A recent article published on Naturopathic Doctor News & Review, Mitochondrial Disruption Explains Systemic Benzodiazepine Side Effects, reports on new research that identifies a possible mechanism for wide-ranging side effects of these antianxiety medications. In addition to side-effects there can also be persistent withdrawal symptoms that continue after they have been tapered:
Benzodiazepines impair mitochondrial signaling across multiple systems in the body, not just GABA receptors in the brain. Mitochondria play a central role in regulating cell energy metabolism, hormone synthesis, oxidative stress balance, and immune response.
Disrupting these pathways has systemic consequences that explain the wide range of symptoms patients report during chronic use and withdrawal.
These findings offer a cellular mechanism for persistent fatigue, pain syndromes, cognitive impairment, and inflammatory symptoms that may continue after tapering.
Many medications impact the mitochondria but this new research has identified a new possible mechanism: tryptophan-rich sensory proteins (HsTSPO1) and reactive oxygen species.
In this blog I share more about HsTSPO1 and this new research, additional symptoms of benzodiazepine withdrawal, what we already know about mitochondria and anxiety, other medications and environmental toxicants that affect the mitochondria, and some key nutrients for mitochondrial support.
Benzodiazepines bind to tryptophan-rich sensory proteins (HsTSPO1)
This article from Virginia Commonwealth University, Researchers may have solved decades-old mystery behind benzodiazepine side effects, discusses the new study and HsTSPO1:
Benzodiazepines produce their therapeutic effect by binding with GABAA receptors in the brain; however, the drug has an equally strong affinity to human mitochondrial tryptophan-rich sensory proteins (HsTSPO1), located on the outer membrane of mitochondria in cells.
This type of protein is linked to several neurodegenerative diseases, including Alzheimer’s, and researchers have suspected that HsTSPO1 may be involved in certain side effects of benzodiazepine drugs.
And “when valium and other benzodiazepines bind to HsTSPO1, they inhibit the protein’s ability to manage ROS (reactive oxygen species) levels in our cells … this both reduces the production and the neutralization of ROS.
This may help explain why such medications cause side effects over time
And the authors propose this: “The new insights into HsTSPO1’s function could help pharmaceutical companies develop improved benzodiazepines.”
I have a better idea and propose we create more awareness about how these and other medications affect the mitochondria. I believe all medications should include a warning about these mitochondrial effects, and that mitochondrial support should be included when these medications are prescribed and then tapered.
This may include a combination of the same nutrients used for neurodegenerative disorders caused by mitochondrial dysfunction – CoQ10, B-vitamins/NADH, L-carnitine, vitamin D, and alpha-lipoic acid. And should also include infrared sauna, red light therapy and other detox approaches.
Ideally, this awareness will increase the use of the amino acids GABA, tryptophan, 5-HTP and DPA (d-phenylalanine), and other nutritional approaches instead of long-term benzodiazepine prescriptions for anxiety, pain and sleep issues. More on that below.
Some of the many other symptoms of benzodiazepine withdrawal
This paper from 1994, The benzodiazepine withdrawal syndrome describes some of the many symptoms:
Physiological dependence on benzodiazepines is accompanied by a withdrawal syndrome which is typically characterized by sleep disturbance, irritability, increased tension and anxiety, panic attacks, hand tremor, sweating, difficulty in concentration, dry wretching and nausea, some weight loss, palpitations, headache, muscular pain and stiffness and a host of perceptual changes.
The mechanism is not addressed in the paper but in the light of this new research, it’s possible that tryptophan-rich sensory proteins, increased reactive oxygen species and mitochondrial dysfunction are factors.
Brain mitochondria: anxiety and fear
I first addressed mitochondrial dysfunction during the 2019 Anxiety Summit: Gut-Brain Axis. One of my guest experts, Tara Hunkin, NTP, CGP, RWP shared these highlights from this review paper – Anxiety and Brain Mitochondria: A Bidirectional Crosstalk:
- Despite the established link between mitochondrial dysfunction and various psychiatric disorders, the contribution of mitochondria in anxiety disorders has not been extensively addressed.
