insomnia

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.

I feel so dependent on my nightly “cocktail” of GABA, 5-HTP, melatonin and Ambien for insomnia – how do I reduce them?

May 2, 2025 By Trudy Scott 3 Comments

I have had insomnia for years. I have used GABA Calm with good results and also 5-HTP, melatonin and Ambien. Recently I discovered I have mild sleep apnea and have made huge progress in modifying my night awakening.

With my sleep apnea issues addressed, I would like to try to reduce my supplements and the Ambien… but the thought of this causes more anxiety. I feel so dependent on my nightly “cocktail”.

What is the best way to reduce the fear of withdrawal and my nagging brain that tells me I “need” these things?

Many thanks for all the wonderful information you share!

Lynn asked this on one of the blogs and since it’s a common question I’m sharing my feedback in this new blog post. I’m pleased to hear she has discovered sleep apnea is a factor as it’s not always checked and it definitely can cause disrupted sleep and waking in the night.

There is no need to taper amino acids and melatonin but I typically have clients gradually reduce them, one at a time, especially when they are concerned and are not sure how much they may still be helping.

She has a nagging feeling she still needs these supplements, feels dependent on them and feels anxious about stopping. All of this, in conjunction with the fact that stopping a sleep medication such as Ambien can also cause rebound insomnia has me advising a go-slow approach in a situation like this. Also, Ambien does need to be tapered very slowly and under medical supervision, so she would need to keep this in mind too.

A go-slow approach and one amino acid at a time

Lynn may still need one or more of the GABA, 5-HTP and/or melatonin and we don’t want to lose any gains.

As mentioned above, there is no need to taper amino acids and melatonin but I typically have clients gradually reduce them, one at a time, especially when they are concerned and are not sure how much they may still be helping.

I would start with assessing other low GABA symptoms and other low serotonin symptoms and if there are none, start with reducing either GABA or 5-HTP over a few weeks, watching for worsening sleep or other symptoms showing up. She could then do the same with melatonin.

As a reminder, other than sleep issues (with physical tension at night), these are low GABA symptoms: feeling anxious with physical-tension and stiff-and-tense-muscles, overwhelm, feelings of panic, and the need to self-medicate to calm down, often with alcohol but sometimes with carbs and sugary foods. You can also experience anger, rage and agitation, poor focus, intrusive thoughts/overactive brain, spasms, visceral pain/belly pain with IBS and more. You can read the entire list of low GABA signs and symptoms here.

With low serotonin, we see sleep issues with ruminating thoughts and worry (at night too), and fears, phobias, ruminations, obsessing, feelings of panic, perfectionism and lack of confidence, low mood, rage, anger and irritability.

Lynn has a nagging feeling she still needs these supplements, feels dependent on them and feels anxious about stopping. All this is a clue she may still need them or at least need one or more to some extent. Doing a reverse-trial of reducing each one, one at a time, with careful tracking is my approach.

I would tackle the above amino acid and melatonin reduction – if she decides to go ahead with it – only AFTER she has worked with her prescribing doctor on a slow taper on the Ambien. Stopping a sleep medication such as Ambien can cause rebound insomnia/discontinuation syndrome and she may find she does still need nutritional support to tide her over the Ambien taper period. This may be the same as she is currently using or she may even need to adjust upwards on one or more.

Ambien: dependence, withdrawal, rebound insomnia, slow tapering, falls and memory issues

Ambien/Zolpidem “is a non-benzodiazepine receptor modulator primarily used in the …short-term treatment of insomnia aimed at patients with difficulty falling asleep,” increasing “GABA inhibitory effects leading to sedation.”

I seldom see it used short-term i.e. 7 to 10 days. With longer-term use, “this drug has a high potential for overuse and daily dependence” and “withdrawal symptoms may occur if the zolpidem dose is tapered off rapidly or discontinued.”

Other factors to be aware of:

Complex sleep behaviors can occur after using zolpidem, such as sleep-driving, sleep-walking, and engaging in activities while not fully awake
Changes in behavior and abnormal thinking have been reported after zolpidem administration. In addition, patients have demonstrated aggressiveness and extroversion uncommon for the person’s usual behavior
Worsening of depression or suicidal ideation may occur with zolpidem therapy

I encourage you to read the article here and be fully informed.

This 2024 paper supports that “long-term use of Zolpidem may lead to drug tolerance, dependence, rebound phenomena, and withdrawal symptoms, making discontinuation difficult.” Other concerns include: dizziness, headache, falls, and cognitive decline.

