Are you saying that because everyone who has high stored iron levels doesn't get heart disease or Alzheimer's, one shouldn't consider accumulating evidence there may be a link between elevated iron storage and disease?
Of course not.
Not all smokers die of heart disease or lung cancer, yet in looking at smoking populations one can clearly see the risk association, even though it has never been scientifically proven in controlled studies with humans.
Right. Except that the Japanese smoke more than Americans do, yet are no more likely to die of lung cancer. So, in stead of looking across
entire populations during a snapshot in time, which are multiply confounded, you get detailed information about the life and lifestyles of
individuals at one point in time, follow them up over the long term, and look at their
later risk of some outcome after
controlling for the many differences you observed between the individuals in your cohort. When you do that, yo see that people who smoke are more likely to get lung cancer than people who don't, and people who smoke
more are more likely to get lung cancer than peole who smoke
less. Whereas, when you do that for body iron load and cardiovascular outcomes, "the vast majority of the epidemiological data does not support the hypothesis that body iron stores are directly related to the risk of developing CHD."
Perhaps we should move on to cancer...
"Moderate elevation of body iron level and increased risk of cancer occurrence and death"
http://onlinelibrary...560312/abstract
"There is evidence, in this cohort, of elevated cancer risk in those with moderately elevated iron level. This pattern was seen in women as well as in men"
Hm. The evidence on the association between
iron load and cancer risk seems to be very mixed. I can't, unfortunately, find a good, current, meta-analysis of prospective studies. Also, there is also significant evidence that
iron deficiency may increase the risk of GI cancer. Notably, "within the spectrum of normal iron metabolism,
ferritin and transferrin saturation were not associated with risk of mortality among people who were not taking iron supplements and did not have a baseline history of cardiovascular disease or cancer".
As to blood donation: a couple of of prospective studies find no significant association of
blood donation with risk of
overall or
colorrectal cancer. The former study included assessment of donation frequency and level of iron reduction. One
clinical trial found reduced cancer risk after blood "donation" in peripheral arterial disease patients.
Another clinical trialA previous report from the same trial found no reduction in overall or CVD mortality from blood "donation" in a similar population, which leads to the question of what is balancing out the cancer deaths.
As an example of the confounding problem I mentioned earlier, a
study (
author manuscript of full text) of recent blood donors in Sweden and Denmark were found to be at substantially lower risk of mortality than the general population. But when the authors did
an analysis in the same databank of blood donors, "individually matched on sex, age, and county of residence ... [and] estimated relative risks of cancer according to number of blood donations made or estimated iron loss
3–12 years before a case patient was diagnosed with cancer, ... No clear association was observed between number of donations and risk of cancer overall" -- although it is worth noting that "between the lowest (≤median, <0.75 g) and highest (>90th percentile, >2.7 g) categories of estimated iron loss, there was a trend (
Ptrend < .001) of decreasing risk for cancers of the liver, lung, colon, stomach, and esophagus, which are thought to be promoted by iron overload (combined odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.58 to 0.84), but only among men and only with a latency of 3–7 years."
This may be significant, but it is far less than what was implied by their
crude analysis of donors vs. the general population, especially if there is no effect on cardiovascular disease. They attributed the substantial reduction in that analysis to the healthier lifestyles and selective screening of blood donors, not (primarily) to the sequelae of having blood removed. "Mortality rates and cancer incidence were lowest for outcomes that are recognized as being related to lifestyle factors such as smoking or to the selection criteria for blood donation": donors smoked less, Hep B and C infectees were screened out, they attempt to exclude heavy drinkers, etc. And, there was a
higher risk for several cancers, including breast:
We speculate that these risks reflect to some extent the selection of persons of high socio-economic status and health awareness into the blood donor population. However, as we did not have access to any specific data on such factors, we are unable to draw any firm conclusions about this issue. Risks may be elevated by increased detection of otherwise sub-clinical cancers, due to donors coming into regular contact with the health care system for blood donation, and perhaps also increased self detection. The greater deficit for cancer mortality compared to incidence points to possible screening effects.
"Blood donors recruited in more recent years exhibited a lower relative mortality than those who started earlier," even granted secular trends in cancer epidemiology, suggesting that thtey were getting better at screening. "Explicit and informal requirements for blood donation in Scandinavia, although mostly of a simple nature, have successfully refined the
selection of a particularly healthy subpopulation." And, blood donors are likely more conscientious than the general population -- a character trait repeatedly associated with lower mortality rates.
Again, to get good data on the effects of any action or habit, you have to track risk in
individuals and control for confounding variables over time. Comparing menopausal women
as a group to men and/or premenopausal women
as a group doesn't tell us much of anything.
I personally keep my ferritin levels at the low-normal end with a vegetarian CR diet.
This topic is becomming very interesting. In the beginning triplecrown wrote about dmae, alcar and piracetam. What is Your oppinion about the effectiveness of these?
There is no evidence that DMAE has any effect on lipofuscin; people are
assuming that it will because it's a constituent of centrophenoxine, which was reported in some studies to lower lipofuscin levels, tho' as noted this seems to be a very dubious finding. Same with ALCAR. I know of no evidence that piracetam lowers lipofuscin burden, aside from
a study "on the cerebellar Purkinje and hippocampal CA3 pyramidal cells in alcohol-treated and withdrawn rats".
Edited by Michael, 02 June 2012 - 07:16 PM.
