![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 30. This is the beginning of the thread.
Posted by linkadge on May 22, 2006, at 17:30:07
I read that some of the TCA's displayed genotoxic effects, yet others didn't. Doesn anyone know which ones are considered genotoxic, and how to find out ?
Linkadge
Posted by BrianBoru on May 22, 2006, at 17:59:46
In reply to which of the TCA's are genotoxic ?, posted by linkadge on May 22, 2006, at 17:30:07
There are six:
amoxapine, clomipramine, desipramine, doxepin, imipramine, and trimipramine
but the genotoxic effects have only been conclusively shown in fruitflies. Please don't have children with fruitflies. ;-)
Posted by linkadge on May 22, 2006, at 20:04:50
In reply to Re: which of the TCA's are genotoxic ?, posted by BrianBoru on May 22, 2006, at 17:59:46
No, but If I recall correctly there was a statsitcally higher rate of cancer in those who had taken the genotoxic TCA's as opposed to the non genotoxic ones. The cancer seemed to appear something like 10-15 years after the drug was taken.
Linkadge
Posted by Phillipa on May 22, 2006, at 21:59:40
In reply to Re: which of the TCA's are genotoxic ? » BrianBoru, posted by linkadge on May 22, 2006, at 20:04:50
Well no TCA's for me then. Love Phillipa
Posted by Meri-Tuuli on May 23, 2006, at 3:18:22
In reply to Re: which of the TCA's are genotoxic ? » BrianBoru, posted by linkadge on May 22, 2006, at 20:04:50
Hi Link,
>The cancer seemed to appear something like 10-15 years after the drug was taken.
Yikes! I've never heard about this. Thats pretty serious stuff. Any idea why its not more well known, or is the research not conclusive enough?
Kind regards
Meri
Posted by ed_uk on May 23, 2006, at 15:11:28
In reply to Re: which of the TCA's are genotoxic ?, posted by Meri-Tuuli on May 23, 2006, at 3:18:22
Hi Meri
Some SSRIs have been associated with cancer too.
Did you start a new AD after moclobemide?
Ed x
Posted by Meri-Tuuli on May 24, 2006, at 3:33:26
In reply to Re: which of the TCA's are genotoxic ? » Meri-Tuuli, posted by ed_uk on May 23, 2006, at 15:11:28
Hi Ed,
Good grief, cancer???
I've started nothing.
The pdoc rang up and suggested remeron and lustral. Pa! There's *no way* I'm touching remeron - the sedation and weight gain?? No way! I have enough trouble being sedated as it is!! And I've also vowed never to touch another SSRI again - I just can't handle the apathy, sleepiness , zero motivation. I'm like this without SSRIs, let alone on them!
I need something stimulating desperately!!
In all honestly, unless the pdoc suggests ritalin (hahahaha) I'm not going to take anything. I'm seriously thinking of going back on the St John's Wort and maybe rhodiola too.
I'm seeing the pdoc on Thursday.
Kind regards
Meri x
Posted by linkadge on May 24, 2006, at 18:42:31
In reply to Re: which of the TCA's are genotoxic ?, posted by Meri-Tuuli on May 24, 2006, at 3:33:26
Yeah, it scared me too. There were 6 TCA's included in the list and one SSRI (I think paxil) which seemed to be associated with higher risk of certain cancer.
I think the TCA's failed certain tests for genotoxicity. It was serious enough that the researchers who designed the study suggested that people change their medication.
Linkadge
Posted by Larry Hoover on May 24, 2006, at 19:28:34
In reply to Re: which of the TCA's are genotoxic ? » Meri-Tuuli, posted by linkadge on May 24, 2006, at 18:42:31
> Yeah, it scared me too. There were 6 TCA's included in the list and one SSRI (I think paxil) which seemed to be associated with higher risk of certain cancer.
I am trained in environmental toxicology. I think I have the background and experience to offer some guidance, here. I hope you also believe that.
The increased risk associated with these drugs is absolutely trivial. It is tiny. Hardly worth a mention. I do not consider it sufficient to change medical treatment in *any* respect, save trying those drugs with this risk last. Not excluding them from use. Why use them first, when choosing a drug is a crapshoot anyway? That's all that I would do differently.
