A study published by Nanchang University in Aging Cell in September 2025 demonstrated that dietary citrate supplementation can activate the AMPK pathway, improve mitochondrial function in senescent endothelial cells, and reduce oxidative stress. This process delays vascular aging, alleviates atherosclerosis, and extends lifespan in mice.
Imagine that humble lemon sitting in your kitchen – its tangy taste could be hiding a key to counteracting the ravages of time and preserving youthful blood vessels. This is not a fantasy. Recent scientific research is spotlighting a common substance found in lemons – citrate – and revealing how it may help "clear the sludge" at the cellular level, slowing down vascular aging.
Vascular aging refers to the degenerative changes that occur in blood vessels as we age, such as reduced elasticity and endothelial dysfunction. Alongside these changes, levels of several aging markers, including cyclin-dependent kinase inhibitors p21 (CDKN1A) and p16 (CDKN2A), rise. These factors increase the risk of cardiovascular and cerebrovascular diseases.
In September 2025, researchers from Nanchang University published a study in Aging Cell titled "Dietary Citrate Restores Age-Related Endothelial Cell Mitochondrial Dysfunction and Alleviates Atherosclerosis". Their findings suggest that dietary supplementation with citrate could extend lifespan in mice by activating the AMPK pathway, improving mitochondrial function, reducing oxidative stress, and delaying vascular aging while alleviating age-related vascular diseases.
https://doi.org/10.1111/acel.70213
1. Citrate Delays Vascular Aging and Endothelial Cell Senescence
Previous studies have shown that dietary citrate can extend the lifespan of organisms like fruit flies and roundworms. In this study, researchers investigated the effects of citrate on vascular aging and age-related vascular diseases in naturally aging and high-fat diet-fed mice.
The researchers established both aging mouse models and high-fat diet-induced vascular injury models. In the aging model, they randomly assigned elderly male mice to either the citrate group or the control group. The citrate group was given 1% sodium citrate solution or fresh water daily for six months or until natural death. In the high-fat diet model, the mice were fed a high-fat diet for eight weeks, while also being supplemented with either sodium citrate or fresh water.
The results showed that long-term dietary supplementation with citrate significantly delayed vascular aging and improved vascular function. In the aging mouse model, mice that consumed 1% sodium citrate displayed more intact vascular structures compared to the control group, including reduced elastic fiber fragmentation, a thinner intima-media thickness, increased lumen area, and decreased collagen deposition. This indicates that citrate can delay age-related vascular aging.
Figure 1: Citrate can delay vascular aging and improve vascular function in aged mice.
Additionally, the overall extent of atherosclerotic lesions in the aorta was significantly lower in the citrate group, further confirming its beneficial effects on vascular diseases.
Compared to young cells, the citrate content in aging cells was significantly lower. The researchers found that external supplementation of citrate could restore the lowered citrate levels in aging cells, delay endothelial cell senescence, and alleviate mitochondria dysfunction induced by aging. Mechanistically, citrate activates the AMPK signaling pathway, enhancing mitochondrial respiratory efficiency and ATP production, reducing ROS levels, and promoting mitophagy and mitochondrial renewal, ultimately improving the energy metabolism of aging endothelial cells. These results suggest that citrate could delay endothelial cell senescence through the AMPK-ROS signaling cascade.
2. What is Citrate?
In 1784, Swedish chemist Carl Wilhelm Scheele first isolated citric acid by crystallizing lemon juice. From a chemical perspective, citric acid is a tricarboxylic acid containing three carboxyl groups and one hydroxyl group, with the chemical formula C₆H₈O₇. It is a naturally occurring weak organic acid found in many fruits and vegetables, especially citrus fruits like lemons and limes, which are particularly high in citric acid, making up 8% of their dry weight.
Citrate is the salt or anionic form of citric acid (C₆H₅O₇³⁻), formed when citric acid loses a hydrogen ion. It commonly exists in forms such as sodium citrate, potassium citrate, and calcium citrate. In the body, citrate exists as the citric acid anion and is an important intermediate in the tricarboxylic acid cycle, playing a central role in cellular energy metabolism, redox balance, and mitochondrial function.
The average daily intake of citrate is around 4 grams. In China, citrate does not yet have a regulatory standard, but its sodium salt, sodium citrate, has been approved as a food additive. It serves as an acidity regulator, stabilizer, antioxidant, preservative, and emulsifier in food processing and flavoring.
In the United States and the European Union, sodium citrate is approved as a food additive for consumption in moderation.
3. Other Benefits of Citrate
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Antioxidant Properties
Citrate possesses antioxidant properties. Not only is it an effective antioxidant itself, but it also reacts with free radicals in the body, reducing oxidative damage to cells and tissues and lowering oxidative stress levels. -
Uric Acid Reduction
Citrate is the most abundant organic anion in urine and is a key endogenous inhibitor of calcium kidney stones. Citrate can help reduce uric acid levels by alkalizing the urine and promoting uric acid excretion. According to the "Chinese Expert Consensus on the Diagnosis and Treatment of Hyperuricemia and Associated Diseases (2023 Edition)", citrate (including potassium citrate, potassium sodium citrate, and sodium citrate) is the most potent endogenous inhibitor of stone formation and can alkalize urine, increasing the solubility of uric acid and dissolving uric acid stones while preventing new stone formation.
Conclusion
This study not only confirms that citrate is a promising natural compound for combating vascular aging but also opens a pathway to promoting vascular health and combating age-related diseases by modulating cellular metabolism.