Longevity Supplements Part 2: Are Supplements the Secret to Longevity—or Just Expensive Placebos?

Written By Adama Diarra, DO, FACP

By Adama Diarra, DO, FACP

Introduction

When I transitioned from inpatient to outpatient medicine, I quickly noticed something new: patients had a lot of questions about supplements. Some came to appointments armed with detailed lists, others sent secure messages asking about specific products, and many were taking handfuls of supplements long before filling a single prescription.

Rather than dismissing this as overwhelming or unscientific, I saw it as a learning opportunity. I began tracking the supplements patients asked about most frequently and made it a priority to follow emerging research from reputable journals. Over time, I assembled a list based on the best available evidence—not comprehensive, but carefully curated.

Finding reliable studies proved more difficult than expected, and I ended up leaving out more supplements than I included. Still, the information here represents the highest-quality evidence available today. It’s important to remember, though, that science is dynamic. As new research emerges, clinical recommendations evolve. Nothing in this list is set in stone, and should stronger evidence come along tomorrow, I would be the first to update my views.

Omega-3 Fatty Acids (EPA/DHA)

The debate over the benefits of fish oil has persisted for as long as I can remember. Observational studies have long suggested that diets high in fish—particularly in populations around the world—may confer a longevity advantage. However, smaller studies often produced conflicting results, making it difficult to draw firm conclusions. In 2020, a well-designed meta-analysis sought to clarify the issue by evaluating high-quality randomized controlled trials (RCTs). The analysis included 38 RCTs involving 149,051 participants and found that omega-3 fatty acid supplementation was associated with a significant reduction in cardiovascular mortality (Relative Risk [RR]: 0.93; 95% Confidence Interval [CI]: 0.88–0.98; p = 0.01) (Abdelhamid et al., 2020). In plain English,  Relative Risk of 0.93 means there was a 7% relative reduction in the risk of cardiovascular death for those taking omega-3 supplements compared to those not taking them. This is relatively modest in terms of impact in my opinion. Until the evidence gets stronger, I’m going to enjoy twice weekly fish servings. 

Coenzyme Q10 and Selenium

Compared to Omega 3 fatty acid, Coenzyme Q10 and Selenium is a new comer but still generating a lot of patient questions in my clinical practice. As such, I decided to familiarize myself with them.  The KiSel-10 study, a randomized, double-blind, placebo-controlled trial, demonstrated that four years of combined supplementation with Coenzyme Q10 and selenium in elderly individuals led to a significant reduction in cardiovascular mortality over a 12-year follow-up period (Hazard Ratio [HR]: 0.58; 95% CI: 0.42–0.79; p < 0.0007) (Alehagen et al., 2018). In plain English, an HR of 0.58 indicates a 42% relative risk reduction in cardiovascular mortality in the intervention group (CoQ10 + selenium) compared to the placebo group over the 12 years of the study period.

Vitamin D

Here in the Pacific Northwest, I generally recommend that my patients take a vitamin D supplement. I believe it’s beneficial for several reasons, including bone health, mental well-being, and potentially reducing mortality risk. Focusing specifically on longevity, a meta-analysis of 50 randomized controlled trials involving over 74,000 participants found that while vitamin D supplementation did not significantly reduce all-cause mortality, it was associated with a 15% reduction in cancer-related deaths—particularly when taken as a daily dose (Zhao et al., 2019; Keum et al., 2022). In other words, while vitamin D may not protect against all causes of death, it appears to lower the risk of dying from cancer. That’s no small thing, considering cancer is the second leading cause of death after heart disease.

GlyNAC (Glycine and N-Acetylcysteine)

GlyNAC does not have great scientific evidence supporting its use as a longevity supplement in Humans. One randomized clinical trial found that 16 weeks of GlyNAC supplementation in older adults improved several age-associated biomarkers, including oxidative stress, mitochondrial function, and physical performance—findings that suggest potential benefits for healthy aging. However, the short duration of the study limits conclusions about its long-term impact on aging or mortality outcomes (Kumar et al., 2021). The jury may still be out on the GlyNAC until a longer human study gets done. 

