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Looking to live longer and healthier? Here's what you need to know about Metformin and supplements for longevity:
- Metformin, a diabetes medication, may extend life by mimicking calorie restriction, reducing inflammation, and promoting cellular repair. A 2025 study found it reduced the risk of death before age 90 by 30% in diabetic women.
- Supplements, like omega-3s, vitamin D, and NAD+ boosters, target aging mechanisms such as DNA repair and cellular health. Omega-3s, for example, are linked to a 4.7-year increase in life expectancy.
Quick Comparison
| Aspect | Metformin | Nutritional Supplements |
|---|---|---|
| Regulation | FDA-approved, standardized | Less regulated, quality varies |
| Cost | ~$5/month | Varies widely, often more expensive |
| Evidence | Backed by clinical trials | Mixed; mostly animal studies |
| Accessibility | Prescription required | Over-the-counter |
| Side Effects | Common: stomach issues, rare: B12 deficiency | Potential interactions, inconsistent dosages |
Metformin shows promise as a well-researched, affordable option for longevity, while supplements are accessible but less regulated. Both approaches work best when paired with healthy lifestyle habits like exercise and a balanced diet.
Journal Club with Dr. Peter Attia | Metformin for Longevity & The Power of Belief Effects
1. Metformin
Metformin has long been a reliable medication for managing type 2 diabetes, but recent research suggests it may also hold promise in the field of longevity science, making it a hot topic for those studying aging and healthspan.
How Metformin Works in the Body
Metformin works at the cellular level by partially inhibiting mitochondrial complex I, which activates AMPK (adenosine monophosphate-activated protein kinase). This activation mimics the effects of calorie restriction, promoting processes like autophagy (cellular cleanup), reducing inflammation, and protecting genomic stability. These mechanisms are thought to play a role in slowing down aging and improving overall cellular health.
Research Findings and Study Results
A groundbreaking study published in May 2025 by researchers at UC San Diego analyzed data from the Women's Health Initiative (WHI). This study tracked postmenopausal women with type 2 diabetes over more than three decades. Their findings confirmed earlier research, showing that Metformin use was associated with reduced mortality rates in diabetic women.
"These findings contribute to a growing understanding of metformin's potential role in promoting human health and longevity", said Aladdin H. Shadyab, Ph.D., M.P.H., Associate Professor at the University of California San Diego Herbert Wertheim School of Public Health and Human Longevity Science and School of Medicine.
Animal studies back up these findings. A 40-month study involving middle-aged and elderly male crab-eating macaques revealed that Metformin improved multiple markers of health. The macaques showed a reduction in protein age by an average of 6.41 years, better cognitive function, less cortical atrophy, and slower aging in key organs like the liver, heart, and lungs.
Tested Populations and Broader Applications
Metformin's benefits have been observed across various patient groups. The most extensively studied include individuals with type 2 diabetes, postmenopausal women, and participants in large-scale studies like the WHI. But the research doesn't stop there - Metformin has also shown promise in reducing dementia risk by 66% in some studies. Beyond diabetes, it has been explored as a treatment for polycystic ovary syndrome (PCOS), weight management, and even as a potential tool for improving survival rates in diabetic individuals compared to non-diabetic controls.
Benefits and Documented Risks
Metformin is known to lower cardiovascular risk in diabetics and may help prevent atherosclerosis in individuals at risk. Additionally, researchers are investigating its potential role in cancer prevention and treatment. However, like any medication, it has its drawbacks. Gastrointestinal side effects are common and can lead to lower adherence compared to other diabetes treatments. Prolonged use may also result in vitamin B12 deficiency, so supplementation is often recommended for long-term users. More seriously, individuals with impaired kidney function may face an increased risk of lactic acidosis, a rare but potentially fatal condition with a high mortality rate.
The ongoing Targeting Aging with Metformin (TAME) trial is expected to provide crucial insights into Metformin's potential to address multiple age-related conditions at once. If successful, it could solidify Metformin's place as a key player in the quest to extend healthy lifespan.
2. Nutritional Supplements
Expanding on Metformin's targeted approach, nutritional supplements present a more accessible way to explore aging-related interventions. Unlike Metformin, which requires a prescription and medical oversight, supplements are widely available and have become a booming industry. These products claim to target various aging mechanisms, from cellular health to brain function, but the strength of the evidence behind these claims can vary greatly.
How Supplements Work on Aging Pathways
Supplements engage with aging through multiple biological processes. For instance, NAD+ precursors like NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) aim to restore declining NAD+ levels, which are crucial for mitochondrial health, DNA repair, and energy production. Quercetin has senolytic properties, helping to clear out damaged cells, while spermidine supports autophagy, the body's internal cleanup system.