The genotoxic effect of broccoli is far far stronger than what is described here. You heard me right.
There are things to worry about in life. And things to not worry about. I, Larry Hoover, place this issue in the second category.
Lar
Posted by Larry Hoover on May 24, 2006, at 19:43:05
In reply to Re: which of the TCA's are genotoxic ? » Meri-Tuuli, posted by linkadge on May 24, 2006, at 18:42:31
Have you ever heard of the Ames test for mutagenicity? Bruce Ames? Here's what he has to say about the subject.
Comments at the bottom.
Mutat Res. 2001 Apr 18;475(1-2):7-20.
DNA damage from micronutrient deficiencies is likely to be a major cause of cancer.Ames BN.
University of California, 94720-3202, Berkeley, CA, USA. bnames@uclink4.berkeley.edu
A deficiency of any of the micronutrients: folic acid, Vitamin B12, Vitamin B6, niacin, Vitamin C, Vitamin E, iron, or zinc, mimics radiation in damaging DNA by causing single- and double-strand breaks, oxidative lesions, or both. For example, the percentage of the US population that has a low intake (<50% of the RDA) for each of these eight micronutrients ranges from 2 to >20%. A level of folate deficiency causing chromosome breaks was present in approximately 10% of the US population, and in a much higher percentage of the poor. Folate deficiency causes extensive incorporation of uracil into human DNA (4 million/cell), leading to chromosomal breaks. This mechanism is the likely cause of the increased colon cancer risk associated with low folate intake. Some evidence, and mechanistic considerations, suggest that Vitamin B12 (14% US elderly) and B6 (10% of US) deficiencies also cause high uracil and chromosome breaks. Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables (five portions a day is advised) has about double the cancer rate for most types of cancer when compared to the quarter with the highest intake. For example, 80% of American children and adolescents and 68% of adults do not eat five portions a day. Common micronutrient deficiencies are likely to damage DNA by the same mechanism as radiation and many chemicals, appear to be orders of magnitude more important, and should be compared for perspective. Remedying micronutrient deficiencies should lead to a major improvement in health and an increase in longevity at low cost.
Okay, anybody want to tell me why our doctors and governments aren't all over this? We are surrounded by propaganda, both negative (i.e. the absence of good information) and positive (i.e. the presence of false information). The more I study nutrition, the more I am convinced that we are being led down a path. A path to sickness. But, why? I can only think of one thing. Money. People would sue their *sses. Or something.It is impossible to obtain the RDA threshold of nutrients, from diet alone, while maintaining reasonable caloric intakes. It is impossible, and I challenge anybody to prove me wrong. The USDA has a database. Go to it. I did the math. It can't be done. Prove me wrong. Please.
Another aspect of nutrition, and one that ties directly back to the original subject, antidepressants....
In the following study, consider that sugar consumption is really a surrogate marker for food processing in general. Sugar is a food extract. A pure substance, normally found associated with all sorts of vitamins, and minerals, and fiber. But what do we do? We process the hell out of it, and derive this pure substance, sucrose. And we add it to everything. Do you have any idea how much B-vitamins are required to metabolize pure sugar? And the thing is, it doesn't come with any vitamins. 7 to 11 teaspoons, per can of soda. Remember what I said, though. I think sugar consumption is really a measure of food processing, more generally. But, consider this:
Depress Anxiety. 2002;16(3):118-20.A cross-national relationship between sugar consumption and major depression?
Westover AN, Marangell LB.
Mood Disorders Center (MDOC), Department of Psychiatry, Baylor College of Medicine, Houston, Texas, USA. anwestover@yahoo.com
We have preliminarily investigated the hypothesis that sugar consumption may impact the prevalence of major depression by correlating per capita consumption of sugar with the prevalence of major depression. Major depression prevalence data (annual rate/100) was obtained from the Cross-National Epidemiology of Major Depression and Bipolar Disorder study [Weissman et al., 1996]. Sugar consumption data from 1991 was obtained from the Food and Agricultural Organization of the United Nations. For the primary analysis, sugar consumption rates (cal/cap/day) were correlated with the annual rate of major depression, using the Pearson correlation coefficient. For the six countries with available data for the primary analysis, there was a highly significant correlation between sugar consumption and the annual rate of depression (Pearson correlation 0.948, P=0.004). Naturally, a correlation does not necessarily imply etiology. Caveats such as the limited number of countries with available data must be considered. Although speculative, there are some mechanistic reasons to consider that sugar consumption may directly impact the prevalence of major depression. Possible relationships between sugar consumption, beta-endorphins, and oxidative stress are discussed.