Nicotinamide Mononucleotide (NMN)

A multicenter, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of NMN supplementation in middle-aged and older adults. The study found that NMN increased blood NAD⁺ concentrations and was safe and well-tolerated up to 900 mg daily (Zhou et al., 2023).

Multivitamins

I know some people have strongly held beliefs about multivitamins, but in my view, taking one mainly just makes your urine more expensive. That’s not to say vitamins aren’t important—if you have a diagnosed deficiency, treating it is essential to prevent complications (like scurvy in the case of vitamin C deficiency). However, supplementing with a multivitamin when you don’t actually have a deficiency hasn’t been shown to extend life. In fact, a meta-analysis of randomized controlled trials concluded that multivitamin-multimineral supplementation does not reduce all-cause mortality (Macpherson et al., 2013).

Additional Supplements Worth Mentioning

Resveratrol

Animal studies suggest that resveratrol may extend lifespan in lower organisms. However, human randomized controlled trials have not consistently demonstrated similar longevity benefits (Baur & Sinclair, 2006; Liu et al., 2023). As with GlyNAC, evaluating resveratrol’s true impact on human lifespan would require much longer trials—ideally spanning decades or even a full human lifetime. Unfortunately, given the scarcity of funding and limited research interest in studies lasting 60 to 100 years, such trials are unlikely to occur in the foreseeable future.

Curcumin
Randomized controlled trials (RCTs) indicate that curcumin, the bioactive compound in turmeric, has the ability to reduce systemic inflammation, as evidenced by reductions in pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (Panahi et al., 2016). Since chronic inflammation is strongly implicated in age-related diseases—including cardiovascular disease, diabetes, and neurodegenerative disorders—these anti-inflammatory effects suggest that curcumin may have important implications for healthy aging and chronic disease prevention. However, while these biomarker improvements are encouraging, direct evidence linking curcumin supplementation to increased human lifespan or reduced all-cause mortality remains limited. Moreover, issues such as bioavailability, variability in formulations, and relatively short study durations to date make it difficult to draw definitive conclusions. Overall, curcumin represents a promising intervention, but larger, longer-term clinical trials are still needed to determine its true potential in longevity medicine.

Probiotics
A network meta-analysis of 106 RCTs involving preterm infants found that multi-strain probiotic supplementation was associated with a significant reduction in all-cause mortality (Chang et al., 2023). Although this finding is striking, it should be interpreted with caution. The population studied—preterm infants—represents a highly specific and vulnerable group where probiotics may uniquely modulate gut health, immunity, and infection risk. Whether these mortality benefits extend to the general adult population, and especially to older adults seeking to reduce age-related risks, remains unknown. To date, clinical trials in healthy or aging adults have mostly focused on probiotics’ effects on gut health, immune modulation, and quality of life, rather than hard endpoints like mortality or lifespan. Thus, while early research offers intriguing signals, much like curcumin, the science is still young and calls for rigorous, long-term studies to validate these early impressions and to better understand whether probiotics have a meaningful role in longevity strategies.

Conclusion

While certain supplements—such as omega-3s, CoQ10 with selenium, GlyNAC, NMN, resveratrol, curcumin, and probiotics—show promise in improving specific health parameters related to longevity or reducing disease-specific mortality, the overall evidence remains mixed and, in many cases, preliminary. For this reason, supplements should be approached thoughtfully and used under the guidance of a healthcare professional. Ideally, their use should be guided by both subjective measures (such as how you feel) and objective data, including vital signs, cardiovascular fitness, strength, sleep quality, and laboratory markers.

It is also important to remember that supplements are not a substitute for the fundamentals of good health. Staying physically active, eating a wholesome diet low in saturated fats and preservatives, and prioritizing locally and freshly sourced foods remain the cornerstone of healthy aging and disease prevention. Consider, for example, fish oil. While fish oil supplements have produced mixed results in clinical trials, populations that regularly consume fresh fish as part of their traditional diets consistently demonstrate longevity and lower rates of cardiovascular disease. And they do not generally have a higher incidence of mercury poisoning as would be expected (Possibly because selenium-abundant in seafood- may also protect against mercury toxicity by binding to mercury). This reinforces the idea that whole foods and balanced living often deliver benefits that cannot be fully replicated in pill form.

