mitochondria

Mitochondrial disruption and systemic benzodiazepine side effects/tapering issues: pain, fatigue, brain fog, insomnia and anxiety

May 16, 2025 By Trudy Scott 19 Comments

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 GABA_A 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.

PQQ for Stress, Sleep, Mitochondria and Gut Health with Dr. Michael Murray: The Anxiety Summit 5

October 28, 2019 By Trudy Scott 7 Comments

Michael Murray, ND is one my guest experts on The Anxiety Summit 5: Gut-Brain Axis and our topic is: PQQ for Stress, Sleep, Mitochondria and Gut Health. What You’ll Learn –

Pyrroloquinoline quinone (PQQ) for calm energy – what it is and how to use it
How it is protective against every known toxin
A study where participants report “improved happiness and fullness of social life”

Pyrroloquinoline quinone (PQQ) is a fascinating nutrient that provides calm energy, helps with sleep, is protective against every known toxin and support mitochondrial health. PQQ also supports digestive health because the liver and gut is mitochondria-dense (Tara Hunkin shares more about this in her mitochondria/anxiety interview).

When I discovered that Dr. Michael Murray, ND is an expert on PQQ I reached out to invite him to speak on the summit. I was not disappointed – our interview is fabulous, meaty and exciting.

(We actually ended up doing it twice because of technical issues with the first one. There are always plenty of “fun and games” when hosting a summit!)

Dr. Murray shares some of the many benefits of this vitamin-like compound that is found in kiwi fruit, leafy green vegetables, papaya and other fruits and vegetables:

It’s been shown to be neuroprotective, protecting brain cells, it promotes nerve growth factors, it’s been shown to be memory restorative in animal and human studies. It has some interesting effects on anxiety and improving sleep quality. And it exerts many synergistic effects with Coenzyme Q10 and some of the other nutritional compounds that influence the mitochondria.

He feels that “eventually, PQQ is going to be recognized as essential for human nutrition.” And in case you’re curious about the pronunciation, this is how you say it: pyrro-lo-quin-o-line quinone.

We discuss this paper: “Effects of Oral Supplementation with Pyrroloquinoline Quinone on Stress, Fatigue, and Sleep” and Dr. Murray shares how PQQ is

really quite interesting because normally when we think of substances exerting an anti-stress or an anti-anxiety effect, we think about things that maybe calm us down and maybe even make us a little tired.

PQQ is able to promote a calming effect, an anti-stress effect, an anti-anxiety effect, but it actually enhances mental energy and physical energy.

The results in the study were pretty profound and I quote some of the findings the study authors report participants experienced (this, of course, was subjective feedback):

Fullness of social life improved
Happiness and fullness in the family life improved
Fullness and satisfaction in overall daily improved

They also found improved quality of life on measures of appetite, and pain, and obsession, as well.

The authors have this conclusion about a possible mechanism: “The anti-oxidative capacity or mitochondrial biogenesis function of PQQ might be responsible for the outcomes in this study.”

Some of the other topics we discuss around PQQ:

why taking PQQ is likely a better approach than using resveratrol
how it compares with vitamin C in terms of being an antioxidant (this really amazes me)
how it “been shown to protect against every known toxin on the brain”
possible benefits for Parkinson’s disease (by preventing the formation of alpha-synuclein) and also for Alzheimer’s disease
how “PQQ influences the microbiome in a very favorable way”
how a single dose, used one time, dramatically reduced C-reactive protein (a marker of inflammation) in one study
possible concerns about oxalates
optimal dosages and when to use it with coenzyme Q10
best products and much more

Be sure to listen to Tara Hunkin’s interview to get a solid understanding of the bidirectional connection between mitochondria and anxiety: Mitochondrial Dysfunction in Anxiety

You can listen to each of the interviews (and get transcripts) by purchasing The Anxiety Summit 5: Gut-Brain Axis.

If you’d like to give feedback or ask a question, please post in the comments section. I’d love to hear from you once you’ve listened in.

Have you already used PQQ and found good results? Please share so we can all learn.

I’ll be reporting back more in the coming weeks and months based on my own personal findings and based on feedback from my clients and my community. I’ve already had this feedback from someone who has seen the speaker line-up:

Registered for the summit today. So excited about it. And excited to see PQQ, one of my favourite, must-have supplements, getting its own piece.

If you’d like to give feedback or ask a question, please post in the comments section at the bottom.

I’d also love to hear from you once you’ve listened in to Dr. Murray’s interview and the others.

Mitochondrial Dysfunction in Anxiety with Tara Hunkin on The Anxiety Summit 5

October 18, 2019 By Trudy Scott 2 Comments

Tara Hunkin, NTP, CGP, RWP is one my guest experts on The Anxiety Summit 5: Gut-Brain Axis and our topic is: Mitochondrial Dysfunction in Anxiety. In this interview you’ll learn:

The role of mitochondria in the gut, brain and anxiety
Causes (such as medications and environmental toxins), testing, and signs and symptoms of mitochondrial dysfunction
Healing nutrients: Carnitine, COQ10, folinic acid, meal timing (as well as antioxidants and many other nutrients such as PQQ)

Tara starts with an overview of mitochondria, the energy powerhouses of our bodies and why they are so important in both physical and mental health.

You can hear some of this background information in this short in-person interview we did in San Diego recently.

(Note: The dates for the 2021 Anxiety Summit 5 is November 8-14, 2021)

You’ll also hear Tara share about this new bidirectional relationship that has been identified between anxiety and mitochondrial dysfunction. One of the papers she is referring to is this 2019 review paper: Anxiety and Brain Mitochondria: A Bidirectional Crosstalk. Here are the highlights:

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.

