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.