We can collect data and research about metformin (or its natural form, Berberine) in this thread. I'm starting off by quoting what we already have on another thread in the forum:
Verneuil's disease AKA Hydradenitis Suppurative
Verneuil's disease AKA Hydradenitis Suppurative
Chu said:I have recently been reading a bit about the drug Metformin, and one thing leading to another, I found these articles which are quite interesting regarding HS, insulin and hormones. So, here are some excerpts, for whoever is interested. What seems cool about metformin is that there are hardly any side effects, for once!
Metformin for the treatment of hidradenitis suppurativa: a little help along the way.
Verdolini R1, Clayton N, Smith A, Alwash N, Mannello B.
Despite recent insights into its aetiology, hidradenitis suppurativa (HS) remains an intractable and debilitating condition for its sufferers, affecting an estimated 2% of the population. It is characterized by chronic, relapsing abscesses, with accompanying fistula formation within the apocrine glandbearing skin, such as the axillae, ano-genital areas and breasts. Standard treatments remain ineffectual and the disease often runs a chronic relapsing course associated with significant psychosocial trauma for its sufferers.
To evaluate the clinical efficacy of Metformin in treating cases of HS which have not responded to standard therapies.
Twenty-five patients were treated with Metformin over a period of 24 weeks. Clinical severity of the disease was assessed at time 0, then after 12 weeks and finally after 24 weeks. Results were evaluated using Sartorius and DLQI scores.
Eighteen patients clinically improved with a significant average reduction in their Sartorius score of 12.7 and number of monthly work days lost reduced from 1.5 to 0.4. Dermatology life quality index (DLQI) also showed a significant improvement in 16 cases, with a drop in DLQI score of 7.6.
Metformin helps control HS with minimal side effects and good patient compliance and can represent a further agent in the spectrum of treatments available in the treatment of this disease.
In our view Metformin provides a new option for the treatment of HS that may represent a new approach. The mechanism as to how Metformin operates in the treatment of HS is not entirely clear and studies are still needed, but it may be that it works through two pathways. The first is through its anti‐androgenic effect, thus influencing expression of the genes possibly involved in this condition and the second might be through lowering the insulin resistance that is usually present in some patients with HS.
Metformin induced a remission of the disease in the sense that if pustules were still present, they were less numerous, less severe and less debilitating. The disease was also not as painful with improvement to quality of life and the majority of patients continued on the treatment well past the time of the trial. The majority of the patients reported that, although the condition was still present, it was more tolerable, and not as debilitating as before.
Very importantly no significant adverse effects were recorded and blood tests regularly taken during the trial period have remained within the normal range for all patients. Only minor gastrointestinal disturbances at the beginning of treatment were recorded. Even patients who did not enroll in the study because of their difficulties in attending appointments (and who remained inconsistent with their follow‐up attendances) continued using Metformin which was prescribed by their GPs.
A Disease-Modifying Approach for Advanced Hidradenitis Suppurativa (Regimen with Metformin, Liraglutide, Dapsone, and Finasteride): A Case Report.
Hidradenitis suppurativa (HS) is a challenging skin disease with limited therapeutic options. Obesity and metabolic syndrome are being increasingly implicated and associated with younger ages and greater metabolic severity. A 19-year-old female with an 8-year history of progressively debilitating cicatricial HS disease presented with obesity, profound anemia, leukocytosis, increased platelet count, hypoalbuminemia, and elevated liver enzymes. A combination of metformin, liraglutide, levonorgestrel-ethinyl estradiol, dapsone, and finasteride was initiated. Acute antibiotic use for recurrences and flares could be slowly discontinued. Over the course of 3 years on this regimen, the liver enzymes normalized in 1 year, followed in2 years by complete resolution of the majority of the hematological and metabolic abnormalities. The sedimentation rate reduced from over 120 to 34 mm/h. She required 1 surgical intervention for perianal disease after 9 months on the regimen. Flares greatly diminished in intensity and duration, with none in the past 6 months. Right axillary lesions have completely healed with residual disease greatly reduced. Chiefly abdominal lesions are persistent. She was able to complete high school from home, start a job, and resume a normal life. Initial weight loss of 40 pounds was not maintained. The current regimen is being well tolerated and continued.
