Promotional Features
Urolithin A: Why the gold standard is key for a healthy market
Recently, Urolithin A has attained an extremely high level of market popularity and shown a growth tendency (see figure 1 below).
However, for any new ingredient, there is inevitably a period of turbulence in quality standards. In the early stages, speculative enterprises entered the market with varying degrees of attention to detail or viewing Urolithin A as a commodity. For professional nutrition practitioners, reputation, company mission, and social responsibility are far more crucial to an enterprise than profit.
For Bonerge, anti-aging is a key focus and producing products that can be consumed with confidence is the original aspiration and mission of the Bonerge team. Bonerge aims to promote the positive development of high-quality standards within a healthy market.
Figure 1: Search of Urolithin A on Amazon.
A 2024 study tested the content of Urolithin A and nicotinamide mononucleotide (NMN) supplements available on the market, revealing surprising results.1 Among the 17 tested NMN supplements, the content varied from -100% to +11.2% compared to the label claims. For Urolithin A, the content varied from -15.5% to +28.6%.1
Whether it is a pharmaceutical or a health supplement, precise content is of utmost importance. Generally, the detection error of drug content should not exceed ±2%.2 A content that is either too low or too high indicates inconsistency of product quality. Such variances beyond this range are surprising for industry insiders and can cause concern among consumers.
Before the detection of NMN and Urolithin A, quality issues of multiple supplements have been reported successively, including berberine, astaxanthin, magnesium glycinate, quercetin, CoQ10, and so on.3 How many dietary supplements still carry quality risks? NMNH, nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide + hydrogen (NADH), calcium alpha-ketoglutarate (Ca AKG), magnesium taurine, and most liposomes. For berberine, the assay issue is just the beginning.
Let’s focus on the quality of Urolithin A. Firstly, we need to sort out some basic and important information (but easily overlooked).
Fundamental quality factors
1. Purity and assay/content
When it comes to detecting the content of active ingredients, purity and assay are two indicators commonly employed in the industry.
Purity detection is akin to playing hide and seek. One needs to be aware of the possible impurities in products manufactured by different processes and then identify these impurities. Meanwhile, assay detection is like a balance, with the Reference Substance (RS) serving as the weight on the balance. Thus, assay analysis is relatively easy to achieve fairness and impartiality.
Purity alone cannot represent the actual content of an ingredient. For some products, the so-called purity of 98% may in fact be less than 50% when assayed, or even 1%. A highly typical example is fisetin. Currently, a mainstream specification for commercially available fisetin is 98% purity and 85% assay. That is to say, although the purity test shows 98%, when detected with a standard substance, the actual content may only be 85%.
2. What conditions should a reliable RS fulfill?
A reliable RS should be characterized using various techniques including high-performance liquid chromatography (HPLC), inductively coupled plasma mass spectrometry (ICP-MS), nuclear magnetic resonance (NMR), fourier transform infrared spectroscopy (FTIR), among others.
It should also include a moisture, ash and inorganic impurity analysis, and provide an absolute content value.
● Fully characterized high purity pure materials and high purity diluents
● Careful assignment of chromatographic purity by multiple methods
● Analysis of residual impurities including water, inorganics and solvents
● Validation process ensuring consistency, accuracy and stability
● Using qualified scales that are accurately calibrated and with minimum increments set for <0.1% relative error
● Traceability to International System of Units (SI)
3. What methods can best determine product quality?
Quality inspection is designed to identify impurities in products to the maximum extent. The fundamental principle of various spectral detections is to use different lights to reveal different substances. Some impurities are visible to the naked eye, yet cannot be detected by HPLC. Different spectra are capable of detecting different substances.
Check the product from its appearance
In general, the higher the purity of a product, the more clean its color will be. For instance, high-quality Urolithin A has a clean, light yellowish hue. However, the colors of Urolithin A on the current market vary widely, ranging from light yellow, yellow, gray, off-white, to brownish-green.
Check the product from its solution
When a product is dissolved, some impurities that cannot be detected by HPLC can be easily observed. For instance, with the solution of Urolithin A, several tens of milligrams of material can be magnified several times, and the color of the product can be better displayed through the magnification effect. On the other hand, different solvents can reveal impurities that are invisible to the naked eye.
Check the assay of product by HPLC analysis
It is essential to measure the content of a product accurately by employing a validated detection method and an reliable reference standard.
Many companies are keen on promoting purity but it is important to understand the distinction between purity and assay. Additionally, the cost of undertaking a series of quality work is very high. The verification of testing methods and the expense of authoritative RS are costly.
So, what are the major quality problems that Urolithin A is confronted with?
Urolithin A quality voids
1. No authoritative RS available currently
Bonerge’s global research has not yet found accurately calibrated Urolithin A Reference Substances, concluding that, currently, only high-purity reagent-grade Urolithin A is available on the market, which is insufficient to serve as a reference standard for content determination.
Recommendation: Firstly, an authoritative institution is called upon to develop an accurate RS as soon as possible. Secondly, raw material suppliers should consider strictly formulating internal RS controls referring to the methods of Primary Reference Standards.
2. Lack of authoritative testing method
Regarding the purity or assay detection of commercial products, it is essential to develop appropriate detection methods based on a comprehensive understanding of the production process. This is to identify and detect impurities that may emerge during production to the greatest extent possible. The detection method for any product must undergo method validation to demonstrate the reliability of the method. An unvalidated method may encounter problems of incompatibility.
Recommendation: Carry out a systematic examination of the detection methods following ICH guidelines and identify deficiencies for improvement and optimization to guarantee the adaptability of the methods.
3. Raw material manufacturers vary in quality
Recommendation: Make the information of raw material manufacturers transparent throughout the supply chain. It would be even better to include the raw material manufacturer on the label to make it transparent to consumers
4. The production technology of different contract manufacturers is uneven
Similar to raw material manufacturers, in recent years, contract manufacturers have obtained orders through price competition but can lack an appropriate quality management system and production techniques. This has resulted in many product quality problems and inconsistencies in quality.
As a raw material supplier dedicated to dietary supplement raw materials as a lifelong pursuit, questions have lingered for Bonerge:
How can consumers be reassured? What actions can be taken to promote the healthy development of this quality ingredient?
Million Dollar Guaranteed Urolithin A
After many discussions internally, the team at Bonerge made a decision: Bonerge would be willing to offer quality assurance for its Urolithin A and hope that other raw material enterprises in the industry can do the same.
An industry always needs pioneers and Bonerge is willing to provide its quality assurance plan – ’Million Dollar Guaranteed Urolithin A’. If there is any quality issue with its Urolithin A, Bonerge promises to pay ten times of its product value. Bonerge is willing to use its reputation to improve the quality standard of Urolithin A.
At Bonerge, work ethic is focused on the effort, not only the reward.
References
1. Sandalova, E.; Li, H.; Guan, L. et al. (2024). Testing the amount of nicotinamide mononucleotide and urolithin A as compared to the label claim. GeroScience 46, 5075–5083.
2. Accuracy. AOAC Guidelines for Single Laboratory Validation of Chemical Methods for Dietary Supplements and Botanicals. 2002
3. NOW. NOW uncovers quality issues for supplement brands sold on Amazon.
