Metformin Caused Psoriasis-like Eruptions, Alternative is Berberine

It is not unusual to develop diabetes or pre-diabetes along with psoriasis. Actually diabetes and pre-diabetes are just the terms used to name the increased blood sugar levels (usually treated with the drugs like metformin) resistant to endogenous (own – produced by the body) insulin.

In my previous articles you can read more details about the cause of type 2 diabetes. But in short what is the cause?

Endotoxins and inflammation, yes the same causes like those of psoriasis.

It is known for more than 70 years that infection is the most common cause of diabetes!

Does metformin help also in psoriasis?

Even though there were some studies and articles published in scientific journals I don’t think that metformin could be any helpful in psoriasis. If we are looking for the real cure and not just a whatever it takes band aid.

The mechanism of action of metformin presented in those papers is again just a suppression of some pathways rather than bringing the balance.[1, 2]

I highly doubt that inhibiting the proliferation of keratinocytes (skin cells) through the MAPK pathway would work any better than any other drug (methotrexate, ciclosporin, biologic drugs) used specifically for psoriasis.

In article from 2013 the authors published their arguments for a pilot trial with metformin as an additional treatment for methotrexate in patients with psoriasis.[2]

Frankly, If I had to, I would rather choose to take just methotrexate for psoriasis. Every additional drug added to this powerful chemotherapeutic agent would not make things much better and possibly even worsen the health in the end.

One study found that adding metformin to already existing insulin therapy for 16 weeks decreased the serum folate (-7%) and B12 levels (-14%) and increased the serum homocysteine (4%).[3]

Acute metformin poisoning leads to “lactic acidosis, cardiac arrest, pancreatitis and hemolytic anemia”.[9]

Metformin caused Psoriasis-like skin eruptions

There is at least one case report of 18 year old woman who developed psoriasis-like skin eruptions one week after starting metformin hydrochloride.

The woman took no other medications and had no family history of psoriasis.

It took 5 weeks after discontinuation of metformin to clear up the skin.

Four months later the patient still had the clear skin until the re-challenge with metformin which produced the psoriasis-like skin eruptions again.[4]

Image Source: Koca, Rafet MD; Altinyazar, H Cevdet MD; Yenidünya, Sibel MD; Tekin, Nilgün Solak MD. Psoriasiform drug eruption due to metformin hydrochloride: A case report. Dermatology Online Journal, 9(3), 2003

By the way, metformin messes up with the thiamine (you can read about it below) and thiamine is extremely important for production of acetylcholine.

Yes, that acetylcholine which is so anti-inflammatory via its effects on vagus nerve and alpha-7 nicotinic acetylcholine receptor.

And in my theory increase in acetylcholine production should help cure psoriasis!

Metformin induced Lactic Acidosis

If you are smart you probably know that every disease has some real cause which is explainable by science.

Lactic acidosis is not caused by lack of “miraculous pH drops”, “sodium bicarbonate from the bottle” or… try to remember some other silly theory.

Lactic acidosis is caused often by deficiency of vitamin B1.

You can read more about it in my previous post “Real Cause of Acidic Blood is Deficiency of These Vitamins…”.

So, the common sense tells us that if metformin induces the lactic acidosis the chances are that it may interfere somehow with thiamine metabolism.

And sure it does!

Metformin is a substrate and inhibitor of the Human Thiamine Transporter – THTR-2. [6]

Another way how metformin interferes with thiamine is through a competitive uptake by Organic Cation Transporter 1 – OCT1. [5]


Thiamine plays a critical role in glucose metabolism,
and thiamine deficiency has been reported to lead to lactic acidosis. Our laboratory recently identified thiamine as a major endogenous substrate for OCT1, which is the major hepatic transporter of metformin and may also contribute to its intestinal disposition. We hypothesized that metformin and phenformin inhibit thiamine uptake via OCT1 through a competitive mechanism, which may contribute to its adverse effect in producing lactic acidosis.  

Metformin and phenformin significantly reduced thiamine uptake in OCT1 expressing cells (IC50: Metformin=1.4mM; phenformin=0.07mM).

Chronic treatment of metformin was associated with reductions in systemic plasma levels of thiamine (saline group: 402±42ng/ml; metformin group: 187±53ng/ml; p<0.01) and its active metabolite, TPP (saline group: 8.2±2ng/ml; metformin group: 4.8±0.8ng/ml;
p<0.05).
” [5]

Natural alternative to Metformin is Berberine

The most popular natural alternative to metformin is Berberine which is found in Oregon Grape (Mahonia aquifolium).

The dosages vary but most people take between 500 mg – 2000 mg of Berberine (not Oregon Grape root powder) daily in divided doses.

Keep in mind that being natural molecule does not eliminate its risks. So don’t overdose with Berberine like some people do and then blame the supplement or vendor of the product.

There was one study conducted on 60 psoriasis patients which concluded that Berberine “cream was more effective than the placebo in reduction of skin lesions of psoriasis patients.”[7]

Actually, this study concluded the similar results as the report of three clinical trials published in 2005.

But my opinion is that Berberine cream or actually any other cream or topical treatment is not the answer for psoriasis.

You can read more about the berberine effects on psoriasis in this PDF paper.

References:

1) WEINING LI, WEIYUAN MA, HUA ZHONG, WENBIN LIU, and QING SUN. Metformin inhibits proliferation of human keratinocytes through a mechanism associated with activation of the MAPK signaling pathway. Exp Ther Med. 2014 Feb; 7(2): 389–392.

2) Hartmut Glossmann, Norbert Reider. A marriage of two “Methusalem” drugs for the treatment of psoriasis? Arguments for a pilot trial with metformin as add-on for methotrexate. Dermatoendocrinol. 2013 Apr 1; 5(2): 252–263.

3) Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJ, Stehouwer CD. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2003 Nov;254(5):455-63.

4) Koca, Rafet MD; Altinyazar, H Cevdet MD; Yenidünya, Sibel MD; Tekin, Nilgün Solak MD. Psoriasiform drug eruption due to metformin hydrochloride: A case report. Dermatology Online Journal, 9(3), 2003

5) X. Liang, E. C. Chen, S. Yee, K. M. Giacomini. Metformin Reduces the Intestinal Absorption of Vitamin B1 (Thiamine) via Organic Cation Transporter 1, OCT1 (SLC22A1) –

6) Liang X, Chien HC, Yee SW, Giacomini MM, Chen EC, Piao M, Hao J, Twelves J, Lepist EI, Ray AS, Giacomini KM. Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). Mol Pharm. 2015 Dec 7;12(12):4301-10.

7) Ghorbani Birgani A, Abedi P, Zare K, Assadpoor S. The effect of berberine on patients with psoriasis. Arak Medical University Journal. 2013; 15 (8) :61-67

8) Gulliver WP, Donsky HJ. A report on three recent clinical trials using Mahonia aquifolium 10% topical cream and a review of the worldwide clinical experience with Mahonia aquifolium for the treatment of plaque psoriasis. Am J Ther. 2005 Sep-Oct;12(5):398-406.

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