Lar
Posted by linkadge on May 25, 2006, at 17:44:54
In reply to Re: which of the TCA's are genotoxic ? » linkadge, posted by Larry Hoover on May 24, 2006, at 19:28:34
Well then, you take them.
I'll add you words to the compilation of opinions.
Linkadge
Posted by Meri-Tuuli on May 27, 2006, at 4:24:00
In reply to TCA's are genotoxic ? Addendum » linkadge, posted by Larry Hoover on May 24, 2006, at 19:43:05
Hey there Lar,
I'm totally with you on the vitamins and minerals issue. I don't think we can get the nutrients we need from the modern foods we have. And thats if we eat relatively healthily let alone with junk'empty calorie' foods in there too. Not to mention soil nutrient leaching, long shelf lives, etc etc. You know the issues.
Yeah, sugar is definately a modern evil. Our bodies aren't equiped to deal with all the sugar/refined stuff we eat!! But yeah, anyway. Do I avoid eating sweet stuff?? Hahahaha no, I can't live without my daily danish pastry!!! *And* both my parents have type II diabetes.
Well as for TCAs and cancer etc, I'm aware of the common notion that 'everything causes cancer' (as my friends lovingly recite when I refuse to eat anything 'chargrilled') but well, if 85% of cancers are preventable, and if 1 in 3 people will get cancer, then I'm sure as hell going to do everything to avoid getting it in the first place, even if that means avoiding TCAs because there might be a *slight* chance of it mutating any of my precious little cells. I'm sure, for example, that living in a polluted urban environment will give me a higher probabilty of getting cancer, but thats a factor thats not easily controlled, eg most jobs are in urban environments. But having the choice of taking a TCA or not, is something I can control to some degree.
So I won't be taking them. Not that I was going to anyway!!!!
I"m going to go back to ye old faithful SJW and maybe some rhodiola.
Kind regards
Meri
Posted by Larry Hoover on May 27, 2006, at 7:30:01
In reply to Re: TCA's are genotoxic ? Addendum » Larry Hoover, posted by Meri-Tuuli on May 27, 2006, at 4:24:00
> Hey there Lar,
>
> I'm totally with you on the vitamins and minerals issue. I don't think we can get the nutrients we need from the modern foods we have. And thats if we eat relatively healthily let alone with junk'empty calorie' foods in there too. Not to mention soil nutrient leaching, long shelf lives, etc etc. You know the issues.I remain in a near constant state of amazement, those issues which "make the news", and those that don't. The criterion is seldom risk itself.
> Yeah, sugar is definately a modern evil. Our bodies aren't equiped to deal with all the sugar/refined stuff we eat!! But yeah, anyway. Do I avoid eating sweet stuff?? Hahahaha no, I can't live without my daily danish pastry!!! *And* both my parents have type II diabetes.
Do you know what's worse than plain old sugar? High fructose corn syrup. Anyway. I'll leave that until another day.
> Well as for TCAs and cancer etc, I'm aware of the common notion that 'everything causes cancer' (as my friends lovingly recite when I refuse to eat anything 'chargrilled') but well, if 85% of cancers are preventable, and if 1 in 3 people will get cancer, then I'm sure as hell going to do everything to avoid getting it in the first place, even if that means avoiding TCAs because there might be a *slight* chance of it mutating any of my precious little cells. I'm sure, for example, that living in a polluted urban environment will give me a higher probabilty of getting cancer, but thats a factor thats not easily controlled, eg most jobs are in urban environments. But having the choice of taking a TCA or not, is something I can control to some degree.Except, it's a false dichotomy. Very few chemicals receive most of the research, while others go on, unnoticed. It's the 80/20 rule, only more like 99/1.
> So I won't be taking them. Not that I was going to anyway!!!!
>
> I"m going to go back to ye old faithful SJW and maybe some rhodiola.Do you know those are safe? Rhetorical. Absence of evidence is not evidence of absence.
