There are certain things that can happen that are the equivalent of the Bat Signal to me; that is, if you can swallow the idea of me being in any way like Bruce Wayne. Call them the Cancer Signal, if you will. When I see the Cancer Signal, I know that I have to head down to the Cancer Cave—wait a minute, that doesn't sound right. Scratch that. In any caes, there are certain studies or stories that basically demand my attention and say, "Blog me, Orac! Blog me right now!!!" Either that, or they're studies that capture my readers' attention, leading them to e-mail me or Tweet at me plaintive requests to blog them. Sometimes I do it. Sometimes I don't. Not every study that interests some of my readers interests me sufficiently for me to put forth the effort to blog about it, and, remember, this blog is all about me. I love that there are a few thousand out there who love what I lay down, but at the end of the day this is all about what interests me. I know that sounds arrogant, but if I started writing about things that didn't interest me that much this blog would rapidly fade into oblivion. My writing would become less interesting, and I'd lose interest, maybe even to the point of giving it up.
Be that as it may, fortunately, the study of the week last week was one that actually did interest me. In any case, this week's Bat Signal consisted of a series of news reports with titles like:
- Vitamin C shows promise as cancer therapy (FOX News).
- Researchers establish benefits of high-dose vitamin C for ovarian cancer patients (Kansas University Medical Center press release).
- Vitamin C injections ease ovarian-cancer treatments (Nature).
- Vitamin C keeps cancer at bay, US research suggests (BBC).
- Vitamin C May Help Cancer Treatment, Study Finds (NBC News).
- IV Vitamin C Boosts Chemo's Cancer-Fighting Power? (WebMD).
- Vitamin C as cancer treatment? High doses boost chemotherapy in study (LA Times).
These stories, to varying degrees, miss the point, from utterly missing it to missing most of it. Unfortunately, I confess that I wasn't able to help at least one of them. A reporter happened to leave me a message Tuesday morning, which is my operating room day, and I didn't have time to read the paper and to get back to her before her deadline. Unfortunately, my real job sometimes gets in the way of my being able to help out a journalist. That paper, by the way, appeared in Science Translational Medicine from Jeanne Drisko and Qi Chen from, yes, Kansas University Medical Center, home to one of the more—shall we say?—dedicated centers of quackademic medicine. This indicates to me that STM's standards are slipping. But then, STM did publish a rather credulous paper by our old friend Ted Kaptchuk on placebos less than a month ago; so maybe I expect too much. Clearly STM appears to be looking for more papers on "complementary and alternative medicine" (CAM) or "integrative medicine." Worse, just last week, one of the associate editors of STM, Yevgeniya Nusinovich, hosted a lovefest of a web chat in which Dr. Josephine Briggs, director of the National Center for Complementary and Alternative Medicine (NCCAM), and Dr. Jeanne Drisko, chock full of pro-CAM tropes, distortions, and cherry picking. Among the cherry picked stories, besides the Trial to Assess Chelation Therapy (which Dr. Drisko was a co-author on), was this study on vitamin C and cancer, mentioned near the end of the web chat and the study that I promised to say more about.
A typical story describes the recently published research thusly:
People with ovarian cancer who receive high-dose vitamin C injections are less likely to report toxic side effects from chemotherapy than people who had chemotherapy alone, according to the results of a small clinical trial.
The study, published today in Science Translational Medicine1, was too small to assess whether the combination of chemotherapy and vitamin C combats cancer better than chemotherapy alone. But accompanying work in mice suggests that the two treatments could be complementary.
The results are the latest salvo in long-running controversy over the use of vitamin C against cancer. Early studies championed by Nobel-prizewinning chemist Linus Pauling in the 1970s suggested that vitamin C could help to fight tumours2. But larger clinical trials failed to substantiate those claims3, 4.
With the spin, from another typical story, being:
One potential hurdle is that pharmaceutical companies are unlikely to fund trials of intravenous vitamin C because there is no ability to patent natural products.
"Because vitamin C has no patent potential, its development will not be supported by pharmaceutical companies," said lead researcher Qi Chen.
"We believe that the time has arrived for research agencies to vigorously support thoughtful and meticulous clinical trials with intravenous vitamin C."
Yes, indeed. The same old tropes are there, from the claim that vitamin C has usefulness in treating cancer to the old ascorbate warriors' lament that there's no patent potential in vitamin C, which means that pharmaceutical companies don't want to invest money into doing science and clinical trials on it because there's no profit potential. Of course, I've written fairly extensively about vitamin C and cancer before, using it as an example of how even a two-time Nobel Prize winner like Linus Pauling could fall prey to bad science when he wandered outside of his area of expertise. Every so often these stories come up suggesting that Linus Pauling has somehow been vindicated and how vitamin C is the greatest thing for cancer patients since surgeons first discovered that some cancers could be cured by cutting them out. Inevitably, I have to throw cold water on such claims. No, Linus Pauling has not been vindicated, and, no, vitamin C for cancer is not all that great. It might even be harmful.
Also, no, contrary to what critics say, I'm not close-minded about vitamin C and cancer. Unlike so many "alternative" cancer treatments, it's actually a chemical and, at the doses used by alternative cancer practitioners, a drug. There's even a (very) weakly plausible mechanism by which it might work. However, in vitro, the concentrations required to provide even a whiff of a hint of antitumor activity are ridiculously high, and the same is true in animal models. Let's just put it this way. Imagine a pharmaceutical company had developed a compound with properties identical to that of vitamin C and could thus own the complete patent on it as a drug. Given the ridiculously high concentrations and doses required in preclinical models to demonstrate a hint of antitumor activity against , that pharmaceutical company would probably retire that compound before even the animal model stage because, as I like to put it, getting any useful anticancer activity out of it would be such a long run for a short slide. A good drug for cancer is, at the very minimum, active at low or reasonable concentrations against the cancer cells being targeted, and vitamin C fails miserably on that count. Worse, there are at least indications that in some cases vitamin C might interfere with chemotherapy.
So does this study change my opinion? Not really. At best, it suggests there might be some utility for ascorbate (vitamin C) against ovarian cancer, but that ascorbate therapy for cancer still remains at best a long run for a very short slide right into the gloved ball of reality for a third out. (OK, I'll stop with the baseball analogies.)
The dubious reasoning begins right in the first paragraph, with the authors' justification for "re-examining" ascorbate as a cancer therapy. Basically, they point out that the pharmacokinetics of oral ascorbate dosing is different from intravenous dosing, to the point where it is possible to obtain serum ascorbate concentrations of 10 mM (millimolar). To give those of you who aren't chemists a rough comparison of just how high that concentration is, most cancer drugs have active concentrations in the nanomolar (nM) to micromolar (uM) range, in other words, a thousand-fold to a million-fold lower than 10 mM. For example, the IC50 (the concentration that leaves only 50% of cells alive) for paclitaxel is in the 2.5 to 7.5 nM nM range, depending upon the cell line, and 50 nM is considered a good, effective therapeutic concentration. You get the idea. You need a lot of ascorbate:
By contrast, when ascorbate is injected intravenously, tight control is bypassed and pharmacologic concentrations of ascorbate are established until excess ascorbate is excreted by kidney. Plasma concentrations greater than 10 mM are safely sustained in humans for ~4 hours (10–13). When patients have normal renal function and glucose-6-phosphate dehydrogenase (G6PD) activity, toxicity is minimal even with intravenous doses as high as 1.5 g/kg, equivalent to 105 g for a 70-kg person (2, 12). These data indicate that intravenous administration of pharmacologic ascorbate doses is safe and similar to drug administration. Therefore, the effect of ascorbate in cancer treatment is worth reexamining.
These are huge doses, consistent with previous experiments in mice with a xenograft from an ovarian cancer cell line (Ovcar5) in which 4 g/kg of ascorbate was administered twice daily for a total of 8 g/kg/day. The result was an inhibition of xenograft growth of around one-third after 30 days. Results for a pancreatic cancer cell line and a glioblastoma cell line were only marginally better.
