Point 1. In a recent post (http://margaret.healthblogs.org/2010/05/08/resveratrol-trial-in-multiple-myeloma-suspended/), I discussed the recent SRT501-chemo trial that was halted because some of the participants, advanced multiple myeloma patients with relapsed/refractory disease and who had failed at least one prior treatment, developed cast nephropathy, a common condition caused by myeloma that can lead to kidney failure. These patients, it turned out, had been taking what boils down to large amounts of resveratrol contained in a new formulation called SRT501…now, according to what I have read, SRT501 is able to get five times more resveratrol into the bloodstream than other resveratrol supplements on the market. These patients were taking 5 grams/day, which would be, unless I am horribly mistaken, the equivalent of 5×5=25 grams/day! Whoa!
I looked up the clinical trial and found that some of the patients were taking bortezomib (Velcade), too. And Velcade certainly can cause several bad side effects (see, e.g.: http://tinyurl.com/3a4sufe).
However, according to the Myeloma Beacon article (the link is in my above-mentioned post), the patients who developed cast nephropathy in this study were taking only the SRT501. Some folks apparently experienced nausea and vomiting, which may have led to dehydration…and that might possibly explain what happened…but this is pure speculation…we will just have to wait until the results of the investigation are released…
Point 2. I recently read about a vitamin D study (http://tinyurl.com/334a6ex) in which women aged 70 and older were given a single, annual, humongous dose of vitamin D: 500,000 IUs. All in one shot! Gee. Anyway, in a nutshell, these women ended up being more susceptible to falls and fractures than the women in the control (placebo) group.
From my viewpoint, the two stories are connected. If we say that the optimal daily dose of vitamin D is 1,000 IUs (=this is based on the Consumer Lab discussion further on, see Point 3, last quote), then 500,000 IUs, that is, the amount given in the above-mentioned study, is 5oo times that amount. 500 times! I mean, really!
Margaret’s crazy scenario: if, like me, you are taking 8 grams of curcumin/day…would you even remotely consider taking 8×500=4,000 grams? And consider this: if you respond well to a low dose of Velcade, would your doctor recommend raising it to 500 mg/m2? Or your Zometa from 4 mg to 4,000 mg? Or testing those amounts in a clinical trial? No, I didn’t think so…
It boils down to the “too much of a good thing may not be…such a good thing” theory. Just because a low dose is good for you, why multiply it 500 or even only 5 times…? Puzzling!
Point 3. Okay, at this point I thought it would be interesting for us to know what Consumer Lab had to say about vitamin D, including the above-mentioned vitamin D study (I received the entire report thanks to a very kind blog reader, incidentally, thank you!!!)…this is a long excerpt, I know, but I thought it was interesting…(my emphasis, btw):
Research has found that men with low levels of vitamin D in the blood (15 ng/mL and lower) were at increased risk for heart attack compared to those with sufficient levels (30 ng/mL and higher) even after adjusting for other risk factors and physical activity. A recent study suggests that this may contribute to the higher rate of cardiovascular mortality among black Americans compared to white Americans, as blacks tend to have lower vitamin D levels.
Lower levels are also associated with a higher risk and severity of depression. A recent study in Italy, for example, showed that older women with low vitamin D levels (below 20 ng/mL) were twice as likely to develop depressive mood as those with higher levels. Older men with low levels were 60% more likely to develop depressive mood.
Low levels of vitamin D are also associated with a higher risk of dementia, and, in women, a higher risk of developing rheumatoid arthritis. There is conflicting evidence about whether vitamin D helps reduce the overall risk of dying from cancer, although studies have consistently shown that higher vitamin D serum levels were associated with decreased risk of death from gastrointestinal cancers.
Studies suggest that vitamin D may also improve balance and reduce the risk of falls in older adults, for reasons that aren’t clear. However, a recent study in women aged 70 and older who were at-risk for bone fracture showed an increase in falls and fractures among those given an extremely high, single, annual dose (500,000 IU) of vitamin D3. This unexpected finding may have resulted from unusual effects of the extreme dose. Hah, no kidding!
