It’s not Topical Steroid Withdrawal its’ Mitochondrial Dysfunction
Introduction
This nightmare journey started in October 2023. My eldest daughter started with patches of eczema, and we just put it down to the fact that we was going into cold weather. She has had eczema before and quite bad at times but we never really figured it out and it was more luck than anything and just went away on its own. Before October 2023, she had been eczema free for maybe 2 years so it was a bit of a shock that it was starting up again. Our first thoughts were to look at her diet and given she had a bad kidney infection over the summer that required antibiotics to overcome we concluded that her gut microbiome had become compromised to breaking point. We adjusted her diet to eliminate the most common allergies. Starting with Gluten and dairy, we followed this for a couple of months but saw no improvement in the condition of her skin in fact she was looking worse. I had even tried putting her on a lectin free diet, can you imagine an 8-year-old going from regular food to lectin free. It was incredibly difficult not just for her (she is actually quite adventurous with food) but also for us having to learn how to cook lectin free food. By late December, her mother was desperate to help her daughter so she took her to see the GP. Keep in mind we do not have a lot of faith in doctors from bad past experiences which I’ll not go into but put it this way, this isn’t the first time I have had to throw myself into intensive medical research in order to salvage my daughters health following bad advice from the “experts”. Visiting the GP was an act of desperation from my wife and I do not blame her as our daughter was really struggling I just cannot forgive the truly terrible advice that came from it.
Were well into January now her skin is still massively inflamed and despite my pleas the steroid creams have gotten increasingly more potent. At one point, she was on a steroid cream that even the manufacturer warns that it’s not be given to children under 12. Our family life at this point was an all-time low we had never argued so much in our lives but it’s like only I could see the damage being done and I was up against my wife, her friends the mother in law and the doctors. I did not agree at all, with the treatments my daughter had received. Looking back I wish I’d have been stronger but in all honesty even if I’d have thrown the steroid creams out the house they would have just gotten more of them.
Found the initial eczema trigger
My uncle is one of those people that has been down far too many rabbit holes and they see the world for what it is (I am definitely not getting into any of that). One evening I consoled in my uncle, we had a great conversation about my daughter that led me down the road toward working out the initial trigger for her eczema flare. His advice was to go back and think about what changed. It didn’t seem it at the time but this seemingly simple advice planted the seed that eventually sprouted a shoot. Well, when it finally clicked I was kicking myself, as it seemed so frustratingly obvious and the pain she has gone through even just to now over something so simple was just heart breaking to think about. In October 2023, our washing machine had broke down and for a week or two, we were using my parent’s washer to clean our clothes. We also really liked the detergent they used so when our new washer came we also switched to that same brand which was Persil non-Bio (for sensitive skin). I immediately began researching natural ways to wash clothes and found soap nuts. Brilliant, it is literally a tree nut that foams up when mixed with water, a completely natural detergent. I highly recommend you all switching to this method of washing. For your whites or just for an extra cleaning boost throw a table spoon or two of bicarbonate soda into the drum. It works wonderfully and it’s completely natural.
It wasn’t long after switching to using the soap nuts that things started to change with our daughter in regards to her skin. Her eczema seemed to improve but only to come back worse again. It was more inflamed than before. My wife goes back to the GP and the doctor’s advise that its eczema and hand over yet more potent steroids and emollients of which boiled my blood, I’ll never forget looking at the warning on the back that literally said highly flammable along with the flame symbol, oh the irony! What they have been doing to us is disgraceful. It’s either incompetence or intentional!
This continues for what seems forever and I am researching all sorts of supplements trying to find something that will end this nightmare. I eventually found an article on topical steroid withdrawal and it felt as though it was written about my daughter. This is it; this is exactly what we are dealing with! I was so angry and yet relieved to discover this, I knew in my gut the steroid creams were just bad news but holy s**t I had no idea just how evil these things really are. My wife began again to try and taper her off the steroid creams as I had said enough is enough we are going to have to stop them at some point lets taper and deal with the fallout.
