The general impression over the many posts on this website is that Lithium acts almost like an ‘anti-Accutane’ medication. In just about every domain of Accutane adverse response, Lithium appears to do the opposite. For example:

1. Lithium induces acne. [1]

2. Accutane causes skeletal weaknesses (maybe the cause of musculoskeletal discomfort reported in adverse events).[2] This is a result of increased bone turnover (enhanced bone reabsorption). [3]This results in increased bone fracturing events. [4] Lithium however enhances bone mass density, by reducing bone turnover. Lithium treatment is therefore associated with reduced incidence of bone fracturing. [5]

3. Accutane significantly increases liver triglycerides and fatty acids. [6] Lithium significantly reduces total liver fatty acids, with a decrease in triglycerides. [7]

4. Accutane induces night blindness, an effect that is often permanent. [8] Lithium enhances night vision [9]

5. Accutane induces hair loss. [10] Topical lithium treatment induces hair growth. [11]

Whilst this all looks very promising, there are concerns. There are issues with individual tolerance that make it hard to predict how somebody may react to a specific dose. Higher doses are associated with suppression of certain sex hormones and hypothyroidism (this in turn has detrimental downstream effects on hair growth). There’s other difficulty in assessing how binding compounds may effect results. Typically the studies use clinical setting formulations of Lithium carbonate, whilst Lithium Orotate is the formulation available over the counter. There are other supplements that enhance beta-catenin accumulation, that are induce similar ‘anti-Accutane’ effects that may be better tolerated. One example is Acetyl-l-carnitine (ALCAR).

As predicted by my proposed mechanism, ALCAR has potential to remediate a whole range of Accutane induced adverse effects. ALCAR has even been found to normalise liver lipids and enzymes whilst taking isotretinoin. [12] ALCAR stimulates hair growth in a mechanism that directly opposes Accutane action. [13] ALCAR improves bone density by reducing bone turnover. [14] ALCAR is likely better tolerated than Lithium, and I would recommend it first until I can finish reviewing all available literature on Lithium dosing.

[1]  https://www.cmaj.ca/content/185/17/1525.short

[2]  https://link.springer.com/article/10.1007/BF01771325

[3]  https://www.sciencedirect.com/science/article/abs/pii/S0960076015300959

[4]  https://www.sciencedirect.com/science/article/abs/pii/S8756328208008181

[5]  https://link.springer.com/article/10.1007/s00223-004-0258-y

[6]  https://pubmed.ncbi.nlm.nih.gov/25474452/

[7]  https://academic.oup.com/jn/article-abstract/104/10/1242/4779566

[8]  https://onlinelibrary.wiley.com/doi/abs/10.1111/ajd.12107

[9]  https://pubmed.ncbi.nlm.nih.gov/3406048/

[10]  https://www.sciencedirect.com/science/article/pii/S2666328722000050

[11]  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116182/

[12]  https://pubmed.ncbi.nlm.nih.gov/10642057/

[13]  https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0625.2007.00611.x

[14]  https://www.sciencedirect.com/science/article/abs/pii/S0944711308000779

Lithium has been found to increase cytoplasmic levels of beta catenin via the Wnt signalling pathway. Lithium acts as an agonist of the canonical Wnt singaling pathway that can inhibit GSK3-beta activity and thus release beta-catenin from the destruction complex. [1] This results in the typical beta-catenin proliferation effects, with relevancy particularly in the brain where it is able to induce neurogenesis in the hippocampus. [2] Hellweg et al.[3] found that Lithium also increases NGF (neural growth factor) in the frontal cortex (+23%), hippocampus (+72%), amygdala (+74%) and limbic forebrain (+47%). These are all regions that have decrease metabolism in isotretinoin treatment. This neurotrophic effects were highly dose dependent however.

Lithium offers effects that remediate the full spectra of PAS/PFS symptoms, these effects are striking because they can only be explained by the mechanism of action I have proposed in this paper. The first intriguing effect is that bipolar patients treated with lithium have far better night vision compared to untreated controls. [4] I hypothesise this is a consequence of ALDH upregulation via beta catenin, to improve rhodopsin formation in the retina. Additionally lithium has been found to cause acne in up to a third of patients. [5] This is expected given that it works almost by the opposite mechanism of isotretinoin. Adding to this picture is lithium’s capacity to increase ACTH, which is the only hormones that’s found to be significantly suppressed by isotretinoin treatment. [5.5]

Lithium also has a modulatory effect on androgen dependent processes, however the direction of effect is highly dependent on dosing. Prostate cancer is an androgen driven pathology which is often treated with androgen deprivation therapy. Lithium has been shown to increase cell proliferation and can theoretically increase androgenic gene transcription by increasing cytoplasmic beta-catenin. When prostate stem cells were incubated with low dose lithium the cells displayed proliferation and low apoptosis. When the concentration was increased by between 50-100 fold, the opposite results were found. [6] Lithium has also been shown to significantly increase bone density whilst reducing bone turnover, which completely mirrors the effect of isotretinoin which reduced bone mineral density whilst increasing mineral turnover. [7] Lithium also counters many of the detrimental metabolic effects of both finasteride and isotretinoin, increasing insulin sensitivity. [8] Lithium, specifically at low doses, can improve musculature by promoting myoblast fusion and myogenic differentiation. [9]

Low dose lithium carbonate (150mg/day) was found to be beneficial in treating ADHD and a plethora of mental health disorders without inducing sexual side effects. [10] The trial was strikingly effective with many of the patients reporting increased motivation, hope, dream recall and improved sleep. This deviates from the doses of lithium used in treating psychosis which are often 10 fold greater (1000-1500mg). Patients taking these much higher doses experienced blunted affect and sexual side effects.

