Discussion in 'Fibromyalgia Main Forum' started by KerryK, Nov 6, 2012.
Have a look. Very interesting.
Two main things about the structure of this study makes the results and conclusions null.
1. How the controls were defined is not stated. This is important because the results are based on a comparison.
2. While the differences in serum 25(OH) vitamin d levels between controls and nonagerian siblings were significant it does not mean they are valid. A significant difference can be achieved when the variance is low which you might expect in these samples (The offspring had significantly lower levels of vitamin D (64.3 nmol/L) compared with controls (68.4 nmol/L; p = 0.002))
Both of these measures: 64.3 (25.76ng/ml) and 68.4 (27.4ng/ml) are vitamin D insufficient or low levels. These numbers are significantly different but are they valid or even reliable?
Also they do not mention other SNP's which can have a bearing on these results, namely: Gc (variant (rs2282679)) and NADSYN1 (variants (rs12785878 and rs3829251)).
I am not convinced at all.
I will see what Dr. Cannell thinks at the Vitamin D council.
[This Message was Edited on 11/07/2012]
I totally agree with Ian on this. I will keep taking my higher dose Vitamin D daily.
View studies with some skepticism. How many were in the study, how were they chosen, was it done scientifically, etc.
One of the worst studies done was the longitudinal study of the effects of estrogen on breast cancer in women. Conclusions were made that estrogen put women at risk of breast cancer. All the women in the study were nurses. They didn't represent women in the population at large. Researchers are now looking at viruses as potential causes of breast cancer, especially EBV, which most everyone has had or been exposed to. Who is exposed to viruses more than people in the medical field. Neither my doc nor I have any confidence in that study.
In response to my request: Dr. Cannell (his associate Brant Cebulla) has written an expose on this study.
[This Message was Edited on 11/08/2012]
64.3 (25.76ng/ml) and 68.4 (27.4ng/ml) are considered significantly different? They don't look that much different. I mean in a clinical setting I don't suppose doctors(even ones who strongly believe in the vitamin d and disease connection) would feel that getting their patients levels from 25.76ng/ml to 27.4ng/ml would be of any significance whatsoever.
By the way I am not critisizing, I genuinely do not understand.
This issue is often important when statistical analyses are applied to studies and is my point.
If the number of people in the study, eg say 1200 people (600 in the dosed group and 600 in the placebo group) have a vitamin D deficiency, like the measures we see in this study and they are all fairly close ie the variance is low then the statistical difference between the two measure can be VERY significant. Its like the polls in the elections, they measure the opinions in the two parties and then also quote a "margin of error" which is a simplified version of variance or deviation from the average (called the standard deviation). So the larger the amount of people you measure the greater the significance of the difference even if the difference might appear very small, such as 49.5% versus 50%.
BUT is the poll itself valid??? Or reliable??? The poll would oly be totally reliable if every perso in the US was in the Poll but they never are. Only a few people are polled.
In this study they are comparing a group of people whos parent/gparent is in 90's compared to people whos parent/gparent is not in 90's. So the latter is like our placebo group. Such grouping of people can also introduce unreliability in studies.
However in a study like this all the people have low levels of vitamin D so my question would be, even though it is statistically different is this difference valid ie. can be applied to the "theory" under study, in this case, low vitamin D level increases life span.
There are so many factors which can influence this result.
eg. there are many different VDR gene (vitamin D receptor gene) polymorphisms or variations of the VDR gene which influence so many different other genes.
People who come from longlived families might spend more time indoors - who knows!
They may have a point though which is worth further investigation but to announce that low vitamin D increases life span is nonesense.
This is why you always take Journalist's announcements of scientific results with a very large pinch of salt.
[This Message was Edited on 11/09/2012]
First, thanks to Ian and others who have the capacity to digest and explain statistical analyses - my brain shuts off at the first hint of this!
Do you all remember the big hormone replacement therapy study published some 10 or 12 years ago or so, which supposedly showed the dangers of HRT? Well, what almost no one pointed out was that the women studied were all taking synthetic hormones (premarin) derived from pregnant horses. The study did not utilize bio-identical hormones, a huge factor. And yet millions of women and doctors are making decisions based on horses' urine studies. There are studies which show the benefits of bioidentical hormone therapy, but of course they are not nearly as large as the earlier study and are not well known.
So all kinds of factors come into play when looking at studies - who paid for them is another big issue. Many many drug studies we find out were done by people on the payroll of pharmaceutical companies. There is so much conflict of interest, or to put it another way, corruption, and so many other factors (as Ian has so eloquently pointed out) in published studies that the studies themselves bear studying.
I am glad you brought this up. I do not know anything about bio-identical vs. premarin. However, I have read a couple articles recently on Medscape and elsewhere recently arguing from more recent evidence that the harms alleged in the Women's Health Initiative (WHI) study of HRT were badly overstated and they are finding good evidence of health benefits across a range of age related diseases. The WHI should not have been shut down prematurely, as it was, and unfortunately, the medical community seems to have overreacted.
WRT vitamin D, I agree with those that the study presented does not give compelling evidence against, but it is a dent in the armor of vit. D advocates.