I don’t remember exactly when we accumulated all the various parts of the protocol that we had started to put in place for her. We of course went to see dermatologists on numerous occasions but the treatment paths they laid out only wanted to further suppress my daughters immune system and there was no way I was going to let them beat up her immune system further. The treatments offered were calcinurin inhibitors, more steroid creams and red light sun bed therapy. We already had a red light panel at home so there was not a lot to be gained from dermatology. From the early days of just dealing with eczema, she was on Vitamin D3 with K2 and a high dose at that, at the height of the inflammation she was on 16,000 IU a day. The list of supplements grew exponentially, we researched and tried all sorts and I have likely missed some off from the list below. I do think they offer some benefits but I’m afraid they were not the silver bullet one would hope for in this situation.
· Vitamin D3 with K2
· Vitamin C (Acerola Cherry)
· Bromelain good for gut health
· Lions-mane (ant-inflammatory)
· Stinging nettle (anti-inflammatory)
· Turmeric or Curcumin (anti-inflammatory)
· Cilantro Metal Detox
· Taurine
· Clean Berberine
· Pure NAC N-Acetyl Cysteine
· Flaxseed oil
· Chickweed
· Zinc
· Antihistamines
You name it we tried it. No silver bullet, not yet I am afraid.
Now going back to my uncle for a minute and about him going down those dark rabbit holes. He told me about a supplement called Methylene Blue (MB) I believe it was sometime around Christmas in 2022 and he even gave me a 1 gram vial of it with an instruction page which I simply tucked away in the cupboard and left alone. When all this with my daughter’s skin was kicking off MB was something I vaguely knew the benefits of but I had not dared to try it myself. January 2024 when in the height of eczema hell, it seemed like a pretty good idea to start doing some more in-depth research and after liking what I was reading I started testing it out. I mixed up the vial and started taking it for myself to test the waters with it, as there was no way I was going to give it to my daughter without trying it for myself first. I consider myself a somewhat healthy person, I am not far off 40 and only in the last couple of years have I stopped being asked for I.D when buying beer and I kid you not camping stove gas canisters. I’m a healthy weight and before I went down the many rabbit holes that TSW has led me down I believed I had a healthy diet. My uncle had told me to start with a very low dose of MB (he also said less is more when it comes to dosage), so I followed his advice and mixed it in a weaker solution than what the instructions advised. The instructions say to mix it with 100ml of distilled water but following my uncle’s advice I mixed it with 200ml. I grabbed a fresh glass of water and dropped in five or so drops of the MB solution. The first thing you notice is the incredible deep blue colour its beautiful really but not something you’d look at and think I wouldn’t mind drinking that. It doesn’t have too much of a taste, it’s like a slightly metallic water flavour. If you can drink the cilantro metal detox water then you will be fine with the taste of MB. I could not believe the impact Methylene Blue had on my energy levels. I was feeling great in regards to energy so I started playing around with the dosage and I had it in my head that I would work up towards a moderate dose which is 4mg of MB per KG of body weight so for me with my more diluted solution that would be 960 drops in a day. I slowly worked my dose up to roughly 1mg per KG and holy smokes I had such an incredible amount of energy that I didn’t sleep for two days and I wasn’t even tired by the following evening. That is when I understood that less certainly is more when it comes to MB and I had heard and read this from the various MB resources that I had checked out while researching it. MB has an incredibly good safety profile but at moderate to high doses, it can be dangerous. Luckily, you do not need anywhere near even a moderate dose to reap the benefits of MB. I now only have 5-10 drops a day and I’m not strictly having it every day but certainly more often than not. So now, I’m comfortable with MB, I have played around with the dose on myself, I have been taking MB for a comfortable amount of time and I haven’t died, turned blue or felt any ill effects at all and quite the opposite… I felt fantastic. I decided it was time to see what MB could do to help my daughter and the results blew us away with how quickly she started to improve. It actually still tears me up thinking about. So were at June now and by this time we had tried all the nonsense creams you have likely been told about (they truly do the opposite of helping). We had the list as long as your arm supplements I’ll caveat this by saying; don’t get me wrong these things are good for base line health but they don’t make you thrive with TSW) and we also now had her on the no moisture treatment protocol (NMT). NMT was brutal at times but it absolutely was the way to go. We found that her skin would heal faster and caused less pain if we simply just left it alone. We had also stopped bathing her, as she just could not handle it. After bathing, she would be in agony and not just for the moments after getting out of the bath, it would take a week or more for her skin to calm down again. At first you might think that is gross but it’s strange your body adapts in fact we still don’t bath her anywhere near as often as what she used to and she doesn’t smell, (we obviously keep / kept her private areas clean) don’t be afraid to try limiting your bathing.