Other compounds, like resveratrol, activate sirtuins - proteins involved in DNA repair and energy regulation. Similarly, berberine activates AMPK, mimicking some of the benefits of calorie restriction.
Research and Clinical Evidence
The research behind supplements offers a mix of promising and uncertain results. Among the most well-supported supplements, omega-3 fatty acids stand out. Studies have shown that higher blood levels of omega-3s are linked to a 4.7-year increase in life expectancy. In fact, omega-3 levels have been found to predict mortality risk as effectively as smoking.
Vitamin D is another standout. Research indicates that supplementing with vitamin D can lead to a 16% reduction in cancer mortality. Additionally, vitamin D3 has been shown to slow telomere shortening over four years, effectively delaying nearly three years of cellular aging.
"VITAL is the first large-scale and long-term randomized trial to show that vitamin D supplements protect telomeres and preserve telomere length", explained JoAnn Manson, the principal investigator of the VITAL study.
Curcumin has shown cognitive benefits for older adults, improving attention, memory, and mood in individuals aged 60-85. It has also been effective in reducing inflammation in arthritis patients, performing on par with some anti-inflammatory drugs.
Other compounds, such as EGCG and fisetin, have extended lifespans in animal studies, though human evidence is still lacking. Similarly, taurine has shown promise in slowing aging in mice.
Populations and Applications
While much of the evidence comes from animal studies, early human trials are showing encouraging results. For example, NMN supplementation in middle-aged adults has been found to significantly boost NAD+ levels within just 30 days. Creatine, often studied in athletes and older adults, has demonstrated improvements in strength and power output by 5-15%.
The supplement market is also shifting toward tailored solutions. More consumers are seeking products designed for specific concerns like cognitive health, hormonal balance, and joint support. This trend highlights the growing demand for personalized approaches to aging, moving away from one-size-fits-all solutions.
Benefits and Risks
Some supplements stand out for their evidence-backed benefits. Omega-3 fatty acids, magnesium, and creatine all receive high ratings (5/5 and 4/5) for their impact on longevity. Vitamin C, NMN, and vitamin D also score well, while compounds like resveratrol and CoQ10 show more modest evidence (3/5).
However, the supplement industry is not without risks. Unlike prescription medications, supplements are less regulated, which can lead to inconsistencies in quality and dosage. For instance, a study of 31 melatonin products found that concentrations ranged from -83% to +478% of the labeled amount, with 71% failing to meet a 10% margin of accuracy. Even more concerning, 26% of these products contained serotonin, a controlled substance.
"You'll be shocked at how many weight-loss and dietary and bodybuilding supplements are adulterated with conventional medications", warned Bill Gurley, principal scientist at the National Center for Natural Products Research.
In 2019 alone, supplements, herbal remedies, and homeopathic treatments accounted for nearly 70,000 calls to U.S. poison control centers. High doses of certain vitamins, like vitamin E and vitamin A, have even been linked to increased mortality. Additionally, some supplements may interfere with the benefits of exercise, a crucial component of healthy aging.
While both Metformin and supplements offer potential anti-aging benefits, they differ significantly in terms of regulation and consistency. Metformin is backed by extensive clinical trials, whereas supplements often face scrutiny for variability in composition.
"The supplements that remain popular will be those that are clinically proven to address the biological mechanisms of aging, rather than just managing isolated symptoms", noted Sébastien Bornet, vice president of global sales and marketing at Horphag Research.
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Advantages and Disadvantages
Looking at the studies mentioned earlier, it's clear that both Metformin and nutritional supplements bring their own sets of benefits and challenges when considered for longevity. Here’s a side-by-side comparison to help clarify their strengths and limitations:
| Aspect | Metformin | Nutritional Supplements |
|---|---|---|
| Regulation & Safety | FDA-approved prescription drug with over 60 years of clinical use | Less regulated; quality and labeling can vary |
| Cost | Very affordable, with a median price of $5 per prescription | Prices vary widely; high-quality options can be costly |
| Evidence Base | Backed by extensive clinical trials; shown to extend life in diabetics | Mixed results; mostly based on animal studies and limited human research |
| Accessibility | Requires a prescription and medical supervision | Available over-the-counter without restrictions |
| Side Effects | Well-documented; about 25% report gastrointestinal issues | Potential for unexpected interactions |
| Consistency | Standardized dosing and quality control | Potency and quality can vary significantly |
Metformin’s standout qualities lie in its affordability, proven track record, and its ability to lower overall mortality rates. It’s even shown potential to slow aging-related diseases, independent of its role in managing diabetes.
"Metformin has as good a safety profile as virtually any drug you can find", says Steven Austad, Distinguished Professor at the University of Alabama at Birmingham and Senior Scientific Director at the American Federation for Aging Research.