The authors did several cell culture studies in which ovarian cancer cell lines were treated with ascorbate and various chemotherapeutic agents. The authors reported an IC50 of between 0.3 and 3.0 mM, which is still incredibly high for an anticancer drug. The authors blithely write that this is "easily achievable" with IV ascorbate. Maybe so, but given the quantities involved, if you're going to use a drug that requires such high plasma concentrations to have activity, that activity had better be awesome. None of the activity shown in this paper can be characterized as being particularly impressive. Worse, the authors, despite testing several ovarian cancer cell lines, only tested one non-tumorigenic immortalized ovarian line, HIO-80, and, finding that the IC50 to kill HIO-80 cells was much higher than all but one of the other cell lines (SHIN3), proclaimed a high degree of specificity for cancer. Moreover, HIO-80 cells are hardly "normal." They likely contain BRCA1 mutations. Finally, the authors only used one assay for proliferation, the MTT assay. This particular assay is very popular (I use it in my lab not infrequently) because it is faster and easier than counting viable cells and also allows for large experiments using 96-well plates. However, the MTT assay depends on the metabolism of cells to produce a dye that is detected. The amount of light absorbance due to the dye is assumed to be proportional to the number of viable cells. Usually, this assumption is reasonable accurate, but lots of things can interfere with this and render that assumption incorrect. For instance, one wonders if very high concentrations of ascorbate can interfere. I'd want to see a control demonstrating that the MTT results correspond to cell number.
In other words, if I were a reviewer for this paper, not so fast, I'd have said. I want to see the results for at least a couple of more non-tumorigenic cell lines and a control validating the MTT in the presence of so much ascorbate (even if just a reference) before I'll let you conclude that the effects of ascorbate are highly specific for cancer over normal ovarian cells. At the very least, I wouldn't have considered it unreasonable to ask for a couple more non-tumorigenic ovarian epithelial cell lines to be tested.
In any case, the authors also did some mechanistic studies, the results of which were consistent with the activity of ascorbate in cancer requiring the production of peroxide (H2O2), as H2O2 scavengers blocked the effect. They also did a series of experiments that indicated synergy between ascorbate and carboplatin, a common chemotherapy drug used in ovarian cancer. One area that, as a reviewer, I'd have gotten on the authors' case was the series of xenograft experiments using ovarian cancer cell lines implanted under the skin of immunodeficient mice, specifically this part:
Two-tailed Student’s t test was performed for comparison of treated groups to control group in the cell and animal experiments, as well as for toxicity comparison between chemotherapy group and chemotherapy + ascorbate group.
No, no, no, no, no! This is some pretty basic stuff here. There are eight different experimental groups, and the authors didn't control for multiple comparisons, as far as I am able to tell. Pair-wise two-tailed t-tests are not the correct statistical test for determining statistical significance in such a case; likely some form of ANOVA would be, given that the dataset consists of tumor weights and volumes of ascites, the latter being a common estimate of ovarian tumor burden in mouse models. Some form of ANOVA, likely factorial ANOVA, would have been the proper test, given that there are combinations of three drugs being used. Whatever the correct test is (and I'll leave that to the statisticians out there), I know that Student's t-test isn't it, and that using Student's t-test will often produce "false positives" that appear statistically significant but aren't.
All of this, however, is the warmup to the part of the study that got it noticed, namely the clinical trial. Without the clinical trial, this would have been yet another in vitro and animal study of high dose vitamin C that provokes a collective yawn throughout the scientific community. The clinical trial itself, was a randomized prospective phase I/IIa clinical trial, which means that the trial was designed to combine an evaluation of toxicity with a pilot study to evaluate efficacy and safety. Its primary objective was to "determine the safety of high-dose intravenous ascorbate when combined with first-line chemotherapy paclitaxel and carboplatin in the treatment of advanced-stage ovarian cancer," along with evaluation for toxicity. Consequently, the two groups were (1) standard carboplatin plus paclitaxel (Cp + Pax) and (2) carboplatin plus paclitaxel plus ascorbate (Cp + Pax + AA) according to this design:
Ascorbate dose for the Cp + Pax + AA arm was established via dose escalation initiated at 15 g per infusion titrated up to a therapeutic range of 75 or 100 g per infusion, with a target peak plasma concentration of 350 to 400 mg/dl (20 to 23 mM) (12, 13). The ascorbate infusion was given at a rate of 0.5 g/min, and 400 mg of magnesium chloride (Wellness Pharma) was supplemented into each infusion. Once the therapeutic dose was established, the Cp + Pax + AA group received ascorbate two times per week in conjunction with chemotherapy for 6 months, and injectable ascorbate was continued for another 6 months after chemotherapy completion.
In addition, the authors noted:
Two subjects voluntarily withdrew from the Cp + Pax arm before treatment commenced because they wanted intravenous vitamin C, and they were excluded from data analysis. Two subjects were removed from the Cp + Pax + AA arm because they were noncompliant with tobacco use, and one was removed from the Cp + Pax + AA arm after in vitro cytotoxic assays detected that her tumor cells were resistant to all chemotherapy. These three subjects received doses of chemotherapy and ascorbate, so their adverse events were counted, but they were excluded from the survival report (table S3). Double blinding was used at enrollment and randomization, but was not maintained during the treatment because no placebo control was used.
So what we have here is a small clinical trial with a 19% dropout rate that wasn't even blinded. It reported zero difference in overall survival (both were, as one would expect for ovarian cancer at this stage, abysmal), and zero statistically significant difference in time to relapse/progression. In all fairness, there would have had to have been an enormous effect to produce a statistically significant effect on survival or progression in such a small study, but these are the two "hard" endpoints that would be least affected by the lack of blinding, although one notes that time to progression could be affected by lack of blinding when the definition depends on interpreting scans. It's also hard not to note that the differences in toxicities are all in the mildest reported toxicities, grades 1 and 2 (out of a scale of 1 to 5, with a score of 1, which denotes mild toxicity that requires no intervention to 5, which is death). There were no statistically significant (or even close to statistically significant) differences in toxicities graded 3 or 4, which are the most troubling kind. Take a look at the graph:
Then, when the authors broke it down, this is what they found:
Notice the types of complaints with the biggest difference: gastrointestinal (which usually includes symptoms such as nausea, abdominal pain; dermatology, which usually includes itching and rashes of various types); pulmonary, which often includes symptoms of shortness of breath, cough, and the like, and renal/genitourinary, which is the only one that's less objective. So, basically, what we have is a study that found no benefit in overall survival or time to progression (not unexpected for such a small study). More importantly, contrary to the way it was trumpeted to the press, the decrease in adverse events actually observed was limited to the least serious adverse events (grade 1 = minor, causing no limitation of activity, no intervention required; grade 2 = moderate, some limitation of activities, minimal intervention indicated) with the most potential to be subject to reporting bias, which in the context of a trial that is not blinded makes the difference reported probably meaningless. In other words, this was probably a negative study, a long run for a short slide, indeed. (Sorry, couldn't resist. Again.)
Not that any of this stops Dr. Drisko from saying things like:
"We now have a better understanding of vitamin C's anti-cancer action, plus a clear safety profile, and biological and clinical plausibility with a firm foundation to proceed," said researcher Dr. Jeanne Drisko, director of the integrative medicine program at University of Kansas Medical Center. "Taken together, our data provide strong evidence to justify larger and robust clinical trials to definitively examine the benefit of adding vitamin C to conventional chemotherapy."
"Firm foundation to proceed"? You keep using that term. I do not think it means what you think it means. All Dr. Drisko has shown is that there is no difference in survival between the group receiving high dose ascorbate and the group receiving standard of care and that, putting the very best possible spin on the data, maybe adding ascorbate to carboplatin and paclitaxel in the treatment ovarian cancer might decrease the most minor side effects of chemotherapy; that is, if there wasn't reporting bias due to the lack of blinding after the randomization.
I'm not impressed. Neither should you be.
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Thank you so much for this. I'm midway through my chemotherapy, and was sent a link about this yesterday by a well-intentioned person. I appreciate and value your stance.
*a link about this study, I mean.
Isn't the C of Vitamin C for cancer? ;-)
OK, now I'm confused.
At start and finish, we are comparing number of reported side effects from chemo.
Then, around the middle, the study seems to be about vitamin C's potential as a cancer cell killer in Petri dishes.
Am I being dense, or are these two different objectives?
The authors of this article are claiming that vitamin C is at the same time killing tumor cells and alleviating side-effects of another drug which is also killing tumor cells?
I would be very interested in an explanation of the possible mechanism of action.
I was told during treatment not to take any nutritional supplements (including Vitamin C) as anything that helped protect cells also protected cancer cells.
Vitamin C is often touted for its anti-oxidative properties which may help cells under stress from certain chemo agents.
One thing i was curious about- and please remember that i am only a chemist so the messy bio stuff is not really my remit...
