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 Low Blood Vitamin C Strongly Predicts Mortality 
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Ascorbate Wizard
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Post Low Blood Vitamin C Strongly Predicts Mortality
The following is one recent study that I wish Linus Pauling had lived to see.

UK STUDY: ANTIOXIDANT VITAMINS AND MORTALITY IN OLDER PERSONS

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

Quote:
RESULTS: Strong inverse relationship for blood ascorbate (vitamin C) concentrations with all-cause and cardiovascular disease mortality, which were only marginally reduced after adjustment for confounders or supplement use. Those in the lowest fifth (< 17 micromol/L) had the highest mortality, whereas those in the highest fifth (> 66 micromol/L) had a mortality risk nearly half that (hazard ratio = 0.54; 95% CI: 0.34, 0.84). Similar results were found after the exclusion of those subjects with cardiovascular disease or cancer at baseline (hazard ratio = 0.51; 0.28, 0.93). In fully adjusted models, there was no evidence for an influence of alpha-tocopherol (vitamin-E), beta-carotene, or retinol (vitamin-A) on total mortality. Dietary antioxidants measured by the food-frequency questionnaire were not associated with all-cause or cardiovascular disease mortality


This study found that those with high vitamin C concentrations were half as likely to die as those with (normal) low concentrations. Note vitamin C was the only factor.

Why is mortality important? Lets illustrate with two groups. In group A, the rate of side effects occured at an incidence of 75%. The other group, B, had only 1% of its population who suffered side effects. Which group would you prefer to be in?

What would your answer be after learning that the side effects in group A were "runny noses and tenderness in the abdomen." The only side effect in group B was sudden death.

The point is that compared to death, not much else matters.

It is interesting that according to statiticians, and others who study the statin cholesterol-lowering drug studies, these statin drugs do not improve overall mortality. (Yet, these studies are the basis on which medical doctors routinely tell their patients that statin drugs improve mortality)


This from Malcolm Kendrick http://www.thincs.org/Malcolm3.htm#July%2029
Malcolm Kendrick wrote:
[study authors] need to make the assumption that mortality has been proven........ Why, exactly, do we need to make this assumption? No study, ever, on primary prevention of heart disease with statins has ever shown a reduction in overall mortality. None, ever. And there have been many. And assuming something so absolutely vital, based on a huge amount of contradictory evidence seems just a tad premature.

I think I shall make an observation, rather than an assumption. As no clinical trial on cholesterol lowering in primary prevention of heart disease using statins (or any other drug actually) has ever demonstrated a reduction in overall mortality, it can be stated categorically that statins have no effect on overall mortality.


Or consider this from Anthony Colpo http://www.theomnivore.com/Lancet_statin_meta_2005.html

Anthony Colpo wrote:
The fact remains that individuals free of heart disease, females, and the elderly have NOT been shown to enjoy any overall mortality benefit from statins whatsoever. No so-called 'responsible' commentator should recommend these drugs to such groups, especially when far less toxic natural cardio-protective strategies (exercise, low-glycemic load and antioxidant-rich diets, omega-3 supplementation, etc) are readily available. The publication of carefully-worded, selectively-presented research does not excuse such behavior, but merely represents further damning evidence that our health care system is largely a corrupt, Big Pharma-dominated sham.


Finally statistician Eddie Vos agrees and also notes http://www.health-heart.org/cholesterol.htm

Eddie Vos wrote:
Some statin fine-print warns "The effects of ... on cardio vascular morbidity [illness] or mortality [death] ... have not [!] been established." And: "Significant decreases in circulating ubiquinone [CoQ10] levels in patients treated with X or other statins have been observed [happens in all users, and this does] .. lead to impaired cardiac function [= heart failure, nerve death] ..". Also: "..in some patients the beneficial effects of lowered... cholesterol may be partially "blunted" [canceled] by a concomitant [linked] increase in Lp(a) levels."

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Tue Dec 13, 2005 10:26 am
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Post Re: Low Blood Vitamin C Strongly Predicts Mortality
ofonorow wrote:
The following is one recent study that I wish Linus Pauling had lived to see.

UK STUDY: ANTIOXIDANT VITAMINS AND MORTALITY IN OLDER PERSONS

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract


Interesting study, although I'm not sure if one can conclude that vitamin C supplementation in the elderly will decrease mortality. The authors don't seem to think that the correlation can be explained by reverse causation, but I am not so sure. One cannot rule out that low plasma ascorbate is due to a subclinical condition.

Another thing to be mindful of is the fact that those in the higher quintiles of plasma ascorbate have higher daily intakes of fruits and vegetables. So how much of the observed benefit is attributed to other nutrients found in fruits and vegetables, and is higher plasma ascorbate simply indicative of a better eating habits? The hazard ratios remain pretty much the same when adjusted for supplement use (and only around 17% were taking supplemental vitamin C).

In my opinion, the findings do warrant interventional studies in the elderly population - either programs aimed at promoting increased dietary intake of vitamin C, or supplements. Most of the RCTs using vitamin C have focused on a younger population, so the results might be different in this case. I'm not sure a very high dose is necessary either - something in the region of 500mg twice a day might be sufficient to increase ascorbate levels in those individuals with low ascorbate levels.