Many of the papers published prior to 2023 do not report many of these issues, however awareness is growing. This 2024 paper, Case report: Additional grounds for tighter regulation? A case series of five women with zolpidem dependence from a Brazilian women-specific substance use disorder outpatient service, also reports adverse effects in women such as “memory and social impairment, falls, seizures” and “withdrawal symptoms, including rebound insomnia, social impairment, and craving.”

The authors recommend tighter regulation, stating that: “The surge in zolpidem prescriptions, driven by its perceived safety and low abuse potential compared to benzodiazepines, may lead to a global health issue of dependence.”

Because of much of this it’s important to work with the prescribing doctor on doing a very slow taper under their medical supervision. She may need to adjust her amino acids up during the taper period if her sleep gets worse in the short-term. And then do the taper approach I mentioned at the start of this blog.

With these safety, dependence and withdrawal issues, I would love to see GABA, tryptophan/5-HTP and/or melatonin (and other nutritional and functional medicine approaches), addressing sleep apnea and lifestyle factors/sleep hygiene be considered as the first approach for sleep issues – instead of Ambien/Zolipdem.

Additional resources when you are new to using GABA, 5-HTP 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.

Wrapping up and your feedback

I appreciate Lynn for asking this question and want to acknowledge that she is wise to be cautious and have concerns about the best way to tackle this. And she may find she does have a physical dependence on the Ambien.

Have you found that GABA, 5-HTP and/or melatonin helped/helps with your sleep issues?

And is sleep apnea a factor for you too?

And have you been prescribed Ambien and had any of the issues mentioned?

And how have you adjusted your amino acids and other sleep supplements as you’ve tapered your sleep medication?

Feel free to share your feedback and ask your questions below in the comments section.

How to accurately measure a small amount of powdered GABA and other GABA options when GABA Calm is not tolerated

April 26, 2024 By Trudy Scott 18 Comments

Brenda finds one GABA Calm helps her sleep but more than one affects her sleep and she suspects the sugar alcohols in the product. She’d like advice on using an alternative and how to accurately measure a small amount of powdered GABA. Here is her question in her own words:

I have been on the FODMAP diet for a while and it is helping but I just realized that when I take GABA Calm I am ingesting sorbitol and mannitol. I take a bit more than one of those tablets each night to help me sleep and am very aware that if I take too much it can keep me awake.

Now that I have realized about the sorbitol and mannitol, I am looking for an alternative source of GABA. I see that you are now recommending the Now GABA Pure Powder product. I was about to purchase this to avoid the sorbitol and mannitol but then realized that I would have to take 1/16th teaspoon of the powder to equate to 150mg. I can’t see me ever getting that measurement correct.

So my question is, can you recommend another source of GABA that would enable me to take 150mg plus a little bit with a fair degree of accuracy and without those added FODMAPs? Thank you very much. I am very grateful for your work.

Brenda has likely been diagnosed with SIBO (small intestinal bacterial overgrowth) or IBS (irritable bowel syndrome) even though she doesn’t mention it. In some folks with SIBO or IBS, sugar alcohols such as xylitol, sorbitol and mannitol can cause digestive upset. Not everyone with SIBO or IBS has issues with GABA Calm. In fact, it’s typically very well tolerated and GABA Calm is a product I have been recommending for many years. However, some folks do have issues and it’s wise to look for an alternative and not push through.

In this blog I share more about sugar alcohols, how to accurately measure out 1/16 teaspoon of the GABA powder to equate to close to 150 mg, how I use my mini measuring spoon, a GABA/theanine product that is low dose and can be opened, and another option she could consider.

Sugar alcohols in GABA Calm and other GABA chewable products

Many of the chewable or sublingual forms of GABA, including GABA Calm contain sugar alcohols which can be problematic and cause digestive upset and often explosive diarrhea. The digestive upset alone could impact sleep.

Sugar alcohols include xylitol, sorbitol, mannitol and erythritol. Your reaction will depend on the amount of sugar alcohols used, how many chewable/sublingual tablets you use and how accustomed you are to sugar alcohols. You may get used to them and eventually be fine with consuming small amounts and yet for others the tiniest amount is an issue.

I share more about sugar alcohols on this blog: Why does chewable GABA make me run to the bathroom and what GABA do I use instead?

Using a mini measuring spoon set and GABA powder

It’s wonderful that GABA Calm is helping Brenda with her sleep issues and when we start to get benefits we do want to increase the amount to see if we can get further benefits.