- Mitochondria are emerging as modulators of anxiety-related behavior, as evidenced both in animal and human studies.
- There is a bidirectional link between mitochondria and anxiety. Mitochondrial, energy metabolism, and oxidative stress alterations are observed in high anxiety; conversely, changes in mitochondrial function can lead to heightened anxiety.
More recent research, published in 2024, The Emerging Role of Brain Mitochondria in Fear and Anxiety, supports this and proposes “a model in which mitochondrial function is critical for regulating the neural circuits that underpin fear and anxiety behaviors, highlighting how mitochondrial dysfunction can lead to their pathological manifestations.”
The new HsTSPO1 research builds on this research, identifying a possible mechanism and further supporting the oxidative stress connection.
On a side note, I’m really intrigued to learn more about these tryptophan-rich sensory proteins!
Other medications and environmental toxicants that impact the mitochondria
Keep in mind that it’s not only benzodiazepines that impact the mitochondria.
This 2023 paper, Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments, explores the correlation between potential mitochondrial dysfunction caused by selected medications, specifically looking at their effects on insulin signalling and glucose handling:
Drug classes such as statins, anti-diabetics, anti-epileptics, NSAIDs, anti-depressants, and certain antibiotics have been identified to induce mitochondrial toxicity.
This 2022 paper, Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature, states this:
Classes of environmental toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, and nanomaterials can damage the mitochondria in varied ways, with changes in mtDNA copy number and measures of oxidative damage the most commonly measured in human populations.
Amino acids and nutritional support: instead of benzos and before/during tapering
As I mentioned above, this awareness will hopefully increase the use of the amino acids GABA, tryptophan, 5-HTP and DPA (d-phenylalanine), and other nutritional approaches instead of long-term benzodiazepine prescriptions for anxiety, pain and sleep issues.
When it comes to tapering, it’s best to be nutritionally stable BEFORE starting to taper. This means eating real whole food that includes quality animal protein, healthy fats, fermented foods and organic vegetables and fruit; eating for blood sugar control; quitting sugar, gluten, alcohol and caffeine; addressing gut and adrenal health; addressing pyroluria and key nutritional deficiencies like low zinc, low iron, low vitamin D and more. This is all covered in my book.
Addressing neurotransmitter imbalances with amino acids before and during the tapering helps immensely too. And so does mitochondrial support.
And a reminder: tapering should always be done very very very slowly and under medical supervision with the prescribing doctor.
Additional resources when you are new to using GABA, tryptophan and other amino acids as supplements
As always, I use the symptoms questionnaire to figure out if low serotonin or low GABA or other neurotransmitter imbalances may be an issue.
If you suspect low levels of any of the neurotransmitters and do not yet have my book, The Antianxiety Food Solution – How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings, I highly recommend getting it and reading it before jumping in and using amino acids on your own so you are knowledgeable. And be sure to share it with the practitioner/health team you or your loved one is working with.
There is an entire chapter on the amino acids and they are discussed throughout the book in the sections on gut health, gluten, blood sugar control (this is covered in an entire chapter too), sugar cravings, anxiety and mood issues.
The book doesn’t include product names (per the publisher’s request) so this blog, The Antianxiety Food Solution Amino Acid and Pyroluria Supplements, lists the amino acids that I use with my individual clients and those in my group programs.
If, after reading this blog and my book, you don’t feel comfortable figuring things out on your own (i.e. doing the symptoms questionnaire and respective amino acids trials), a good place to get help is the GABA QuickStart Program (if you have low GABA symptoms). This is a paid online/virtual group program where you get my guidance and community support.
If you are a practitioner, join us in The Balancing Neurotransmitters: the Fundamentals program. This is also a paid online/virtual program with an opportunity to interact with me and other practitioners who are also using the amino acids.
Wrapping up and your feedback
Are you aware that benzodiazepines and many other medications can play a role in mitochondrial disruption? And that this mitochondrial disruption is likely a factor when it comes to systemic benzodiazepine side effects and tapering issues such as pain, fatigue, brain fog, insomnia and anxiety (and more)?
