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research: iron mutation may affect glutamate regulation


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For what it is worth, here is some information for some of you out there who may be suffering from benzo. withdrawal and genetic iron loading (and a potential interaction between the too):

 

Recently, blood tests showed that I have iron loading (increased transferrin saturation and low UIBC).  So, I underwent genetic testing for hereditary hemochromatosis, and the results found that I have two mutated copies of the H63D gene related to iron.  Though the H63D mutation does not pose much risk for hemochromatosis, it is being increasingly linked to other conditions.  I did some research--

 

It had been previously hypothesized (Allison & Pratt, 2003) that as part of compensatory mechanisms to benzodiazepine-induced GABAergic

inhibition, excitatory mechanisms (including the glutamatergic system) become more sensitive, contributing to the expression of withdrawal

symptoms.  Now, it is being suggested that the expression of the H63D mutation is associated with increased calcium-induced glutamate secretion and decreased cellular glutamate uptake (Mitchell et al., 2011).

 

In my limited understanding of these findings, I am tempted to speculate that someone with two copies of the H63D mutation may experience a more difficult benzodiazepine withdrawal syndrome than they would otherwise have, but I understand the limits of such speculation, as it is difficult enough to demonstrate a direct link between the glutamatergic system and benzodiazepine withdrawal, let alone an additional link to any contribution associated with H63D.  We can all hope that eventually research will help us to better understand the factors that contribute to the severity of our withdrawal!

 

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Alison, C. & Pratt, J.A. (2003). Neuroadaptive processes in GABAergic and glutamatergic systems in benzodiazepine dependence. Pharmacology & Therapeutics, 98 (171-195).

 

Mitchell, R.M. et al. (2011). HFE polymorphisms affect cellular glutamate regulation. Neurobiology of Aging, 32 (1114-1123).

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What's UIBC?

 

UIBC is Unsaturated iron-binding capacity.  Along with TIBC (Total iron-binding capacity), it is a test doctors use to investigate suspected iron deficiency or iron overload.

 

Here is a link to the lab tests online page related to iron tests.  I especially like the chart at the bottom that shows you how the various iron tests are evaluated in relation to each other:

 

http://labtestsonline.org/understanding/analytes/tibc/tab/test

 

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  • 9 months later...

Hi,

I have a question for you, do your withdrawl symptoms rev up when you take iron supplements?

 

I am slightly amenic and very low on energy, so I decided so take B12 supplements. That went well, it felt as if I had a little bit more energy.  I am all in all doing pretty well, the main problem is that may sleep is still fragmented and the fact that I get easy tired which in turn has a negative effect on my sleep.

 

Then I went on to iron supplements, I just woke up of a horrible night of w/s!!!!!

 

Do you react to iron supplements? What has the doctor prescirbed you?

 

 

Elizabeth

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Elizabeth,

 

My iron gene mutation (H63D) causes too much iron in my system, so I have not taken iron supplements. In fact, I donate blood at different points in the year to reduce my iron levels.  Iron is one of those things that you do not want too much of in your system, as it can build up in the liver and has been found to cross the blood brain barrier. In all my readings, I have found that they recommend that someone only start an iron supplement regimen after getting advised to do so by a doctor. Otherwise, you could unknowingly cause new symptoms when iron deficiency wasn't the true cause of your problems. Now, if your doctor has told you to take iron, I know that it isn't always the easiest thing to take, either. Many people (who aren't even undergoing benzo withdrawal) have found that they get GI problems like constipation.  Also, there is scientific research that is starting to examine how both dysregulation of iron and glutamate are found in a number of neurological disorders.  I guess the bottom line is, if your doctor hasn't told you to take it, it is probably not a good idea to start. By all means get iron tests to see where your levels are at, and if your doctor does ask you to take supplements, have a conversation with her or him about your concerns over its relationship to your side effects. Best of luck to you!

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thanks for your answer! Its food for thought!

The bummer is that I don't have a holistic doctor, I just have the traditional ones!

 

 

 

 

 

 

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In my limited understanding of these findings, I am tempted to speculate that someone with two copies of the H63D mutation may experience a more difficult benzodiazepine withdrawal syndrome than they would otherwise have, but I understand the limits of such speculation, as it is difficult enough to demonstrate a direct link between the glutamatergic system and benzodiazepine withdrawal, let alone an additional link to any contribution associated with H63D.  We can all hope that eventually research will help us to better understand the factors that contribute to the severity of our withdrawal!

