Metformin: Prescription against age and disease?

Metformin is a drug for treating diabetes.

Like rapamycin that I wrote about last week, metformin has humble beginnings. It is derived from a kind of French lilac, reputedly used to treat diabetes-like conditions in medieval Europe.

In type 2 diabetes one of the fundamental problems is elevated blood sugar. Insulin is the hormone we all have that controls blood sugar. When cells become resistant to insulin we can inject more insulin. But it is much better to improve the effectiveness of the insulin we have. This is what metformin does. It is an insulin sensitizer, and it is the first medicine your doctor will prescribe if you have type 2 diabetes.

However, metformin does much more than lower blood sugar by making your insulin work better.

Let me review some ways that researchers are looking to — and finding ways — that metformin may be a pharmaceutical giant’s dream drug, and then explain why it has the effect it does on so many diseases…

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Metformin for anti-aging

Beginning in 1972 with Russian scientists, metformin was found to slow down aging, plus reduce obesity and prevent cancer in rodents. Then more studies corroborated this knowledge but for many years these publications were ignored. That’s because nobody believed that changing blood sugar metabolism could slow aging.

It became evident that metformin decreases death from all causes in people with diabetes. It is not as powerful for anti-aging as rapamycin, but it is certainly not without its own merit.

Of note is the effect it appears to have on AMPK signaling. Adenosine Monophosphate-Activated Protein Kinase (AMPK for short) is an enzyme found in every cell in the body. It is like the “master switch” that determines how our bodies process energy.

AMPK is an anti-aging enzyme and, of course, its signaling function declines with age beginning a cascade of cellular changes that are what we know as the signs of aging.

Research supports that metformin is able to kickstart AMPK signaling, which if this is so, slows the aging process which also impacts the diseases associated with aging.

Let’s talk about a few of those…

Metformin for Alzheimer’s disease prevention

We know that metformin improves metabolic dysfunction. Well, wouldn’t you know it… scientists have found that one of the two main proposed mechanisms of how Alzheimer’s dementia develops is through metabolic dysfunction.

At least since 2014 scientists have reported that metformin reduces the risk of cognitive decline and dementia. Just this month of October 2019 yet another study has shown how metformin reversed amyloid-beta (Aβ)-induced mitochondrial dysfunction in mice. They concluded, “Our results point to metabolic dysfunction as an early and causative event in Aβ-induced pathology [dementia] and a promising target for intervention.”

Previously in 2016, research showed that metformin improved memory recall in older adults with mild cognitive impairment.

Metformin to prevent cancer

Metformin also appears to inhibit the proliferation of a range of cancers, including breast, endometrial, colon and prostate.

In fact, the research on cancer is outstanding:

• One study found that diabetic patients who were taking metformin had a 46 percent lower risk of developing head and neck cancers compared to non-diabetic patients.
• Research has found similar positive effects of metformin on the risk of stomach cancer.
• Another study of more than 24,000 patients found that in people with early-stage colon and rectum cancers, metformin use improved overall rates survival by 31 percent, and cancer-specific survival by 42 percent.

Recently, a study showed that metformin was strongly associated with ovarian cancer prevention. The authors suggested, “…a potential use for metformin in ovarian cancer prophylaxis.” They quoted a Taiwanese study that had previously found that among patients with type 2 diabetes taking metformin there was an 82 percent reduction in ovarian cancer.

Metformin and heart health

Additionally, metformin appears to prevent androgen deprivation therapy (ADT)-induced metabolic syndrome during prostate cancer treatment, which can cause cardiovascular morbidity — meaning a patient could survive the cancer but die from heart problems. Studies have shown that even short-term use of ADT significantly increases fat mass and decreases insulin sensitivity in men with prostate cancer, so we can see how metformin can certainly help here.

Other research found metformin can help prevent the development of atherosclerosis — or hardening of the arteries.

Getting a prescription from your doctor

One of the problems for you will be to convince your doctor that you need metformin to help slow aging. That’s because mainstream medical doctors do not generally know that metformin treats more than diabetes or metabolic syndrome.

The dosage has not been established for these other potential indications, but in diabetes, the dosage ranges from 500 once daily to 1000 mg twice daily.

And there are side effects to consider, including nausea, fatigue, muscle weakness, constipation, heartburn, and flatulence to name a few.

So, it’s certainly a decision you’d need to weigh and discuss with your doctor. Additionally, there are non-prescription ways you can help boost your AMPK enzyme but I wouldn’t expect quite the same results as metformin.

Sources:

1. Metformin and Prostate Cancer: a New Role for an Old Drug — Current Urology Reports
2. Dil’man VM, Riabov SI, Tsyrlina EV, Kirsanov AI, Kovaleva IG. [A decrease in body weight, cholesterol and blood sugar under the influence of phenformin (phenylbiguanide) in patients with cancer and atherosclerosis] — [Article in Russian] Vopr Onkol. 1972;18:84–86
3. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M, Re F, Franceschi C. Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice — Exp Gerontol. 2005;40:685–693
4. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Yurova MV, Kovalenko IG, Poroshina TE, Semenchenko AV. Metformin slows down aging and extends life span of female SHR mice — Cell Cycle. 2008;7:2769–2773
5. Novelle MG, Ali A, Dieguez C, Bernier M, de Cabo R. Metformin: A Hopeful Promise in Aging Research — Cold Spring Harb Perspect Med. 2016;6:a025932
6. Gosmanova EO, Canada RB, Mangold TA, Rawls WN, Wall BM. Effect of metformin-containing antidiabetic regimens on all-cause mortality in veterans with type 2 diabetes mellitus — Am J Med Sci. 2008;336:241–247
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8. Blagosklonny MV. From rapalogs to anti-aging formula — Oncotarget. 2017 May 30;8(22):35492-35507. Review. PubMed PMID: 28548953
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10. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients — BMJ. 2005;330:1304–1305
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12. Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin prevents tobacco carcinogen–induced lung tumorigenesis — Cancer Prev Res (Phila) 2010;3:1066–1076
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16. How Metformin, A Diabetes Drug, Got Into the Aging Market — Elysium Health
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