This is pumping a lot of weak acid into the body. does this not affect the pH regulating mechanisms or is it buffered in some way? Similarly millimolar is high enough to start affecting osmolarity, no?
Help out a poor physical scientist with the wonders of bio...
It seems relevant to mention that at 8 g/kg/day of Vitamin C, a 75 kg patient (165 lb) is going to be getting 600 grams by IV per day, or about 1.3 pounds of dry ascorbate dissolved in saline. If the course of treatment is two weeks, the patient will have absorbed 18 lbs?
Did I miss something? Clearly there's no way for that to metabolize and excrete... Are they exploring something that's clearly infeasible?
Oh... nope.
"toxicity is minimal even with intravenous doses as high as 1.5 g/kg, equivalent to 105 g for a 70-kg person "
I have to say, I am getting annoyed by researchers ignoring recent findings in this field. The term "ovarian cancer" refers to a group of tumors of several histologic types, thought, until recently, to arise in the ovarian surface epithelium. That seems to not be the case. The most common type, serous carcinoma, appears to arise in the Fallopian tubes, and the other types appear to arise in endometriosis, and thus the endometrium. It's kind of an involved story which would not be appropriate to discuss in a comment. This is a tentative finding. There is a group that has accumulated a large series of these cases, and we are waiting for them to publish their findings so we can get a better idea of what is really going on.
This raises the question of what are these researchers really studying? Did they lump all of these tumor types together? Did they look at them separately? I have grave reservations about a study in which we can't even be certain what tumor type is being discussed.
The headline of the BBC article has been changed to "Vitamin C 'gives chemotherapy a boost'". I think they received complaints.
I encountered the adjusted Beeb headline, last night. I skimmed through it, thought "Something that might help ameliorate the side effects of chemo and/or enhance it's efficacy? Awesome! Oh, wait, better see what Orac et al have to say about this..."
Now I'm probably going to have to talk my father's woo-prone wife out of demanding vit C injections while he's undergoing chemo for leukemia. Sigh.
(And have I mentioned I'm ready for cancer to be DONE messing with my family..? Meh. )
I agree with the comment above from Helianthus which points out that all the bluster about how Vitamin C might kill cancer cells is irrelevant - the only supposedly significant finding was that it eased some minor side effects of chemotherapy, and no plausible mechanism is even half-heartedly touted for that one.
Clearly, in an unblinded study (where we know some people already opted out because they didn't want to be in the arm without added Vitamin C) such minor subjective differences are most likely to be due to reporting bias on the part of the study subjects.
I must also ask why this study was allowed to proceed - surely the simplest of power calculations would tell them that there is not a fart's chance in a thunderstorm of finding significant survival outcomes with such a tiny group of subjects?
@inky
Indeed. And remember the usual woo explanation for developing cancer is that the body is already too acid, and we all need alkalinisation.
The claims must be credible if a recognized university is studying it, right?
http://www.theguardian.com/commentisfree/2014/feb/07/if-vitamins-dont-w…
But dingo--lemons are alkaline, remember? Vitamin C works the same way...
Back in my grad student days (the days of the dinosaurs -- mainframe computers), when I was one of the few biologists with any degree of statistical competence in the department, I would always advise consulting with a statistician before designing the experiment. Physiologists in particular had trouble with repeated measures in Anova. The advice was seldom followed. Apparently not much has changed.
Some parts of the clinical trial paper refer to AA (ascorbic acid), but when spelled out it is almost always referred to as "ascorbate", which is the salt form. Science journal always limits your text down to nothing, so the methods section is too short of detail to reproduce an experiment properly. It is most likely (imho) that the solution as administered to patients is buffered to pH 7.4 (normal human blood pH, very very slightly alkaline but really nearly neutral). I'm not a physician, but I think doing otherwise risks killing or overly stressing your patients.
I have no idea what was the pH of the solution as given to the cells in the in vivo work. Mammalian cell lines are very finicky, dying for almost any reason, and they're pretty sensitive to pH. I hope the researchers weren't idiots, but then, they were MDs and pretty royally screwed up the clinical study by making it unblinded. (Yes, MDs have a bad reputation with research scientists. Most MDs are simply just not trained to do experiments. Orac is an exception and seems to have more than half a brain- it must be the added circuit board and blinking lights.)
Orac,
On this side of the pond (you know, where you keep sending your foul weather, courtesy of the gulf stream) the BBC helpfully titled their news item on this subject Vitamin C keeps cancer at bay, US research suggests"
http://web.archive.org/web/20140209173212/http://www.bbc.co.uk/news/hea…
This has been subsequently amended (following complaints) to the equally untruthful but marginally less bad: "Vitamin C 'gives chemotherapy a boost'"
[This comment seems to have vanished... Trying again, hoping it does not post twice. JA]
Some parts of the clinical trial paper refer to AA (ascorbic acid), but when spelled out it is almost always referred to as "ascorbate", which is the salt form. Science journal always limits your text down to nothing, so the methods section is too short of detail to reproduce an experiment properly. It is most likely (imho) that the solution as administered to patients is buffered to pH 7.4 (normal human blood pH, very very slightly alkaline but really nearly neutral). I'm not a physician, but I think doing otherwise risks killing or overly stressing your patients.
I have no idea what was the pH of the solution as given to the cells in the in vivo work. Mammalian cell lines are very finicky, dying for almost any reason, and they're pretty sensitive to pH. I hope the researchers weren't idiots, but then, they were MDs and pretty royally screwed up the clinical study by making it unblinded. (Yes, MDs have a bad reputation with research scientists. Most MDs are simply just not trained to do experiments. Orac is an exception and seems to have more than half a brain- it must be the added circuit board and blinking lights.)
A side note, since IV vitamin C was one of the Tijuana Terapiz: Oral argument in the Sarah Hershberger appellate case is Thursday.
lemons are alkaline, remember?
And 2 + 2 = 5 for sufficiently large values of 2.
I learned my lesson the hard way many years ago when, not knowing any better, I did what the authors of this paper did and used Student's t-test to analyze pairs of data from an experiment with more than two experimental groups. In my defense, it had been a few years since I had taken a statistics course because I had gone back to my residency and then returned to the lab, and I just didn't remember. Dumb, but, trust me, it's a mistake I won't make again, particularly now that I usually just ask our statistics core to help me and tell me what the proper test is.
I can't see any reason to think that an essential nutrient like vitamin C would be toxic to cancer cells. Even in excessively high doses it would probably be just as bad for normal cells as cancerous ones.
Also, most animals can synthesise their own vitamin C, humans are one of the few who can't. This is one case where using mice to test a treatment to be used in people is a bad idea, guinea pigs would have been a better choice.
The stats discussion reminded me of my own research. I was doing a study where repeated measures ANOVA was appropriate, so I looked forward to that chapter in my graduate ANOVA class. The prof summed it up by dismissing the entire technique because he said it was only used in those "customer satisfaction surveys" where the dealership calls you 6 months after you buy your car to see if you still like it. I said I agreed that was a trivial application, but my lab used it, and what about cancer survival rates? He started yelling, accused me of insubordination, and threatened to call Security. (He's from Korea. Apparently this is typical instructor behavior there.)
I never did learn anything in that class about the statistics I needed for my thesis. Had to keep bugging my thesis advisor, who, fortunately, didn't mind teaching me after all.
In any case, I recognize the invalid use of Student's T-test as the major complaint about MOST papers students presented in seminar classes. It's scary how many invalid conclusions are out there based on misuse of statistics.
You might think its totally harmless to give cancer patients vitamin C. But the first chemotherapy trial used folic acid and caused leukemia blood counts to skyrocket.