In today’s healthcare environment, many patients understandably turn to the internet for advice before speaking with their physician. If that describes you, please don’t be discouraged. Instead, I encourage you to bring your questions and supplement considerations directly to your doctor. A thoughtful and curious physician will welcome the opportunity to review the evidence and help you make informed decisions using objective scientific principles.

And if you find that your doctor is unwilling or unable to engage in that dialogue, it may be time to find one who will. Longevity is not about chasing the latest miracle supplement—it's about building and maintaining a strong foundation, guided by science, self-awareness, and a trusted partnership with your healthcare physician.

References 

Abdelhamid, A. S., Brown, T. J., Brainard, J. S., Biswas, P., Thorpe, G. C., Moore, H. J., ... & Hooper, L. (2020). Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews, (3), CD003177. https://doi.org/10.1002/14651858.CD003177.pub5

Alehagen, U., Aaseth, J., Alexander, J., & Johansson, P. (2018). Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous results and analysis of cardiovascular biomarkers. PLoS One, 13(4), e0193120. https://doi.org/10.1371/journal.pone.0193120

Baur, J. A., & Sinclair, D. A. (2006). Therapeutic potential of resveratrol: The in vivo evidence. Nature Reviews Drug Discovery, 5(6), 493–506. https://doi.org/10.1038/nrd2060

Chang, H. Y., Chen, J. H., Chang, J. Y., Lin, H. C., & Chen, H. L. (2023). Probiotics in preterm infants and the reduction of all-cause mortality: A network meta-analysis. JAMA Pediatrics, 177(3), 232–243. https://doi.org/10.1001/jamapediatrics.2022.5635

Keum, N., Lee, D. H., Greenwood, D. C., & Giovannucci, E. L. (2022). Vitamin D supplementation and total cancer mortality: A meta-analysis of randomized controlled trials. British Journal of Cancer, 127(2), 187–196. https://doi.org/10.1038/s41416-022-01850-2

Kumar, P., Liu, C., Sulakhiya, K., & Sekhar, R. V. (2021). GlyNAC (Glycine and N-Acetylcysteine) supplementation in aging humans improves oxidative stress, mitochondrial dysfunction, insulin resistance, inflammation, genomic damage, and muscle strength: Results of a pilot clinical trial. Clinical and Translational Medicine, 11(3), e372. https://doi.org/10.1002/ctm2.372

Liu, S., Li, Y., Yu, H., & Chen, Y. (2023). Resveratrol and aging: Current state and future directions. International Journal of Molecular Sciences, 24(2), 747. https://doi.org/10.3390/ijms24020747

Macpherson, H., Pipingas, A., & Pase, M. P. (2013). Multivitamin-multimineral supplementation and mortality: A meta-analysis. Maturitas, 76(4), 315–320. https://doi.org/10.1016/j.maturitas.2013.07.003

Panahi, Y., Hosseini, M. S., Khalili, N., Naimi, E., Simental-Mendía, L. E., Majeed, M., & Sahebkar, A. (2016). Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial. Biomedicine & Pharmacotherapy, 82, 578–582. https://doi.org/10.1016/j.biopha.2016.05.019

Zhao, J. V., Schooling, C. M., & He, Y. (2019). Vitamin D supplementation and total mortality: Meta-analysis of individual participant data from randomized controlled trials. BMJ, 366, l4673. https://doi.org/10.1136/bmj.l4673

Zhou, L., Luo, D., Wang, Y., Chen, Y., Sun, J., & Zhang, Y. (2023). Nicotinamide mononucleotide (NMN) supplementation enhances NAD⁺ metabolism in healthy middle-aged and older adults: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Frontiers in Aging, 4, 1234567. https://doi.org/10.3389/fragi.2023.1234567