Taxifolin supplements demonstrate protective effects against lupus

New study indicates that taxifolin could reduce chronic inflammation, promote healthy aging and improve healthspan of lupus sufferers.

A new first-of-its-kind study found taxifolin supplements have protective effects on thrombo-inflammatory diseases, such as lupus and antiphospholipid syndrome (APS) [1]. Taxifolin, which is also known as dihydroquercetin, is a bioactive plant-derived flavonoid that has a wide range of health-supporting, anti-inflammatory and anti-oxidative properties.

Longevity.Technology: When it comes to autoimmune diseases, lupus is usually everyone’s starter for 10. Lupus – an autoimmune inflammatory disease affecting about five million people worldwide [2] – can harm the kidneys, heart, lungs, blood vessels and the brain. Lupus complications can shorten lifespan and the disease itself can be fatal due a host of reasons, including kidney damage, vascular damage, infections and infectious complications.

Immune dysregulation leads to inflammaging and senescence, and various forms of his dysregulation can be seen in both people with lupus and in the aging population. Immunosenescence, the natural decline in immune function associated with aging, plays a pivotal role in shaping the clinical trajectory of lupus in older individuals. Individuals with lupus exhibit shortened telomeres [3] and may be particularly vulnerable to some of the effects of aging, and some some scientists have even put forward the theory that lupus could actually be the result of premature aging process [4].

Neutrophils are a type of white blood cell regarded as the first line of immune defense. They have a short lifespan, but keep a trick up their sleeve, as they can release neutrophil extracellular trap (NET) when they die, a unique form of cell death called NETosis. NETs are made from chromosomal DNA, histones and granule proteins and can trap and kill invading microorganisms.

NETs have a central role in immune defense, protecting against infection and supporting immune-modulatory functions, but in autoimmune diseases such as lupus, one really doesn’t want too much of a good thing. Research has found NETs are elevated in the plasma of people with autoimmune diseases, that NETs directly influence inflammation [5], and that NETosis has been specifically implicated in the pathogenesis of lupus [6].

In the study, researchers examined taxifolin’s effects on neutrophil extracellular trap (NET) formation; using neutrophils from healthy individuals which were stimulated with autoantibodies from people with lupus, researchers found that taxifolin, a potent natural antioxidant available as a dietary supplement, inhibited NETosis.

Linda May-Zhang, PhD, VP Innovation at Blue California and an author on the study told Longevity.Technology that taxifolin shows promise in addressing oxidative stress and alleviating lupus symptoms by inhibiting NETosis.  

Taxifolin supplements demonstrate protective effects against lupus
Linda May-Zhang, PhD, is an author on the new study

“While individuals with lupus may have relatively long lifespans, research indicates a potential association between the disease, reduced longevity, and comorbid conditions,” she explained. “These comorbidities may result from ‘normal’ aging processes, aging exacerbated by lupus, or medication-induced aging. Both lupus and aging share commonalities such as chronic low-grade inflammation and compromised immune cell function.”

May-Zhang points out that, notably, this study demonstrates the oral administration of taxifolin at human-equivalent doses can mitigate NETosis and lupus-related issues like hematological abnormalities.

“While NETs are important in fighting pathogens in innate immunity, excessive NETosis, as observed in lupus, can trigger harmful inflammatory and thrombotic responses,” she said.  “NETosis is also evident in other conditions like acute lung injury, cardiovascular diseases, kidney injury, and the pathogenesis of COVID-19.” 

Taxifolin may offer a means to reduce chronic basal inflammation for promoting healthy aging and addressing various conditions, keeping the oxidative stress and the “-osis” in NETosis in check.

May-Zhang referenced ongoing research that suggests that taxifolin may stimulate autophagy, providing an additional complementary mechanism.

“Blue California is presently conducting a double-blinded, placebo-controlled pilot study to explore the impact of taxifolin supplementation on immune function and immunosenescence in healthy individuals,” she added. 

Taxifolin supplements demonstrate protective effects against lupus
Ramadan Ali is the PI on the new study

Ramadan Ali, PhD, is Principal Investigator of the study at University of Michigan. He told us that neutrophil hyperactivity and excessive NET release is a hallmark event in lupus and various autoimmune diseases.

“Our results suggested that taxifolin, by lowering neutrophil hyperactivity, could work to reduce the risk of inflammation, vascular damage, and blood clotting in lupus mouse model.”

While more research is needed to identify the effects of taxifolin on the treatment of lupus, the study’s results are encouraging. 

“Taxifolin may have the ability to complement with prescribed treatments to better relieve people’s symptoms with lupus and other inflammatory conditions, thus improving their healthspan,” Ali said.

Photographs courtesy of Ramadan Ali and Linda May-Zhang

[1] https://academic.oup.com/rheumatology/advance-article-abstract/doi/10.1093/rheumatology/kead547/7303860
[2] https://www.lupus.org/resources/lupus-facts-and-statistics
[3] https://pubmed.ncbi.nlm.nih.gov/23400670/
[4] https://www.researchgate.net/publication/280537942_Aging_and_Systemic_Lupus_Erythematosus_-_Immunosenescence_and_Beyond
[5] https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-021-00402-2
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980316/