My initial thoughts on this blog is that maybe it is helpful and not a waste of time (as the author seems to be saying) to explore the combination of vitamin C and cancer treatments. I can see where the author is coming from, however, no one up until now has found a legitimate cure for cancer, so why not try anything and everything to ease the side effects of cancer treatment in the mean time? I don't believe, from what I have read, that vitamin C is harmful in any way to treating cancer patients. I think that if we haven't found a cure yet in this day and age, even with all the new technology that we have, we should try anything that would even remotely help. Why wouldn't we? I think larger clinical trials and tests to examine the benefit of vitamin C with easing chemotherapy symptoms would be reasonable and a good idea to further the knowledge about it. In the extra couple links that were mentioned, The University of Kansas Medical Center reported that vitamin C can kill cancer cells. They did a study on 27 patients with stage 3 and stage 4 ovarian cancer. Researchers found that patients who received high doses of intravenous vitamin C along with chemotherapy experienced fewer toxic effects from these drugs. Also, in another external link posted in this blog, it stated that this idea may be controversial. Doctors have tried using vitamin C for years. But, it has had mixed results in trials. Mouse tests showed that the combination of chemotherapy and vitamin C did no harm, but when it came to testing women, there were not enough to tell whether it was actually effective or not. Maybe if there would have been more women to test, the results would have been more accurate and useful. I agree with the fact that vitamin C is a useful addition to add to cancer treatment due to its low toxicity characteristics. Some existing comments on the blog that I found interesting was one that said there is no way to metabolize and excrete that amount of necessary vitamin C. "Are they exploring something that's clearly infeasible?" Another commenter tied this subject into chemistry. This can also be related to physics. Physics is everywhere, and in many instances, in the medical field. In my own personal experience, when my friend's aunt had cancer, she was on a strict diet to help with treatment, and this was one that contained substantial amounts of vitamin C. This is why this topic and blog interested me. I have heard of people doing it before and have a little background on it. In some cases it may prove to be helpful; in other cases, maybe there isn't enough evidence just yet. Overall, the author seems a bit skeptical as to wether they go together successfully or not. He thinks that the articles on the outside links that I have previously mentioned tend to miss the point. He says, "No, vitamin C is not all that great. It might even be harmful." I can say that I have a hard time buying into this because there is no clinical or statistical evidence proving that it doesn't work or is harmful. From my personal experience, I think that it can't be harmful, and could be useful. More experiments could be done to verify whether it helps ease chemotherapy side effects or not. Cancer is a big problem and issue in today's world, so I think it's best that we try anything that shows a sign of helping the cause.
Jenna
If the aim is to ease the side effects of treatment, why not use a method that makes sense?
http://www.ncbi.nlm.nih.gov/pubmed/24156014
Jenna, the point is not to seek evidence that it doesnt work but to prove that it does. There is no evidence that dancing round a maypole doesnt cure cancer, after all. And your initial statement about there being no cure for cancer is essentially wrong. there are many treatments for many cancers, it is after all a group of diseases, not one disease. ad some cancers are indeed curable and may cancers are effectively cured every year via chemo, surgery and radiation. Not all by any means, and we all wish it worked better. but it does work, and we have the evidence to show not only that it does work, but exactly how well.
You claim you can see no harmful effects from vitamin c but you seem not to be looking at the quantities involved here. that is what is making people uncomfortable because it is a LOT. Maybe it isnt harmful but its certainly a vast quantity of chemicals to be loading into a body. Its hard to believe that wont have any effect at all.
But the real problem here is that even this study didnt show any effect that is worth the heric measures being taken to load this large quantity of acid into peoples system.
what is teh difference between a 'legitimate' treatment and all others, jenna? For many cancers standard of care treatments demonstrably improve likelihood of survival, quality of life, and in with some types of cancers (testicular cancer for example.) can result in catual cures.
The idea that until we identify a cure for a particular type of cancer we it's reasonable to attempt anything and everything anyone claims will be effective, in the absence of any actual evidence suggesting their claim is right, simply isn't tenable, as their argument reduces readily to "We should do something; this is something, therefore we should do it."
As for Qi Chen's Kansas City study, I think I'll wait for the results to be presented as something other than a press release before giving it serious consideration.
One's kidneys might not appreciate high-dose supplementation. At all.
Really confused- From the National Cancer Institute
www.cancer.gov/cancertopics/pdq/cam/highdosevitaminc/patient/page2
"Laboratory studies have shown the following:
•Treatment with high-dose vitamin C slowed the growth and spread of prostate, pancreatic, liver, colon, malignant mesothelioma, neuroblastoma, and other types of cancer cells."
www.cancer.gov/cancertopics/pdq/cam/highdosevitaminc/patient/page2
Did you happen to notice that "Laboratory Studies" means in vitro (in a glass dish) not in vivo (within a cancer patient's body)?
Those megadoses of Vitamin C lead to some very painful episodes of renal calculi and sometimes require surgery:
http://www.kidneystoners.org/information/stone-gallery/
anon, #31:
anon, #32:
Why are you confused? It's not uncommon for proposed meds to affect cancers of the petri dish: that is, cells isolated from various cancer sources and tested in a piece of laboratory glassware. Unfortunately, further testing usually shows the proposed meds to be either unsafe or essentially useless within an actual human body.
If you read the entire reference, you might see that ascorbic acid did not pass the "further testing" part.
Megadoses of vitamin E increase cancer mortality. WHY ARE YOU SUCH AN EXTREMELY BIASED COMMENTATOR?
anon: You ought to read Dr. Paul Offit's book "Do You Believe in Magic, which was released last summer. The book has sections about every type of quackery, such as alternative cancer treatments, megadoses of vitamins and supplements, dangerous herbal concoctions, homeopathy and "autism cures".
I had the please of meeting Dr. Offit at the Cold Spring Harbor Laboratory where he discussed his book. He's an exceptional public speaker and his book is very well written.
It bears repeating: substance X may kill cancer cells in a Petri dish, but so does a handgun.
Now, if it was shown to selectively kill cancer cells...
anon, perhaps we would understand you more if you would write out a full sentence about the link you are providing. Make sure that it relates coherently to the subject of the article at the top of the page.
This one is about a study that was poorly done, with too much reading into the results, since it says:
Though at least it wasn't in a petri dish.
Bill Price, "It’s not uncommon for proposed meds to affect cancers of the petri dish" is an awesome quote. Do you mind if I stash it in my quotefile? ;-)
I guess you can call me a grave digger- unearthed this one.
Enjoy!
https://www.seleneriverpress.com/historical-archives/all-archive-articl…
So you've barfed up a 57-year-old article (the original was published earlier in French) suggesting a hypothesis that is by now demonstrably false, and?
COI disclosure- have taken large doses of Vit C for 44 years-the only problem so far is I look 15 years younger than my age. Quit smoking at that time also. Eat well.
The rest I attribute to fortunate genes.
@anon - you know that over a certain amount, the body can't metabolize all of those "vitamins" and you're literally pissing them away, right?
Lawrence- Can you cite the research on this? $20 bottles of wine are pissed away too. (but they are more fun)
@anon - actually, this was even discussed here:
http://scienceblogs.com/insolence/2013/12/19/supplements-flushing-your-…
Lawrence- Thanks
anon -- I look quite a bit younger than my age too, which in my case I attribute *entirely* to fortunate genes. Though I still haven't shed my irritation at being mistaken for a child when i was younger. When I was in college, I actually got carded for pumping gas, which you have to be 16 to do. I was old enough to buy liquor at that point, but looked like I was in junior high. I'm now weirdly jealous of my husband because he started graying a few years ago, and my hair has been getting darker instead. I do not look as mature as I am, and I do lament that. I suppose in another twenty years I'll be happy about it, but I thought that twenty years ago. ;-)
Calli- At 13 they thought I was 17 at 25 i looked 25.
@Callie: at 31, out to dinner with husband, inlaws and 2 preschool children, I got carded. I feel your pain. However at the other side of 50, it's great fun looking in your 40's! I've even had the sideshow carnies be very wrong at how old I am.
@anon, did you ever answer the question as to why you disagree with the current vaccine schedule?
Calli Arcale continues to look 23. Just sayin'.
"Fortunate Genes" would be a good name for an altie rock band.
"Unfortunate Jeans" would be good, too.
Calli Arcale, March 4, 2014:
Aw, shucks **drops head and shuffles feet** Calli. I know the idea isn't original, but I'm not clear about the wording. Do with it as you see fit.
When I look in the mirror I see the same image I see when I see a certain photograph of my mother. It is quite freaky.
What is even more freaky, I am presently fifteen years older than my mother when she died. (don't read any health issue in that, she died in a plane crash)
I don't take supplements. Since I am very fair, I am a big fan of sunblock.
I wonder a bit about the "expensive urine" claims when it comes to ascorbate. Animals that make their own ascorbate from glucose also excrete excess in their urine. Rats, for example, synthesize 2.6 mg/100 g bw per day, the equivalent of 1.82 grams per day in a 70 kg human. Of this they excrete 15% in their urine, the equivalent in a human would be 273 mg per day.
That's fairly 'metabolically expensive', so presumably this must confer survival advantages to the rat that outweigh the loss of that much glucose.