So now the protocol is
· Base line vitamins: D3 5700IU with K2, C and some anti-inflammatory ones like turmeric
· Red light therapy as often as we could
· Limit sugars and high inflammatory foods
· No Moisture Treatment
· Methylene Blue (low dose)
We went from this on June 3rd (it is still hard to look at this picture)
To this on July 23rd
Here she is August 30th looking fantastic (I’ve cropped the image but she has an incredible smile on her face.) She’s smiling again and it’s an absolute joy to watch her fall asleep peacefully.
So now, life is good again and my marriage has somehow survived this high stress ordeal. We amazingly even have another child on the way, which I am super super excited about! You can throw any parenting challenge at me now and I will kick its ass, that’s how I feel after dealing with this.
I am a software developer by day and I consider myself a very methodical thinker. I knew what we were doing was working for her but I wanted to better understand why and how. Therefore, I continued researching and what I’ve come to realise is that this really ought to be obvious for anyone that has studied the function of mitochondria, which you know is only practically every doctor ever! My wife is in her third year of a natural science degree and I think she covered it in year one. Anyway, let us dig in and you will begin to understand why I have chosen the title ‘It’s not topical steroid withdrawal its mitochondrial dysfunction.
I am going to pull from various resources that I will link at the end so you can see for yourself how this puzzle came together.
To clear up any doubt, this isn’t a chat with an AI bot, this is the natural progression of citable research towards discovering the required data. The first few results are the typical vague overview of what steroid creams do so I didn’t bother to reference those results (I might add them for completeness at some point) but this information is what most people already know about TCS’s. I absolutely referenced the mechanism of action as that is the data I needed and it’s from a reputable source.
How steroid creams work?
Topical steroids work by reducing inflammation in the skin... ok that is a bit vague, how?
Reversing enlargement of blood vessels in the area they are applied to. They cause a narrowing of the blood vessels.
Steroid creams restrict the blood supply to the skin, which in turn prevents any immune system response from getting to the applied area. Ok got it but how?
Mechanism of Action
The mechanism of action of topical corticosteroids is vast, consisting of anti-inflammatory, anti-mitotic, and immunosuppressive effects.
The anti-inflammatory effect of topical corticosteroids consists of vasoconstriction, inhibition of the release of phospholipase A2, and a direct inhibitory effect on DNA and inflammatory transcription factors.
Vasoconstriction of the blood vessels within the upper dermis decreases the number of inflammatory mediators being delivered to the region applied.
The anti-inflammatory effect also occurs from the synthesis of lipocortin which inhibits phospholipase A2, ultimately decreasing the production of prostaglandins and leukotrienes.Topical corticosteroids also act directly at the DNA level to increase the expression of anti-inflammatory genes and indirectly inhibit inflammatory transcription factors, such as NFkb, to decrease the expression of pro-inflammatory genes.
The anti-mitotic effect of topical corticosteroids play a great role in the treatment of psoriasis; it is proposed that this decrease in epidermal mitosis is secondary to an increase in lipocortin, an endogenous glucocorticoid-regulated protein. An anti-mitotic effect is also present in the dermis which inhibits cell proliferation and collagen synthesis.
The immunosuppressive effects of topical corticosteroids involve the inhibition of humoral factors involved in the inflammatory response as well as suppression of the maturation, differentiation, and proliferation of all immune cells.
Reference: 1
Pathophysiology of the ‘red skin’
The widespread red skin seen in this condition is thought to be the result of prolonged fixed vasodilatation. TCSs have a suppressive effect on nitric oxide in the endothelium and the release of accumulated endothelial nitric oxide stores results in hyperdilatation of vessels.
Reference 2
Ok, I hate it but I get it now. I have highlighted a couple points taken from the above sources that I want to focus on but first, you are perhaps wondering what exactly is mitochondria?
