Urolithin a (hereinafter referred to as UA) is a metabolite of intestinal microorganisms and cannot be directly supplemented through dietary channels. However, its precursor ellagitannin is rich in pomegranate, strawberry and other fruits.
The first encounter between humans and UA can be traced back to 2005. The research team of scientist CERD á first discovered the existence of urolithin A and confirmed that it was the work of gut microbiota.
In the following ten years, the number of studies on UA has maintained a continuous growth trend, and its rich functions of anti-oxidation, anti-cancer, anti-inflammatory and anti-bacterial virus infection have been found one after another. This magical substance derived from nature has come into the view of more and more scientists.
So, what is the mechanism behind these colorful functions of urolithin a? How does it help organisms fight against aging and prolong life?
No.1 anti aging
Since it was found in 2016 that it can effectively extend the life span of Caenorhabditis elegans, the anti-aging efficacy of urolithin a in various levels (hematopoietic stem cells, skin tissues, brain (organs), immune system, individual life span) and species (Caenorhabditis elegans, Drosophila melanogaster, mice, humans) has been strongly demonstrated.
Scientists have also given a reasonable explanation for the mechanism behind it.
In animal and clinical trials, scientists have found that UA can inhibit the proliferation of aging mitochondrial dysfunction and prolong the life of mitochondria by inducing autophagy of dysfunctional mitochondria and regulating mitochondrial biosynthesis, and can also induce mitosis of cells, which is exactly opposite to the effects of aging.
Note: as a mitotic inducer, urophyllin a can restore the decline in mitosis caused by aging
After reading the mechanism, let's take a look at the most concerned question: how does the anti-aging efficacy of UA perform in human clinical trials?
Up to now, clinical human trials on the anti-aging efficacy of UA have mostly focused on the improvement of age-related skeletal muscle function problems (perhaps because the improvement effect is easier to appear and easier to observe). Several studies have confirmed the good safety and bioavailability of UA in humans.
In addition, in these studies, the authors mentioned that UA plays an anti-aging role by improving the mitosis and mitochondrial function of corresponding cells, which is also consistent with the mechanism mentioned above.
Another interesting point is that UA improved the endurance and physical fitness of aging people in these trials, but could not improve the best performance of activities, which also implied the identity of UA as a function maintainer rather than an amplifier.
No.2 has three classic effects: anti-inflammatory, antioxidant and anticancer
After finishing the anti-aging protagonist, let's take a look at the first and most studied three major effects of UA: anti-inflammatory, antioxidant and anti-cancer.
Some scholars have confirmed that UA can inhibit mitochondria related apoptosis pathway and regulate P-38 MAPK signaling pathway, thereby inhibiting oxidative stress-induced apoptosis. For example, UA can improve the survival rate of neurons stimulated by oxidative stress and has good neuroprotective function.
Photo note: UA may be like fresh-keeping film on the surface of fruit for the body.
Photo source: https://vinepair.com/articles/what-is-oxidation-in-wine/
Compared with its antioxidant capacity, UA has more powerful anti-inflammatory activity and can significantly inhibit TNF- α And other typical inflammatory factors, which is why UA plays a role in various inflammatory treatments, including brain, fat, heart, intestine and liver tissues, and can alleviate the inflammation of various tissues.
In a series of human cell models, UA has been confirmed to play an anticancer role by inducing apoptosis and blocking the cell cycle, with colon cancer and prostate cancer being the most prominent.
No.3 protective effect: nerve, gastrointestinal tract and cardiovascular
At the system level, UA has also been proved to have excellent protective effects on the nervous system, gastrointestinal system and cardiovascular system. It can be said to be our excellent health bodyguard.
For example, in neurodegenerative diseases caused by aging, studies have reported that UA can activate SIRT1 signaling pathway, downregulate mTOR signaling pathway, and activate autophagy to prevent D-galactose-induced brain aging, thereby improving cognitive impairment in aging mice.
No.4 improves obesity and regulates intestinal flora environment
In addition, studies have shown that UA has the magical effect of improving obesity and regulating the intestinal flora environment. However, due to space limitations, today, paipai will not make more introductions here.
Having said so much, a friend must have been anxious to ask, UA has so many benefits, and it is a pure natural product derived from natural fruits and vegetables, so how can we supplement UA in our life?
Nature is better? No! Labor may be better!
As a gift from nature, the precursor of UA, ellagitannin, has a high content in various common plants and fruits. Pie pie has also sorted out the corresponding table for your reference below:
Ellagitannins and ellagic acid content in food products
On the other hand, the industrial production of UA can also be achieved by chemical synthesis, and its safety has been proved by a large number of toxicological studies.
In fact, as early as 2018, UA has been designated as a "recognized safe" edible substance by the US Food and drug administration, which can be added to protein milkshakes, meal substitutes, instant oatmeal, nutritional protein bars and milk drinks (up to 500 mg / share), Greek yogurt, high protein yogurt and milk protein milkshakes (up to 1000 mg / share).
Moreover, relevant studies have also confirmed that direct oral administration of UA can significantly improve the UA content in blood and achieve the same health benefits than taking UA rich foods such as pomegranate juice.
Metabolic synthesis differences among people, UA: my good, you may not enjoy it
Regarding UA supplementation, another bad news is that supplementing foods rich in UA precursors may not be effective for all people.
The reason for this unfair result is due to the differences of intestinal microbes in different human bodies.
Image source:https://decodeage.com/blogs/gut-microbiome/11-health-benefits-of-urolithin-a-on-ageing-muscle-endurance-and-gut-health-1
A study conducted by Tom á s-barber á n in 2014 showed that humans can be divided into three phenotypes according to the different metabolic and synthetic abilities of urolithin, namely, "phenotype a", "phenotype B" and "phenotype 0". Among them, only those with metabolic phenotype a can synthesize a large amount of urolithin a normally. ROC í o Garc í a-villalba found the fourth phenotype in 2019, "R", and this kind of population is also unable to synthesize urolithin a.
Cite:Ellagic Acid Metabolism by Human Gut Microbiota: Consistent Observation of Three Urolithin Phenotypes in Intervention Trials, Independent of Food Source, Age, and Health Status（https://pubs.acs.org/doi/10.1021/jf5024615）
Interestingly, other studies have shown that there is a correlation between urolithin metabolic phenotype and aging. In healthy young adults (5-30 years old), phenotype A accounts for about 70-80% and phenotype B for about 10-20%. With the increase of age (30-90 years), the proportion of phenotype a decreased, the proportion of phenotype B increased, and finally reached 50% and 40%, respectively, while the proportion of phenotype 0 (10%) remained basically unchanged.
Of course, if you unfortunately find yourself not a member of the "God selected a", you don't have to be too sad. We just can't supplement UA by eating food. As mentioned above, oral UA is also effective, or even better.
Xi'an Green Spring Technology Co., Ltd. is a manufacturer and supplier of natural sweeteners. We have been engaged in the production and sales of Urolithin A Powder for more than 22 years. We produce high-quality natural sweeteners, including stevia extract, erythritol, aloketose, momordica grosvenorii extract, etc. At the same time, we can customize compound sweeteners according to your needs.