Frequent cannabis use was linked to lower levels of Klotho, a protein associated with healthy aging, in middle-aged adults | Research

The takeaway

An analysis of nearly 6,000 middle-aged U.S. adults found that frequent cannabis use was associated with significantly lower serum Klotho, a biomarker of aging and metabolic health, with the effect persisting after excluding smokers.

Aging researchers, middle-aged cannabis users, preventive health clinicians

Frequent cannabis users had significantly lower Klotho levels (p = 0.027) with dose-dependent trend

What the researchers found

Frequent cannabis users had significantly lower Klotho levels than never users (adjusted estimate = -57.94, p = 0.027), with a significant dose-dependent trend (p = 0.022). The association persisted in non-smokers (p = 0.047), confirming a cannabis-specific effect. Amplified reductions appeared in those with prolonged sedentary behavior (>240 min/day), higher vitamin D, and cancer.

Why it matters

Klotho is increasingly recognized as a key biomarker of biological aging, with lower levels linked to cardiovascular disease, cognitive decline, and metabolic dysfunction. If frequent cannabis use reduces Klotho, it could accelerate aging-related health problems.

The numbers in context

5,827 adults aged 40-59; frequent users: -57.94 Klotho (p = 0.027); dose-dependent trend (p = 0.022); persisted in non-smokers (p = 0.047); E-value = 4.77 (95% CI: 1.37-8.57); population attributable fraction: 3.13% (95% CI: 0.47-6.54%)

How the study worked

Cross-sectional analysis of 5,827 adults aged 40-59 from NHANES 2007-2016. Cannabis use was self-reported via computer-assisted interviews. Serum Klotho was measured by ELISA. Weighted multivariable generalized linear models with subgroup analyses, interaction tests, and E-value sensitivity analysis were used.

What this study cannot tell us

Cross-sectional design cannot establish causation. Self-reported cannabis use may be inaccurate. Klotho was measured at a single time point. Cannot determine if lower Klotho preceded or followed cannabis use. The 3.13% population attributable fraction is small.

How to read the evidence

Moderate: large nationally representative sample with robust statistical methods and sensitivity analyses, but cross-sectional design limits causal inference.

When this study was published

2026 publication analyzing NHANES data from 2007-2016.

The bigger picture

This connects cannabis use to a biological aging marker for the first time using nationally representative data. The finding that the effect was stronger in metabolically healthier subgroups is counterintuitive and warrants further investigation.

Questions still open

Does reduced Klotho from cannabis use translate to actual accelerated aging or disease? Why was the effect stronger in metabolically healthier people? Would cessation of cannabis use restore Klotho levels?

Common questions

What is Klotho and why does it matter?

Klotho is a protein linked to aging and metabolic health. Lower levels are associated with cardiovascular disease, cognitive decline, and shorter lifespan. This study found frequent cannabis use was linked to lower Klotho in middle-aged adults.

Could this effect be from tobacco smoking rather than cannabis?

The researchers tested this by analyzing only non-smokers and found the association persisted (p = 0.047), suggesting a cannabis-specific effect independent of tobacco.

Read the original research

Association between cannabis consumption and serum Klotho levels in middle-aged U.S. adults: NHANES cross-sectional analysis.

Journal of cannabis research, 8(1), 18

View on PubMed ↗Publisher’s paper ↗

Citation

Wang, Li; Ji, Yanjing; Wang, Tianxiao; Wang, Weijian; Zong, Gangjun. (2026). Association between cannabis consumption and serum Klotho levels in middle-aged U.S. adults: NHANES cross-sectional analysis.. Journal of cannabis research, 8(1), 18. https://doi.org/10.1186/s42238-025-00380-x