Why we are interested: Menopause and perimenopause are often accompanied by declines in muscle mass, metabolic health, and cognitive function. In the recently published CONCRET-MENOPA randomized controlled trial, creatine supplementation was explored as a potential way to ameliorate some of these symptoms. 1
What they showed: The investigators split 36 healthy, menopausal and perimenopausal women into 4 groups: low-dose creatine hydrochloride (750 mg/day), medium-dose creatine hydrochloride (1,500 mg/day), creatine hydrochloride plus creatine ethyl ester (800 mg/day), or placebo. A variety of functional tests and biomarkers were measured before and after the 8-week intervention, and results revealed that, compared to placebo, supplementation with medium-dose creatine hydrochloride had statistically significant—albeit modest—effects on enhancing reaction times, favorable modulating serum lipid profiles, and increasing frontal brain creatine levels. There was also a potential benefit of creatine in reducing mood swings, but this effect did not reach statistical significance. Notably, however, there were no significant effects on most menopausal symptoms including fatigue and exercise tolerance.
A great deal of research has indicated that creatine may have numerous benefits, and women generally have lower endogenous stores of creatine than men, such that it is not unreasonable to consider creatine supplementation. While this small study was largely negative, it still provides some additional evidence that creatine supplementation could be helpful for some middle-aged women. The doses used in the study were quite small, and so it may also have been that higher doses are needed to see the full benefits. Further research will be required to elucidate the exact nature of the benefits of creatine, the difference between alternative forms of creatine, and optimal dosing.
doi: 10.1080/27697061.2025.2551184
Why we are interested: Evidence is continually emerging regarding the microbiome’s potential to impact human health in various ways. In parallel, research is also uncovering ways in which simple interventions designed to improve the health of the microbiome might therefore offer benefits for the treatment and prevention of certain diseases. Such interventions include probiotics (which contain live bacteria such as Lactobacillus and Bifidobacteria) and synbiotics (the combination of a probiotic with a prebiotic—i.e., indigestible fiber and other nutrients that serve as food for gut bacteria and supports their growth), and one area where they have gained particular attention is in the context of systemic inflammation that often accompanies metabolic disease.
What they showed: This systematic review and meta-analysis analyzed data from 22 randomized trials comprising a total of 1321 individuals with prediabetes and type 2 diabetes (T2D), of which 683 individuals had received a pro- or synbiotic intervention and 628 had served as controls.2 The authors reported that supplementation with probiotics and synbiotics significantly reduced levels of inflammatory cytokines, including C-reactive protein (CRP), IL-6, and TNF-α. The strongest effects were seen in patients with greater burden of these cytokines and in studies involving longer duration of supplementation (≥12 weeks).
Using the standard GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, the authors reported that the quality of evidence was moderate for both CRP and TNF-α and high for IL-6, despite some inconsistency in results across trials. This inconsistency could stem from the fact that each study included in this analysis used different probiotics/synbiotics, containing different microbes at different doses. However, the finding of any consistent trend using such a variety of supplements is noteworthy and points to promising benefits of probiotics and synbiotics for reducing inflammation associated with diabetes and prediabetes when administered for at least 12 weeks.
doi: 10.1016/j.advnut.2025.100526
Why we are interested: We often emphasize the importance of strength for longevity, as it’s well known that frailty in old age is associated with poorer health outcomes and increased mortality. But while we have often focused those discussions on the devastating effects that frailty—and consequent falls and fractures—can have on those in their 70s, 80s, or beyond, this recent study reminded us that the dangers of frailty are not limited to old age.3
What they showed: This study analyzed over 650,000 emergency hospital admissions for individuals between the ages of 18-74, randomly sampling all admissions during an 8-year period in England. Patients were assigned a Hospital Frailty Risk Scores (HFRS) between zero (no frailty risk) and 173.2 based on several frailty-related diagnostic codes, and scores were binned as zero (the reference group), low, intermediate, and high risk.
Results showed statistically significant associations between frailty risk and length of hospital stay, hospital costs, and hospital mortality, and while the magnitude of the correlations increased with age, they remained significant even in the youngest age group studied (ages 18-24). For example, those aged 18-24 with an HFRS in the “high” category remained in the hospital for an average of 4.5 days longer than those with an HFRS of zero (95% CI: 3.8–5.3 days) and were 0.3% more likely to die while in the hospital (95% CI: 0.16–0.48). For comparison, adults in the 45-54 age group with high HFRS stayed in the hospital 6.2 days longer than their peers with HFRS of zero and had a 0.8% higher likelihood of in-hospital mortality, while those in the 85-94 age group stayed in the hospital 15.3 days longer than their peers with a zero HFRS and had a 2.2% higher risk of in-hospital mortality. These findings support the idea that a frail patient of any age has worse outcomes when admitted to the emergency room.
doi:10.1016/j.lanhl.2025.100740
Why we are interested: Metformin has long been of interest as a potential “anti-aging” intervention. As we’ve detailed in a past premium article, observational and animal studies have suggested that this drug could have the potential to improve longevity even in healthy populations. However, recent research and re-analysis has called into question many of the early findings, and much of the excitement has turned into uncertainty.