Humans have developed highly efficient ways of conserving ascorbate, and we also use uric acid as a substitute antioxidant, so we can't directly extrapolate from an animal that synthesizes ascorbate to humans. Still,as I say, whenever I see that "expensive urine" jab I do wonder a little.
Does 'young looking' actually have any correlation with longevity, anyway? Both sides of my family do well on looks (just last week, a nurse at my mum's new GP practice double-checked her birth date, because she thought my mum had to be younger than her records said), but only one of my grandparents lived into their eighties. And my young-looking and active father died of a stroke a couple of years ago, aged 71.
Don't get me wrong, I don't mind that people are surprised when I tell them my age, but I'd never assume that it's actually an indicator of anything medically meaningful.
Callie, MI --
I'm sure Lord Draconis would appreciate a little acknowledgement of the anti-aging vat treatments he provides to worthy shills...
:)
Krebiozen - I suspect the term "expensive urine" does not refer to metabolic expense but cash money. Rats can excrete all the ascorbate they want, but they didn't pay for it in the commercial/economic sense.
I suppose rats might have some sort of underground economy, but I've not seen any evidence for that.
M.O'B.,
Perhaps you miss my point. Calories are expensive for an organism like a rat. In the wild they have to expend a lot of effort, what humans would call work, to get them, so I would expect them to spend them wisely. Why synthesize ascorbate from valuable glucose when 15% of it will be excreted unchanged in urine?
I can think of a couple of possible reasons:
Firstly it may be beneficial to have the urinary tract flooded with ascorbate. I can't think of any evidence for this, offhand, though it is a claim made by advocates of high dose vitamin C.
Secondly it may be an unavoidable consequence of keeping blood concentrations high. Ascorbate is involved in a number of crucial biochemical pathways, including collagen synthesis, so I imagine there is high demand, and that may require relatively high blood levels to ensure there is enough available, since it isn't stored.
I think the second is the probable explanation, but it has been adopted by some as evidence that humans should be taking large enough doses of vitamin C to maintain blood levels similar to those in ascorbate-synthesizing animals. As I wrote above, I think ascorbate-conserving mechanisms in humans, as well as uric acid as a substitute antioxidant probably refute their arguments, but I'm not entirely convinced.
It's a pedantic personal bugbear of mine really. The fact that humans excrete excess ascorbate is not prima facie evidence that paying money for ascorbate is a waste. There might be benefits of increasing blood levels a little, there might be benefits of having ascorbate in the urinary tract. I'm not convinced there are, but neither am I convinced there are not. The same goes for risks.
Really I would like to see some studies of people like anon who have taken true megadoses of vitamin C for years. Even a retrospective case control study would be interesting, given the grandiose claims made by ascorbate aficionados. There aren't many high quality studies of vitamin C being taken in multiple gram quantities for anything but cancer (and those aren't entirely satisfactory for various reasons). I think any useful benefits are unlikely, but I sometimes wonder a bit.
And...
because of its role in synthesis of collagen, woo-meister general Null prescribes it for....
rejuvenating aging skin. You probably need several thousand mg per day, split into 5 doses. I just re-heard this a few days ago which explains his proverbial 'perpetual youthfulness'**. He always recounts tales of people telling him that he looks "exactly the same" as he did in the 1970s. ( see photos at websites).
I never take megadoses of anything and attribute my own fabulous well-preserved look to genetics. And avoiding the sun. As a child I noticed that extremely attractive older relatives were also preteraturally white- because they stayed out of the sun.
And -btw- Draconis has nothing to do with it. And there is no secret, frightening protrait hidden in an attic.
** that and using 30 year old photos and surgical procedures.
Heh -- I do look older than 23 now. At least, they don't card me at the liquor store very often anymore. I will be turning 40 next year.
That's a good question. Youthful looks and late maturation are common in my family. However, we just buried my grandfather at 86, and many of his family died younger. Possibly worth mentioning is that his grandparents were Christian Scientists, leading to a general disdain for medicine in his family -- his grandfather died at home, refusing any treatment, and the family waited so long to call an ambulance that rigor mortis had set in - which was especially awkward given that he died *upstairs* in a house with a very narrow and twisted staircase. Reportedly, he had to be stood up to get him down the stairs. My grandfather did eventually start making good use of modern medicine, but, well, he was a stubborn Swede. ;-) It took him a long while to get the idea that not everything should be just borne. We had some family members on my grandmother's side who lived into their late 90s; my great-aunt died just a few months shy of her centennial, dying after falling and breaking her hip. On my father's side, some look younger and some look older; my uncle went bald around 25. And living into the 90s is fairly common on that side.
Krebiozen - I didn't miss your point, which I quite agree with. I deliberately walked straight past it, gave it a nod, and went on my way.
Water would be another example. I suspect that every drop of water you drink (assuming you are not gaining weight) is also lost nearly as rapidly as it comes in. We do know that if you drink too little water you can have bad health consequences - even though the amount you drink and the amount lost balances out. We also know, of course, that drinking too much water too quickly can kill you.
Is it possible that consuming a lot of ascorbate has a positive effect even though the amount you eat and the amount you excrete balances above a certain amount? I haven't the foggiest and don't know what the research shows. The impression I've had is that the research hasn't shown any particular benefit, so any amount consumed above the level necessary for optimum health (whatever that is) so anything more consumed would be wasted. But then, that's just my impression.
@Denice All my relatives looked old at my age and did stay out of the sun. My grandmothers looked very old, so did my aunts.
It does not correlate with longevity so I may be a younglooking corpse( vit c does not improve gallows humor) I was called "a pisser" once.
@ anon:
Mine were variable: some looked young, others average. Some lived into their 90s, others into their 70s and 80s. It's only one side of the family that is/ was ultra white- I believe that *those* benfitted from a lack of sun- this is esp apparent now with my cousins whose father was from Ireland.
anon, my paternal grandmother looked very old by her forties. But that was because she had been a farmer's wife in the high desert where they grew peaches. They had moved from Appalachia to west of Rockies for her health, she had tuberculosis. She died when she was 56 years old.
Lots of folks early the twentieth century suffered from the after effects of illness, even though they survived them as children. Things like Scarlet Fever and measles could cause heart conditions (rheumatism), etc.
Please go up to Comment #50, and read it.
@chris I answered on a different blog
@50@notation My son was born in ’69 fully vaccinated acccording to the schedule at the time. He is a very healthy competitive bike racer, treker, surfer, granola cruncher who vaccinated his kids according to a different schedule. They are very healthy. I see nothing wrong with that decision and resent having “opinions” shoved down my throat.
(His mother-in-law is a nurse practiioner.)
@Chris@65 My father died at 59 from untreated hyperthyroidism. My aunt lost 2 babies from Rh factor incompatibilty. Another aunt had a brain damaged child from lack of oxygen at birth.
These conditions are now treatable and to me are the real advances in addition to vaccines. I had blood poisioning as a child, Thank God for penicillin. Fortunately I had no ill effects from german measles, chicken pox, mumps -a neighbor child developed polio. Modern medicine has truly brought wonderful advances. Older relatives would be dead if not for bypass surgery, angioplasty, antibiotics. Luckily no one suffered ill effects from VPD.
@Chris Unfortunately aunt, cousin, friend did not make it past the 5 year survival rate for cancer after chemo. Their quality of life was hellish on chemo.
M.O'B.,
Yes, but water loss does something useful: it either cools the body down through sweating or it helps excrete soluble waste in the kidneys. Water loss is very closely controlled by the brain and kidneys. In the rat, excreting unchanged, i.e. reduced, ascorbate does nothing obvious of use, at least nothing that's obvious to me. Either keeping blood levels above the renal threshold is beneficial to rats, or G_d had another off-day.
It's the level that's necessary for optimum health that people argue about. Other ascorbate-dependent higher primates in the wild consume comparatively more ascorbate than we do, though studies in captivity show similar results to those on humans i.e. clear scurvy below a certain intake, and some evidence of benefits in higher doses.
There is quite a bit of evidence of variable quality suggesting mostly modest health benefits to megadoses of ascorbate in humans if you feel inclined to trawl the literature.
Even ascorbate for colds, which is generally held to have been thoroughly debunked in sceptic circles, shows some intriguing results, I think. For example this one this Cochrane review concluded:
It's results like these that make me reluctant to close the door on megadose ascorbate entirely. These are hard endpoints - someone either has a cold or they don't - unlike the usual studies of CAM that find barely statistically significant results on subjective self-measured endpoints in trials with poor blinding.
I still think there might be a signal lurking in the noise here.