She has a few options and one is to use the NOW GABA powder (or another GABA powder) with a mini measuring spoon set like this one (my Amazon link). This is mine and it is very easy to use, convenient and accurate.

As you can see it comes in various sizes: 1/4 teaspoon, 1/8 teaspoon, 1/16 teaspoon, 1/32 teaspoon and 1/64 teaspoon.

It is important to look at the product and work out how much you need to measure out. For example, the NOW GABA powder states 1/4 teaspoon is equivalent to 500 mg GABA. This means 1/16 is equivalent to 125 mg GABA. So if Barbara wants to take 150 mg she would use a little more than what would be in the 1/16 spoon (maths is coming in handy after all!)

Keep in mind that product equivalents do differ. For example tryptophan is typically lighter and fluffier than GABA. My tryptophan states 1 teaspoon is 1000 mg tryptophan so a typical starting dose of 500 mg tryptophan would be 2 x 1/4 teaspoon since each 1/4 is 250mg.

I love my mini measuring spoon and use mine on a daily basis for theanine in the day, calcium citrate after dinner (for my oxalate issues), and for GABA and tryptophan at bed time.

Combined GABA and theanine: GABA-T SAP as one option

Another option is using a lower mg GABA/theanine product and opening it. Nutritional Fundamentals for Health GABA-T SAP is another favorite of mine. This product is pleasant-tasting when opened on to the tongue and works very well when GABA Calm can’t be used. It contains 300 mg GABA and 150 mg theanine, so can easily be halved to provide the 150 mg GABA she is looking for.

Research shows that the combination of GABA and theanine may improve sleep: GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. The authors share the sleep and anxiety benefits of both GABA and theanine:

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABAA receptors favours sleep.

l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits.

But Barabra is going to have to do a trial to see if this combination works for her.

Mixing and matching as an other option

And finally, if she was also taking GABA Calm in the day for stress and overwhelm, she could do a trial of using this during the day (for the convenience factor) and then at night use the GABA powder or opened GABA/theanine capsule (because it’s a bit more finicky). This way she’s consuming less sugar alcohols overall.

Both GABA products, the mini measuring spoon set and where to find them

Today I mentioned the Now GABA Powder and NFH GABA-T SAP. You can purchase these from my online store (Fullscript – only available to US customers – use this link to set up an account).

If you’re not in the US, the Now GABA Powder and Nutricology ZenMind (a GABA/theanine combination comparable to GABA-T SAP) is available via iherb (use this link to save 5%).

And the mini measuring spoon set can be found here (my Amazon link)

Additional resources when you are new to using GABA and other amino acids as supplements

As a reminder, low GABA can cause physical tension, anxious feelings, feelings of panic and problems sleeping, as well as self–medicating with alcohol or carbs to relax or fit in. As always, I use the symptoms questionnaire to figure out if low GABA or other neurotransmitter imbalances may be an issue.

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 too). This is a paid online/virtual group program where you get my guidance and community support.

Wrapping up and your feedback

I do always appreciate questions like this so keep them coming so I can share and educate further.

Now I’d love to hear from you – do you have issues with the sugar alcohols in GABA Calm or another chewable GABA product? (if yes which one?)

Did you move to a GABA powder and do you use a min spoon set? Or does another GABA product work for you?

Please share how GABA helps and how much helps you?

If you’re a practitioner do you use GABA powder and mini spoons with your clients/patients?

And please let me know if it’s helpful that I’m now including product recommendations and where to get them.

Feel free to share and ask your questions below.

DLPA vs DPA for pain, food cravings, depression, grief, lack of joy; and impacts of DLPA on sleep, and feeling more stressed/anxious

April 5, 2024 By Trudy Scott Leave a Comment

A very common question I get is from folks asking about the difference between the amino acids DPA (d-phenylalanine) and DLPA (dl-phenylalanine) for endorphin support and endorphin/dopamine support. I dedicate an entire blog to this question explaining the differences and which one I use for weepiness, heart-ache, pain and energy. I also discuss where tyrosine (for dopamine support) fits in. If you missed that or need a recap you can read about this on the blog.

The blog post generated some great questions that I’m sharing today, with my feedback, in case you have similar questions. I discuss a question about DLPA vs DPA for pain and impacts on sleep; a question about DLPA (used by mistake) raising already high dopamine levels and why DPA isn’t working any more for food cravings; a question about using DPA with GABA; and a question about DPA for depression and lack of joy caused by grief.