Metformin for the treatment of hidradenitis suppurativa: a little help along the way
First published: 11 August 2012
Background Despite recent insights into its aetiology, hidradenitis suppurativa (HS) remains an intractable and debilitating condition for its sufferers, affecting an estimated 2% of the population. It is characterized by chronic, relapsing abscesses, with accompanying fistula formation within the apocrine glandbearing skin, such as the axillae, ano‐genital areas and breasts. Standard treatments remain ineffectual and the disease often runs a chronic relapsing course associated with significant psychosocial trauma for its sufferers.
Objective To evaluate the clinical efficacy of Metformin in treating cases of HS which have not responded to standard therapies.
Methods Twenty‐five patients were treated with Metformin over a period of 24 weeks. Clinical severity of the disease was assessed at time 0, then after 12 weeks and finally after 24 weeks. Results were evaluated using Sartorius and DLQI scores.
Results Eighteen patients clinically improved with a significant average reduction in their Sartorius score of 12.7 and number of monthly work days lost reduced from 1.5 to 0.4. Dermatology life quality index (DLQI) also showed a significant improvement in 16 cases, with a drop in DLQI score of 7.6.
Conclusion Metformin helps control HS with minimal side effects and good patient compliance and can represent a further agent in the spectrum of treatments available in the treatment of this disease.
nicklebleu said:Very intersting articles - thanks Chu for posting. Metformin has some quite interesting properties, and it has recently genberated quite some interest in other fields than diabetology. See for instance:
The generally accepted mechanism of metformin's effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin's beneficial effects. It may help to identify new targets for treatment of diabetes and metabolic syndrome. Moreover, metformin is now attracting the attention of researchers in fields other than diabetes, as it has been shown to have anti-cancer, immunoregulatory and anti-aging effects. The aim of this review is to describe the potential anti-cancer and anti-aging properties of metformin and discuss the possible underlying mechanisms.
Source: Postepy Hig Med Dosw (Online). 2017 Mar 2;71(0):170-175
I had a look at the last article you quoted as to metformin dosages used:
Metformin was up-titrated from a starting dose of 500 mg once ⁄ day (OD) in the first week, to 500 mg twice ⁄ day (BD) in the second week, with a maximum dose of 500 mg three times ⁄ day (TDS) introduced from the third week onwards.
The maximum Metformin dose that nine patients in the series could tolerate (due to gastrointestinal discomfort or lifestyle compromise) was 500 mg BD. The Metformin dose for another patient with a particularly high BMI was suitably adjusted to 850 mg BD.
Of course anyone trying this drug should do that under the care of a sympathetic medical practitioner, as it can induce low blood sugar - having said that apparently if you are not a diabetic person, this seems to happen infrequently.
Thanks again, Chu!
Gaby said:That is pretty interesting research on metformin and hydradenitis suppurativa.
Some people in longevity circles are using it to sensitize insulin levels, e.g. Dominic D'Agostino and his keto protocol. Others prefer nature's metformin: berberine.
It seems that anything that sensitizes your insulin is pretty good. I received a notification a few months ago on a liraglutide study showing that it reduced cardiovascular disease and had some benefits like metformin. Liraglutide is another insulin sensitizer.
I think it mostly highlights how insulin resistance is so evil. However, there might be other mechanisms of action to metformin that researchers don't know about and/or are studying.
Several studies are underway on metformin and cancer research.
There is some controversy on metformin's effect on cognitive function, but it appears there is not enough data to blame it:
I have been an advocate of metformin for everyone, and enthusiastic about Nir Barzilai’s trial of metformin as an anti-aging drug. Last week, I learned from Brian Hanley that metformin has a dark side, to wit, a statistical association with higher frequency of Alzheimer’s disease [ref, ref]. There is a biochemical mechanism that makes the epidemiology more compelling. B12 supplementation may mitigate the risk.
Other studies [ref, ref] have found that diabetes patients have elevated risk of dementia, and that that risk is reduced when they take metformin. So it’s fair to say that there is contradictory evidence, and the direction of the effect may depend on individual variation. Here is a balanced view of both sides.