Sun Mar 08, 2009 1:40 pm
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Ascorbate Wizard
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Post Re: Low Blood Vitamin C Strongly Predicts Mortality
This is one of the few studies that measured serum ascorbate levels (as opposed to food questionaires in many other observational studies). Almost every study that I am aware of that has examined serum vitamin C levels has found a benefit from higher serum ascorbate levels. I'm thinking of a recent study in particular that looked at the incidence of strokes. The benefit was something like a 70% reduction.

In this particular study, the researchers found no effect on mortality from other vitamins, so I don't understand the comment that maybe fruits and vegetables explain the result. Serum levels of vitamin C were the only relevant factor. I suppose that one could concoct an experiment to examine whether the form of vitamin C has any profound effect. From what I know, I doubt it. This question was examined back in the 1930s and 1940s as related by Pauling and others. Bioflavonoids and other factors had no additional effect on colds or other conditions studied.

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Mon Mar 09, 2009 5:06 am
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Ascorbate Wizard
Ascorbate Wizard

Joined: Tue Nov 22, 2005 3:16 pm
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Location: Lisle, IL
Post Re: Low Blood Vitamin C Strongly Predicts Mortality
This is one of the few studies that measured serum ascorbate levels (as opposed to food questionaires in many other observational studies). Almost every study that I am aware of that has examined serum vitamin C levels has found a benefit from higher serum ascorbate levels. I'm thinking of a recent study in particular that looked at the incidence of strokes. The benefit was something like a 70% reduction.
http://www.neurologyreviews.com/nov00/n ... _vitc.html

Quote:
To my knowledge, this is the first prospective study to make the correlation between vitamin C in the bloodstream and incidence of stroke," said lead author Tetsuji Yokoyama, MD, a research associate in epidemiology at the Medical Research Institute of Toyko Medical and Dental University. "The risk of stroke was inversely related to vitamin C in the bloodstream and frequency of vegetable consumption." Higher intake of fruits, vegetables, and other foods rich in vitamin C and potassium have been associated with lower stroke rates in previous studies.

In rural Japan, researchers examined a cohort of 880 men and 1,241 women ages 40 and older who were initially free of stroke when examined in 1977. Baseline examination included a measurement of serum vitamin C concentration. Incidence of stroke was determined by annual follow-up examinations. During the 20-year observation period, 196 strokes occurred, including 109 cerebral infarctions, 54 hemorrhagic strokes, and 33 strokes of undetermined type. The risk of stroke was 70% higher among those in the lowest quartile for serum vitamin C than among those in the highest.



In the UK study of the elderly, the researchers found no effect on mortality from other vitamins, so I don't understand the comment that maybe fruits and vegetables explain the result, other than people who don't supplement need to acquire their vitamin C in some fashion. Serum levels of vitamin C were the only relevant factor. I suppose that one could concoct an experiment to examine whether the form of vitamin C has any profound effect. From what I know, I doubt it. This question was examined back in the 1930s and 1940s as related by Pauling and others. Bioflavonoids and other factors had no additional effect on colds or other conditions studied.

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Mon Mar 09, 2009 5:09 am
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Post Re: Low Blood Vitamin C Strongly Predicts Mortality
ofonorow wrote:
In the UK study of the elderly, the researchers found no effect on mortality from other vitamins, so I don't understand the comment that maybe fruits and vegetables explain the result, other than people who don't supplement need to acquire their vitamin C in some fashion. Serum levels of vitamin C were the only relevant factor. I suppose that one could concoct an experiment to examine whether the form of vitamin C has any profound effect. From what I know, I doubt it. This question was examined back in the 1930s and 1940s as related by Pauling and others. Bioflavonoids and other factors had no additional effect on colds or other conditions studied. [/color]


If you look at the tables showing the characteristics of each quintile, you'll see that for Vitamin E and plasma retinol, there is no significant increase in dietary intake of fruits and vegetables with increased plasma levels.

On the other hand, which each successive quintile of vitamin C, there is a higher daily intake of fruits and vegetables. There is also a significant trend between beta-carotene and daily intake of fruits and vegetables, although it does not appear as strong as the correlation for Vitamin C. This makes it difficult to rule out other factors that might at least contribute to the observed effect - it could be bioflavonoids, trace elements, fibre...pretty much anything that's found in a diet rich in fruits and vegetables. And again, it could be something else entirely...something not discerned in the analysis. This is good observational evidence, but it cannot substitute for an interventional study.

The same applies for the study shown an inverse relationship between plasma levels of Vitamin C and stroke. I'm not saying that vitamin C does not have any beneficial effect - but how much of the observed effect is due to vitamin C, and how much is due to other factors like other dietary nutrients commonly coexisting with vitamin C or unadjusted factors?

I do know of a clinical trial showing that vitamin C can lower blood pressure, although to my knowledge the findings have not been replicated (it would be interesting to see if short-term Pauling Therapy can corroborate these findings). So it would not be surprising if Vitamin C lowers the risk of stroke, if indeed it can lower blood pressure. But by how much would need to be determined through a controlled trial to eliminate potential confounders.