Tara shares how important the mitochondria are when it comes to digestion and gut health too:

the liver is heavily mitochondrial-dense and is needed to help eliminate toxins we are exposed to (toxins that affect our mitochondria and increase anxiety)
the mitochondria are also important when it comes to digestion – the lining of digestive tract (the epithelial cells of the microvilli) contain large numbers of mitochondria

The authors also highlight that “Pharmacological manipulation of mitochondria may be a potential therapeutic approach to relieve high anxiety symptoms.” One of the objectives of this summit is to highlight non-pharmacological approaches and Tara does exactly this in our interview.

She covers both lifestyle and nutritional approaches for addressing mitochondrial dysfunction (acetyl-l-carnitine, glutathione, antioxidants, coenzyme Q10, folinic acid and many more).

I also mention two other interviews on the summit where we talk about nutrients that also support mitochondrial function: PQQ (pyrroloquinoline quinone) and TUDCA (tauroursodeoxycholic acid).

Be sure to listen to these interviews for more about these two nutrients:

Jay Davidson, DC, PScD: Parasites, Anxiety and TUDCA for Your Liver
Michael Murray, ND: PQQ for Stress, Sleep, Mitochondria and Gut Health

We also discuss testing and all the environmental factors that impact the mitochondria including medications such as risperidone/risperdal (and antipsychotic medication), valproic acid (used for seizures), fluoroquinolone antibiotics like Cipro (and others) and also benzodiazepines (the commonly prescribed anti-anxiety medications).

You can listen to each of the interviews (and get transcripts) by purchasing The Anxiety Summit 5: Gut-Brain Axis.

If you’d like to give feedback or ask a question, please post in the comments section. I’d love to hear from you once you’ve listened in.

If you’d like to give feedback or ask a question, please post in the comments section at the bottom.

I’d love to hear from you once you’ve listened in to this interview and the others.

Mitomics – genetics of the mitochondria and food based antioxidants like curcumin

August 7, 2017 By Trudy Scott 2 Comments

Dr. David Haase, a functional medicine doctor and a leader in the field of genetics and genomics, covers mitomics in this very interesting interview on the upcoming Interpreting Your Genetics Summit which runs August 21-28, 2017.

Mitomics is the genetics of the mitochondria themselves. The mitochondria have their own set of genes. And that’s often given a lot of importance because we get our mitochondria from our mothers and therefore we inherit this genome from the mother and we get our mother’s energy per se.

But when you step back a little bit, you recognize that the genetics of the mitochondria are not just nuclear. It’s not just thirty-seven genes that hang out in the mitochondria, but rather, there is over a thousand genes that are in the nucleus that control the proteins or make proteins and influence the mitochondria at great levels. I’ve used a company called Courtagen who do whole mitome analysis. And in individuals with chronic fatigue syndrome or bizarre multi-system dysfunction, this is instrumental in giving a new plan of action to address.

He shares the story of a patient who had had chronic pain, fatigue and irritable bowel syndrome (a mitochondrial symptom)

She had tachycardia, palpitations, some dizziness. And so we actually did a whole mitome analysis on her and we found that she had a uniqueness in something called the TRAP1 related disease. I think it’s clever because the acronym is T1RED.

And this TRAP actually codes for a protein, which is a chaperone to the mitochondria and it’s involved in antioxidant defenses. And what’s been shown is that individuals with this TRAP1 related disease will be queasy, they’ll have pain and they’ll be fatigued and highly aggressive.

But when we found that she had this heterozygote for this particular abnormality – and it was associated with her having a lot of oxidative stress and elevation of hydroxyguanidine, which is a marker of genetic damage and oxidative damage, and elevations in her CK [creatine kinase], which was a marker of muscle injury. We went into this very intense antioxidant program with a lot of food-based antioxidants: sulforaphane, curcumin, resveratrol, CoQ10 and alpha-lipoic acid.

We went after this as aggressively as I think I’ve ever gone after this in a single patient with doses that are in excess of what I would typically use. And she had a remarkable recovery.

I share this snippet because with the tachycardia (an abnormally fast resting heart rate of at least 100 beats per minute) and palpitations, you may think it’s anxiety with a root cause such as low GABA or low serotonin or high cortisol or even Hashimoto’s thyroiditis, when in fact these symptoms are caused by mitochondrial TRAP-1 related disease.

I hope you can join us on Interpreting Your Genetics Summit, August 21-28, 2017. You can register here.

Here are some other reasons to attend:

once you register you’ll have immediate access to these interviews: Epigenetic Mastery for Everyone from Andrea Nakayama, CNC, CNE; The Current State of Genetics from Jeffrey Bland, PhD; and Your Genetics and Autoimmune Diseases with Dr. Tom O’Bryan, DC, CCN.
my digital ebook is available to you if you choose to purchase the series: Anxiety, Benzodiazepines and Your Genetics
as part of the lead up to the event, summit host, James Maskell will even be doing three of his own genetic tests and getting them interpreted by speakers from the summit

James Maskell has gathered world-renowned leaders from genetics, genomics and functional medicine and this promises to be a cutting-edge online event. These pioneering experts are on the front lines interpreting genetic data!

Hope to “see you” on the summit.

UPDATE August 11: I just went to the site and see this message today “Courtagen has closed its diagnostic laboratory and will no longer be accepting samples.”

They have a link to this press release of July 18 so it’s a brand new change: “Courtagen Life Sciences Inc. announced today that the company will be shifting the core focus of its business to medicinal cannabis genetics and testing. As the company reorients its business to respond to the growing opportunities in the medicinal cannabis industry, the company has made the decision to wind down its diagnostic neurology testing division.”