Here is the question from Gloria who shared this feedback about her use of DLPA (as part of a pain relief product) but says she can’t use it past noon. She also wants to know more about DPA for pain relief:

My experience with DLPA is as part of a supplement called Curamin for pain relief from arthritis that also has curcumin and boswellia. It works quite well in the AM but I can’t tolerate it past noon or it negatively affects my sleep.

Interesting to learn it is similar to tyrosine which I have had sleep problems with in the past.

Does DPA work as well for pain? Is it best to take amino acids on an empty stomach for best absorption? Does that mean an hour before a meal or two hours after? Thank you for your blogs and book!

It’s great that this combination product offers pain relief and it’s good that she has made the connection to poor sleep when it’s used after noon. This is a popular product that I would like to see include the possible impacts on sleep and the other precautions for DLPA . It is a proprietary formulation so you don’t actually know how much DLPA you’re getting. I really don’t like not knowing.

One other concern is that curcumin is high-oxalate and for some this can make pain worse. Otherwise, curcumin and boswellia are excellent for pain relief and reducing inflammation.

DPA is more effective for pain than DLPA because it offers a bigger endorphin boost. If oxalates are not an issue, one option could be to continue with the Curamin before noon and if needed, add standalone DPA in the afternoon and evening, for added pain relief.

Amino acids are more effective on an empty stomach and even more effective when opened on to the tongue. I share more about opening DPA onto the tongue in this blog.

DLPA (used by mistake) raised already high dopamine levels and why isn’t DPA working any more for food cravings?

Rhonda shared how she found out the difference between DPA and DLPA the hard way and wants to go back to DPA:

I certainly found out the difference the hard way. I had used Lidtke Endorphigen for a few years and I think it helped a bit with food cravings. As I am in Australia, I depend on my sister’s visits from US for my supply. When I ran out last year, I bought DLPA by mistake.

After 1 week I was unable to cope with life, totally stressed out about everything, wanting to cry or scream or run away. Zero tolerance towards anyone. After 10 days I realized my mistake and I went back to normal in 24 hrs.

I believe DLPA resulted in very high dopamine as I already have a very slow COMT gene activity for breaking down dopamine.

I now take Endorphigen again but not seeing much effect on sugar cravings this time.

That is quite the reaction she experienced but I’m glad she figured it out so quickly. It’s not uncommon for some folks to react to DLPA like this, feeling more stressed and even anxious. High dopamine, and norepinephrine and epinephrine (so a huge adrenalin rush), related to slow COMT activity could well be the cause.

When Endorphigen (or any of the amino acids) work well initially we continue with trials of higher doses to find the ideal dose. It may also be that a reset is needed after the shift in dopamine.

Rhonda did say she thinks Endorphigen “helped a bit with food cravings.” When it only helps a bit it may be that the dose isn’t high enough or we may need to consider other neurotransmitter imbalances. They can all cause cravings for slightly different reasons: GABA/stress, serotonin/worry or low mood, glutamine/low blood sugar. More on that and the respective amino acids here.

Can GABA be used with DPA?

Ray asks: “Can I use GABA 25mg and also take DPA? Would either/or offset the other?”

My feedback: If someone has low GABA symptoms and GABA helps and they also have low endorphin symptoms and DPA helps then they are absolutely fine to use together and even at the same time. However, I have my clients trial one at a time in order to find the ideal dose and so you know how each one is working

What can I use for my depression and lack of joy, caused by grief?

Vee says she needs something “to get through my grief depression”:

Completely flat, no joy. I always had a calm flat disposition, but now it’s a complete zero. I need my brain to produce some oxytocin so I can like myself, my family and remember all I should be grateful for. I sleep good. I don’t take any meds, and I don’t abuse alcohol. Does tyrosine affect the brain in the way of producing oxytocin?

My feedback: I use DPA/Lidtke Endorphigen for this very purpose. It’s wonderful for grief, depression, lack of joy and the weepiness we see with low endorphins. It also helps with emotional eating that can show up as we try to self-medicate with treats in order to try and feel better.

When the depression also includes being flat, blah and curl-up in bed we use DLPA instead of DPA, or a combination of DPLA/DPA or tyrosine/DPA. Trials of each, one by one, helps you figure out what works best for your unique needs.

And for some folks GABA is helpful as shared by this woman who found GABA allowed her to sit with a feeling of peace and calm most of the time after her mum passed away.