This study gives no "evidence" against the use of vitamin D supplements or getting more sun to raise levels to 50 ng/ml. Which is the natural level we should all have. They have provided no evidence at a scientific level because the structure and analysis provides bad data, then interpreted wildley.
No study has ever said that if you have higher levels of vitamin D you will live longer, except in the case of specific VDR related diseases. Just, logically you can't tell me that people who live inside all the time would live longer.
Read the report by Brant Cebulla on the Vitamin D council site.
Henry Lahore from the vitamindwiki said:
“If you have inherited longevity genes you can take 200 IU less vitamin D”
"That is just one of many possible other interpretations of the data from that poor study."
These sort of studies pop up now and then just as some bad studies support the value of vitamin D. I trust more specific studies which show reduction in mortality in particular disease groups. We have to filter out the crap based on our knowledge of how a good study should be conducted.
We are told we should have VitD levels of at least 50, preferably higher. Here's where I am unsure of the truth of this.
1) my 22 year old son is the healthiest person I know. Extremely active and athletic, always outdoors. Works construction in the summer so very tan and gets plenty of sun. Did the normal blood tests on him this fall and they are perfect----except his VitD is only 32. So my take on this is that everyone's body works a little differently, so a low level may be perfectly fine for some people!
2) there are many blood tests we get that the experts on this and other forums say are not reliable measures of the vitamins and minerals in our bodies. So how do we know how reliable the VitD tests really are?
I am very ill and my D level is 36. But I can't take even the smallest crumb of VitD because it immediately makes me feel worse. And sitting out in the sun or in a tanning bed are just as bad. So the whole thing has me confused and wondering.
But why is "sitting out in the sun or in a tanning bed are just as bad"?
The relationship between disease and vitamin D is complex. Simply saying the higher your level the better is not correct. Estimates of the ideal level of around 50ng/ml have come from various studies around the world where people get optimal sun exposure and the assumption is that we should all be around that level. I do agree that in the Western world our sun exposure has decreased markedly. I also agree that the vitamin D blood level is associated with certain diseases severity and onset. The evidence is overwhelming. The evidence is also strong for using vitamin D to ameliorate symptoms of many diseases and within that the symptom reduction sometimes requires quite low levels (20ng/ml-30ng/ml) and sometimes requires quite high levels.
Most disease (aside from autism and schizophrenia) associated with vitamin D deficiency occurs in older people (55+ years) BUT the preconditions for the illness are laid down many years beforehand in people who's vitamin D levels might be chronically low or low at birth. For most people where it is quite low wll function quite healthily in their "youth"
The second issue relates to genetics.
Once vitamin D3 enters the blood circulation it binds to the vitamin D binding protein
(DBP), which carries vitamin D3 to the liver and kidney for activation.
There are two steps in activating it.
This is technical:
In the first step D3 is hydroxylated by the
enzyme 25-hydroxylase to 25-hydroxyvitamin D3 (25OHD3) mainly in the liver.
This reaction is slow, which is why the level of 25OHD3 (the first activated form) in the serum
increases in proportion to vitamin D3 intake. The enzyme is synthesised by the gene CYP2R1.
Note; this blood level and clearance varies among people, partly depending on activity of the enzyme and on amount of fat on the body. (the more fat the less the vitamin D will appear in the blood)
This is technical"
In the second step the biologically active hormone 1,25-dihydroxyvitamin D3 1,25(OH)2D3 is generated by hydroxylation of 25OHD3. This reaction is catalyzed by the enzyme 25-hydroxyvitamin D3-1-alpha-hydroxylase (1alpha-hydroxylase) and it occurs mainly in the kidney. The enzyme is synthesised by the gene CYP27b1.
note: This activation also varies in people.
In all there are, at the basic level many genes involved in regulation of vitamin D
GC, VDR, CYP2R1, CYP24A1, CYP27B1 as well the deactivating enzyme CYP 27a1.
Each of these genes has been shown to have polymorphisms (literally different forms) which relect in the regulation of vitamin D.
Read some of this here: (bit technical though)
A more recent paper has looked at the effect of these polymorphisms (I don't have the original paper but you can read a summary on the Vitamin D wiki):
In essence what we are finding is that levels of vitamin D in the blood are different for different people. Now whether these differences will translate in different susceptability to diseases is not yet known. I suspect they will but in combination with other genes which are related to those diseases.
As to the reliability of tests. Basic tests measure serum levels of 25(OH)vitamin D (the first activated form) This only approximates the true measure of the main activated form 1,25(OH)2vitaminD. some research has shown it can be a poor measure in some people.
Whether you want to "artificially" increase vitamin D levels is a personal choice. If you have any of the diseases related to vitamin D deficiency it would be prudent to either get more sun or take a supplement. If you take a supplement, then anything between 1000IU and 5000IU would be useful. 5000IU has been shown to be perfectly safe. If you don't have any of these diseases in your family then one reason to take vitamin D or get more sun would be as an insurance policy for old age.
I can see no reason why not to take vitamin D unless as you say it causes some discomfort. I am not sure why that is but you are not the first person with ME or FM to say this. For this reason Prof. Nancy Klimas recommends taking vitamin D when eating the fattiest part of your meals.
[This Message was Edited on 11/13/2012]
Separate names with a comma.