> Kind regards
>
> MeriBack at ya,
Lar
Posted by SLS on May 27, 2006, at 8:33:38
In reply to Re: TCA's are genotoxic ? Addendum » Meri-Tuuli, posted by Larry Hoover on May 27, 2006, at 7:30:01
Hi.
> > So I won't be taking them. Not that I was going to anyway!!!!
Can someone direct me to some information regarding TCA and mutagenicity?
Thanks.
- Scott
Posted by linkadge on May 27, 2006, at 16:09:04
In reply to Re: TCA's are genotoxic ? Addendum, posted by SLS on May 27, 2006, at 8:33:38
http://www.nature.com/bjc/journal/v86/n1/abs/6600013a.html
But I think there was more than one study.
Linkadge
Posted by ed_uk on May 28, 2006, at 11:31:41
In reply to TCA's are genotoxic ? Addendum » linkadge, posted by Larry Hoover on May 24, 2006, at 19:43:05
Hi Lar
It's good to hear what you said about TCAs because I often taken a bit of amitriptyline.
Thanks Lar
Ed
Posted by Larry Hoover on May 28, 2006, at 11:47:48
In reply to Re: TCA's are genotoxic ? Addendum » Larry Hoover, posted by ed_uk on May 28, 2006, at 11:31:41
> Hi Lar
>
> It's good to hear what you said about TCAs because I often taken a bit of amitriptyline.
>
> Thanks Lar
>
> EdI'm glad there was some reassurance in what I said. When I first entered toxicology, every discovery I read about had me freaking out. Plasticizers leaching into food in the microwave. Stuff getting into water supplies via sewage. Just plain old pollution exposures. And so on.
Maybe I'm jaded. But I don't think so.
The abstract linkage put up concludes with this remark, and it is critical in contextualizing the risk: "However, our results may have been confounded by the effects of other determinants of breast cancer associated with tricyclic antidepressant use."
Chronic pain is correlated both with tricyclic use and cancer risk. So is depression itself. Both syndromes themselves are correlated with poor diet and lack of exercise. Etc. Etc.
I almost never use etc. But this time, it's important. Any co-factor that increases relative risk above 1.000000 is a confound (as are those which reduce that risk, but I can't think of many of those). There are gazillions of them, probably, these confounds. And, unless you correct your test for significance for all of the confounds, your significant outcome is merely suggestive.
Lar
Posted by ed_uk on May 28, 2006, at 11:59:19
In reply to Re: TCA's are genotoxic ? Addendum » ed_uk, posted by Larry Hoover on May 28, 2006, at 11:47:48
Hi Lar :)
>And, unless you correct your test for significance for all of the confounds, your significant outcome is merely suggestive.
That seems to be the problem with most studies.
Ed
Posted by Larry Hoover on May 28, 2006, at 12:31:18
In reply to Re: TCA's are genotoxic ? Addendum » Larry Hoover, posted by ed_uk on May 28, 2006, at 11:59:19
> Hi Lar :)
>
> >And, unless you correct your test for significance for all of the confounds, your significant outcome is merely suggestive.
>
> That seems to be the problem with most studies.
>
> EdYou're right. The more you know, the more realize how little you know. You know?
Lar
Posted by ed_uk on May 28, 2006, at 14:29:43
In reply to Re: TCA's are genotoxic ? Addendum » ed_uk, posted by Larry Hoover on May 28, 2006, at 12:31:18
>The more you know, the more realize how little you know.
Words of wisdom Larry.
Ed
Posted by linkadge on May 28, 2006, at 15:42:03
In reply to Re: TCA's are genotoxic ? Addendum » Larry Hoover, posted by ed_uk on May 28, 2006, at 14:29:43
Just cause you're not paranoid, doesn't mean somebody isn't watching.
Linkadge
Posted by ed_uk on May 28, 2006, at 16:01:07
In reply to Re: TCA's are genotoxic ? Addendum, posted by linkadge on May 28, 2006, at 15:42:03
Hi Link
I sure hope no one is watching because I haven't had a bath today :S
Ed
Posted by Larry Hoover on May 29, 2006, at 10:08:22
In reply to Re: TCA's are genotoxic ? Addendum » Larry Hoover, posted by ed_uk on May 28, 2006, at 14:29:43
> >The more you know, the more realize how little you know.