Research does shows a link between dopamine and oxytocin, with oxytocin “emerging as one particular neural substrate that may be influenced by the altered dopamine levels.” Also, for oxytocin support I’d focus on hugs, massage, touch, laughter, making love, yoga, and petting a dog or cat.

DPA and DLPA product options

Products I recommend include Lidtke EndorphiGen (which is DPA) and Pure Encapsulations DL-Phenylalanine (DLPA). You can purchase these from my online store (Fullscript – only available to US customers – use this link to set up an account).

If you’re not in the US, these products are available via iherb: Doctor’s Best D-Phenylalanine (or DPA) and Life Extension D, L-Phenylalanine (or DLPA) (use this link to save 5%).

Additional resources when you are new to using DPA and DLPA, and other amino acids as supplements

As always, I use the symptoms questionnaire to figure out if low endorphins or low dopamine or other neurotransmitter imbalances may be an issue for you.

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 too). This is a paid online/virtual group program where you get my guidance and community support.

Wrapping up and your feedback

I do always appreciate questions and feedback like this so keep your questions coming. I do hope my sharing these ones have been helpful to you.

How has DPA or DLPA helped your pain, depression, lack of joy, weepiness, and grief? And has DLPA affected your sleep or made you feel more anxious or stressed?

If yes, which products have helped and do you find swallowed or capsule opened is more effective?

If you’re a practitioner do you use DPA and/or DLPA with clients/patients?

And please let me know if it’s helpful that I’m now including product recommendations and where to get them?

Feel free to share and ask your questions below.

Collagen causes anxiety and sleep problems for some people. I would never have connected the dots but apparently I am one of those people.

March 1, 2024 By Trudy Scott 13 Comments

Thank you for solving my sleeping problem! I would never have connected the dots regarding collagen causing anxiety and sleep problems for some people, but apparently I am one of those people.

Although I would fall asleep instantly at bedtime, I would wake up 3 or 4 hours later and while my body was tired, my mind was wide awake and I was unable to go back to sleep for at least 2 or 3 hours. I would think about all the things I needed to do and the challenges I was having. These things would not bother me as much in the day. No matter what I tried – like praying and listening to calming music, I could not shut off my anxious thoughts.

Then it occurred to me that when I go out of town to visit my family, I sleep better. After hearing Trudy’s collagen presentation on the Osteoporosis Summit, I connected the dots! For the last 6 months, I have been putting about 10 grams of Vital Protein collagen in my coffee each morning. I don’t take the collagen with me when I travel. So I stopped using it and lo and behold, I am sleeping the best sleep I have slept in a long time! I even look forward to going to sleep.

So I thank you Trudy from the bottom of my heart for enlightening me. And Margie, I thank you for the wonderful Summit you put together with so much great information. I would still be sleep deprived if it wasn’t for you both!

I was so pleased to receive this lovely thank you email from Merrilyn (sent to me and summit host Margie Bissinger) and said how happy I am for her. I asked if I could share her feedback as a new blog so we can enlighten others who may have similar issues and because it’s an opportunity to share some of sleep/collagen research that supports a possible mechanism. She kindly said yes and answered my questions:

How long had you been using collagen and how long after starting it did the sleep issues start?
And how quickly after stopping the collagen did your sleep improve?
Did you consider using tryptophan or 5-HTP so you could continue to use the collagen? And are you prone to low serotonin?

Read on for some background on the serotonin-lowering effects for some folks who consume collagen, Merrilyn’s responses to my questions, my insights, some of the research, and the tryptophan and 5-HTP products I recommend.

The original collagen/gelatin serotonin-lowering blog/research from 2017

I first addressed this potential cause for anxiety, mood and sleep issues in a blog in 2017 – Collagen and gelatin lower serotonin: does this increase your anxiety and depression?

Margie invited me to share this information and some of the research with those who are using it or planning to use it for osteoporosis. I’m so glad I accepted because clearly there are still folks who are not aware of the potential serotonin-lowering effects of collagen. And I’m sharing Merrilyn’s results via this new blog in case it’s also new to you.

Briefly, collagen and gelatin are used in tryptophan-depletion studies to lower serotonin levels. It does this because neither collagen or gelatin contain tryptophan. Some people seem to be adversely impacted by acute tryptophan depletion/ATD caused by collagen or gelatin consumption while others are not.

If this is all new to you, I encourage you to read the original blog and search for “collagen” to find other information on this topic on my site.

How long had you been using collagen and how long after starting it did the sleep issues start?

