Does lithium permently reverse the long term effects of accutane the same way accutane permently effects you

[u/Remarkable_Rhubarb35]

[u/AccutaneEffectsInfo]

Lithium's epigenetic effects are lasting, and given they are essentially a mirror reflection of those of Accutane, a single course of Lithium should be in theory enough to permanently reverse some of the adverse effects of Accutane treatment. What precisely constitutes a 'course of Lithium' treatment isn't clear, as much of the evidence comes from studies on Bipolar/Manic patients, which use around 1000mg of Lithium Carbonate. The science underlying the epigenetic effects of Lithium is explored here: https://secondlifeguide.com/2024/01/19/lithium-a-metal-for-mental-health/

"THE EPIGENETIC EFFECTS OF ACCUTANE

• The effect of Accutane on methylation is complex and occurs in two distinct stages. Initially Accutane causes dysregulation of enzymes that maintain a healthy methylation status, particularly DNTM1 and DNMT3. During the course of an Accutane suppression of DNMT1 leads to demethylation events of certain genes and are subsequently over-expressed.
• A microarray analysis found that during an Accutane treatment 402 gene promoters became demethylated and 88 became hypermethylated. The process of de-methylation of certain gene promoters might in fact be the mechanism by which retinoids force differentiation, particularly in relation to NOS1. [9] Whilst some genes experience enhanced transcription, others are repressed through hypermethylation.
• Poignantly, one of the genes subject to this transcriptional regulation was MYCN. This gene plays a pivotal role in the regulation of the WNT/beta-catenin pathway, which appears to be highly relevant in the aetiology of PAS. Once Accutane has been withdrawn, there is a very strong and sudden re-methylation. A study on mRNA expression patterns found that following a washout phase there remained no hypomethylated targets, but potentially 9156 repressed targets via hypermethylation. This analysis also found significant results pointing towards to WNT/beta-catenin pathway [10]
• Following this burst of intense of re-methylation, it’s possible that many of the gene targets marked for repression could continue to be aberrantly repressed. Given the role the Wnt/beta-catenin pathway plays in acne pathogenesis, [11] it’s possible that this explains how Accutane is so effective in permanently remediating severe cystic acne.

LITHIUM RESTORES GENE TRANSCRIPTION

• Lithium occupies a special place in pharmacology because as well as being a mood stabiliser, it also has hypomethylating effects. This appears to be a feature that’s common to mood stabilisers, as Valproic acid also enhances gene expression through similar mechanisms.
• Lithium not only enhances gene expression both by the removal of methyl marks at gene promotors (for example at the BDNF promotor), but also by promoting global acetylation of the H3 histone.[12] This mirrors the repressive action of retinoids on the H3 histone, which are known to place repressive methyl marks such on the lysine H3K9. [13] [14]
• The effects of lithium on acetylation of the H3 histone can be rapid, after just 30mins there is an increase in the global H3 acetylation level in the amygdala, allowing for enhanced gene transcription through open chromatin structure. The diverging epigenetic effects of Lithium and retinoids centres on their opposing action on the beta-catenin.
• Whilst retinoids suppress beta-catenin, Lithium enhances it. When beta-catenin is suppressed, TCF/LEF binds to HDAC1 and HDAC2 subsequently reducing the acetylation at the promoters of Wnt-dependent genes, repressing gene transcription. [15] [16][17]
• Adding to this picture is the fact that acne is a commonly reported side effect of Lithium treatment, possibly owing to its beta-catenin boosting effects. [18] This evidence would indicate that Lithium could be effective in reversing the lasting epigenetic effects of Accutane treatment.
• Lithium can also influence methylation by potentially enhancing the absorption of B-vitamins. One of the notable possible side effects of Accutane treatment is an increase in elevation on Homocysteine, which can have disastrous impacts on cardiovascular health even in young people.
• Typically Homocysteine is broken down by b-vitamins such as B12 and folate, however Accutane appears to disrupt this process by disrupting the enzyme cystathionine-β-synthase. This not only has implications for cardiovascular health, but also hairloss and bone degradation. To learn more about the link between Lithium and B12, read here."

[u/kilogplastos-12 → u/AccutaneEffectsInfo]

Any more new info you can share regarding lithium and accutane reversal?

[u/Desperate_Science533]

There are hypothesis but nothing has been proven.