Gifted Issues Discussion homepage Forums Twice Exceptional Rhodiola success

One other insight about herbals (as compared to extracted active components or to synthetic pharmaceuticals)-- they tend, on average, to be less "clean" from a pharmacology standpoint.

They frequently have several mechanistic effects at multiple receptor types, and often have variable activity depending upon season and location of harvest, age of plant material harvested, etc. etc.

Foxglove, anyone?

The actual problem, though, is that as often as not, the active principal is unknown-- at best, it may be assumed based on structure-activity analogies.

Hawthorn would be a 'cardiac' drug cocktail in this category; unknown mechanism, unknown active agents, unknown concentrations, unknown, unknown, unknown... all that IS known about it is that the action seems to be "not ____" (since it doesn't 'compete' with a number of other known drug classes), and that the known components don't explain its activity by any stretch.

Okay, so if you assume that "molecule A" is the active ingredient, and you standardize on that basis, what happens if you're... er.... well, wrong? What if it is actually molecule H that has the activity that is desirable?

That concentration might vary WILDLY in an herbal preparation if it isn't even being evaluated, leading to study results which really ARE merely anecdote and placebo effect.


So that is reason number one why I'm personally not a fan of any herbal that isn't already a widely used foodstuff. I make an exception for, say, cranberry juice capsules or fish oil.

The other reason why I'm particularly wary is that, as Val indicated, the neuropharmacology of many pharmaceuticals is simply not well-studied in children to start with. What is known about that pharmacology suggests very strongly that neurochemistry and receptor populations can be permanently altered by the administration of some substances (including some natural ones).

Okay-- back to 'pharmacological cocktail, much of it unknown' for a moment:

the reason why toxicity/adverse event reporting is often so scarce with herbals is that they aren't well-studied to start with. Most of the people doing the research studies in this field aren't looking for those effects. Nor are they looking longer-term.

This is the reason why I'm wary of newly approved mainstream pharmaceuticals, too. I consider the first five years of rollout to be another clinical trial phase. LOL.

The difference is that at least there IS an agency keeping track of that stuff for pharmaceuticals. There isn't one for herbals.

The problems have to be massive in scope and in scale for an herbal to be pulled from the market. (Ephedra, for example.)

http://www.ncbi.nlm.nih.gov/pubmed/22928722

http://www.ncbi.nlm.nih.gov/pubmed/10948380

Please note what the FDA recommends for toxicity studies in herbals:

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070491.pdf

but bear in mind that this is VOLUNTARY. I know of no company actually doing all of those things to the extent that it probably should be done.

While not all of the best quality in terms of citations, this is a good starting point for anyone considering an herbal as a DIY intervention:

http://en.wikipedia.org/wiki/List_of_herbs_with_known_adverse_effects

Don't misunderstand me-- I'm all for risk-benefit analysis. If I were ever in a position where I had no modern pharmacology to rely upon, I'd certainly use what I know about ethnobotany to improve the health of my family with herbals. As noted above, we already do use a select handful of things. The more I understood about the pharmacology/toxicology, though, the smaller that number of trusted herbals became for me personally. MOST herbals (and not a few vitamin supplements) are in the "not worth it" pile for me personally at this point.

Would I give my own child Rhodiola? Probably not. But I'm not someone who is seeing potential benefit as being worth the risk that I know about for any herbal product. I'm not living in Irena or Ultramarina's shoes, though.

Ultramarina-- I'm really not questioning your decision to try this with your child. I'm just providing information based on my professional opinion re: herbals/supplements as opposed to pharmaceuticals.

The level of scrutiny of the one versus the other is really huge, and that is something that it's important to weigh in decision-making.

You've clearly done that. But I know that you aren't necessarily endorsing this for anyone else, right?

Well, I'm certainly not selling the stuff. Nor am I wildly recommending it, a la "You all should go out and buy this ASAP."

In this case, I feel encouraged by what appears to be hundreds of years of folk use. It's not a new remedy by any means.


Right. There does appear to be some understanding of this with Rhodiola, but I'll freely admit that I'm in no position to judge if it's correct.

I guess I'll just reiterate that this herb appears to have had far more scrutiny than most and to have come out looking better. But I agree that it's a calculated risk. Is it more or less of a risk than RX meds for depression or anxiety for her? I personally believe it is less of one. YMMV, obviously.

this herb appears to have had far more scrutiny than most and to have come out looking better

I disagree. (With all due respect-- this is an area that I've worked professionally in, and rhodiola seems to me to be rather typical for a well-known folk herbal.) I would say that it has a long history of ethnopharmacological use in traditional herbal practice. But so do many Ayurvedics and TCM's that have recently uncovered toxicity or contraindications, too. It's probably okay since there doesn't seem to be any ACUTE toxicity noted. However, that says nothing about chronic toxicity or clearance times.

Mechanism is unknown. It's assumed, but unconfirmed. (And honestly-- in some cases, actively contradictory from one study to the next.)

That means that any suggestions about what the active component actually is are conjecture at this point. You can't really "standardize" what you can't identify.

There are some disconcerting reports in the older literature that indicate that it might be pretty dirty stuff from a pharmacology standpoint. Antiarrhythmic affect may well indicate cardioactive principles such as beta-blockers or MAO/ACE inhibitors.

http://www.drugs.com/npp/rhodiola.html

http://altmedrev.com/publications/7/5/421.pdf

Even the fairly generous (IMO) latter review uses terms like "purported," "assumed" and "putative" when describing activity and mechanism.

