Nootropics Depot: Bringing pharma-grade quality testing to botanical and mushroom supplements

Advancements in analytical instruments are closing the quality analysis gap between botanical supplements production and pharmaceutical rigor. With a suite of advanced testing methods, Nootropics Depot warns of the risks that come with “identity-only” botanical testing and reliance on “by input” paperwork that bypass actual bioactive assays. 

The US-based manufacturer and retailer operates multiple laboratories and production buildings equipped with analytical instrumentation and live-cell research capabilities, which are typically reserved for “Big Pharma” development, not conventional supplement manufacturing. This is done to ensure identity and bioactive potency of botanicals, which it says are uncommon in the wider US market.

Many botanical and fungi products in the US are marketed as dietary supplements, which are regulated by the FDA under the Dietary Supplement Health and Education Act. Unlike pharmaceutical products, supplements in the US do not require pre-market authorization but manufacturers must follow current good manufacturing practices to ensure their identity, purity, quality, strength, and composition.

Nootropics Depot’s facilities leverage a live-cell research program — featuring the Incucyte SX5 — to monitor real-time cellular responses to botanical ingredients like lion’s mane. The company notes that its analyses have revealed “repeated discrepancies” between labeled claims on botanical supplements and measured levels of key bioactives across products such as turkesterone, Ecklonia cava, and tongkat ali.

In this first part of an in-depth series on bridging pharma and nutrition quality analysis, Nutrition Insight speaks to Nootropics Depot founder and CEO, Paul Eftang, about the differences in analyses and testing methods legally required in these industries and opportunities for supplement brands to go beyond minimal requirements by testing for bioactive compounds.

What is missing from “lab tested” claims supplement brands make on botanical and fungi supplements?
Eftang: Most brands in the US supplement industry aren’t doing any lab testing of their botanical and fungi products. They are either using supplier certificates of analysis (COAs) from Chinese manufacturers or they are getting COAs from their contract manufacturers. Very few are actually testing at International Organization for Standardization (ISO) accredited labs.

Unlike pharmaceutical products, supplements in the US do not require pre-market authorization but manufacturers must follow current good manufacturing practices.Many of the companies that are testing will only be testing for heavy metals and microbial analysis. However, this testing isn’t doing the two most crucial things a lab test needs to do: testing for the identity of the ingredients and assaying for bioactives. Showing that your product doesn’t have a ton of heavy metals and microbes is a small part of what a quality system should have. If the product isn’t even what you say it is, and doesn’t contain any bioactives, then it’s a fraudulent product.

Several years ago, Amazon said it was going to force all supplement brands to show batch testing for every product sold on its site, and this testing needed to be done at an ISO accredited lab. This sounds good in theory, but the practical implementation of it has been anything but.

What some labs have done is allow what they are calling “by input testing,” which allows brands to send them their master batch records (MBRs). The lab then looks at the MBR, reads what the brand or contract manufacturer says they put in the product, and then issues a passing COA for it. So all a brand has to do is send an MBR that says there is 500 mg of lion’s mane in a sample.

Then the brand gets issued a passing COA that they use to get Amazon to allow them to sell it on the platform. No identity testing is done to show there is even lion’s mane in the sample, and no assay testing is done to show what quality of lion’s mane is in there, or if there are even any bioactives. It’s a document review, not lab testing.

What you should be asking is if brands are actually doing any real lab testing at all. The answer to that question will upset many people.

Why is there a public perception that the supplement industry is an “unregulated” market?
Eftang: There is a lot less money in the supplement industry than in pharma, so the capability gap can stem from a lack of funding to do the more sophisticated methodologies or testing. That’s absolutely the case with the race to the bottom on pricing.

However, what really results in the gap is the lack of strict regulations on how quality should be defined, and lack of consumers demanding those high standards from brands. The pharmaceutical industry has stricter guidelines for manufacturing and testing of finished products under the 21 Code of Federal Regulations (CFR) 211 regulations.

Under 21 CFR 111 for the supplement industry, manufacturers must use “appropriate tests or examinations” and “scientifically valid methods” that are “fit for the intended use.” The regulation requires adherence to recognized industry standards but does not mandate the same level of formal method validation documentation.

Eftang flags a lack of strict regulations on how quality should be defined, stressing the need for consumers to demand those high standards from brands.Under pharma’s 21 CFR 211.165(e): “The accuracy, sensitivity, specificity, and reproducibility of test methods employed shall be established and documented.” This requires formal analytical method validation, meaning each test method must be demonstrated to work reliably before it is used for batch release decisions.

Furthermore, §211.194(a)(2) requires that testing methods be verified under actual conditions of use. In supplements, the regulations require verification that controls are followed.

However, the concept of prospective process validation, demonstrated through documented evidence that a process consistently produces a product meeting specifications, is absent. This means that functionally, the supplement industry is given more general guidance on setting specifications and having processes to ensure you meet those specs, whereas the pharmaceutical industry has stricter guidance on exactly how those processes should be set up to ensure every dose of every batch meets very specific requirements.

The standards in the supplement industry should be held to a higher minimum standard for quality, but as of now, that is up to the individual brand and manufacturer to decide.

Why is compound‑specific testing critical for botanicals/mushrooms?
Eftang: This mainly comes down to two reasons: efficacy and consistency. Let’s talk about efficacy first. What consumers really care about when they take any supplement product is whether or not they get the effects they intend. What delivers those effects is not the mushroom or botanicals themselves, but the bioactives contained within them.

If you have a supplement that contains 500 mg of lion’s mane (Hericium erinaceus), but that lion’s mane is low quality and contains no bioactives, the consumer is not going to get the effects they expect.

Eftang highlights that many companies that are testing will only be testing for heavy metals and microbial analysis, rather than bioactives content. This is the primary reason standardization is necessary. It’s all about the benefits these supplements will give when consumed.

The second reason is consistency. Let’s say you have a batch of lion’s mane you released in 2023 that contained 1% erinacines. However, you are not standardizing to erinacines as part of your standardization protocol.

Hypothetically, when customers buy this initial batch, they love the effects they get and decide to only buy your lion’s mane going forward. Then let’s say you sell out of that batch, and you make a new lot of bottles from a new batch you get in 2024. This batch has 0% erinacines.

It still tests out as H. erinaceus. It’s still lion’s mane. It just doesn’t have bioactives. Customers then run out of their bottles they bought in 2023, rush to your store to buy another bottle, take the capsules and get zero of the effects they felt before.

Now, they start questioning whether or not they really did get benefits the first time, or if it was just a placebo effect. The brand technically didn’t lie. They never made an erinacine claim on the label, so this new batch doesn’t technically fail testing.

However, there is no consistency from batch-to-batch. Standardization ensures that your product will give the intended effect consumers expect, and that it delivers that intended effect every time they buy the product.