Colds can be miserable, and even a modest shortening gets my vote. A 50% reduction in colds in those exposed to extreme stress is remarkable. This also makes me look again at the extraordinary results that Dr Fred Klenner reported in the 40s and 50s (later too) using huge doses of oral or IV neutral ascorbate to treat various illnesses. With antibiotic resistance becoming more and more of a problem, other potential ways of dealing with infection are worth looking at. It would be a shame if we missed something important and/or useful just because it was associated with woo.
As I said, I wonder, but only a bit. Less than I used to.
I still think there might be a signal lurking in the noise here.
Can you swear that this is not just another rationale for consuming spicy food? (IIRC, it was a plate of paprika-rich goulash that finally provided Szent-Györgyi with a sufficiently-concentrated source of Vit-C to isolate it).
Disclose your COIs, Krebiozen!
One thing I've been wondering about huge IV doses of ascorbate the past couple of days is whether there's a question of screwing with the useful roles of reactive oxygen species.
Mmmmm, goulash.....
@anon: That does not answer the question I asked you. What is your reason for rejecting the current schedule? Do you believe it is somehow harmful? If so, why?
I don't see anyone shoving anything down your throat.
HDB,
Dammit, does nothing get past you?! There's lots of vitamin C in chillies generally, by the way.
re the spicy food:
There's a meme amongst the fashionable that eating highly spiced food - e.g. Thai- enables weight loss- supposedly you eat less and feel full or suchlike.
I know, I know: another excuse.
Narad,
That's certainly a theoretical possibility, and since ROS are involved in both apoptosis and killing pathogens, this would probably be a bad thing. However, since we have evolved for several million years with relatively large amounts of ascorbate in our systems one might hope that we have mechanisms to protect against this.
The remarkable safety profile of ascorbate* would appear to support this. I'm surprised you can give a patient such large amounts IV with, apparently, so few physiological effects. I wonder about the sodium load, or do they give a mixture of sodium and potassium (maybe even magnesium) ascorbate?
The whole idea that oxidation is bad is about as sensible as the idea that acidity is bad. Healthy metabolism requires a balance between the two, and without either we are dead. Randomly screwing with this balance by taking vast amounts of an antioxidant (or an alkali for that matter) doesn't seem very sensible when looked at in this way.
It is also worth noting that ascorbate can act as a prooxidant too in some contexts, and there is some complex stuff going on with dehydroascorbic acid too. To complicate matters even more, some of the animal studies may have used ascorbate in drinking water that had oxidized in air, making results unreliable. The whole area is, IMO, a bit of a mess, and the sheer volume of data out there makes it very hard to interpret.
* I'm not convinced by the claims of oxalate from metabolism of ascorbate leading to renal calculi. These seem to mainly rest on a single case history of a patient on dialysis whose renal failure was caused by oxalate calculi in the first place. Still, I understand the precautionary principle, risks without clear benefits etc..
Denice,
I must admit I do like the endorphin rush that eating very spicy food induces. I also find it interesting how we can learn to reinterpret the pain that chilli induces as pleasure. I believe psychologists call it a "constrained risk", like riding a rollercoaster or watching a horror movie. The pain chillies induce is merely an illusion, no damage is done, just polymodal nociceptive neurons stimulated into firing. The pain can even be blocked by a substance called capsazepine, which I am considering marketing to people who want to appear macho by eating ridiculously hot chillies.
The irritation capsaicin causes is real enough, but appears to be the result of our bodies overreacting to the substance, rather than any damaging effects of capsaicin per se. I reckon it should rival acupuncture as a placebo; it is already used in medicine as a counterirritant. Capsaicin, by the way, has an LD50 in mice of 47.2 mg/kg, almost twice as toxic as thimerosal with an LD50 of 75 mg/kg*, so pretty harmless really ;-)
I don't remember if I have mentioned here a CAM guru I came across years ago who believed that chilli tincture (basically an alcoholic solution of capsaicin- very hot indeed) cures almost everything. He recommended it for cardiac arrest instead of CPR, which he claimed is a killer. I find the idea of someone squirting chilli tincture into a person's mouth while they are having a heart attack horrifying and hilarious in approximately equal measure.
* A 5 gram chilli might contain up to 300 milligrams of capsaicin, or 9% of a lethal dose for a 70 kg human. The world's hottest chilli is the Naga Viper, a hybrid created in England (ironically, as popular wisdom holds it as the spiritual home of bland food) , by the way, more than 150 times hotter than a japapeno. Why? Beats me.
the Naga Viper [...] more than 150 times hotter than a japapeno. Why? Beats me.
As you said yourself, "people who want to appear macho by eating ridiculously hot chillies".
re spicy food: much as I try, I just simply cannot handle much more than slightly hot spices in foods. My husband loves hot peppers and can chomp on jalapeños with nary a blink. I can barely tolerate any heat. It just burns! I can't even taste anything! It irritates me--we live in an area where wonderful ethnic restaurants abound, but unless they're willing to tone down the fire, it's useless for me to go to them.
I am so *not* macho.
I take it you're ignoring all but the immediate effect.
Obligatory Johnny Cash link>.
Even the subsequent sensations, though not pain, would normally be associated with ill-health, wouldn't they? Flushing, sweating, feelings of warmth and perhaps mild gastroenteritis?
notation,
I'm English, living in the UK, and my wife is American. When she first came here she was unable to tolerate more than the slightest bit of heat in her food, which was ironic since she once won a chilli-making competition in the wilds of Michigan once. I like to think it has been my subtle but steady pro-chilli propaganda that has converted her into an aficionado of the sacred fruit. She has even developed a couple of excellent curry dishes of her own that leave me sweating. She worked her way up to this slowly, using plenty of yogurt on the way.
I think it's partly a matter of building up tolerance, and partly a matter of learning to love the sensation. Don't get me wrong; too much chilli undoubtedly ruins a dish, and even the most macho chilli fiend has his limits. When the heat plays its proper part in the orchestra of gustatory sensations the results can be exquisite, but when it overpowers everything it's just horrible.
Happens sometimes with one spicy solution or another in cartoons and graphic novels, generally to wake up one of the characters. Based on the results, the subject certainly wakes up, but tends to run on walls and ceiling for a bit.
Sadly, real life characters like us lack the amazing physiology of the average wild coyote...
which was ironic since she once won a chilli-making competition in the wilds of Michigan
Do not confuse Midwestern versions of chili with actual chili. My late mother in law's recipe calls for boiled potatoes and canned tomato juice.
@Kreblosen, I'm glad your wife has been able to raise her tolerance level. Believe me, I am able to use more hot spices than previously, but I'm a long way from being able to enjoy curries from the local Indian restaurant without pain. Last fall, at a terrific place in San Francisco, we had a pizza that was just delicious---right up until I bit into a chili pepper (I have no idea what kind it was). My eyes watered, my face flushed, and I had to resort to gulping down multiple glasses of water and gnawing on bread to put out the fire.
Sigh. Maddening.
My sweetie and I are contemplating a move to the midwest. Shay's comment about the chili is giving me serious pause. Bad enough I'm going to have to give up fabulous sashimi... (I know, I know, first world problems!)
Johanna, in the interests of fairness, I must admit that we live in one of the largest counties east of the Mississippi and it's 89% farmland.
If you like sweet corn and pork chop sandwiches, you'll do fine.
Pork chop WHAT?
...maybe I'll open a sushi restaurant...
Srsly, though, I'm ready to trade off a few things in exchange for living in a place where a studio apartment doesn't cost $2200/month. The aforementioned sweetie and myself have decided that it's not unreasonable to want enough space for our bodies AND our hobbies, but apparently that's too much to ask from the SF Bay Area. Granted, we both have space-consuming hobbies, but still...
So we're kicking around ideas like Minneapolis and Madison. I've never lived more than 50 miles away from salt water, so I'm a bit trepidatious. (Lakes, no matter how huge, aren't the same!)
Krebiozen, I am what is known as a "super taster."
There are these little pieces of paper that when put on the tongue produce different reactions. Most folks say "meh, don't taste anything" or "meh, not bad." For me it was a gagging "Oh no! Yuck! Aaagh!" reaction. I spent the rest of the evening trying to rinse the foul taste out of my mouth.
So no real hot chilies for me. And absolutely no cilantro (I can actually smell it from a meter away). It literally tastes like soap.
Chris, a foodie friend of mine suggested I might be a super-taster as well. How does one get tested? I'd love to be "super" at something! ;)
John Lee Super Taster!!!!
