Two medications commonly prescribed to prevent malaria have emerged as unexpected candidates for longevity research. A large observational investigation involving healthcare records from Israel and the United States found that people prescribed atovaquone-proguanil or mefloquine had lower mortality rates and fewer diagnoses of several diseases associated with aging. The findings raise questions about whether persistent parasitic infections could influence long-term health, although they do not prove that either drug extends life.
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Researchers affiliated with Tel Aviv University, Leumit Health Services, Ariel University, and other institutions examined medication histories and subsequent health outcomes across independent patient populations. In this Longevity and Wellness News report, the striking results include associations with reduced dementia, diabetes, heart disease, respiratory illness, and certain cancers. The research appeared as a medRxiv preprint posted in September 2025 and had not been peer reviewed, making careful interpretation essential.
A Surprising Discovery in Israeli Medical Records
The investigation began with a broad screening of medication purchases recorded by Leumit Health Services, an Israeli healthcare provider serving approximately 730,000 members. Researchers compared 14,986 people who died before sex-specific longevity thresholds with 14,986 matched individuals who lived beyond those thresholds.
The thresholds were 84 years for women and 77 years for men. After examining medications purchased during the preceding decade, only atovaquone-proguanil and mefloquine remained significantly associated with longer survival after correction for multiple statistical comparisons.
Mefloquine exposure was associated with 68% lower odds of belonging to the shorter-lived group, while atovaquone-proguanil was associated with 57% lower odds. These figures describe statistical relationships, not demonstrated benefits from treatment.
Lower Mortality and Fewer Chronic Diseases
The researchers then assembled another Israeli cohort comprising 3,876 people who had received either medication and 77,820 unexposed controls. Both groups had an average age of 56.3 years.
Medication exposure was associated with a mortality hazard ratio of 0.40, equivalent to approximately 60% lower observed mortality during follow-up. Dementia showed a 48% lower hazard, diabetes 17%, heart failure 24%, and heart attacks 22%.
Other associations included 36% lower hazards of liver failure, 27% lower hazards of chronic obstructive pulmonary disease, 30% lower hazards of gastrointestinal cancers, and 48% lower hazards of lung cancer.
These findings were notable because they involved several organ systems.
However, smoking rates differed substantially: 14.5% of treated participants were current smokers, compared with 21.8% of controls. Such differences could explain some of the apparent advantages.
American Data Reinforces the Pattern
To investigate whether the findings extended beyond Israel, the team examined the U.S. TriNetX research network, containing records from more than 120 million patients across 69 healthcare organizations.
After matching participants on factors including age, sex, smoking, diabetes, and body mass index, researchers compared 24,498 atovaquone-proguanil recipients with matched controls and 3,400 mefloquine recipients with their controls.
Atovaquone-proguanil exposure was associated with approximately 74% lower observed mortality, while mefloquine exposure was associated with approximately 67% lower mortality. Associations involving dementia, diabetes, kidney impairment, cardiovascular disease, and certain cancers were also reproduced.
The researchers additionally studied 124,681 recipients of the COVID-19 antiviral nirmatrelvir-ritonavir, known as Paxlovid, alongside matched controls. Its inclusion helped examine whether healthier international travelers might account for the antimalarial findings. Paxlovid exposure was associated with approximately 50% lower mortality, although its shorter follow-up and different treatment circumstances complicate interpretation.
Could a Common Parasite Influence Aging?
The researchers proposed that Toxoplasma gondii, a widespread intracellular parasite, might help explain the associations. This organism can persist in human tissues without obvious symptoms and has previously been linked in observational research to neurological and cardiovascular conditions.
Atovaquone has established activity against the parasite, while mefloquine has demonstrated activity in laboratory and animal studies. The authors speculate that suppressing persistent protozoal infections could reduce inflammation and immune disturbances associated with chronic disease.
They also note that ritonavir and related antiviral compounds have shown antiprotozoal activity under experimental conditions. However, Paxlovid itself has not been established as a treatment for Toxoplasma infection.
Crucially, the investigation did not measure parasite clearance or demonstrate that Toxoplasma caused the observed illnesses. The proposed mechanism remains a hypothesis requiring direct testing.
The possibility is particularly relevant to preventive medicine because inflammation, metabolic dysfunction, and immune changes often develop gradually before serious symptoms emerge. Still, a biological theory cannot substitute for evidence that treating an infection improves survival, especially when the proposed intervention carries meaningful medical risks.
Potential Risks Cannot Be Ignored
The apparent benefits were accompanied by concerning associations. In Israel, treated patients experienced 25% higher hazards of hearing loss and dry-eye or Sjögren’s-related diagnoses, alongside a 54% higher hazard of lichen planus, an inflammatory skin condition.
American data showed similar increases in hearing problems and certain eye and skin disorders. Researchers suggested that localized inflammation following parasite suppression might contribute, but this explanation remains unconfirmed.
These medications also have established adverse effects. Mefloquine, particularly, can cause serious neuropsychiatric reactions. Neither medication should be taken for longevity purposes based on these findings.
What the Findings Mean for Healthy Aging
The study offers an intriguing direction for investigating whether chronic infections contribute to aging-related disease. Replication across two national healthcare systems strengthens the case for further research, but observational comparisons cannot establish causation. Differences in lifestyle, underlying health, medical access, and treatment selection may influence the results.
Controlled clinical trials and laboratory investigations must determine whether the medications themselves provide protection, whether persistent parasites play a meaningful role, and whether any benefits outweigh potential harms. Until then, these findings should encourage scientific investigation rather than preventive self-medication.
The research paper is available at https://doi.org/10.1101/2025.07.01.25330644.
Medical Disclaimer: All content published by Thailand Wellness News is based on scientific research and is intended for informational and educational purposes only. It is not medical advice, diagnosis, or treatment. Readers must not attempt to use, apply, or experiment with any protocols, compounds, or therapies mentioned without first consulting a qualified and licensed medical doctor. Many findings discussed are experimental or preliminary, and only a licensed healthcare professional can determine what is safe and appropriate for an individual’s specific medical condition.