Mon Mar 09, 2009 1:06 pm
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Ascorbate Wizard
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Joined: Tue Nov 22, 2005 3:16 pm
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Post Re: Low Blood Vitamin C Strongly Predicts Mortality
Quote:
If you look at the tables showing the characteristics of each quintile, you'll see that for Vitamin E and plasma retinol, there is no significant increase in dietary intake of fruits and vegetables with increased plasma levels.

What tables are you referring to? The percentage in the quintiles consuming more than 5 portions daily? How did you arrive at the above conclusion?

I am not sure I follow this line reasoning even if more vegetables are required to raise vitamin C levels. This is a study of serum levels, and while it is interesting how many portions are required to reach certain levels, I do not understand the logic that serum vitamin C may be correlated with increased intake of fruits and vegetables, or how that invalidates the finding that increased ascorbate confers the increase in mortality.

In any event, this can be tested using supplementation, and I believe the Harvard Nurses study which found a "modest" decrease in CVD mortality - but only in nurses who supplemented with vitamin C pills. (Note that there was no correlation among women who didn't supplement: http://www.ncbi.nlm.nih.gov/pubmed/1287 ... d_RVDocSum.)

But to test my understanding of your criticism, 18% with a consumption of more than 5 portions raised the ascorbate to quintile 1, 37% with a consumption of more than 5 portions raised their vitamin E level to quintile 1, 27% with a consumption of more than 5 portions raised the Beta Carotene level and 36% with 5 or more portions were able tor raise their vitamin A to quintile 1 levels. Doesn't this mean that less fruits and vegetables were required to raise serum vitamin C to the lowest quintile?

The middle quintiles were similar. Yes, to raise ascorbate to the middle quintile required about 8% more with 5 servings than the others (44% versus about 36%).

You must be focusing on the upper quintiles, but as you mention - ascorbate and Beta Carotene have similar percentages.

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Tue Mar 10, 2009 5:43 am
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Post Re: Low Blood Vitamin C Strongly Predicts Mortality
ofonorow wrote:
I am not sure I follow this line reasoning even if more vegetables are required to raise vitamin C levels. This is a study of serum levels, and while it is interesting how many portions are required to reach certain levels, I do not understand the logic that serum vitamin C may be correlated with increased intake of fruits and vegetables, or how that invalidates the finding that increased ascorbate confers the increase in mortality.


It's a question of correlation vs. causation. If there is in fact a higher intake of fruits and vegetables amongst those with higher vitamin C serum levels than those with low vitamin C serum levels, then that is a potential confounder. By the way, this study does NOT show that increased ascorbate confers a decrease in mortality, but rather that it is associated with a decrease in mortality.

Quote:
In any event, this can be tested using supplementation, and I believe the Harvard Nurses study which found a "modest" decrease in CVD mortality - but only in nurses who supplemented with vitamin C pills. (Note that there was no correlation among women who didn't supplement: http://www.ncbi.nlm.nih.gov/pubmed/1287 ... d_RVDocSum.)


Interesting study, but still with an observational design - it's impossible to say from this study whether the vitamin C itself is responsible for the marginal benefit seen or whether some other unmeasured factors are at play. The best way, as I've said before, is to have an interventional study with a randomized design. It's already been done with the Physician's Healthy Study, and Vitamin C didn't have any significant benefit IIRC. You may argue that the 500mg dose used was too low, but I would like to see how that compares to the doses taken by the majority of users in the Nurses' study.

Quote:
But to test my understanding of your criticism, 18% with a consumption of more than 5 portions raised the ascorbate to quintile 1, 37% with a consumption of more than 5 portions raised their vitamin E level to quintile 1, 27% with a consumption of more than 5 portions raised the Beta Carotene level and 36% with 5 or more portions were able tor raise their vitamin A to quintile 1 levels. Doesn't this mean that less fruits and vegetables were required to raise serum vitamin C to the lowest quintile?

The middle quintiles were similar. Yes, to raise ascorbate to the middle quintile required about 8% more with 5 servings than the others (44% versus about 36%).

You must be focusing on the upper quintiles, but as you mention - ascorbate and Beta Carotene have similar percentages.[/color]


I'm not sure what you mean by x% raised their vitamin level to so-and-so quintile. I'm not saying it's definitive that their serum level is caused by higher fruit and veggie intake, only that there is a significant, positive association that cannot be ignored.

Yes, the middle quintiles are not very different in terms of % with consumption of >5 servings of fruits and veggies, but the hazard ratios are not very different either. Just FYI:
Quintile - % >5 FV - HR(unadjusted for vitamin supplementation)
1_______18.2%_______1
2_______33.9%______0.96
3_______44.4%______0.59
4_______51.6%______0.61
5_______55.3%______0.51

It's interesting to note that in the top three quintiles, the hazard ratio doesn't even change much. So even if you take the data at face value, what does this suggest about raising serum levels of vitamin C with megadose supplements?


Mon Oct 26, 2009 5:43 pm
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