I asked how long she’d been using collagen and how long after starting it did she notice problems with her sleep. This wasn’t clear to her and many folks like Marrilyn unfortunately don’t connect the dots right away.

I started Vital Proteins collagen on July 1, 2023. I did mark that down because as I add supplements to my diet, I try to make notes and only do one at a time in case they cause a problem. I did note that I was not consistent with taking it daily and I was only taking 5 to 10 grams daily ( in my cup of coffee!).

I have always had a bit of a problem with waking up at night, but normally go right back to sleep. I can’t remember exactly when the sleeping problems worsened and I never connected them to collagen.

Seems like over time, the sleeping and waking up with ruminating thoughts was getting worse. I had started trying Tylenol PM or Advil PM, only taking 1/2 of one with one plain Tylenol or Advil to help me sleep and relieve any muscle tension from exercise. That did not always help. Taking a whole PM was better, but I felt groggy the next day. I don’t need any now that I have stopped the collagen.

How quickly after stopping the collagen did your sleep improve?

When the cause of waking in the night is due to low serotonin, it’s common to notice improvements very quickly after stopping collagen. This was the case with Merrilyn:

I would say my sleep improved immediately after stopping it. I realized that on the days I was out of town and didn’t take the collagen, I slept better. … but I attributed it to the fact that it is cooler there and my 6 year old grandson wears me out by the evening. I do not take the collagen with me and I had not connected this to the sleep pattern.

I returned home after one trip and started the collagen that next morning and the sleepless nights started again. I can’t remember when I listened to your talk, but I am guessing around January 18th, because I noted that I stopped after that day and according to my Fitbit and my memory, I slept great the night of January 19th and other than one night, I have slept well since.

I do want to commend Merrilyn for keeping a log of new supplements and sleep patterns. It’s something I recommend for all my clients.

Did you consider using tryptophan or 5-HTP so you could continue to use the collagen and are you prone to low serotonin?

I also asked if she considered using tryptophan or 5-HTP (some folks do better on one vs the other) so she could continue to use the collagen – she had not considered this. And I wanted to know if she has been prone to low serotonin or suspects low serotonin currently.

I do believe I am prone to low serotonin based on the little I have read in your book. I have thought about using tryptophan with the collagen and might later. For now, I just want to enjoy sleeping and focus on improving my diet.

I also have evenings when I crave sugar. I can do without it during the day, but evenings are worse. Something else to work on.

She’s referring to the low serotonin symptoms questionnaire in the amino acid chapter of my book, The Antianxiety Food Solution. It’s also on the blog here.

A big clue is the insomnia and anxiety caused by consumption of collagen, and also the evening cravings. There are cravings with all the neurotransmitter imbalances, with afternoon/evening cravings common with low serotonin.

It is possible Merrilyn’s anxiety and insomnia effects are for reasons other than low serotonin: glutamate, oxalate, arginine or a histamine reaction are all possible with collagen intake). Doing a trial of tryptophan or 5-HTP while consuming collagen would confirm a serotonin connection.

Osteoporosis, allergies, serotonin and coffee

Merrilyn also shared that she is in her early 70s and besides osteoporosis and allergies, is generally healthy and takes no prescription drugs. Interestingly, research finds there may be a role for 5-HTP (and presumably tryptophan) for allergies and asthma, so this may be another clue for her.

Of course, reducing her cravings – tryptophan and/or 5-HTP make it easy – will also improve her nutrient status of zinc, magnesium, iron, vitamin B6 and other B vitamins etc. all of which are key when it comes to osteoporosis.

Quitting coffee altogether will likely prevent any waking in the night – yes, even just one cup a day can make a difference – and also help improve the status of many of these nutrients. This is often the least favorite change my clients make but Merrilyn will read about all this in the caffeine chapter in my book and may find tyrosine helps her do so.

Research: Daytime tryptophan depletion altered night-time sleep

A paper published in 2002, Mid-morning tryptophan depletion delays REM sleep onset in healthy subjects, reports the following:

Rapid daytime tryptophan depletion in healthy volunteers significantly decreased plasma tryptophan levels during the day and the evening, followed by alterations in the characteristics of night-time sleep, including increased sleep fragmentation, REM sleep latency, and REM density during first sleep episode.

In this randomized double-blind cross-over study, participants received “a tryptophan-free mixture of amino acids at 10:30 am…. resulting in a 77% decrease and 41% decrease of serum tryptophan at 3:30 pm. and 9:30 pm.” Keep in mind that collagen is a blend of certain amino acids and is tryptophan-free.

