This Plant Compound Can Save Your Arteries from Calcification

Why Most Doctors Still Don’t Mention It

How Fisetin May Help Prevent Vascular Calcification

You may be familiar with fisetin as a popular anti-aging supplement, but new research published in Aging suggests that it may play a direct role in protecting your blood vessels. Scientists have found that fisetin may significantly reduce vascular calcification, a process that can stiffen and narrow your arteries and raise your risk of serious cardiovascular complications.

Why Calcification Matters to Your Health

Vascular calcification is not the same as atherosclerosis. While atherosclerosis is caused by plaque buildup, calcification happens when phosphate in your blood causes calcium to crystallize. These crystals form where they do not belong, leading to dangerously stiff and narrow arteries. This process is typically regulated by your body, but if you suffer from chronic kidney disease or systemic inflammation, those regulatory mechanisms can fail.

Smooth muscle cells in your arteries, called vascular smooth muscle cells or VSMCs, become senescent when exposed to too much phosphate or glucose. Once they become senescent, they contribute to calcification. Research has also shown that activating the p38/MAPK pathway makes this worse, while inhibiting it prevents calcification.

Fisetin’s Unique Role

Fisetin is a plant-based flavonoid found in several trees and plants. Researchers had already found that senolytic compounds, which remove senescent cells, might fight calcification. However, fisetin had not been tested in this specific context before.

To establish its effect, researchers exposed human aortic cells to calcium and phosphate. These triggered high levels of calcification markers. However, adding just one micromole of fisetin dropped those markers to near-normal levels. Higher doses did not improve results further.

Fisetin only worked when it was present during the pro-calcification exposure. It had no benefit if used before or after, and it had no effect on cells that were not exposed to calcium and phosphate. However, when researchers mimicked chronic kidney disease conditions, fisetin successfully reduced both senescence and calcification markers.

Understanding the Mechanism

The study found that fisetin increases DUSP1, a molecule that negatively regulates the p38/MAPK pathway. Blocking DUSP1 made fisetin ineffective, while silencing DUSP1 led to more calcification. When p38 was directly inhibited in these cells, the benefits returned, showing that fisetin works through the DUSP1 to p38/MAPK pathway.

Animal Studies Confirm the Benefit

Researchers then moved to mouse models. In explanted mouse aortae exposed to pro-calcification conditions, fisetin reduced both senescence and calcification markers, just as in cell cultures. In living mice given cholecalciferol to induce calcification, fisetin again delivered protective effects. The arteries of treated mice closely resembled those of the healthy control group.

While these results are promising, the researchers caution that mouse models do not perfectly mimic human chronic kidney disease, especially in terms of vitamin D metabolism. There may also be sex-specific responses to fisetin that require further investigation. Still, because fisetin is already sold as a supplement, conducting a clinical trial may be relatively easy and inexpensive.

Your Call to Action for Fisetin and Vascular Health

If you are concerned about arterial stiffness or have risk factors like chronic inflammation or kidney disease, you should pay attention to the emerging science on fisetin. Although more human studies are needed, this flavonoid already shows potential in reducing vascular calcification and cellular senescence in preclinical models. Talk to your healthcare provider before adding any supplement to your routine, especially if you have underlying health conditions. Stay informed, because your choices today can help protect your arteries for years to come.

Reputable Suppliers & Discount Codes:

Use the discount code ‘MYNMN’ to get between 10% & 15% off from these reputable suppliers of Fisetin:

ProHealth Longevity (15% off): http://tiny.cc/bskk001

Study Links:

Voelkl, J., Cejka, D., & Alesutan, I. (2019). An overview of the mechanisms in vascular calcification during chronic kidney disease. Current opinion in nephrology and hypertension, 28(4), 289-296.

Voelkl, J., Egli-Spichtig, D., Alesutan, I., & Wagner, C. A. (2021). Inflammation: a putative link between phosphate metabolism and cardiovascular disease. Clinical Science, 135(1), 201-227.

Zhang, M., Li, T., Tu, Z., Zhang, Y., Wang, X., Zang, D., … & Zhou, H. (2022). Both high glucose and phosphate overload promote senescence-associated calcification of vascular muscle cells. International Urology and Nephrology, 54(10), 2719-2731.

Yamada, S., Tatsumoto, N., Tokumoto, M., Noguchi, H., Ooboshi, H., Kitazono, T., & Tsuruya, K. (2015). Phosphate binders prevent phosphate-induced cellular senescence of vascular smooth muscle cells and vascular calcification in a modified, adenine-based uremic rat model. Calcified Tissue International, 96, 347-358.

Yang, Y., Sun, Y., Chen, J., Bradley, W. E., Dell’Italia, L. J., Wu, H., & Chen, Y. (2018). AKT-independent activation of p38 MAP kinase promotes vascular calcification. Redox biology, 16, 97-103.

Kang, J. H., Toita, R., Asai, D., Yamaoka, T., & Murata, M. (2014). Reduction of inorganic phosphate-induced human smooth muscle cells calcification by inhibition of protein kinase A and p38 mitogen-activated protein kinase. Heart and vessels, 29, 718-722.

Ceccherini, E., Gisone, I., Persiani, E., Ippolito, C., Falleni, A., Cecchettini, A., & Vozzi, F. (2024). Novel in vitro evidence on the beneficial effect of quercetin treatment in vascular calcification. Frontiers in Pharmacology, 15, 1330374.