However, Metformin isn’t perfect. It requires medical oversight, which can be a hurdle for those without existing health conditions. Side effects, such as gastrointestinal discomfort, are common, and long-term use has been linked to vitamin B12 deficiency. Additionally, some experts strongly discourage its use by healthy young adults.
"I am horrified to learn that young people (<40) without diabetes would consider taking metformin for longevity", warns Nir Barzilai, founding director of the Institute for Aging Research at the Albert Einstein College of Medicine.
On the other hand, nutritional supplements are easily accessible and don’t require a doctor’s approval, making them an attractive option for those seeking quick solutions. But their lack of regulation comes with risks. Inconsistent quality and potency, along with potential safety concerns, can make their use unpredictable. Hidden risks, such as interactions with other medications, further complicate their appeal.
While Metformin’s need for medical supervision ensures proper monitoring and dosage adjustments, this safeguard is missing with over-the-counter supplements. For some, this accessibility is a draw, but it also introduces the possibility of misuse or unforeseen complications.
Conclusion
Recent research sheds light on strategies for promoting longevity. For example, studies have found that postmenopausal women with type 2 diabetes who used metformin had a 30% lower risk of dying before age 90 compared to those who relied on sulfonylureas.
One of the key advantages of metformin is its affordability - it costs less than $1.00 per day for many Americans. Meanwhile, the ongoing TAME trial is expected to provide more concrete evidence about its potential anti-aging effects.
While metformin shows promise, nutritional supplements present an alternative, albeit with mixed evidence. Supplements are widely available, but they lack consistent quality and strong human research due to limited regulation. For instance, animal studies suggest that resveratrol can extend life in yeast by as much as 70% and in certain fish by 19–56%. However, there is still no solid human data to confirm these effects.
"I don't know if metformin increases lifespan in people, but the evidence that exists suggests that it very well might."
This perspective from Steven Austad, senior scientific advisor at the American Federation for Aging Research, highlights the potential of metformin while acknowledging the need for further research.
Ultimately, a balanced approach is essential for healthy aging. Research consistently points to lifestyle practices - like regular exercise, a plant-based diet, and maintaining strong social connections - as the foundation for longevity. For those seeking to enhance their lifespan, starting with these proven lifestyle changes is a smart first step. Adding metformin under medical supervision could be a helpful addition for some, while supplements might play a secondary role. However, given the current evidence, supplements should not be relied upon as primary solutions. In the end, healthy habits remain the cornerstone of longevity, with metformin offering a potential medical option and supplements serving as complementary aids.
FAQs
How does Metformin stack up against supplements for longevity and what are the potential side effects of each?
Metformin has garnered attention for its potential to slow aging and combat age-related diseases. Some studies even hint at its ability to extend lifespan. That said, the evidence is still under debate and far from definitive. Meanwhile, supplements like berberine have shown promise in managing blood sugar levels, but their role in directly influencing longevity remains uncertain.
When it comes to side effects, Metformin is known to cause gastrointestinal discomfort, like nausea or diarrhea, and prolonged use may lead to vitamin B12 deficiency. Although rare, a serious condition called lactic acidosis has been reported. Supplements, on the other hand, generally cause milder side effects, such as minor stomach upset. However, their long-term safety and potential benefits for longevity still need more thorough investigation.
What are the risks of using supplements for longevity compared to Metformin?
Supplements promoted for longevity aren't without risks, especially when overused. For instance, taking too much magnesium can lead to muscle weakness or confusion, while high doses of vitamin E might increase bleeding risks. These issues often arise due to incorrect dosing or nutrient imbalances caused by supplementation.
Metformin, meanwhile, tends to cause gastrointestinal side effects like nausea or diarrhea. In rare cases, it can lead to lactic acidosis or vitamin B12 deficiency, the latter potentially resulting in anemia or nerve damage. While supplements often pose risks of toxicity or nutrient imbalances, Metformin's concerns are more focused on specific organ effects and deficiencies. To use either safely and effectively, consulting a healthcare provider is essential.
Can healthy people take Metformin to live longer, and what should they consider before using it?
Metformin has been gaining attention for its potential role in promoting longevity. Research suggests it may help by reducing inflammation, offering protection against age-related conditions, and possibly slowing down the aging process. However, it’s important to note that it’s not officially approved for this purpose in healthy individuals. Additionally, caution is advised, as it can cause side effects like stomach discomfort and, in rare cases, serious issues such as lactic acidosis - particularly in individuals with kidney problems.
If you’re thinking about using Metformin for longevity, make sure to talk to a healthcare provider first. They can evaluate your overall health, discuss any risks, and help determine if it’s a safe choice for you.