One of my kids' favorite songs by They Might be Giants.
re the spicy food:
I never had ANY until a university friend took me to an Indian place and I was immediately hooked - although I don't always like the hottest of the hot ( that includes men)- medium hot will do.
@ Joanna
BE trepidatious. Your vague feelings of distress are a fair warning. I don't think it's just about the water but the fact that places near water tend to be liberal enclaves of art and iniquity and you - like me- probably need that.
I have never lived away from large international cities where big business, fashion and universities rule ( partially due to families fromthose places). And multicultural people and food are everywhere. I've found in my travels that those are the places i'd prefer to visit and live- like SF. That place is a gem. It's a great - and that costs money. Even if you have to live 30-40 miles away, it's worth it for the cultural and business/ career opportunities.
Proceed with caution.
- a few years ago, a relative asked me if I thought him mad to move to the country and I , being diplomatic, said that I thought it would be wrong *for me* but I should have said what I really meant because he's not happy where he is and now has the added burden of being seriously ill in a rural area.
Ooops! Sorry.. JOHANNA
@Denice
You spotted the "H" so no harm done. But thank you for noticing. ;)
We're kicking around a lot of options. My sweetie's a professional artist (in many media) so going somewhere with reasonable support for the arts - or an industry that requires those skills (such as computer gaming) - is mandatory for wherever we end up and thus, I hope, reduces the odds that we end up in someplace like Fargo.
(Artists are lovely people, but rarely overpaid. I'm a glorified secretary. Even at our maximum earning potential, we'd be hard-pressed to afford a two-bedroom apartment even in the 'burbs of the Bay Area. I love it around here, I really do, but the cost. Oh dear gods, the cost...). We've agreed that giving up on things like sushi and cocktail mixers at the museum would be a fair trade for a house that could accommodate us AND our hobbies. (Among sweetie's many talents is sculpture. That damn clay piles up after a while. And some of it SMELLS.)
We're casting the net pretty wide, as it's all still in strictly-hypothetical stage and it costs us nothing to talk and research places online. Sweetie's lived in some midwestern places that he found bearable, so I'm willing to consider them as we're pretty sympatico on what makes for an acceptable local culture. That said, I'm sure I'd be happier if we landed near a coast (greater Boston area, Philadelphia) rather than snow-and-tornado country. ;)
(Snownado?)
Well, Johanna, we paid $56,000 for a 1500 square foot Craftsman classic bungalow -- with detached two car garage -- on a double lot.
(BUT -- speaking as a city girl, it was a bit of an adjustment to settle down in a village of 900 people. The spousal unit grew up here, so it didn't bother him a bit).
I'm not sure what employment opportunities are like there, but Stillwater, MN, is a lovely town, right on the river. Every other business seems to be a used bookstore, too.
The winters may take some getting used to.
@Shay
One of the places under consideration is Minneapolis as it's a surprisingly progressive town (Michelle Bachman notwithstanding). I can cope with snow, but the SHEER FREEZING COLD might take some getting used to. My sojourn in New England was a long time ago...
(But, as was pointed out by a friend, elsewhere, best to move somewhere too cold for ice storms because, whoa, those suck.)
That said, I totally want to live somewhere that has actual thunderstorms. I miss those!
notation: " How does one get tested?"
I went to a presentation on food sponsored by a local natural history museum which consisted of several ten-fifteen minute talks. The little pieces of tasting paper were given out by a researcher who specialized in the biology of the senses (I think).
I've seen similar things at science museum events. And with a bit of a check, I see it is some science you can buy for home. Oooh, and looking down that list I see different kinds of strips (one has four different kinds). I can see this as an activity for a ten to twelve year old birthday party (for my youngest we did egg drops).
Minneapolis is great! Don't let this particular winter scare you off; this is the worst we've had since the early 80s, and the summers are awesome. (Plus, thanks to the winters, we have less venomous critters!) And though we do get severe thunderstorms, we're out of the worst of tornado alley so the threat is really pretty mild. And although we aren't within 50 miles of an ocean, we are within 150 miles of Lake Superior. Which . . . well, don't let the word "lake" fool you. It's freshwater, but it's gargantuan. It really looks like the ocean. Of course, Duluth is nice too, and right *on* the lake, and has lots of steep roads like you might be used to in San Fransisco. ;-) But they do get more snow than Minneapolis, and it does get colder as well (especially if you're not on the lake side of the ridge; the lake moderates the temperatures for a short distance only). Duluth is a pretty interesting place to visit, though. It's a bona fide deepwater port, and busy. In the winter, there are at least half a dozen big lakers tied up, waiting for the ice to go out, and they are BIG. Some are over a thousand feet long.
And while lakes aren't the same as the ocean or even the Great Lakes, we've got some really wonderful lakes (the Minneapolis chain of lakes is quite a jewel, and completely accessible to the public), and three great rivers that come through the metro -- the Mississippi, the Minnesota, and the St Croix. So you will not want for water. ;-) In fact, Minnesota has one of the highest per-capita boat ownerships in the nation. We love us our water!
And yeah, we rarely get ice storms. Occasionally. But not very often. It's usually too cold. The best winter weather, in my view, is when the high is in the mid-teens to low-twenties, because that's the sweet spot where bundling up is adequate but the snow is cold enough to not be very sticky.
Michele Bachman, BTW, is not in Minneapolis but in the northeast metro. Outer metro, at that. Easy to avoid. ;-) Most of us regard her as a trainwreck in progress, but cannot vote her out as we're not in her district.
@Calli
re: Minnesota
I looked at a couple of cost-of-living estimators, compared 'em to the salaries on offer for a person of my skills and experience and I liked what I saw! A place like that, me and my sweetie could get by with him only working half-time, so he would have time to, y'know, BE an artist. :)
Johanna, most university towns would fit your bill. And if you are willing to go to Minneapolis, you might want to check out Eau Claire, WI.
A smaller college town, but not too far from Minneapolis (a couple of hours). I always enjoyed visiting relatives there. My grandfather had a house on Lake Wissota in nearby Chippewa Falls.
I have a former employee who is now in Madison, WI (University of Wisconsin). She loves it, for all the reasons Chris has mentioned. Their governor notwithstanding, Wisconsin's pretty nice.
(And you could always help vote him out of office).
As I don't drive, I have to keep public transit options in mind, which I must admit, rather complicates things. So it'll probably be a bigger town/metro area...
@Shay: Hm, I have a friend working there too, although I doubt it's the same person as your ex-employee... Unless they're a librarian?
One nice thing about having been a social butterfly all my life, where-ever I end up, I'll probably have at least one chum within a hundred miles. ;)
I'm trying to think of the several college towns I have been in, but often they do not have a couple of the criteria like near a large body of water or a good transit system.
Some I thought of include:
Pullman, WA
Flagstaff, AZ
Tuscon, AZ (though I am not fond AZ politicians)
Eugene, OR
Austin, TX
Olympia, WA
On vacations we have liked a couple of towns that I would not mind retiring to; Astoria, OR and Stevenson, WA. Both are on the Columbia River not far from Portland, though the former is also on the coast.
I happen to live very close to a large university, but we bought when the area was not quite catching up to the San Francisco area (new assessment of our house has it three times more than what we bought it for twenty years ago). But there is decent transit to less expensive parts of the county:
http://metro.kingcounty.gov/
We are starting a five year plan to downsize from our family sized house to a retirement abode. So we are repairing twenty years of wear and tear (including kid/pet damage) along with looking for a suitable place.
@Chris #99: Thanks! Love the idea of using it for a kid party, too.
No, there's pain. Whether one can find an endorphin rush from it may be a matter of temperament. Understand the Johnny Cash reference.
Johanna,
I've had good sushi in St. Paul, Minnesota, and I'm told there's good sushi in Minneapolis proper as well.
Don't remember eating sushi or sashimi in Madison, but there's quite a bit of other good food, including on State Street between the capitol and the UW campus.
Chris,
I'm not convinced your chili and cilantro reactions are part of being a super-taster. I can taste bitter things like PTC very strongly, making me a super-taster; my wife can't taste them at all. She can't tolerate cilantro, even the smell makes her gag; I don't mind it. I love hot chilis; she has developed a tolerance but still can't tolerate as much as I can. I love the taste of brassicas, she isn't at all keen.
There's more than one thing going on here, I think.
Chicago's a damn sight cheaper than the Bay Area, and there's plenty of public transportation. You can even get decent sashimi.