Have you considered or used mitochondrial support when tapering one of the benzodiazepines and has this approach helped?
And has it helped to be nutritionally stable BEFORE tapering and using amino acids to help with tapering? What changes did you make and which amino acids helped?
If you’re a practitioner is this a topic you discuss and address with your clients/patients?
Please do share in the comments below.
Do you recommend 5-HTP or tryptophan for low sertonin?
Andrew
I typically start clients on tryptophan if they have signs of low serotonin (worry, fears, OCD, ruminations, low mood, afternoon/evening carb cravings etc). If we don’t get expected results we switch to 5-HTP as some people do better on one vs the other.
Have you used either and found one to be more effective than the other?
Thank you so much for replying. I haven’t tried either one. I do have a panic disorder 🙁 as well as intense evening carb cravings.
I was hoping one of these might give me some relief from the constant fight or flight response I go into
Andrew
Please do keep us posted and if you find you need support in the way of accountability and being able to ask questions consider the upcoming Serotonin Quickstart program (6 weeks online group pgm with LIVE Q&A)
Hi Trudy
What do you think about long term damage?
I overdosed on benzodiazepines and a cocktail of other pharmaceuticals 8.5 years ago, during a particularly depressive episode.
I know now that mold in my house caused a myriad of biochemical issues and am well on my way to full health.
But are my mitochondria permanently altered?
No doctor ever discussed any long term effects – they just discharged me and sent me on my way!
Natural health has been my lifesaver.
Kerry xxx
Kerry
Wonderful to hear you are on your way to full health and that natural health has been your life saver. I’d love to hear more about what has helped you – dietary changes, amino acids GABA and/or tryptophan (and others), addressing nutritional deficiencies?
The mitochondria can recover once the affects of meds and environmental toxicants (mold is one example) are removed. With the world we live in, ongoing nutritional mitochondrial support and detox is key. It’s one reason I’m such a fan of infra-red sauna and red light therapy.
Thank you Trudy. You name it, I’ve tried it! So the biggest game changers for me were a long slow mold detox with the help of a Naturopathic Professional (detoxing not just physically, but emotionally and spiritually), definitely addressing nutritional deficiencies and implementing dietary changes (I’m now 100% Organic with lots of eggs and daily Organic Beef Liver capsules), Tryptophan and GABA helped immensely (your book was a wealth of info).
My health is now both a passion and a lifestyle – exercise, gentle cleanses and detoxing, nutrition and sleep are my top daily priorities.
Genetics, MCAS, Histamine and Perimenopause symptoms raise their heads at different times but I mostly manage these as they arise.
I’m now addressing Sympathetic Dominance and learning ways to help calm my nervous system.
Kerry
Kerry
So wonderful to hear – this is how it should be – a passion and a lifestyle and ongoing adjustments as other causes/factors show up. And now that you have all this in your tool box it makes it so much easier.
Love hearing that tryptophan and GABA helped immensely – can you share a bit more?
And yes to mold detox and ongoing detox/cleanses; and sleep as a priority; and organic/protein – all so important! May I ask what your diet was like before?
I am schizoaffective and have been taking nightly Xanax since August 2019 as well as other psych drugs. Yes, these are evil poisons and a couple I take can even induce serotonin syndrome, something to dread.
This article gives me moderate hope, though in talking about developing ‘better’ benzos, I don’t think they can get rid of the addictive properties of the drug.
I have been wary of the aminos, Trudy, because of the unknowns of interactions with psych drugs. These poisons condition your brain receptors in an unnatural way, which makes them almost impossible to taper & wean.
I have been concerned over GABA overload because the benzos act on changing the GABA-a receptor. Similarly, recent psychedelic remedies act on serotonin, making serotonin syndrome possible.
I am not in a position to pay for your courses, Trudy, but you do wonderful work & I read every mailing with interest. Thank you.
