Scientists discovered that a natural molecule called NADPH plays a key role in keeping blood vessel cells young and healthy. When blood vessels age, a specific enzyme called G6PD becomes more active and increases NADPH levels in cells. Researchers found that boosting this process protects blood vessels from aging damage. Surprisingly, they also discovered that folic acid—a common B vitamin—can activate this protective pathway. In studies with mice, folic acid successfully slowed down vascular aging. This finding opens a new door for treating age-related heart and blood vessel problems using a safe, affordable vitamin that many people already take.

The Quick Take

  • What they studied: How a molecule called NADPH affects aging in blood vessel cells, and whether increasing it could slow down vascular aging
  • Who participated: Laboratory studies using human endothelial cells (the cells that line blood vessels) and two groups of mice: young mice given a substance that mimics aging, and naturally aged mice
  • Key finding: Increasing NADPH levels in blood vessel cells protects them from aging damage. Folic acid, a common B vitamin, successfully activated this protective process in both types of mice studied
  • What it means for you: Folic acid supplementation may help protect blood vessels from aging-related damage, potentially reducing heart disease risk. However, this is early research in animals—human studies are needed before making changes to your supplement routine. Talk to your doctor before starting any new supplements

The Research Details

This was a laboratory research study that combined multiple approaches. Scientists used special fluorescent markers to watch NADPH levels in living blood vessel cells as they aged. They then tested what happened when they increased or decreased the enzyme G6PD that controls NADPH production. To find practical treatments, they screened 1,419 FDA-approved drugs to see which ones could boost NADPH levels. Finally, they tested the most promising candidate—folic acid—in two mouse models: one with artificially induced vascular aging and one with natural aging from getting older.

The researchers used genetic tools to turn genes on and off, allowing them to prove that NADPH was actually responsible for the protective effects they observed. They measured multiple markers of vascular aging, including oxidative stress (cellular damage from harmful molecules) and the activity of proteins involved in aging.

Understanding exactly how blood vessels age at the molecular level is crucial for developing new treatments. Previous research knew that blood vessels deteriorate with age, but didn’t know the specific mechanisms. By identifying NADPH metabolism as a key player, this research provides a clear target for therapy. The fact that they found an existing, safe drug (folic acid) that works through this pathway means potential treatments could reach patients quickly without waiting for new drug development.

This research was published in Nature Communications, a highly respected scientific journal. The study used multiple complementary approaches (cell studies, genetic manipulation, and animal models) which strengthens confidence in the findings. The researchers tested their theory in two different aging models, showing the effect isn’t limited to one specific situation. However, the work was done in laboratory and animal settings—human studies are still needed to confirm these results apply to people.

What the Results Show

The main discovery was that NADPH levels in the cytoplasm (the fluid inside cells) increase as blood vessel cells age, while mitochondrial NADPH (in the cell’s energy factories) stays the same. This increase comes from higher activity of an enzyme called G6PD. When researchers artificially increased G6PD activity, it protected blood vessel cells from aging damage. Conversely, when they reduced G6PD, aging accelerated.

The protective mechanism works through two pathways: NADPH helps create a protective molecule called reduced glutathione that shields cells from oxidative damage, and it also blocks an aging-promoting protein called HDAC3. When researchers tested folic acid in mice with artificially induced vascular aging, it successfully slowed the aging process. The same benefit appeared in naturally aged mice, suggesting the effect works across different aging scenarios.

The researchers identified that folic acid works by being converted into a form that generates NADPH through an enzyme called methylenetetrahydrofolate dehydrogenase. This explains why folic acid, a common B vitamin, could have such a specific protective effect on blood vessel aging.

The study revealed that G6PD activity is controlled by a chemical modification called S-nitrosylation at a specific location (C385). Blocking this modification increased G6PD activity and enhanced protection against vascular aging. This finding suggests that controlling this specific chemical modification could be another way to activate the protective pathway. The research also showed that NADPH’s protective effects depend on both the glutathione pathway and HDAC3 inhibition—blocking either one reduced the protection, indicating both mechanisms are necessary.

Previous research established that vascular aging involves oxidative stress and cellular senescence (cells stopping division and aging), but the specific role of NADPH metabolism wasn’t well understood. This study fills that gap by showing NADPH is not just a passive byproduct but an active player in vascular aging. The finding that folic acid helps is particularly interesting because folic acid has long been known to be important for heart health, but the mechanism wasn’t clear. This research provides a molecular explanation for why this common vitamin matters for blood vessel function.

This research was conducted in laboratory cell cultures and animal models, not in humans. Mouse studies don’t always translate directly to human biology. The study didn’t test different doses of folic acid or compare it to other potential treatments. The research focused on one specific type of blood vessel cell (endothelial cells), so it’s unclear if the same mechanism applies to other blood vessel components. Additionally, the study was conducted in controlled laboratory settings—real-world factors like diet, exercise, and other medications weren’t considered. Long-term safety and effectiveness in humans remain unknown.

The Bottom Line

Based on this research, folic acid supplementation may help protect blood vessels from aging-related damage (moderate confidence level, pending human studies). Current dietary guidelines already recommend adequate folic acid intake (400 micrograms daily for adults), which can be obtained through leafy greens, legumes, and fortified grains. If you’re considering supplementation beyond dietary sources, consult your healthcare provider, especially if you take medications or have specific health conditions. This research suggests folic acid may be particularly beneficial for cardiovascular health, but it’s not a replacement for established healthy habits like exercise, not smoking, and managing blood pressure.

This research is most relevant to people concerned about heart and blood vessel health, particularly those with risk factors for vascular disease or those interested in healthy aging. It may be especially interesting to people already taking folic acid supplements or those with family histories of heart disease. People with certain genetic conditions affecting folate metabolism should discuss this with their doctor before making changes. This research is not yet ready to guide treatment decisions for diagnosed vascular disease—those decisions should remain with healthcare providers based on established treatments.

In animal studies, protective effects appeared within weeks to months. In humans, vascular benefits from improved nutrition typically take months to years to become apparent. You shouldn’t expect immediate changes in how you feel. If you start folic acid supplementation, give it at least 3-6 months before evaluating any potential benefits, and track markers like blood pressure and energy levels. Remember that vascular health improvements are usually gradual and work best when combined with other healthy lifestyle choices.

Want to Apply This Research?

  • Track daily folic acid intake (through food or supplements) and correlate it with monthly blood pressure readings and resting heart rate measurements. Set a goal of consistent folic acid intake and monitor cardiovascular markers over 3-6 month periods to identify trends
  • Add one folic acid-rich food daily (spinach, lentils, asparagus, or fortified grains) and log it in your nutrition tracker. If supplementing, set a daily reminder to take folic acid at the same time each day and mark it complete in the app. Pair this with tracking other cardiovascular health behaviors like exercise minutes and sleep quality
  • Create a quarterly cardiovascular health dashboard tracking: folic acid intake consistency, blood pressure trends, resting heart rate, exercise frequency, and subjective energy/wellness scores. Compare quarterly reports to identify whether consistent folic acid intake correlates with improvements in these markers. Share trends with your healthcare provider during annual checkups

This research is preliminary and was conducted in laboratory and animal models, not humans. The findings suggest folic acid may support blood vessel health, but human clinical trials are needed to confirm safety and effectiveness. This information is educational and should not replace professional medical advice. Before starting any new supplement regimen, especially if you have existing health conditions, take medications, or are pregnant or breastfeeding, consult your healthcare provider. Folic acid supplementation is generally safe at recommended doses, but excessive intake can have side effects. This article does not constitute medical advice or a recommendation to treat, cure, or prevent any disease.