Interestingly lithium also has the potential as a hypomethylating agent, whereby gene potentially silenced by isotretinoin (via promoter hypermethylation) can become active again. Bipolar responders to lithium treatment experienced decreased global methylation. [11]

[1]  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458451/

[2]  https://www.nature.com/articles/s41398-021-01695-y

[3]  https://journals.sagepub.com/doi/10.3727/096368909X471251#bibr122-096368909X471251

[4]  https://pubmed.ncbi.nlm.nih.gov/3406048/

[5]  https://derickdermatology.com/wp-content/uploads/2016/02/everydayhealth_com_lithium_and_acne.pdf

[5.5]  https://www.nature.com/articles/1395913

[6]  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038888/

[7]  https://pubmed.ncbi.nlm.nih.gov/18992857/

[8]  https://link.springer.com/article/10.1007/s00424-021-02543-0

[9]  https://www.mdpi.com/2073-4409/8/11/1340

[10]  https://www.sciencedirect.com/science/article/pii/S2468171720300053

[11]  https://academic.oup.com/ijnp/article/17/4/561/645000?login=false

The most important consideration when taking lithium is the dose (this really cannot be understated!) A good parallel to be drawn is with Accutane itself, low dose supplemental vitamin A is completely healthy and beneficial but concentrated high doses in the form of Accutane can wreak havoc on your body.

Contrary to popular opinion Lithium isn’t just a medication for the Manic and Psychotic, in fact, it’s in your water (at very very low doses). The World Health Organisation event recognises it as an essential mineral. The amount you might typically expect to absorb through water though is between 0.2-0.5mg. This is well below the typical over the counter supplement at 5mg. Even still, this low concentration of Lithium passively absorbed through the groundwater is still correlated with mood and wellbeing! Fascinatingly, areas with higher lithium concentrations in the ground water have much lower rates of suicide and depression.

Why does Lithium get such a mixed reputation then? The doses used in treating psychosis are way way higher than that available through the groundwater or from supplementation. Typical psychotic doses are 1000mg-1500mg. At this very high dose patients experience a flattened affect, and suppressed cognition. (Although, in this case, this is entirely intended as mania is excessively heightened mood, libido and energy). As a lower dose conjunctive or monotherapy in depression at doses of around 100mg, there’s significantly improved tolerability and safety profiles.

Treating Hair Loss: One of the side effects often cited with clinical doses of lithium (1000mg+ ) is hair loss. This isn’t anything to do with lithium’s effect on beta-catenin, but rather a secondary effect on thyroid hormones that only occurs at clinical doses. In fact, low dose lithium grows hair*,* by contracting the telogen loss hair cycle phase and initiating new hair growth much quicker:

“We treated several cohorts of mice in late telogen and ascertained the effect of GSK3B inhibitor lithium chloride compared to the sodium chloride control. As with PaPI treatment, lithium chloride treatment significantly shortens the length of telogen, inducing a new anagen in an average of 5 days. Consistent with anagen induction, LiCl-treated sections show increased staining for ABC compared to sodium chloride-treated sections . The 70% reduction in telogen length seen during LiCl treatment mirrors that seen with PaPI treatment and provides further evidence of the role for the proteasome and Wnt signalling in hair cycle control“  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116182/#:~:text=Partial%20proteasomal%20inhibitors%20(PaPIs)%20appear,anagen%20and%20dramatically%20shortened%20telogen .

For people strictly concerned with hair loss, there are topical lithium solutions in the form of shampoos. They’re typically used in the context of treating dry itchy scalps, but are an ideal treatment for PAS. I’d recommend this treatment first to avoid the hassle of titrating an oral dose. Here’s an example but I don’t necessarily endorse a particular brand:  https://www.alliumherbal.es/en/p/lithio-ds-anti-dandruff-shampoo-from-lacatal

Hormonal effects: Again, as with every other effect of lithium, the effect on hormones is highly dose dependent. In this study 0.1mg/100g B.W. (in rats) caused no impact on FSH, LH, PRL and T along with unaltered activities of testicular Δ5 −3β −HSD, 17 β−HSD. This dose is approximately equivalent to 10mg for a 70kg man. However doubling the dose to 20mg, or quadrupling to 40mg equivalent for a 70kg man began to show suppression of these sex hormones.  https://www.sciencedirect.com/science/article/abs/pii/002432059090045S

Whilst I’m recommending low doses here there is evidence that Lithium treatment has positive long lasting effects due to it’s hypomethylating properties. It’s theorised that clinical doses of lithium have life long improvements on suicide and mental health statistics because of it’s epigenetic properties. 