CJ
I’m pleased to hear this article gives you hope. When there are multiple psych meds involved we need to focus on a food-first approach. I do hope you have my book “The Antianxiety Food Solution” and have been making changes as needed – eating real whole food that includes quality animal protein, healthy fats, fermented foods and organic vegetables and fruit; eating for blood sugar control; quitting sugar, gluten, alcohol and caffeine; addressing gut and adrenal health; addressing pyroluria and key nutritional deficiencies like low zinc, low iron, low vitamin D and more.
Mitochondrial support in the way of nutrients and detox approaches could also be used.
It is 2 years now I started tapering of benzos,and 1 year since I stopped it. I am still experiencing withdrawal syndrome eg anxiety, fear and little auditory halucination. I feel fearful and nervous and the OCD symptoms seemed to be amplified.I feel very despondent which further make me feel terrible. There is nothing the Pscyhiatrist advises as such, I mentioned Tryptophan but it seems as though she does not advise that.
I am grateful for your information about Mitochondria, something I never read or heard about before, with regards to withdrawal syndrome
Thank you so much
Radha Persad
Radha
I’m sorry to hear about your struggles. Unfortunately many psychiatrists are not aware of the mitochondrial impacts or the power of tryptophan, GABA (and other amino acids) and nutritional psychiatry. I do hope you have my book “The Antianxiety Food Solution” and can either help educate your psychiatrist or find one who is open to all this. The good news it’s never too late to incorporate a nutritional approach and mitochondrial support. With symptoms of anxiety, fear and OCD I’d be looking into serotonin support as a starting point.
May I ask which benzodiazepine, why was it prescribed and how long had you been taking it?
Thank you, Trudy. Yes, your book is the bible!
I’ve been a fishetarian for 60 years. I do eat healthy as you recommend. Organic is getting easier here in Thailand. iHerb is an easy source for supplements here & Amazon ships for free over $35.
Complicated, isn’t it? I take T3 monotherapy & monitor my temps. We all connected!
Radha, I feel for you. I’m in much the same place. Remember doc is not god spelled backwards! Shrinks are mostly no more than pharma shills.
I’m concerned about serotonin syndrome with GABA but perhaps Trudy could suggest other aminos for relief.
CJ
Glad to hear all this and love that you have my book
There is no concern with GABA being a factor with serotonin syndrome
Please can you say if an ongoing high adrenaline load in the blood can cause skin burning and tingling? Do you have any material on the physical
effects of ongoing acute stress (years)?
Thanks for all you offer, and the book, it has literally saved my life, being very ill from severe bullying and nightnoise from antisocial neighbours
Suze
I would say not and would look into neuropathy, histamine/MCAS issues and oxalate issues to start.
Re ongoing stress, I’d review these articles on the blog https://www.everywomanover29.com/blog/?s=stress and https://www.everywomanover29.com/blog/?s=adrenal
I’m so pleased to hear my work/book has helped – now I would love to hear how my work has helped with severe bullying and nightnoise from antisocial neighbours?
And you are so welcome!
My Naturopath had me on 5HTP but I never felt a benefit, and PharmaGaba was a histamine trigger. After reading your book I tried Tryptophan and spent many months on 2 x 500mg at bedtime. This helped with sleep and definitely stopped the surges of anger that happened often. I read a lady say her staple was 2 x GabaCalm at bedtime and on rising, so I tried this and it helped. I now take both Tryptophan and GabaCalm only if I feel niggly mood symptoms.
My previous diet was standard vegetarian, then vegan for several years.
I now have lots of protein in the form of beef liver capsules, eggs and protein powder. I don’t like meat.
Kerry
Wonderful results with tryptophan and GABA Calm! And yes many folks who don’t respond to 5-HTP do well with tryptophan and vice versa. And pharamGABA can cause a histamine response in some individuals. Glad you figured out what works for you!
And yep quality animal protein is so important. Keep in mind, with meat aversion we look into low zinc
(I plan to share some of your feedback in a new serotonin blog I’m working on – to give others hope – will share a link here)
Thank you!
I had no idea about low zinc contributing to meat aversion. That’s fascinating.
Having harmonious chemistry makes everything in life much easier to move through. I wish everyone this understanding.