This is more concrete-- but as a parent, this would scare me, honestly, more than it would reassure me:

http://www.ncbi.nlm.nih.gov/pubmed/23430930

A lack of toxicity data doesn't mean that it is safe-- only that nobody has examined it and published those findings.


Other reviews that I think are well worth looking into:

http://www.ncbi.nlm.nih.gov/pubmed/19468971

http://www.ncbi.nlm.nih.gov/pubmed/22643043

"Rhodiola rosea has an excellent safety profile, according to a the study reported in "The Journal of the American Botanical Council. The lethal dose of rhodiola rosea has been determined by animal toxicity studies to be 3,360 mg/kg. The toxic dose for an average 70 kg adult would be around 235,000 mg, and with clinical doses around 200 to 600 mg per day, patients likely have no need to worry about a fatal overdose."

Not sure if that is the toxicity data you mean.

I appreciate the additional studies. I can't actually make head or tails of this one: http://www.ncbi.nlm.nih.gov/pubmed/23430930

but the last two are certainly far more comprehensible to me, and meaningful.

Ultra, I'm not second-guessing your choice for your DD, but wanting to know your logic here. I have always felt in making these (harrrrrd) choices for my DS that it's a safer bet to go with RX meds that have been long studied, known to not be addictive, etc. rather than unregulated and less-studied herbals/naturals. Can you explain a bit more?

DeeDee

Well, that certainly suggests that acute toxicity is not a problem under ordinary conditions.

But that is the kind of thing that usually would already be well-known about a botanical which has as long a history as this one does.

That study is one that I find a bit worrisome. The same researcher is cited in most of the studies that show efficacy over the past decade, which is not a good sign when coupled with the observation that other labs seem to not always reproduce those results.

There is tissue culture work that seems to reflect G-coupled receptor signalling up-regulation (and down-regulation, fwiw)... but that system is so complicated that it's hard to say what else is happening as a result.

There are a lot of feedback loops in whole organisms surrounding that signalling pathway. If you tweak one side of it, the whole raft moves, basically, and there's no way to shut off that connectedness.

Renin-angiotensin is another one like that, which is why I look at any agent that purports to have cardiotonic or hepatotonic benfits and think... Hmmmm... really? So what else is it doing, then? Ohhh.... nobody has looked. GREAT. (Not.)

Agents that act in the renin-angiotensin pathway have a tendency to do things downstream that work on the cardiac muscle receptor subtypes for a whole host of ligands. For example, I mean.

Many of the kinds of things that I worry about here are the sorts of things that eventually result in black box warnings on pharmaceuticals, or lead to them being pulled off the market. Mostly its related to unintentional downstream effects that are intrinsic to the class of molecules. The COX-2 inhibitors are a good example, as is a drug like Avandia.

The things that I really stay away from are those that seem-- really-- too good to be true. That's because I know in my heart of hearts that nothing is really that effective AND that 'clean' and that the truth is probably that they just don't (yet) know what it is doing otherwise.

Elidel is a great example of one of those.

The thing that freaks me out about herbals as a class is that the majority of them are like those drugs. Only partially elucidated mechanisms, no real idea about dosage (because you can't quantify something if you don't even know what it is) and a lack of long-term safety data. Ethnobotany has a real problem in collecting safety data for traditional remedies; the reason is that in traditional herbal practice, it was very likely that a condition which was serious enough to require intervention was: a) already life-threatening to start with, so little additional harm in trying other approaches, and b) already treated in a variety of other non-allopathic ways. So if a person dies after treatment with Ma Huang, there's little to suggest that it wasn't the asthma that did them in, and the threshold for establishing that something is "risky" long-term is VERY VERY high, because in the traditional cultures where such medical practice developed, life-expectancies weren't that great to begin with, and "long term" might mean something different than it does to modern first-world residents.

It's worth recalling that Coca was initially greeted with many of the same-- in fact, the EXACT same-- support and claims as Rhodiola; improvement in stamina, "balancing" neurotransmitters, better focus and concentration, sense of well-being, etc. etc. There is a lot of hand-waving surrounding the pharmaceuticals which impact the biogenic amine neurotransmitter systems, too-- but I'm suspicious of ALL of those claims on the basis of what I know about that system. ALL of them come as a package deal with permanent changes in neurotransmitter kinetics, and induce dependence, and the reason is that the two parts of the molecules that seem to do those things... overlap. No way to separate them.

Same red flags for dirty pharmacology here, too. In other words, I'm suspicious that it seems to do too many different things that have little to do with one another at the molecular scale. It has to be a cocktail if it's really doing that stuff. If it's a cocktail, then that increases the risk that it's doing something harmful.

Acute toxicity data doesn't pick up mutagenic, carcinogenic, or teratogenic effects very well.

Nor does ethnobotanical history, which is by definition a collection of anecdote.

DeeDee: The well-known increased risk of suicidal behavior in children and teens taking antidepressants is why I do not want my DD taking these medications. We have experienced self-harm talk from our DD (not in a long time, fortunately) and I do not want to mess around with this risk.

At this time, we believe DD's primary problem to be depression. The main RX prescribed for her age is Prozac:

http://www.netdoctor.co.uk/depression/medicines/prozac.html

Further, though I have not done extensive research on this, I understand there is increasing evidence that the actual efficacy of Prozac may be significantly less than once thought.

Absolutely. Most of the SSRI's (as well as the less-selective ones) don't really alter the underlying affective problems appreciably. They just move the temporary setpoint-- but the system tends to respond by regulating to offset the changes anyway.

(Not to get too far off track, but this is another reason why I have some skepticism about medications in this class or related ones-- for ANY pediatric condition, actually.)