Well, all this simply makes no sense to me…and really, it is starting to look as though there is some sort of bizarre “conspiracy” going on…I mean, it would not surprise me in the least if we soon heard about a clinical trial testing a super mega dose of curcumin, nanocurcumin or injectable curcumin, on patients who, as a result, might develop all sorts of weird symptoms, from orange nose hairs to…ah yes, quite right, it is pointless to speculate, but you can bet all your orange nose hairs that I would be the first to denounce such a study! Oh no…no…no!, I am beginning to sound like Mel Gibson in “Conspiracy Theory”…! 😉
Okay, back to the Consumer Lab report on vitamin D. Again, a long excerpt (my apologies):
D2 or D3? Several years ago, studies indicated that, at very high doses (4,000 IU per day for two weeks or a single dose of 50,000 IU), the D3 form of vitamin D is more efficient at maintaining serum 25-hydroxyvitamin D levels, than the D2 form. However, a more recent and longer term study using a more common dosage, 1,000 IU daily, showed the two forms to be equally effective at raising and maintaining serum levels. An even more recent study showed that the two forms are also equally efficient whether taken daily as an oral supplement or in a fortified orange juice, based upon a dose of 1,000 IU per day.
The next paragraph deals with what are considered to be the desirable levels of vitamin D: 30 ng/ml. Deficiency: anything < than 15 ng/ml. Insufficient: < 30 ng/ml. Then there is a paragraph on U.S. children and adolescents: 61 % of them have insufficient vitamin D levels. Wow. And an additional 9% are vitamin D-deficient, which means that they most likely have higher blood pressure and lower levels of HDL (=good) cholesterol than other children. This quote tells us how much vitamin D we should be taking (according to Consumer Lab):
A rule of thumb for raising serum levels of 25-hydroxyvitamin D is that about 100 IU of vitamin D2 or D3 daily will raise serum levels by 1 ng/ml in an adult. With moderate (1,000 IU per day) supplementation, it has been shown to take about 6 weeks for serum levels to reach their peak. For example, during winter with no significant sun exposure, supplementation with 1,000 IU has been shown to increase levels of around 20 ng/mL up to about 30 ng/ml at six weeks. In such a scenario, sun exposure or a dosage higher than 1,000 IU would be necessary to further elevate levels above 30 ng/mL.
Note: of course, we myeloma folks must be careful not to take too much vitamin D, since it can lead to hypercalcemia = too much calcium in the blood. That would not be good!…
But let us also not forget that, according to a 2009 Mayo Clinic study, multiple myeloma patients with low vitamin D had worse outcomes than those with normal vitamin D levels. Low is bad! See my December 10 2009 post on this topic: http://margaret.healthblogs.org/life-with-myeloma/what-is-multiple-myeloma/myeloma-and-vitamin-d/
So, if you haven’t done this already, please have your vitamin D levels checked…and if they are low (as mine were), do consider taking a good D supplement. Vitamin D levels should really be a standard test for all myeloma patients, especially newly diagnosed folks. We should really push for that to happen!
That 500,000 iu dose was high, but in the following study the subjects were treated with 700,000 iu over a 14 day period!
I wonder then what happens when we are taking 1000 IU of vitamin D AND have sun exposure. It would seem that we could then be in the overdose scenario. Then the challenge for me would be whether to stop the supplement when I know I’m going to have sun exposure.
If you have time to watch it, this is a very interesting informative video on vitamin d by one of the better known and respected scientists in the field of vitamin d research. He has been on the cutting edge of vitamin d research for decades now.
Also, check out some of the vitamin d videos on the right hand side of the page……there are some really good ones there relating directly to cancer and vitamin d.
It is only nessesary to take vitamin D supplements in wintertime .
In the summertime a good sun exposure of 1 hour without suncreme makes 10,000 to 20,000 IU vitamin D in the blood.
An additional pill with 1,000 IU D it`s peanuts!
With all drugs and vitamins there is always an optimal dose -the problem is knowing what that does is. Of course that’s why much research is done to find this out. And it is quite wrong to say “the more the better” because once you exceed that optimal dose you are very likely going to have toxic effects even with vitamins and minerals.
Also with exceedingly high dosages you may well have these substances entering the cells in dosage that were never meant to be. With a massive dose of 500,000 IU you have no idea where all of it will end up — although it is likely much of it will end up being passed out in the urine, making it largely useless.
Measuring blood and/or serum levels is a good way to montor these substance but even that does not give a totally accurate picture because you don’t always know what the intra-cellular level is, ie what’s inside the cells.
So it’s very risky to go with massive doses of anything. Essential components like iron and calcium and vitamin D all etc have optimal doses. Biologic systems are too complex for a “more is better” approach.