Supplements are widely used by people hoping to slow aging, but most have little human evidence linking them to biological age measures. To identify which products might warrant more rigorous testing, researchers examined whether their use was associated with epigenetic age (a DNA-based estimate of biological age) in a large group of health-focused adults.

The study analyzed 4,260 adults who had taken at least one saliva test for epigenetic age and provided information on their supplement use, medication use, and health-related factors. Among participants with complete questionnaire data, the average age was about 54. Roughly 71% reported supplement use, giving the researchers enough data to screen 84 commonly used supplements. The researchers then examined whether supplement users tended to have an epigenetic age that was higher or lower than expected for their actual age. A smaller group of 755 participants had repeat tests, allowing the researchers to examine whether those age estimates tended to move lower or higher over time.

• Adults who reported taking a delayed-release calcium-alpha-ketoglutarate (dAKG) supplement with added vitamins had biological age estimates about 1.8 years lower than expected for their actual age. The difference was 1.27 years when the comparison was narrowed to users and non-users with similar health and lifestyle profiles.
• The pattern did not clearly extend to regular alpha-ketoglutarate. That makes it unclear whether the association reflected alpha-ketoglutarate itself, the delayed-release formulation, the added vitamins, or other differences among users.
• Several other supplements looked promising at first, including carotenoids, calcium, CoQ10, curcumin, vitamin D3, and NAD+ boosters. But most of these early links faded after more careful statistical testing.
• Among people tested more than once, CoQ10 and dAKG users were more likely to see their biological-age estimates move in a younger direction. However, that signal also fell short under the more rigorous analysis.

Many of the supplements that showed positive signals in this study have plausible roles in aging biology, from antioxidant defense and inflammation to vitamin signaling, mitochondrial function, and cellular energy metabolism. The clearest finding, however, centered on dAKG. Alpha-ketoglutarate is a central metabolite in cellular energy production and also serves as a cofactor for enzymes involved in epigenetic regulation, including processes linked to DNA methylation, the molecular pattern used to estimate epigenetic age. The weaker results for the other supplements should not be read as evidence that they have no health value. Instead, they suggest that any effects they may have were not clearly captured by this specific epigenetic-age measure and dataset.

One limitation of the study is that it was observational, so it cannot prove that any supplement lowered biological age. Supplement quality, dose, frequency, and duration were also not reported. For now, product claims based on biological age scores should be treated cautiously, with greater weight placed on controlled trials showing benefits on established biomarkers, physical function, or disease risk. In this clip, Dr. Steve Horvath discusses whether epigenetic clocks play causal roles in aging.

High doses of creatine have recently been shown to help preserve cognitive performance during acute sleep deprivation, but it is less clear whether a lower dose can provide similar benefits.

A new study included 29 healthy adults aged 20 to 40 in a crossover trial. Each participant completed two separate sleepless nights in random order, receiving a single dose of 0.2 grams of creatine monohydrate per kilogram of body weight (0.2 g/kg; about 14 grams on average) on one night and a placebo on the other. Participants stayed awake from about 7 a.m. until around 4:30 a.m. the next morning. Cognitive testing was performed several times throughout the sleep-deprivation period, with creatine or placebo given after about 14 hours of wakefulness.

• The clearest benefit was on reasoning questions. Across the three overnight tests, participants scored 6.1% higher with creatine than with placebo after accounting for their starting scores. On the placebo night, reasoning performance fell by 6.8%.
• A few other measures also leaned in favor of creatine compared with placebo, but the evidence was statistically less robust. Participants scored 6.2% higher on numerical reasoning questions, answered verbal questions 12.3% faster, and had 9.2% less variation in their reaction times, while average reaction speed changed little.
• Creatine did not clearly reduce sleepiness or fatigue compared with placebo. By 4 a.m., sleepiness had risen 155% from the 6 p.m. baseline measure with creatine and 173% with placebo. Fatigue also rose in both conditions, by 148% with creatine and 115% with placebo.
• Not every measure improved with creatine: word memory, memory for number sequences, the ability to briefly hold visual information in mind, and language accuracy were not clearly better than with placebo.

Creatine supports cellular energy through the creatine kinase and phosphocreatine system, which helps regenerate ATP, the main energy molecule used by cells. Sleep deprivation is a stress condition that may strain energy reserves and make creatine uptake more relevant than it would be after a restful night, especially during demanding cognitive tasks. This could explain why creatine modestly helped preserve performance during the sleepless night, even though participants still felt increasingly sleepy and fatigued.

This was a small, one-night study in healthy young adults, so it is unclear how well the findings would apply outside this controlled setting. Still, the results suggest that creatine may help preserve some aspects of cognition during sleep loss even at 0.2 g/kg, although the effects appeared less pronounced than in earlier work from the same group using 0.35 g/kg. In this clip, I explain why I increased my creatine intake and how creatine may support brain energy during sleep loss and mid-afternoon dips.

Glioblastoma is an aggressive form of brain cancer, and researchers are still working to understand how sex hormones influence its growth. A new study tested whether androgens, a group of hormones that includes testosterone, shape immune responses to this disease.

The main experiments used young male mice in which glioblastoma cells were placed in the brain, with some mice undergoing castration to remove the main source of androgens and others receiving sham surgery. To test whether androgen signaling acted on the cancer cells themselves or instead changed how the brain environment responded to tumors, the researchers also grew the same cancer cells outside the brain, including under the skin. In additional experiments with glioblastoma cells placed in the brain, they used a drug to block androgen signaling in males that had not been castrated or gave testosterone back to males that were castrated. For the human analysis, the researchers reviewed health records from 1,333 men older than 65 with glioblastoma who received standard treatment, then compared those who also had supplemental testosterone listed in their records with those who did not.

• Androgen loss worsened brain tumor outcomes in male mice. In one glioblastoma brain tumor model, median survival was 26 days after sham surgery and 20 days after castration, with larger tumors in the androgen-depleted mice.
• Tumor location changed the direction of the effect. When glioblastoma cells were placed in the brain, androgen loss shortened survival. When the same glioblastoma cells were grown under the skin, androgen loss delayed tumor growth. The researchers also found shortened survival after castration when bladder cancer and melanoma cells were placed in the brain.
• Blocking androgen signaling with a drug shortened survival in male mice with glioblastoma cells placed in the brain, from 19 days to 17.5 days.
• Testosterone supplementation extended survival in mice with glioblastoma cells placed in the brain: from 20 to 22 days in castrated males, and from 21 to 36 days in males that had not been castrated or treated with the androgen-blocking drug.
• Among the men reviewed, 61 with recorded supplemental testosterone use had a median survival of 16 months, compared with 12 months in those without testosterone use. After accounting for other factors, testosterone use was linked to a 34% lower death rate over the study period.

The findings point to a brain-specific pathway affected by androgen loss. In male mice with brain tumors, losing androgen signals appeared to make the brain more inflamed. Those inflammatory signals then helped activate the body's stress-hormone system. The resulting stress-hormone activity appeared to shift myeloid cells, a group of immune cells that shape the tumor environment, toward a more immune-suppressing state, weakening T cells that help recognize and attack cancer.

The main limitation is that the causal evidence comes from mouse experiments, while the human survival finding is observational and based on medical records. If confirmed in clinical trials, the findings could especially matter for older men, whose testosterone levels are often lower due to age-related decline. But the human data in this study do not prove that testosterone supplementation improves glioblastoma survival or is safe for this use. In Aliquot #116, I discuss testosterone optimization strategies for men.