up your own criteria as to what is biased and what is not, and otherwise bend the rules, you can produce a study that says whatever you’d like. And that is exactly what the researchers did in an “anti-antioxidant” study published in February in the Journal of the American Medical Association.1
This paper, a meta-analysis produced by a team of Danish, Italian and Serbian researchers, was designed to assess the effects of the antioxidant supplements vitamin A, beta-carotene, vitamin C, vitamin E and selenium on death rates in healthy people and people suffering from a disease or condition. The researchers began with 815 studies, and after excluding 747 of them came to a startling conclusion that contradicted a wealth of existing scientific evidence: not only were these antioxidants ineffective in reducing mortality, treating people with beta carotene, vitamin A and vitamin E might actually increase mortality!
The media quickly printed alarming headlines that claimed that antioxidants were harmful, without stopping to analyze the study or ask experts in the field about the validity of the results. Yet a careful review of this meta-analysis reveals that it is full of flaws and draws an unwarranted, even misleading, conclusion that’s not based on a full analysis of the facts.
Some of the major problems with the JAMA study:
• The study is a meta-analysis, which involves combining the data from existing studies to create a single, large “pool” of data that is then used for statistical analysis. But a meta-analysis is only as good as the studies used to construct it. The stunningly obvious problem with the JAMA study is the exclusion of a massive amount of positive research. Out of 815 studies, 747 studies (a full 91 percent) were excluded, leaving only 68 studies for the statistical analysis. Some 400 studies were rejected because none of the participants in these studies died. But if you eliminate almost half of the studies specifically because there was no mortality, it is unfair to use the small number of the remaining studies to “prove” that antioxidants are deadly.
• The clinical trials used in the study were too diverse. They involved several different synthetic antioxidants, widely varying dosages, different durations of use and different types of volunteers. For example, one of the studies looked at the effects of 200,000 IU vitamin A over the course of a single day—a huge dose used for a ridiculously short amount of time. Yet other studies used moderate doses of antioxidants over a period of years. In addition, many of the studies examined the effects of antioxidants such as lutein and zinc that were not even one of the five nutrients that the meta-analysis was focusing on. Using the data from this jumble of studies to create some sort of conclusion is like using 20 different brands of bricks to build a house which later falls down, then claiming the failure was entirely due to Brand X.
• Some of the studies included in the meta-analysis were treatment trials using synthetic antioxidants, designed to test whether taking an antioxidant might cure heart disease or another serious illness. Studies based on such a simplistic premise are bound to fail. Yet their results were included, giving the false impression of a strong correlation between antioxidants and risk of death.
Professor Balz Frei, Director of the Linus Pauling Institute at Oregon State University, summed it up thusly: “All the new study really demonstrates is a bias toward identifying studies or research that show harm caused by antioxidants, and selective removal of research that shows benefits.”What the Study Didn’t Say About Antioxidants
A large body of scientific evidence has found that taking antioxidant supplements can indeed reduce the risk of serious disease. One of the classic antioxidant studies, published in the New England Journal of Medicine in 1993, tracked for eight years more than 87,000 female nurses, ages 34 to 59, all of whom were free of diagnosed cancer and heart disease at the beginning of the study.2 During the course of the study there were 437 nonfatal heart attacks and 115 deaths due to coronary disease. Upon analyzing the nutrient consumption of the volunteers during the eight-year period, the researchers found that the risk of suffering a heart attack fell by about a one-third in those who consumed the highest amounts of vitamin E, compared to those who consumed the lowest. A companion study compared the amount of vitamin E consumption by 39,910 American male health professionals and found that those who took at least 100 IU per day for at least two years had about a 33 percent lower risk of developing coronary disease than those who did not take vitamin E supplements.3
During the 14 years since the publication of these studies, many other researchers have found strong associations between consumption of antioxidants and a lower risk of heart disease, cancer and other diseases, as well as overall mortality. And just the presence of elevated levels of antioxidants in the blood appears to reduce the risk of suffering from serious ailments. For example:
• In a Japanese study involving 3,016 adults, high serum levels of antioxidant carotenoids (alpha-carotene, beta-carotene and lycopene) were “significantly associated with low hazard ratios for cardiovascular disease mortality.”4
• A 2005 study published in the American Journal of Clinical Nutrition compared the levels of alpha-carotene, beta-carotene and alpha-tocopherol in elderly Europeans. The results of this prospective study indicated “that high plasma concentrations of carotene are associated both with lower mortality from all causes and with cancer in the elderly.”5
• A case-control study, nestled within the European Prospective Investigation into Cancer and Nutrition (EPIC), found that “higher plasma concentration of some carotenoids, retinol and alpha-tocopherol are associated with a reduced risk” of developing gastric cancer.6
• In 2006, Australian researchers found that selenium offered protection against cancer of the colon and rectum, and that dietary levels of vitamins E and C “were statistically significantly protective for both colon and rectal cancer at all levels of consumption, and for both vitamins there was a dose-response effect of increasing protection, particularly so for colon cancer.”7
This is just a small sampling of the large number of antioxidant studies with positive outcomes that have emanated from research centers around the world. Yet very few of these were included in JAMA’s anti-antioxidant meta-analysis, which “proved” antioxidants are harmful. Is it because the researchers decided in advance what the conclusion would be, then cherry-picked studies that would support their view?