The authors discuss the fact that serotonin is involved in sleep regulation but interestingly the mood of study participants was not affected.

Even more interesting is another study that found collagen used before bedtime improved sleep and cognitive function in physically active males. It’s possible it’s doing this because it is lowering serotonin that is too high.

Tryptophan and 5-HTP product options

Products I recommend include Lidtke 500 mg Tryptophan, and Pure Encapsulations 50 mg 5-HTP. You can purchase these from my online store (Fullscript – only available to US customers – use this link to set up an account).

If you’re not in the US, Doctor’s Best L-Tryptophan 500mg and Source Naturals 50 mg 5-HTP are products I recommend on iherb (use this link to save 5%).

Additional resources when you are new to using tryptophan or 5-HTP and other amino acids as supplements

We use the symptoms questionnaire to figure out if low serotonin or other neurotransmitter imbalances may be an issue for you.

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 too). This is a paid online/virtual group program where you get my guidance and community support.

Have you made the connection between your collagen consumption and anxiety/insomnia (or other low serotonin symptoms)?

Did you end up simply stopping collagen or have you successfully used it with tryptophan or 5-HTP?

If you’re a practitioner do you see this with your clients/patients who are prone to low serotonin?

And please let me know if it’s helpful that I’m now including product recommendations and where to get them?

Feel free to share and ask your questions below.

Reactive hypoglycemia in binge eating disorder, food addiction and intense sugar cravings, and how glutamine stops the cravings

February 9, 2024 By Trudy Scott 6 Comments

A number of years ago a woman came to see me looking for help for her anxiety, insomnia and out of control sugar cravings which she described as an “almost demonic urge to eat sugar and all things sweet.”

Before working with me she had been trying to control her low blood sugar levels (or hypoglycemia) by eating the right foods at the right times i.e. healthy fats and quality protein especially at breakfast. But this wasn’t enough to eliminate her intense sweet cravings. She would make and eat sweet treats all day long, using “healthier” sweeteners like monk fruit and maple syrup.

I had her complete the brain chemistry symptoms questionnaire and she scored high on all the low blood sugar symptoms as well as low GABA and low serotonin. We focused on low blood sugar first and the solution for her cravings was using 500 mg of glutamine opened onto her tongue.

Initially she was sure this would NOT work – how would she possibly be able to use glutamine in the midst of experiencing reactive hypoglycemia or low blood sugar?

I had the same conversation that I have with all my clients who would obviously rather eat something sweet than open a glutamine capsule onto their tongue: “If you have an intense craving for something sweet, tell yourself that you’re going to indulge, but also humor your nutritionist and take the glutamine anyway. You may be surprised to find your urge completely disappears.”

She did that and it worked time and time again, ending her demonic urge to eat something sweet every time and very quickly. And it helped her with all her low blood sugar symptoms.

This blog addresses the role of low blood sugar or reactive hypoglycemia in intense sugar cravings, binge eating disorder and food addiction, and how glutamine helps.

Research: Reactive hypoglycemia in binge eating disorder and food addiction

The 2023 paper, Reactive hypoglycemia in binge eating disorder, food addiction, and the comorbid phenotype: unravelling the metabolic drive to disordered eating behaviours, highlights the fact that “impaired metabolic response” such as fasting blood glucose fluctuations are a factor in binge eating and food addiction, driving out of control and “repetitive consumption of highly processed food.”

The researchers “investigated hypoglycemia events during a 5-hour-long oral glucose tolerance test” in 200 participants and “the association between the severity of eating psychopathology and the variability in hypoglycemia events was explored.”

The authors conclude as follows:

People with binge eating disorder/BED or food addiction/FA are prone to experiencing reactive hypoglycemia; food addiction severity may predict early and symptomatic hypoglycemia events. This can further reinforce disordered eating behaviours by promoting addictive responses, both biologically and behaviourally.

You can read the study here.

It’s worth noting that the participants did not have diabetes. I mention this because most of the reactive hypoglycemia research looks at diabetic patients. Reactive hypoglycemia in the non-diabetic population is considered controversial even amongst functional medicine and/or integrative practitioners. This paper stands out for this reason.

It’s also recently published which makes me excited. This research is confirming what we see clinically.

This research is very much in line with the demonic urge my client described, and directly tied to her low blood sugar and blood sugar swings. My client did not do a 5 hour oral glucose tolerance test. Instead we used the low blood sugar symptoms questionnaire (see below) and a trial of glutamine.