What is a mitochondria
Your mitochondria is only the greatest energy producer in the entire world! Your body needs fuel and it all starts with the food that you eat. Your mitochondria is the guy responsible for converting the fatty acids and glucose from your food into a useable chemical energy known as adenosine triphosphate (ATP). ATP is essential for life, as it fuels nearly all cellular processes. Put it this way, every cell in your body has a mitochondria cell supporting it, including your skin cells. The body produces ATP primarily through aerobic respiration in the mitochondria, where either fatty acids or glucose is fully oxidized to produce large amounts of ATP.
The first highlighted point is ‘Phospholipase A2’. What that hell is that you say? If Phospholipase A2 stared in the anchorman it would deserve the line: “I’m kind of a big deal”.
Overview of Phospholipase A2
Phospholipase A2 plays a crucial role in mitochondrial function by modifying mitochondrial membrane composition, influencing mitochondrial dynamics, and contributing to key signaling pathways. Through its actions on phospholipids, PLA2 can impact processes such as ATP production, ROS generation, apoptosis, and overall mitochondrial health. Its activity is tightly regulated, as both excessive and insufficient PLA2 function can lead to mitochondrial dysfunction and contribute to various diseases, including neurodegenerative disorders, cardiovascular diseases, and cancer.
If you want to read more about how crucial Phospholipase A2 is then check out reference 3 but as you can see from the snippet above, it’s kind of a big deal.
Nitric Oxide (NO)
The second highlighted point from the sourced data is on Nitric Oxide suppression. From my own studying of mitochondrial function this one immediately stood out to me as NO plays several crucial roles in the function of mitochondria, impacting cellular metabolism, energy production, and overall mitochondrial health.
Ok so we have applied steroid creams that disrupt at least two major components of our mitochondrial function by creating an environment where these two enzymes are being suppressed. No wonder we are suffering. Let’s now look at how in a little over a month my daughter went from picture 1 to picture 2 and continues to thrive even today.
The role of Methylene Blue
I have recently done a deep dive to enhance my understanding on how methylene blue helps our mitochondrial function. It was during this research that I also started looking into each of the components that led to TSW which then pieced it all together.
Let’s take a look at the components of your mitochondria cell. I’m honestly trying to keep this as simple as possible and not too sciency but stick with me and I’ll explain it as plainly as I can without overloading you.
The picture above shows the structure of a mitochondria cell
Your mitochondria cell consists of an outer and an inner membrane and within the inner membrane are four complexes labelled I, II, III, IV and also a key hole looking one labelled ATP synthase. There is also a Q and Cyt c together these components form the electron transport chain and imagine them as like a factory production line. They each do their part and pass their product onto the next person in the chain to make whatever it is they are making and in the case of the electron transport chain, the end product is ATP. In a healthy functioning cell, this process really is the most efficient energy producer in the world. However, what if the conditions are not healthy and perhaps one or more of the complexes are blocked. How would our cells get the fuel they need to thrive? For example; let’s look at complex I this complex takes NADH and oxidises it to extract the hydrogen atoms which then forms NAD+. The mechanism of action of the TCS’s restrict blood flow to the upper epidermis through the suppression of Nitric Oxide (NO) which causes vasoconstriction (narrowing of the blood vessels), thus preventing cells from receiving the nutrients they need. So complex I is not getting the nutrients it needs to produce ATP and so the electron transport chain becomes blocked. The Dr Ian Myles study shows that people suffering from TSW have raised amounts of NADH which to me makes sense given you are cutting off NADH demand by restricting blood flow to your largest organ. When the steroids stop NO is no longer being suppressed, the blood vessels begin to open up again and the backlog of nutrients and enzymes comes flooding back in to the previously cut off areas. The problem now though is the cells there are damaged and overwhelmed so they start spewing out free radicals which cause further oxidative stress. Remember, PLA2 is also being suppressed which is a crucial enzyme for mitochondrial health and one of its many roles is triggering mitophagy which is the organised removal of damaged mitochondria. Not surprising we have mitochondrial dysfunction now, is it?