Disclaimer: These are my results with Lithium in treating PAS. By no means am I a medical professional I’m doing this out of desperation. My results are mine and mine alone I don’t know anyone else recording there results at the moment. I welcome people to ask me question directly but before you do, read my entire post please. If you do want to ask me questions, be polite and have some manners or your getting blocked. I have a short fuse for morons and I don’t want to help them procreate.

Hello My name is Brett, I’ve been dealing with PAS for 10 years now, most my young adult life. A back story to the difference between Lithium orotate and Lithium Carbonate. Carbonate is a medical dosage and lithium orotate is more what you would find in food and only has trace of lithium in it, hints why you can buy it over the counter. I ran tests on the lithium orotate I was taking, I have a machine at my college that delouts it in water and I can actually analyze how much lithium is in 130mg of lithium orotate. Interestingly enough there are only 4.9-5.5mg of lithium in 130mg of lithium orotate. May be why none of us are seeing results from these low dosages. I started by upping my dosage for lithium orotate to 1g. That’s when I started getting morning wood and started getting better as far as sexual function as well as feelings, but not as much as I would like, it got me back to 40% Pre PAS. That’s when I decided to go on 300mg of Lithium Carbonate. Medically speaking that is a low dosage, high dose of lithium Carbonate can go up to 1200mg. Keeping in mind Carbonate is a concentrated form of Lithium. I’ve been on Carbonate for 7 days now and getting aroused is starting to become no effort. I’m closer to 60% now. How I attained Lithium Carbonate was I had to talk to a psychiatrics physician. Of course exercise caution when taking this medicine because lithium carbonate can shutdown your kidneys and give you lithium toxicity. Only side effect I’ve had so far is feeling tired. Considering what most of us are having to deal with it is worth the risk because its not living when you’ve been dealing with this kind of thing. They will take blood tests as well to make sure you are doing ok with the medicine. Good luck to all and hope you all get better.

HAIR LOSS TREATMENT: What I used to treat hair loss is a derma roller .5mm, I use a machine called the derminator or you can just get a pin that goes this length. I did sessions of 10 minutes till scalp was bloody then let it heal. Derma rolling causes damage to skin which in terms triggers the healing process which produces collagen. Better than finasteride so that way you don’t run the risk of sexual side effects from that as well. This will cause shedding but overall will improve the strength of the hair follicles and cause new growth. Stumbled on this when I was reading about a man who was in a fire and burned part of his scalp, the man was bald and had been for some time. Weeks after the incident there was new hair growth, SCIENCE!!

WEEK 1 date 5/28/24: First week down results showing constant and no draw backs as of yet. Feeling tired most days due to lithium’s treatment. other than that feel good, socially I’m comfortable, comfortable in the same way that I was pre Accutane so its nice to connect with people and not feel like its labored. Hair feels thicker and fuller, noticing some shedding but no more than out of the norm. Sex drive has been pretty consistent along with ED seems to be getting better, I can say for sure its not getting worse, there is more sensation now then I have felt in a long while. Overall I would say I’ve made improvements more to 64%. No crash’s, mood is good. Sex drive is still not as high as I was hoping, still about the same, but that’s because lithium reduces T. I won’t get to see the full effect of lithium until my T levels are back in the norm. Considering upping my dosage next month to 600mg. Nothing else major to report as of now.

WEEK 2 date 6/4/24: Still going strong, no draw backs yet except hair is dry, sometimes wake up in the middle of the night with a full on erection, which I guess is good. Everything else still staying about the same if not improving by a smidge. Lithium is taking a lot of energy out of me, feel absolutely drained after my workouts but I kind of like that feeling. feelings are popping out of no where sometimes, finding certain people attractive again which is very nice but not the extent of I need them now kind of like how I use to feel. Kind of feel like the benefits are slowing down and wondering if I might need to up my dosage to 600mg. Upon doing more research on lithium it also reduces feelings of mania and feeling really excited. So that may be why I’m not feeling a bunch but I can notice ED is going away. Lithium can take several weeks to work its full magic. Nothing else major to report as of now.

WEEK 3 date 6/11/24: No crashes, everything staying about the same. No huge improvements now seems it might have capped off. So here in a week I will get off the medication and report back and record the way I feel post medication and from there will determine whether or not to continue. But I had I think got back to 70% roughly, but While on the medication it can be hard to tell. When I draw closer to taking my dosages I notice feelings start, not alot but a little. I think once I’m off the medication things might change. Lithium does keep your emotions really baseline prevents you from both feeling supper happy and sad. none the less I got improvements. ED is a thing of the past. Of course dealing with these things for 10 years I have PTSD so I’m gonna have to deal with that in my own time.

@all_knight did you ever bump up to 600 mg?

@all_knight did you ever up your dose?  Or did you stop?  Did anything change after your last post?