 

---

 

Alison, C. & Pratt, J.A. (2003). Neuroadaptive processes in GABAergic and glutamatergic systems in benzodiazepine dependence. Pharmacology & Therapeutics, 98 (171-195).

 

Mitchell, R.M. et al. (2011). HFE polymorphisms affect cellular glutamate regulation. Neurobiology of Aging, 32 (1114-1123).

 

Your wrting style and how you quote excerpts with citations indicate to me that you have a way, way above level of comprehension of molecular pharmacobiology. Because of my scientific and occupational background in adverse drug event monitoring and reporting help me to understand what you write.

 

I particularly find your statement "...it is difficult enough to demonstrate a direct link between the glutamatergic system and benzodiazepine withdrawal..." most noteworthy.

 

I have often questioned why most economic resources are directed to either controlling the use, distribution of benzos or developing similar molecular related substances than on identifying a particular biochemical process. My personal opinions tend to 'WIIFM' (whats in it for me) as it relates to economic gain as opposed to true scientific research.

 

I always hate it when I read the FDA mandated full prescribing package insert and in the section pharmacology it states someting like: ... although the actual mode of action of - "whatever" - is not precisely understood, it is thought to... very disturbing.

 

Philosophically - Does the the human brain actually have the capacity to truly get to the level needed to understand the complexity of how it works?

 

 

 

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  • 6 months later...

I started this thread back in 2011 after I found out I have two copies of an H63D mutation.  At the cellular level, this mutation has been associated with increased cellular iron, oxidative stress, increased calcium-induced glutamate secretion and decreased cellular glutamate uptake. As such, research suggests that this mutation (that is estimated to affect 13.5% of the U.S. population) promotes glutamate toxicity.

 

Being in Benzodiazepine withdrawal, we are already wary of the imbalance of GABA and glutamate due to the down-regulation of our GABA receptors.  Now that I have learned that my body may produce excess glutamate (and limit re-uptake), I am looking for natural ways to protect my cells from glutamate excitotoxicity.

 

There is research to suggest that certain antioxidants may have a protective effect against glutamate-induced cytotoxicity. I am planning on taking several antioxidants to see if I can counter some of the nasty effects of excess glutamate.  After all, I am still having a heck of a time with benzodiazepine withdrawal even almost 21 months out (particularly with continued problems with light sensitivity, balance, vision, and brain fog) and I’d like to do what I can to combat any glutamate imbalance.

 

My criteria for these antioxidants is that they have been shown in research (even if it is rodent research) to be effective in protecting cells from glutamate toxicity, are commercially available to consumers,  have a side effect profile that I can live with given what I know about my personal health, and don’t have interactions with any other medicine I take (i.e. amlodipine).

 

I have found a few that I plan to phase-in slowly, one at a time, to examine whether or not they will also rev up my symptoms, in the process.  Here are the antioxidants and the research that supports them in protecting cells from glutamate excitotoxicity:

 

Vitamin E/alpha-tocopherol (I plan on taking grape seed extract to get this one)

 

http://www.ncbi.nlm.nih.gov/pubmed/10828535

 

http://link.springer.com/article/10.1186/1471-2202-12-78

 

http://www.ncbi.nlm.nih.gov/pubmed/20736061

 

Rutin

 

http://www.ncbi.nlm.nih.gov/pubmed/21753864

 

http://openi.nlm.nih.gov/detailedresult.php?img=3133556_mv-v17-1784-f2&query=the&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&simResults=f0a0c94%20f0a1c77%20f0a2c1%20f1a0c78%20f2a0c804%20f2a1c54%20f3a0c139%20f4a0c363%20f4a1c222%20f4a2c3&npos=95&prt=2

 

Alpha-lipoic acid

 

http://www.ncbi.nlm.nih.gov/pubmed/7790411

 

http://www.ncbi.nlm.nih.gov/pubmed/9374822

 

Superoxide dismutase(SOD)- (I will take the GliSODin version for proper absorption)

 

http://www.ncbi.nlm.nih.gov/pubmed/17674707

 

http://www.ncbi.nlm.nih.gov/pubmed/9690736

 

I’ll update this thread to describe how it is going for me.

 

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thanks for the update

 

I'm going to read over your citations.

 

I think the Vit E in the grape seed is a good choice.

 

I started with the Rutin, and it really seemed to rev up my symptoms-- I really can't recommend it.  I then moved on to the Grape Seed Extract.  I found a brand that doesn't include extra vitamins (like a huge dose of vitamin C, etc), and so far, so good-- I am much more hopeful that this one will work out :)

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