How can MB help dysfunctional mitochondria? MB acts as a mitochondrial electron carrier, it’s also a powerful antioxidant. MB is also highly bioavailable and can pass the blood brain barrier. When MB finds it’s way into a dysfunctional mitochondria cell it can bypass certain dysfunctions in the electron transport chain, particularly at Complex I (NADH dehydrogenase), by accepting electrons and transferring them directly to other components in the chain. What’s even more amazing is there is strong evidence that MB can stand in for any of the components being blocked so it not only helps dysfunctional cells at complex I but any of the other complexes and what’s even more amazing still is that MB can even help with the final complex, the ATP pump.
One important consideration is that while methylene blue does increase ATP production by aiding the mitochondria cells with the process. What it doesn’t do is fix your underlying mitochondrial dysfunction. In a normal healthy functioning mitochondria cell the presence of MB would actually reduce the output of ATP, as this ancient drug is really no match for how beautifully complex and amazing our mitochondrial function is. It’s about supporting its function through the hard times and creating a stable environment that will allow healing to occur. The level of inflammation I’ve seen not only my daughter but other TSW patients experience is highly concerning and I wouldn’t be surprised if down the line there are links to elevated risks of cancer.
So piecing all this evidence together you can conclude that MB is the reason my daughter is continuing to thrive. If you look at the symptoms of mitochondrial dysfunction in complex I, you will see ‘failure to thrive’, which she absolutely was and still would do even now. I tried reducing her MB dose down to nothing in September and the oxidative stress / inflammation started creeping back in within about three weeks of no MB. Back on the MB and she is thriving again.
Methylene blue has a great safety profile but there are certain risks to be aware of.
People with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as use of MB could lead to severe red blood cell breakdown and anemia. It can also be harmful to developing babies, so pregnant women should avoid taking methylene blue. Remember ATP production in a healthy cell would be hindered by the presence of MB and the part of the body with the highest amount of mitochondria is your reproductive system. I would imagine it takes a lot of energy to create new life so you don’t want anything burdening that process.
You cannot take MB while also taking SSRI medication. Monoamine oxidase inhibitors (MAOI) are known to cause serotonin toxicity (ST) when administered with selective serotonin reuptake inhibitors (SSRI). Methylene blue (methylthionium chloride, MB), a redox dye in clinical use, has been reported to precipitate ST in patients using SSRI.
If you are taking any medication I would encourage you to research the drug interactions. I know some antihistamines cannot be taken with MB and you must leave it two weeks stopping one before you can start the other. Best to check your other medications are safe before starting on MB.
This is where my research has almost concluded (for now anyway). I now understand that while MB can help stand in for dysfunctional mitochondria cells it sadly does not fix them. So MB is a useful tool to support mitochondrial function while you work on what is now your most important job… feeding your mitochondria with what it needs to thrive. Quick research on this led me to an ancient medicine called Shilajit that provides essential nutrients for our mitochondria. I just so happened to have heard of Shilajit before embarking on this research and luckily I already had some in the fridge. What dad just has Shilajit on stand by in the fridge, the kind of dad that’s gone through TSW nightmare and has every supplement going. The updated protocol is:
· Base line vitamins: D3 5700IU with K2, C
· Red light therapy as often as we can
· Limit sugars and high inflammatory foods - No seed oils
· No Moisture Treatment
· Methylene Blue (low dose)
· Shilajit (one dose/ tablet per week)
I will continue to update this community on my research as I feel it in my gut that I am on the right path. I want to help others, this has been the hardest thing I have seen a loved one go through, I would not wish this on anyone. It breaks my heart that others are going through this and if I can help, I absolutely will. Let me remind you though that I am not a doctor, I am a father dedicated to seeing his children thrive. I’m sharing this as the information I have found I strongly believe it will help others to make sense of the underlying problem caused by topical steroid creams. If you are reluctant to try MB for yourself I would then encourage you to look into the benefits of fasting for periods of more than 24 hours to trigger autophagy. Autophagy is the process your body starts after the digestive system has shutdown. This process starts after roughly 24 hours of fasting and the longer you stay in this state the higher the level of cellular cleaning achieved. Don’t use fasting as an excuse to eat anything you want after, always seek out high nutritional food and protein to further enhance your health. I wanted my daughter to fast right back when in the eczema hell days but that caused arguments and ultimately it was too much to ask of an 8 year old at the time. I still think we way have to revisit that in light of this research.