My client was also not diagnosed with binge eating disorder or food addiction but didn’t have to be for us to recognize the issue and have her benefit from nutritional support in the way of glutamine and learning to eat for blood sugar stability.

Unfortunately the authors do not discuss glutamine as a solution in this particular paper or in any other research on human participants who are non-diabetic. There are a few animal diabetes studies, with this 2013 study reporting that “glutamine was more effective in promoting glycemia recovery if compared with glucose, lactate, glycerol, or alanine.” The authors call for further investigations which I look forward to reading.

Low blood sugar symptoms and a glutamine trial

As a reminder here are the signs of low blood sugar:

Sugar cravings, binge eating and addiction symptoms:

Crave sugar, starch or alcohol any time during the day
Very intense cravings for sweets/sugar
Binge eating and/or food addiction (updated with this based on this research)

There are also anxiety, mood, sleep and energy symptoms when you have low blood sugar:

Nervous, anxious, panic attacks
Irritable, shaky, headachey – especially if you go too long between meals
Lightheaded if meals are missed
Agitated, easily upset
Eating relieves fatigue
Waking in the night or early hours with a jolt of anxiety/shakiness (I blogged about this here)

As I mention in the waking with a jolt/low blood sugar blog the good news is it’s relatively easy to figure out if low blood sugar is causing your symptoms. First I have clients rate their symptoms on the low blood sugar questionnaire and do a trial of glutamine. Next is figuring out the dosing and timing of glutamine, looking at a current food log and making dietary changes as needed.

Glutamine is always best opened on to the tongue but it must be used this way for stopping the intense sugar cravings quickly – as in immediately. It’s also used away from meals like all the amino acids.

If you notice improvements it’s very likely that reactive hypoglycemia or low blood sugar is a factor.

Glutamine for low blood sugar cravings: dosing and timing

As I share in my book and other blog posts, typically 500 mg glutamine is a good starting dose for intense cravings for sugary foods. We may increase based on individual needs and you may find you do need to use 500 mg -1000 mg two to three times a day when the intense desire for something sweet strikes – as blood sugar dips. Using a glutamine powder is a great way to use it especially if you find you do need more than 500 mg each time.

As I mentioned above when you use glutamine powder directly on the tongue (rather than mixed in water), the benefits are seen almost immediately and even if you don’t believe it could possibly work – like my client – your desire for sugar disappears.

GABA and serotonin support too

My client also needed GABA and serotonin support for her anxiety and sleep issues. Again, we used the low GABA and low serotonin symptoms questionnaire and did trials of GABA and tryptophan for her which helped further.

Sugar cravings and binge eating with other neurotransmitter imbalances too

Keep in mind that there is a sugar cravings aspect to all the neurotransmitter imbalances. The type of craving can be found on the above symptoms questionnaire. It’s not uncommon to need support more than one area:

Low blood sugar /hypoglycemia – glutamine for intense cravings at any time of the day
Low serotonin – tryptophan or 5-HTP for afternoon/evening cravings
Low endorphins – DPA for comfort/reward eating
Low catecholamines – tyrosine for low energy sugar cravings
Low GABA – GABA for stress eating

Glutamine product options – capsule vs powder

Products I recommend include Pure Encapsulations 500 mg l-glutamine (capsules opened on to your tongue) and Designs for Health l-glutamine powder as you find you need higher amounts. You can purchase these from my online store (Fullscript – only available to US customers – use this link to set up an account).

If you’re not in the US, Now l-glutamine 500 mg and Doctor’s best l-glutamine powder are products I recommend on iherb (use this link to save 5%).

Additional resources when you are new to using glutamine and other amino acids as supplements

We use the symptoms questionnaire to figure out if low blood sugar and/or low serotonin and/or low GABA and other neurotransmitter imbalances may be an issue for you.

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 too). This is a paid online/virtual group program where you get my guidance and community support.

Have you had success with glutamine for blood sugar stability and binge eating, food addiction and intense cravings for sugar and carbs?

Have you also found it helps with sleep, leaky gut and anxiety during the day?

If yes, how much helps you? And how often do you use it? And what sugary foods have you been able to stop eating?

If you’re a practitioner do you use glutamine and with clients/patients with these low blood sugar cravings? Do you recognize reactive hypoglycemia as a very real issue in non-diabetics?

And please let me know if it’s helpful that I’m now including product recommendations and where to get them?

Feel free to share and ask your questions below.