I am still doing research on different non-toxic substances. Nothing really grabbed my attention until a few weeks ago, when I found the studies on resveratrol and MM cells. Resveratrol, a compound found in the skins of red grapes, in red wine, berries, broccoli, peanuts and onions, kills MM cells in vitro..

This study, co-authored by Prof. Aggarwal, was published in “Blood” in December, 2006:

http://tinyurl.com/yshgm4 

This is a study from Denmark, published in “Cancer Research” in 2005:

http://tinyurl.com/ys7lal (full text is free)

And here is a study from China, published in Cancer Genetics and Cytogenetics in 2006:

http://tinyurl.com/24mv4p

Prof. Aggarwal recommended that I start with 500 mg of resveratrol. He also told me that it will not interfere with my daily dose of curcumin. I will begin taking resveratrol later this month (April 2007).

Update: this test failed because Italian customs stopped my shipment of resveratrol capsules. I will do another test in the fall or winter of 2007.

July 27 2007 post: a lot has been written about the healthful compounds contained in wine, red wine in particular. For us MMers, the most important compound is resveratrol, which is an MM-cell killer in vitro. See my page on resveratrol for more information. And other wine polyphenols have antioxidant properties, too. Of course, since you would probably have to drink a case of wine or more to get enough polyphenols to make any difference, capsules containing the concentrated form are the way to go. However, if you only have gum disease, apparently just a little bit of wine can make all the difference.

I recently read a June 2007 University of Pavia abstract on wine and oral bacteria. These Italian researchers found that wine kills streptococci, the nasty bacteria which can cause sore throats, cavities and tooth decay (I didn’t know that until I read this abstract!). Interestingly enough, wine’s phenolic compounds (tannins and anthocyanidins) did not produce such an effect. What turned out to kill the nasty streptococci were the organic acids in wine, specifically: succinic, malic, lactic, tartaric, citric, and acetic acid (see: http://tinyurl.com/2vqmkl) Taken separately, in a concentrated form, these acids had an almost 100% success rate against eight streptococci strains, whereas when when mixed in with wine (which is the way we would imbibe them), their killing effect was not as powerful. However, even a small amount of wine was found to inhibit the proliferation of the harmful bacteria.

A Canadian study published in 2006 had already examined the effects of grape seed extract on gingivitis and periodontal disease: http://tinyurl.com/2sb9go The abstract concludes that proanthocyanidins have potent antioxidant properties and should be considered a potential agent in the prevention of periodontal diseases. So, those who enjoy a bit of wine with dinner have another excuse to raise their glasses!

Confession: I rarely drink wine, even now that I know that it contains resveratrol. I really don’t care for the taste, unless it’s a really special wine, like a nice Brunello di Montalcino served in a proper wine glass at the proper temperature etc. And I live in Tuscany, the region of wonderful Chianti oh dear, what can I say?

A final comment: I read that these wine acids may weaken our tooth enamel. So I guess that I will put off learning to love the taste of a good Chianti for a while yet. In the meantime, I am dashing off to brush my teeth.  

Update, October 26 2009 post. A European clinical trial testing resveratrol alone or in combination with Velcade on myeloma patients began in June 2009, see: http://tinyurl.com/yjqev5o

UPDATE, May 20 2010 post (also see May 8): 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!

May 8 2010 post. I read the news about the SRT501 (a special high-dose formulation of resveratrol; for general info on resveratrol, see: http://en.wikipedia.org/wiki/Resveratrol) clinical trial suspension on the Myeloma Beacon a few days ago. Today we have a few more, rather scary, I must say!, details (see: http://tinyurl.com/39j8buw).

My first impression, as I have already written on three (!) Facebook pages (1. my personal Wall AND 2. my blog’s FB page AND 3. the new multiple myeloma support group’s FB Wall), is that this goes to show that too much of a (possibly) good thing may not be such a…good thing!

And this is precisely why I always stick to the recommended dose of any new supplement that I decide to try. Indeed, I usually start out by taking less than the recommended dose (as I did back in January 2006 with curcumin, after all). For example, right now I am testing Reishi (scientific name: Ganoderma lucidum), which seizes myeloma cells by the neck and squeezes the life out of ‘em…sorry, got a bit carried away there…Anyway, I have been taking one Reishi extract capsule, not two (two capsules=recommended daily serving), just to be on the safe side. So far, so good. Next week I will go up to the (recommended) two-capsule dose…then, blood tests in June.

And, I would like to add, the “too much of a good thing might not be so good” theory is also why I will never ever take more than eight grams of curcumin…

I would also like to note that my friend Sherlock and I tested resveratrol a couple of years ago (see my July 2008 results)…and even though we remained stable, our MM markers went up a wee bit, so I was very disappointed and will almost certainly NOT test this substance again. Oh, another thing: my cholesterol went UP with resveratrol, not down as expected. Weird.

Hmmm, a question just popped into my mind: are any of you having good results from resveratrol? If so, please leave a comment on this post…thank you!