I will write another article in the near future more focused on diet. To give you a quick taste. Look into seed oils, rapeseed, sunflower, canola, sesame, vegetable oil. These oils cause massive oxidative stress that destroys your mitochondrial function and TSW sufferers are already dealing with enough of that so cut them out completely! There is no safe amount of these toxic oils. MB can help with oxidative stress but it will not offset a poor diet, nothing will.
Please note I may also update this article from time to time as and when new research comes to my attention.
Thanks for reading and god bless
References:
National library of medicine, Topical Corticosteroids, Sarah Gabros; Trevor A. Nessel; Patrick M. Zito, July 10, 2023: https://www.ncbi.nlm.nih.gov/books/NBK532940/
Royal Australian College of General Practitioner, Topical corticosteroid addiction and withdrawal – An overview for GPs, Belinda Sheary, June 2016 https://racgp.org.au/afp/2016/june/topical-corticosteroid-addiction-and-withdrawal-an#ref-4
Sciencedirect, Phospholipase A2-activating protein induces mitophagy through anti-apoptotic MCL1-mediated NLRX1, oligomerization, August 2023: https://www.sciencedirect.com/science/article/pii/S0167488923000599
Dr Ian Myles YouTube channel, Topical steroid withdrawal: Results from an early study, explained to patients, 7th May 2024: https://youtu.be/TSFiKlrIDUI?si=xOylI20gW8uXLAEh
Update 13/12/2024: I sent this research to Dr Ian Myles after a user commented to say that my findings were closely aligned with his own research. Dr Ian Myles has responded to me with the below. Please note, he has given me permission to share his message:
On 13 Dec 2024, at 15:10, Myles, Ian (NIH/NIAID) [E] mylesi@ wrote:
Hi yes very interesting. My only edit would be the title should be TSW is (iatrogenic) Mitochondrial Dysfunction since the mito-dysfunction is coming from TSW. I had not thought of trying MB but it makes sense with our data on Complex I. I’d also be interested to see “Clean Berbeine” tested. ConsumerLabs tested 13 or so brands and only 3 had any berberine in them and only 2 had the indicated amounts. They did not test the Clean brand so I wonder if your daughter was taking “Berberine” on the bottle but not getting any of the actual molecule. But I’m glad MB worked out. Our paper should be coming out in a month or so, which we hope will help the TSW community.
You should consider writing this up as a ‘case report’. It is valuable information to note that someone with TSW was successfully treated with MB. The Reddit post will hopefully reach the patients, but the report might also reach some providers. We are hoping that when our paper is out, the physician-resistance to the diagnosis will go away but we shall see.
Thanks for sharing Ian
PS – we also work on environmental triggers – such as what you found with the detergent and fabric choice. Please see attached papers for our summary of what we think are the most important things to avoid/consider.
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Hi Ian,
Thank you for coming back to me and for the title suggestion. Do you mind if I share your thoughts on my Reddit post? How do I go about officially making this into a case study, is that something you could assist me with?
The berberine we used to treat my daughter was from British Supplements - Clean berberine from Amur Cork tree bark 435.6mg. Perhaps we didn’t use berberine for long enough to see it working. I started using MB as soon as I fully understood the benefits to mitochondrial function and once I was satisfied that it was safe enough to try. The results were staggering.
I would be really interested to see a wider study with patients being treated with MB.
I look forward to the release of your paper. Thank you for your continued support to the TSW community.
Kind regards,
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By all means share. I read your post but not any of the comments. For the case report – myself and one of the students can take what you wrote and convert it to a case report, then we can send you the draft to make sure we got it correct and to have you fill in any needed details. Then we can submit, including you as an author, for review. I think the MB part will be of greater interest to the med community following our paper suggesting mitochondrial dysfunction is the root of the problem. I would think it would take us a week or so to write up – but with the holidays there could be delays (and to be honest, the journals won’t get to it during the holidays either).
What do you think about that plan?
Ian