Our understanding of antioxidants is still evolving, and there are still gaps in our knowledge. Researchers are currently comparing the effects of natural and synthetic sources of antioxidants, of antioxidants in their different chemical forms, of single antioxidants versus combinations, and of varying doses. However, it is clear that both high levels of antioxidant consumption and high levels of antioxidants in the blood are associated with better health and increased longevity.
Posted by KayeBaby on April 3, 2007, at 5:27:47
In reply to Re: Orthomolecular medicine, posted by Squiggles on March 27, 2007, at 14:06:59
Hmmm..I'm thinking that replenishing nutrients, vitamins and minerals to these starving children is an excellent model of orthomolecular medicine.
So many of their ills owe directly to a spectrum of deficiencies brought about by the inability of their bodies to procure and process essential nutrients. Provide them with the right molecule in the right dose and much healing will commence.By mouth, by vein, via yams and meat deliver the building blocks of life to these children. This is the right medicine for them.
On the other hand you could treat their lethergy with dexedrine, depression with Zoloft, give them antibiotics, anti-virals whatever handfuls of pharmacopia you will, it is unlikely to be of much help until they are fed the molecules that are missing, none of the drugs will be able to save the starving child.
Nutritional medicine is fundamental not futuristic. How long ago the discovery that V-C banished scurvy. Amazing to them then that citrus fruits could heal such poor health.
Rickets, Beri Beri, and more. Brought on by nutritional deficiency. How about Schizophrenia, depression, PMDD, etc. Could nutritional imbalances cause or contribute? It's only wise to at least make sure the body has what it needs before overpowering it with drugs.
Feeding is the simplest form of OM medicine that we practice everyday. Allopathic medicine is emergency medicine.
If you have low iron anemia eat meat, cook in iron skillets and add supplements (iron V-C)
If you cut off your finger a Dr. will staunch the bleeding, provide you with pain killers, infection control and mabe even be able to re-attach it for you. Hooray for Modern Medicine!!!
Our bodies need a dynamic inflow of nutrients for optimal health. Which nutrients and in what amout varies considerably. Using tests, observations and trials OM medicine attempts to give a body what it need to do it's job properly. When these needs have been addressed we can then see what illness survives a nutritionally balanced body to be treated further with modern therapies and drugs.
Squiggles,
I was unaware that we were engaged in a debate. I thought we were sharing info and I was trying to offer encouragement to you as you expressed an interest is something that I have been immersed in that has provided me with remarkable benefit. Thats all.I have respect for your position. I have had an aversion to particular methods and meds before and I honored that in myself. I didn't have to have a concrete reason. Inner wisdom. I trust it.
Peace,
Kaye
>
> And one more thing -- with one and a half million kids starving in Africa, i think a meal with water, approximating the average nutritional needs, would be scientifically acceptable to them, thank you very much -- you can go to Oxfam.org for that. The orthomolecular research is for the future benefit of mankind - very future.
>
> Squiggles
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