Ah, public transit. Well, we do have public transit, but I'm not sure "good" is the right word for it. Unfortunately, you'll find that's true of most midwestern towns, a byproduct of the suburban sprawl that our flat geography permits. If you do consider the Twin Cities, you'll definitely have to choose your location well because some parts of the metro are much better served than others. We've got the Metropolitan Transit Authority running most of the buses, but in the south metro where I live, we also have a second transit company, the Minnesota Valley Transit Authority, which connects to MTA. And we're finally getting light rail. The Hiawatha Line runs from the Mall of America to downtown Minneapolis, with stops in between at places like the MSP airport and various parts of south Minneapolis (including the spectacular Minnehaha Falls park), and the Central Corridor connecting downtown St Paul to downtown Minneapolis will open this summer.
Krebiozen: "There’s more than one thing going on here, I think."
I also believe there is more going on. Especially since I am not as a supertaster supposed to like broccoli and Brussels sprouts, but I do. Though I have read that there has been some research showing some genetic link to cilantro (basically being more sensitive to alkaloids).
This is why I was surprised to see there was more than one kind of tasting paper. They seem to be pinpointing more differences.
I don’t always like the hottest of the hot
The tradition among Indian restaurants here, when a curry is ordered "hot", is to seek further clarification -- "Kiwi hot or Indian hot?"
Speaking of curry: it is also among the things I dislike. I don't know why, but it is not because of the heat.
@ Chris:
Perhaps you dislike that musty/ pungent aspect?
At any rate, I'm not sure if I'm a super-taster or not but I despise Brusself sprouts and cabbage - only broccoli florets are tolerable, not the stem parts.
I like cayenne and ginger but not black pepper and I absolutely loathe cinnamon, dill, alllspice, mustard and a few others that presently escape me. Cilantro is alright.
@ herr doktor bimler:
Kiwi hot= Indian mild-medium.
@ Johanna:
Oh, you must learn to drive. It is one of the most wondrous abilities with which humankind has blest.
Then you could live in Sonoma or Mendocino. And drink organic wine.
@denice
Massive, hyperventilating anxiety strikes me when sitting behind the wheel of a parked car. You don't want to know what happens when I try to actually drive it.
The roads are safer with me OFF them. :)
And I can get organic wine at Whole Foods. :)
@Johanna: I currently live by the ocean (Atlantic) and I'm not totally impressed. I grew up by the Great Lakes. One fond memory I have is my Long Island born and raised (now-ex) husband waking up at my parents' cottage thinking he was on the ocean because Lake Huron just happened to be having a bit of a tantrum and was tossing up 12-15 foot waves... He couldn't believe it, since he never really believed the Lakes could have "real waves". I didn't tell him about the time Lake Erie had 30 foot waves during a storm and I was on it in a boat with family.
@Johanna, I am green with envy. Almost no grocery stores in my *ahem* tax-happy county are permitted to carry any wine or beer.
@ Johanna:
You know that anxiety, panic and phobias are not unavoidable consequences of living: i.e. there is science based help for these miseries.
See, this is what I don't get--from the Washington Post: "Gaeng par hed at Doi Moi It takes only a bite or two of Chef Haidar Karoum's wild mushroom curry for the sweats to begin, brought on by spice so intense it flushes your cheeks and sends you reaching for your Thai tea. Inspired by a Thai jungle curry, Doi Moi’s vegan dish has no coconut milk to temper its wild heat. "
That appeals to me about as much as eating chicken gristle, as I was urged to do in Japan. Urrrgh. Dinner is SO OVER!
notation, if you are going to hang out here on RI, you have to expect that some of the RI Regulars are foodies.
Rather than organic California wine, why not try Two Buck Chuck, available at Trader Joe's?
http://en.wikipedia.org/wiki/Charles_Shaw_wine
Whole Foods? My daughter refers to that emporium as Whole Paycheck.
Johanna -- the Great Lakes have it all over the ocean in two respects, as I learned whilst living on the island of Okinawa for three years after growing up in Michigan.
No sharks.
You can open your eyes under water.
No jellyfish.
Okay, three things.
@lilady: oh, I have no issue with foodies! I LOVE to cook and eat. I just can't take the burn. I am familiar with the Two Buck Chuck, but my tastes run more toward the $$ wines, especially bubbly. Laurent-Perrier is sublime. My cheap addiction is Dibon cava, though. Loverly, and only ~12-14 bucks a bottle.
"Okay, three things."
NOBODY expects the Spanish Inquisition! Our chief weapon is….
More on the "super taster" issue: I love Brussels sprouts and broccoli, as well as asparagus. Not so crazy about cilantro or fennel, though.
I love dill...ask Narad about tarragon pickles.
Cilantro? Um, no.
Cruciferous veggies are actual "good" for you:
http://www.cancer.gov/cancertopics/factsheet/diet/cruciferous-vegetables
Fennel is yummy (minus the licorice taste), when it is roasted in the oven with potatoes and carrots, preferably under a chicken.
I will take this opportunity to scorn and mock whatever freakishly ignorant mindset has driven the price of freaking garden-variety prosecco north of $10 for 750 ml.
Chris,
Same here; I wonder if they are an acquired taste for supertasters. It took me a while to learn to like the taste of English bitter beer too, but I persevered ;-)
What about coriander seeds? It's the same plant, but presumably different chemicals that make the aroma. My wife has a serious cilantro (coriander leaf) aversion, but loves the seeds in curries etc..
I sometimes wonder what it would be like to experience someone else's gustatory system. There are clearly some large variations.
@Denice - I hate to use the word 'phobic' because it's so abused but, well, suffice it to say that every reasonable attempt has been made to alleviate the situation (re: my non-driving) and, no dice. I'm really much happier this way.
@notation - goodness! Where do you live? Salt Lake City?
@lilady - I too, call it Whole Paycheck, and only venture there for things I *cannot* get anywhere else. As I'm not a speshul snowflake, that's not very often, which is a relief as there's one within walking distance of my office and, man, they do some yummy stuff for lunch. Not cheap, but yummy!
I use Two Buck Chuck to make sangria. That's really all it's good for, imho. My default table wine is whatever NZ sauvignon blanc on special for about $10 a bottle. A sommelier, I ain't. ;)
@ Johanna:
As long as you're happy with it. That' what counts.
Buses, trains, planes and an artist who drives.
@ Krebiozen:
" I sometimes wonder what it would be like to experience someone else's gustatory system".
And there's the subject of your next short story/ article.
We have a supermarket chain in the UK called Morrison's. They usually have 'better than half price' offers on wine. Pay about a fiver for something usually priced at a tenner. Usually Australian red. Can't go wrong. Better offers on cava at Asda (owned by Walmart so maybe you get similar deals over the pond too) though. Took me a while to remember that cilantro=coriander but I made a load of Nepali friends at uni so we were always having curry in one form or another. Meatball curry was the best, if any meatballs made the perilous journey from deep fried to pan without being eaten.
Do not believe the lies of the broccoli-industrial complex.
Johanna, I love white wine sangria.
NumberWang...your "fiver" and "tenner" in Pounds Sterling?
MO'B: No goopy sauces for me; broccoli (or cauliflower), sauteed with garlic in a bit of olive oil.
Lilady, I'm with you on the broccoli, but there's an Indian dish with cauliflower that I beeline to whenever its' on the buffet. Couldn't tell you the name if my life depended on it. Turmeric, tomatoes, onions, garlic and maybe just a soupcon of red pepper.
Damn. I had a tuna fish sandwich for lunch and now I'm hungry.
Shay, the DH does the Indian restaurants with his buddy, a chap from the U.K.; Geoff is the connoisseur.
I use red pepper occasionally. I just made batches of chimichurri for my grilled rare flank steak.
Gobi masala or some "gobi" variation.
I've got stage 4 colon cancer and I had cyto-reductive/HIPEC surgery in October. I've been doing intravenous vitamin c (10,000 mg) one day a week on weeks I'm not getting the adjuvant chemotherapy as a way to build my immune system. Is this effective or just a waste of money?
I'd say waste, but check with the experts.
@Ralph - it is my understanding that the evidence that intravenous vitamin C provides a benefit for building the immune system and helping cure cancer is minimal to non-existent. However, I am a lay person and have made no special study of this. I do, however, wish you all the best.
@Ralph, you should talk to your oncologist about Vitamin C and any other supplements you may be taking. There can be unfortunate interactions among drugs, including supplements.
I too wish you the very best of luck.