>
> Words of wisdom Larry.
>
> EdThanks, my friend.
I'm going to take another shot at contextualization of risk. What you think a risk is, compared to the reality.
Does anybody remember the Alar in apple juice controversy, from maybe fifteen years ago? Alar was the brand name for an agricultural chemical. It was sprayed on apple trees early in the season, but later on, it was discovered in commercial juice made from those apples. An agricultural chemical in apple juice, which we feed to babies!
Sounds pretty straight forward, right? Better get that apple juice off the shelves! Wrong. Totally wrong.
Sure, if you go and read the MSDS (Material Safety Data Sheet) for Alar, the official risk management document for that chemical, you would find some seriously scary stuff. When rats and mice were fed this stuff, there was a significant toxic effect. Not only that, but there was genetic, carcinogenic, and reproductive disruption.
No one had any doubt that Alar was not a good food to eat.
However, in order to consume sufficient Alar to cross what was believed to be the minimum toxic threshold, by drinking Alar "contaminated" apple juice, a human being would have to drink 118,000 litres of apple juice a day. I think I actually calculated that, way back then, just to see. I think I'm remembering the details correctly.
That's about a quarter of the volume of an Olympic sized swimming pool, more or less. Every day.
And that's how much a person would have to drink to hit the *minimum* possible dose to cause problems. Most people wouldn't be affected at that minimum dose. The most sensitive people would be, but not most people.
The apple juice was withdrawn from the market. The world was saved by a vigilant press.
Meanwhile, tons of mercury/silver amalgam tooth fillings continued to leach heavy metals into the mouths of Americans. There's less than 20% silver in a "silver" filling. About 50% is mercury. I note that the dentists don't call them mercury fillings, even though the largest percentage is mercury. And that heavy metal is in the mothers' milk.
And life goes on.
Now, there is a ***lot*** more to the Alar story than I mentioned here, and there is more propaganda being thrown around on this subject than any similar subject in human history. I gave you one propaganda version, above, and I know there are substantial counter-arguments. I'm trying to address perception of risk, and compare it to what the scientists are really saying when they talk about risk ratios. For a more balanced view of the Alar story, go to:
http://www.ewg.org/reports/alar/alar.htmlAlar was, in fact, withdrawn for good reason. It helped all the apples ripen at one time, so that the farmer could pick the trees once, rather than gradually, as Mother Nature ripened the fruit the normal way. There is no valid justification for continuing to use a carcinogen for such a picayune reason. Period.
What scares me is all the chemicals that we use all the time, that have *never* been tested. Like food additives on the GRAS list. That means Generally Recognized As Safe. What it really means is, "Stuff We Used Before They Started Testing Stuff". The absence of evidence of any risks associated with e.g. GRAS food additives is not evidence for the absence of ill effects. It just means nobody ever looked.
Lar
Posted by FredPotter on May 29, 2006, at 15:34:05
In reply to Re: which of the TCA's are genotoxic ? » linkadge, posted by Larry Hoover on May 24, 2006, at 19:28:34
Larry you mentioned broccoli. I've been thinking about fresh green leafy veggies. Why would they be good for us? I thought many plants evolved spines and poison on and in their leaves and stems which helped to prevent them being eaten. Many leaves are poisonous. However giving us cancer some years down the track would be of no benefit to the plant. But most plants don't "want" their leaves to be eaten.
However nuts and fruits "want" to be eaten. That's why they taste good and are good for us (they want to keep being eaten - for seed dispersal in a pile of dung preferably). So while the advice on fruit is sound I doubt the advice on leafy veg. Is there any truth in what I'm saying? Anyway I find them pretty tasteless
Fred
Posted by linkadge on May 29, 2006, at 17:58:39
In reply to Re: which of the TCA's are genotoxic ?, posted by FredPotter on May 29, 2006, at 15:34:05
Its not so much that any one chemical may rise to a level that is deemed toxic, it is that when we are exposed to too many chemicals at "safe" doses, strange things can happen.
So a TCA might do a little bit of dammage, then along comes another toxin, and another, and another. Soon enough, you're dying of cancer.
Linkadge
Go forward in thread:
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.