What they showed: The authors of this review evaluated the current literature on metformin and explored the various sources of weakness in the metformin-as-longevity-agent story.4 Exciting research in various experimental models (e.g., invertebrates and rodents) fueled early interest, but more recent studies, including those done as part of the National Institute on Aging’s Intervention Testing Program (ITP), have not shown replicable lifespan benefits in mice.
Human evidence is likewise underwhelming. While some research seemed to suggest that people with diabetes taking metformin actually lived longer than people without diabetes, reassessment of this evidence indicated that various types of confounding, selection effects, and biases were likely affecting the results, such that it is difficult to draw any firm conclusions from the epidemiological data. Similarly disappointing are the randomized controlled trials that have been attempted: they have been few, small, and with largely ambiguous or negative results.
Metformin remains an intriguing molecule, and one that continues to have an important role in treating diabetes and other types of metabolic dysfunction. The initial promise of metformin as a geroprotective agent for the general population, though, has mostly failed to materialize. It is possible that future large-scale randomized controlled trials will show clear positive results, but for now the data are not convincing in terms of its use in otherwise healthy people.
doi: 10.1016/j.arr.2025.102817
Why we are interested: Atherosclerotic cardiovascular disease remains the leading cause of death worldwide, despite the existence of several medications that are effective in reducing risk by lowering circulating levels of atherogenic lipoproteins (mainly low-density lipoproteins, or LDLs). Various classes of these lipid-lowering drugs can have additive effects and differ in side effect profiles, and thus, the availability of numerous options increases the likelihood that any given patient will be able to achieve effective lipid management in a manner that is safe and well tolerated. These drugs come up often on the podcast, but their variety and mechanisms by which they act can be difficult to keep straight. This review—published in the European Heart Journal last month—serves as an excellent reference for understanding both established lipid-lowering medications and those that may be on the horizon.5
What they showed: As this was strictly a review, the information contained within it has all been published previously. However, the value of this article lies in the synthesis and organization of the broad field of research on lipid-lowering drugs into a single resource, complete with tables and figures that clearly delineate the various classes of such medications and how they function. In addition to providing this information for drugs that are already in use, the authors also discuss new drugs that have reached the later stages of the development pipeline, many of which target elements of lipid metabolism that are distinct from the targets of existing medications. Thus, this paper serves as a guide not only for the current landscape of lipid-lowering drugs, but also for the likely future of these therapies—topics which are sure to come up time and again throughout our content.
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References
1. Korovljev D, Ostojic J, Panic J, et al. The effects of 8-week creatine hydrochloride and creatine ethyl ester supplementation on cognition, clinical outcomes, and brain creatine levels in perimenopausal and menopausal women (CONCRET-MENOPA): A randomized controlled trial. J Am Nutr Assoc. Published online August 25, 2025:1-12. doi:10.1080/27697061.2025.2551184
2. Ballantyne CM, Norata GD. The evolving landscape of targets for lipid lowering: from molecular mechanisms to translational implications. Eur Heart J. Published online September 5, 2025. doi:10.1093/eurheartj/ehaf606
3. Setayesh A, Karimi M, Valizadeh F, et al. Probiotics and synbiotics supplementation reduce inflammatory cytokines in individuals with prediabetes and type 2 diabetes mellitus: Findings from a systematic review meta-analysis. Adv Nutr. 2025;(100526):100526. doi:10.1016/j.advnut.2025.100526
4. Street A, Maynou L, Blodgett JM, Conroy S. Association between Hospital Frailty Risk Score and length of hospital stay, hospital mortality, and hospital costs for all adults in England: a nationally representative, retrospective, observational cohort study. Lancet Healthy Longev. 2025;6(8):100740. doi:10.1016/j.lanhl.2025.100740
5. Keys MT, Hallas J, Miller RA, Suissa S, Christensen K. Emerging uncertainty on the anti-aging potential of metformin. Ageing Res Rev. 2025;111(102817):102817. doi:10.1016/j.arr.2025.102817