A reader of this blog, George Goldsmith has written to me that berberine is a good herbal substitute for metformin. Everything we know about berberine looks really good–it is an anti-inflammatory as well as helping preserve insulin sensitivity, acting through the AMPK pathway. But we have much more experience with metformin, both clinically and in the lab. Metformin increases life span in mice, and to my knowledge, this test has yet to be performed with berberine. Magnesium supplements also can help prevent insulin resistance, and there are other good reasons to take magnesium.
Gynostemma pentaphyllum, sold by LEF under the brand name AMPK Activator, is another herbal alternative to metformin.
What is Metformin? And Why Do Scientists Think It Can Extend Your Lifespan?
Yas said:Very interesting! I've never heard of metformin before...
I did a very brief search on the natural alternative that Gaby mentioned and found an interesting article in Dermatology News that could give a clue as to why it could work for HS.
Mahonia aquifolium, also known as Oregon grape root, belongs to the Berberidaceae or barberry family. This evergreen shrub, native to the American northwest and adjacent areas of Canada, has been used in folk medicine to treat chronic eruptions and various rashes, especially those containing pustules or resulting from consumption of fatty foods (Dermatol. Ther. 2003;16:106–13).
In numerous investigations, Oregon grape root has displayed a wide range of biologic activities, including antioxidant, antimicrobial, and antimutagenic properties. Although this column will focus on the Mahonia aquifolium species, it is worth noting that Mahonia bealei (also of the Berberidaceae family), native to China, exhibits anti-influenza effects in vitro (Zhong Yao Cai. 2003;26:29–30).
Research on the extract of the bark of Mahonia aquifolium has indicated that its primary bioactive characteristic is the inhibition of lipid peroxidation, and that its main constituents are the alkaloids berberine, berbamine, and oxyacanthine (Planta Med. 1994;60:421–4).
Mahonia aquifolium bark extract has been shown to inhibit keratinocyte growth. In one study, berberine was as effective as the mahonia extract at inhibiting cell growth, while berbamine and oxyacanthine, the benzylisoquinoline alkaloid constituents of mahonia, were three times as effective at cell growth suppression (Planta Med. 1995;61:74–5).
Berberine-containing herbs have been used in folk medicine to relieve neonatal jaundice (Comp. Med. East West 1977;5:161–8), as anti-inflammatory agents (for lumbago and rheumatism), and as antinociceptive and antipyretic medications (Life Sci. 2002;72:645–57; J. Ethnopharmacol. 1998;59:211–5). Further, researchers studying the use of berberine as an antiacne medication in Japanese Kampoh (Japanese herbal medicine based on Chinese methods) found that the alkaloid inhibited lipogenesis in hamster sebaceous glands by 63% (Skin Pharmacol. 1993;6:56–60).
From what I can understand so far about HS, "keratinocyte growth" and "lipogenesis in sebaceous glands" are very linked to it, so it makes sense that it would help.
It seems like a promising finding Chu! Thanks for sharing!
nature said:Interesting knowledge! We never end learning.
I knew metformin only as anti-diabetic. I ignored there were plants with same properties. Finally, all remedies are in nature! (plants, soils, minerals, sunlight, earthing, some energetic waves, etc)
Chu said:Yas, you are one of the people I was mostly thinking of while reading all this, given how you are quite sensitive to carbs, and how HS in your case (and many others) also has some relationship with hormones. So, in your case, I would definitely ask my doctor about it, and see if metformin has the same effect as berberine, and in what dosages.
I'll start a new thread where we can collect more data we find. This may be something potentially useful for people with cardiovascular diseases, insulin resistance, skin problems, etc.
Nature, yes indeed! It is said to be for only diabetics, but it would make sense that it is being tested on cancer, if we take the hypothesis that cancer can be of metabolic origin, and that cancer cells feed from sugar.
Another thing that caught my attention was that, if metformin/berberine helps evacuate the sugar from the smallest vessels irrigating the organs, then it could be good for any systemic problem related to glucose/insulin. Not just cancer cells floating around, but also, say, viral infections, systemic candida, psoriasis, arthritis, etc.?
As far as drugs go, and if berberine doesn't happen to be quite as effective (?), I have to say that I wouldn't mind taking metformin. From what I head it's an old-school drug (not being pushed by pharmaceuticals), and has hardly any side effects.